Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Δευτέρα 10 Σεπτεμβρίου 2018

Prevalence of Phototherapy in the Age of Biologics

Background: The prevalence of narrow-band ultraviolet B (NB-UVB) use in Europe for moderate and severe psoriasis is unknown, because national registries for psoriasis do not monitor this treatment. Objectives: To quantify the use of phototherapy, biologics or conventional treatments in psoriasis, in a setting where European Medicines Agency (EMA) eligibility criteria for biologics were strictly applied, and phototherapy was included among first-line treatments. Methods: We followed a cohort of 1,090 patients who were referred to the only centre entitled to prescribe biologics and phototherapy during a 5-year period. Results: The cumulative number of treatment cycles was: 1,047 with NB-UVB phototherapy, 650 with systemic treatments and 239 with biologics; 754 patients received at least 1 course of NB-UVB phototherapy, 422 at least 1 course with a systemic treatment and 137 with a biologic; 595 patients were treated only with phototherapy. Conclusions: Regular use of NB-UVB as first-line treatment for moderate and severe psoriasis and adherence to the EMA eligibility criteria for biologics led to a relatively restricted use of biologics.
Dermatology

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Epidemiological and Clinical Patterns of Kaposi Sarcoma: A 16-Year Retrospective Cross-Sectional Study from Yaoundé, Cameroon

Background: The burden of Kaposi sarcoma (KS) is increasing fast among HIV-infected populations, but the disease remains desperately underexplored in Cameroon, where the burden of HIV is high. Methods: This is a retrospective cross-sectional study carried out over a period of 16 years (January 2001 to December 2016) at the HIV day care unit of the Central Hospital of Yaoundé, Cameroon. The diagnosis was based on clinical aspects and histological confirmation, and we used a preconstructed questionnaire for data collection through patients' electronic and physical files. Results: Among 14,220 files reviewed, 316 cases of KS were identified, yielding a cumulative incidence of 2.2%. In the end, 266 patients (55% male) were included in this study. The patients' age ranged from 17 to 72 years, with a mean of 37.8 ± 9.5 years. KS was the presenting manifestation of HIV in 89.8% of the cases. Cutaneous lesions occurred more often (81.6%), mainly located on the lower limbs (47.7%); mucous lesions were found in 15.8% of the patients, while 8 patients (3.0%) had associated visceral lesions. The lesions predominantly were lymphedemas (28.6%) and papulonodules (21.1%). At the diagnosis of KS, the median CD4 count was 175 cells/mm3 (interquartile range 80.5–288.5), and 150 patients (56.6%) had CD4 counts #x3c; 200 cells/mm3. Conclusions: KS is frequent among our HIV-infected patients; it seems to occur most often at a younger adult age and represents one of the presenting manifestations of HIV/AIDS in our context. It seems to equally affect men and women, occurring more often when CD4 counts are #x3c; 200 cells/mm3.
Dermatology

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Intracranial bleeding (ICB) as a catastrophic complication of Streptococcus gordonii infective endocarditis (IE) in an immunocompetent patient

We present an interesting case of late-onset intracranial bleeding (ICB) as a complication of Streptococcus gordonii causing infective endocarditis. A previously healthy young woman was diagnosed with infective endocarditis. While she was already on treatment for 2 weeks, she had developed seizures with a localising neurological sign. An urgent non-contrasted CT brain showed massive left frontoparietal intraparenchymal bleeding. Although CT angiogram showed no evidence of active bleeding or contrast blush, massive ICB secondary to vascular complication of infective endocarditis was very likely. An urgent decompressive craniectomy with clot evacuation was done immediately to release the mass effect. She completed total 6 weeks of antibiotics and had postoperative uneventful hospital stay despite having a permanent global aphasia as a sequel of the ICB.



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Rare cause of gastric outlet obstruction: xanthogranulomatous cholecystitis

Description 

A 62-year-old Indian female patient presented with right upper quadrant pain and multiple episodes of vomiting for 10 days. She denied history of fever, jaundice, past anorexia/weight loss and previous surgeries. She was dehydrated, tachycardia (120/min) was present, and there was tenderness in the right upper quadrant. Routine investigations revealed presence of anaemia (haemoglobin 9.1 g/dL), raised total leucocyte counts (17 x10^9/L) and hypokalaemia (2.8 mEq/L). All other blood tests (liver function/kidney function/blood sugar and coagulation profile) were normal. Patient was stabilised with intravenous fluids, antibiotics and other supportive management. Imaging with ultrasound (USG) was suboptimal due to the massive intestinal gas and uncooperative nature of the patient. A collapsed gallbladder (GB) and a mass with a smooth curvilinear surface and posterior acoustic shadowing in the distal part of the duodenum were the only distinguishable findings. Due to repeated episodes of vomiting, the patient underwent an upper gastrointestinal endoscopy, which was...



https://ift.tt/2CJ60d5

Tubercular septal abscess in a postoperative patient: a novel entity

Extrapulmonary tuberculosis is a rather uncommon and potentially challenging phenomenon. Such manifestation, particularly in the scenario of a late postoperative period, is extremely rare and requires a high index of suspicion, prompt diagnosis and appropriate treatment.

We present the case scenario of a patient with history of successfully treated pulmonary tuberculosis many years earlier, without any signs of recurrence, who developed primary nasal septal tuberculosis after undergoing septoplasty to correct his septal deviation. His postoperative course remained uneventful for 4 months. He then presented with a spontaneous nasal septal abscess, which proved to be tubercular in nature on investigations. Appropriate diagnosis was established, and the patient was treated successfully with antituberculous therapy.

Recurrent tuberculosis may present a diagnostic challenge for healthcare professionals. Only a high index of suspicion, modern diagnostic tools and institution of appropriate treatment including surgical intervention as required will ensure a promising outcome.



https://ift.tt/2x4Hpdq

Penile cutaneous horn: still an enigma

Description

A 60-year-old man with history of Johanson's staged urethroplasty for pan anterior urethral stricture due to lichen sclerosus et atrophicus 3 months previously presented to us with a cutaneous horn over his glans penis. This horn was previously excised superficially, and now had recurred over the same site in the last 1 month. It was initially small in size and then gradually increased to a size of around 2.5 cm (figure 1). The patient had no documents mentioning the histopathology of previously excised horn. The patient had been circumcised in childhood. He had no history of genital malignancy or other factors that could have been implicated in cutaneous horn formation. He was managed with excision of the horn along with deep biopsy from base of the lesion to rule out any malignant pathology. The excision site healed well, and biopsy revealed benign pathology. At present, patient has...



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Unusual right internal carotid artery supraclinoid segment fenestration associated with multiple aneurysms treated with flow diversion and coiling

Description 

The supraclinoid (carotid-ophthalmic) segment of the internal carotid artery (ICA) under the Bouthillier classification is defined as the segment between the ophthalmic and posterior-communicating arteries.1 We describe an unusual congenital anomaly of the supraclinoid internal carotid artery characterised by a large fenestration of its carotid-ophthalmic segment, associated with multiple aneurysms.

A 60-year-old female patient underwent investigation for persistent headaches and was found to have what appeared to be irregular fusiform dilatation of the intracranial right internal carotid artery on 1.5 T magnetic resonance angiography (MRA) time-of-flight imaging. Cerebral digital subtraction angiography (DSA) performed to further characterise this abnormality demonstrated two discrete aneurysms, one measuring 5 mm and the other 2 mm, arising from the posterior limb of a supraclinoid ICA fenestration (figure 1A).

Figure 1

(A) Three-dimensional reconstruction of a rotational digital subtraction angiogram (DSA) demonstrating the supraclinoid right internal  carotid  artery  (ICA) fenestration....



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Drug-induced autoimmune hepatitis associated with turmeric dietary supplement use

Turmeric dietary supplement sales, which accounted for US$69 million in spending in 2016, have been increasing exponentially in the USA, making this one of the most popular botanical supplements sold in the USA. Herbal supplement use, which is generally regarded as safe by consumers, is not usually reported to healthcare providers. We reported here on a case of autoimmune hepatitis, occurring in a 71-year-old woman taking turmeric dietary supplements for the maintenance of cardiovascular health, which resolved rapidly following discontinuation of the turmeric supplements. Of particular note, turmeric use was not documented in the patient's medical records and the potential causative role of the turmeric supplementation was ultimately identified by the patient rather than the healthcare providers. To our knowledge, this is the first documented report of turmeric supplement-induced autoimmune hepatitis.



https://ift.tt/2CHeHEJ

Gender differences in doxorubicin pharmacology for subjects with chemosensitive cancers of young adulthood

Abstract

Purpose

For many cancers, adolescents and young adults (AYA) have worse outcomes than for children and adults. Many factors may contribute to the AYA survival gap, including differences in biology, therapeutic intent, and adherence to therapy. It has been observed that male AYAs have poorer outcomes than females. The purpose of this work was to test the proposition that gender-related pharmacologic factors may account for a component of the AYA survival gap.

Patients and methods

A prospective, multi-institutional pharmacologic study of 79 patients in total with chemosensitive cancers (Ewing sarcoma, osteosarcoma and Hodgkin lymphoma) was conducted, with conventional doxorubicin treatment. Pharmacokinetic data of 13 children, 40 AYAs and 13 adults were valid for analysis. Population pharmacokinetics models were developed for doxorubicin and its metabolite doxorubicinol based on the data created in this study. Consequently, model-based analysis was conducted to investigate the relevant topics.

Results

The clearance of doxorubicinol (normalized to body surface area), the main active metabolite of doxorubicin, appears faster in male AYAs than female (p = 0.04, 95% CI 0.1–3.9 L/h). The exposure of doxorubicinol (normalized to dose) is lower in male AYA than female (p = 0.03, 95% CI − 0.005 to − 0.0002 h/L). These might be correlated to the observed difference on nadir neutrophil count between male AYA and female (p = 0.027, 95% CI 0.09–1.4).

Conclusion

Gender-related differences in doxorubicin pharmacology may account for worse outcomes for male AYAs with chemosensitive cancers compared to females. These findings may reduce the AYA survival gap compared to other age groups.



https://ift.tt/2NuP6Dn

Characterization of bacterial and microbial eukaryotic communities associated with an ephemeral hypoxia event in Taihu Lake, a shallow eutrophic Chinese lake

Abstract

While the important roles of microbial communities in oceanic hypoxic zones were beginning to be understood, little is known about microbial community associated with this phenomenon in shallow lakes. To address this deficit, both the bacterial and microbial eukaryotic communities of an ephemeral hypoxic area of Taihu Lake were characterized. The hypoxia provided nutritional niches for various bacteria, which results in high abundance and diversity. Specific bacterial groups, such as vadinBC27 subgroup of Bacteroidetes, Burkholderiales, Rhodocyclales, Pseudomonas, and Parcubacteria, were dominated in hypoxic sites and relevant to the fermentation, denitrification, nitrification, and sulfur metabolism. Conversely, most of microbial eukaryotes disappeared along with the decline of DO. An unexpected dominance of fungi was observed during hypoxia, which partly explained by the accumulation of toxic algae. Mucor was the single dominant genus in the hypoxic zone. We proposed that this group might cooperate with bacterial communities in the anaerobic degradation of algal biomass and woody materials. Generally, the hypoxic microbiome in shallow lakes is mainly involved in fermentative metabolism depending on phytodetritus and is potentially influenced by terrestrial sources. This study provided new insights into the unique microbiome in short-term hypoxia in shallow lakes and lays the foundation for studies that will enhance our understanding of the microbial players associated with hypoxia and their adaption strategy on the global scale.



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Current Utilization of Biologicals

FACIAL PLASTIC SURGERY CLINICS OF NORTH AMERICA

https://ift.tt/2x2F3v0

Copyright

ELSEVIER

https://ift.tt/2Nxl021

Forthcoming Issues

Skin Cancer Surgery

https://ift.tt/2x63uaI

Contributors

J. REGAN THOMAS, MD

https://ift.tt/2NyxXIM

Contents

Gregory S. Keller

https://ift.tt/2x63lnG

Oncogenic MYD88 mutations in lymphoma: novel insights and therapeutic possibilities

Abstract

Oncogenic MYD88 mutations, most notably the Leu 265 Pro (L265P) mutation, were recently identified as potential driver mutations in various B-cell non-Hodgkin Lymphomas (NHLs). The L265P mutation is now thought to be common to virtually all NHLs and occurs in between 4 and 90% of cases, depending on the entity. Since it is tumor-specific, the mutation, and the pathways it regulates, might serve as advantageous therapeutic targets for both conventional chemotherapeutic intervention, as well as immunotherapeutic strategies. Here, we review recent progress on elucidating the molecular and cellular processes affected by the L265P mutation of MYD88, describe a new in vivo model for MyD88 L265P-mediated oncogenesis, and summarize how these findings could be exploited therapeutically by specific targeting of signaling pathways. In addition, we summarize current and explore future possibilities for conceivable immunotherapeutic approaches, such as L265P-derived peptide vaccination, adoptive transfer of L265P-restricted T cells, and use of T-cell receptor-engineered T cells. With clinical trials regarding their efficacy rapidly expanding to NHLs, we also discuss potential combinations of immune checkpoint inhibitors with the described targeted chemotherapies of L265P signaling networks, and/or with the above immunological approaches as potential ways of targeting MYD88-mutated lymphomas in the future.



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TUEF2016-environmental pollution: problem and solution



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Penicillin allergy skin testing is safe in pre-lung transplant patients with low lung volumes

Penicillin allergy is the most frequently reported drug hypersensitivity reaction with a prevalence rate of around 10% in the US 1,2; however, true reactions exist in only around 3% of patients reporting a penicillin allergy 2. Penicillin allergy stigma results in higher health care costs and increased prevalence of multidrug resistant (MDR) organisms. In the pre-lung transplant population there are no data on penicillin skin testing in the setting of severely compromised lung function.

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Comparing Asthma Control Questionnaire (ACQ) and National Asthma Education and Prevention Program (NAEPP) Asthma Control Criteria

Adequate assessment of control is critical to asthma management. The Asthma Control Questionnaire (ACQ) and the National Asthma Education and Prevention Program (NAEPP) criteria are commonly used measures of asthma control.

https://ift.tt/2OdJ8Uc

How Do the Accrual Pattern and Follow‐Up Duration Affect the Hazard Ratio Estimate When the Proportional Hazards Assumption Is Violated?



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Results from a Monocentric Long‐Term Analysis of 23 Patients with Ovarian Sertoli‐Leydig Cell Tumors

AbstractBackground.Sertoli‐Leydig cell tumors (SLCTs) represent less than 0.5% of ovarian tumors. Because of the rarity of this tumor and its peak in frequency at around 25 years of age, this study aimed to describe SLCT management strategies.Objective.The objective of this study was to determine the management (i.e., conservative surgery and adjuvant chemotherapy) of ovarian SLCTs.Results.This retrospective analysis included 23 patients treated for ovarian SLCTs. A centralized pathologic review of the tumors was conducted. Patients were referred to or treated in our institution for an ovarian SLCT between 1994 and 2015. The median age at diagnosis was 33 years (range, 4–82 years). According to the 2014 Federation of Gynecology and Obstetrics classification, tumors were classified as stage Ia (n = 15: well differentiated, n = 1; of intermediate differentiation, n = 8; undifferentiated, n = 4; and undefined, n = 2), stage Ib (n = 1), stage Ic1 (n = 5), stage IIb (n = 1), and stage IIIc (n = 1). Surgery was conservative in 13 patients (Ia, n = 7; Ib, n = 1; Ic1, n = 5) and radical in 10 patients (Ia, n = 8; IIb, n = 1; IIIc, n = 1). Seven patients received adjuvant chemotherapy with a cisplatin‐based regimen (Ia, n = 2; Ic1, n = 3; IIb, n = 1) or docetaxel + gemcitabine (IIIc, n = 1). Median follow‐up was 61 months (range, 15–252 months). Eight patients experienced a relapse (Ia, n = 2; Ib, n = 1; Ic1, n = 3; IIb, n = 1; IIIc, n = 1). Of these, six had at least one peritoneal carcinomatosis, and four died (Ic1, n = 2; IIb, n = 1; and Ia, n = 1). Two patients had a local relapse (one uterus and one ovary) and survived without disease after relapse treatment. The median time between the initial treatment and relapse was 28 months (range 9–70).Conclusion.Conservative surgery was safe for patients with stage Ia ovarian SLCTs. The place of conservative surgery for stage Ic1 remains to be defined. The best chemotherapy regimen remains to be defined.Implications for Practice.For stage Ia disease, conservative surgery (in women of reproductive age) was safe and effective for treating ovarian Seroli‐Leydig cell tumors. Adjuvant chemotherapy should be proposed for stage Ia when poor prognostic factors are present (poor differentiation, retiform pattern, or heterologous elements). For stage Ic1 and more severe stages, radical surgery and adjuvant chemotherapy should be considered. The combination of bleomycin, etoposide, and cisplatin was the most frequently used regimen, but the best chemotherapy regimen remains to be defined.

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Ivermectin-induced fixed drug eruption in an elderly Cameroonian: a case report

Cutaneous adverse reactions to medications are extremely common and display characteristic clinical morphology. A fixed drug eruption is a cutaneous adverse drug reaction due to type IV or delayed cell-mediate...

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Distinguishing histopathologic features of acantholytic dermatoses and the pattern of acantholytic hypergranulosis

Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.


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Specialized group intervention for compulsive exercise in inpatients with eating disorders: feasibility and preliminary outcomes

Abstract

Background

Patients with eating disorders (ED) often suffer from compulsive exercise behavior, which is associated with lower short-term response to treatment and poorer long-term outcome. Evidence-based interventions specifically targeting compulsive exercise behavior have been scarce so far. We developed a manualized group therapeutic approach integrating cognitive-behavioral therapy, exercise therapy and exposure with response management to promote healthy exercise behavior. Our objective was to examine the feasibility and acceptance of this new approach as add-on to regular inpatient treatment in a pilot study. Additionally, we wanted to estimate preliminary effect sizes.

Methods

Thirty-two female, adolescent and adult eating disordered inpatients were recruited. According to the 4th ed. of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), twenty-six patients met criteria for Anorexia nervosa (AN), two for Bulimia nervosa and four for eating disorder not otherwise specified. Semi-structured interviews were conducted for qualitative evaluation of feasibility and acceptance of the new intervention. Patients completed the Commitment to Exercise Scale (CES) and the Compulsive Exercise Test (CET) for assessment of compulsive exercise, the Eating Disorder Inventory-2 for assessment of eating disorder pathology, the Beck Depression Inventory-II and Brief Symptom Inventory for assessment of depressive and general psychopathology and the Emotion Regulation Skills Questionnaire for assessment of emotion regulation before the beginning and at the end of the group intervention. Additionally, weight gain was monitored.

Results

Feasibility of our approach was confirmed. All patients reported a high satisfaction with both structure and content of the group. Between pre- and post-intervention, patients showed significant reductions in compulsive exercise (effect size CES: 1.44; effect size CET total: 0.93), drive for thinness (effect size: 0.48), depressive symptoms (effect size: 0.36), general psychopathology (effect size: 0.29) and acceptance of emotions (effect size: − 0.62). Patients with AN also showed significant mean weight gain during the intervention (effect size: − 0.44).

Conclusions

Results of our pilot study indicate that our integrative approach to compulsive exercise in ED patients might represent a promising new therapeutic option. Feasibility and acceptance of the intervention were confirmed. Preliminary effect sizes on most outcomes were promising. As improvements in Body-mass-index, eating disorder and general psychopathology are also to be expected by routine inpatient treatment, a large randomized trial is currently underway to evaluate the efficacy of this new intervention.



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Prevalence of disturbed eating behavior and associated symptoms of anxiety and depression among adult males and females with type 1 diabetes

Abstract

Background

The increased prevalence of disturbed eating behaviors (DEB), depression, and anxiety in type 1 diabetes (T1D) is generally well established; however the majority of existing research to date has focused on female adolescents and young adults. Data on males and older females is scarce. The aim of this study was to assess prevalence of DEB and symptoms of depression and anxiety among adult males and females with type 1 diabetes, to investigate differences between individuals scoring below and above the cut-off on psychopathology, and to examine patterns of eating disorder psychopathology by age and weight.

Methods

A total of 282 adults with type 1 diabetes aged 18–79 years participated in the study. Measures included the Diabetes Eating Problem Survey – Revised (DEPS-R), the Hospital Anxiety and Depression Scale (HADS), and clinical data from the Norwegian Quality Improvement of Laboratory Examinations (NOKLUS) system.

Results

A total of 20.3% of the whole sample (13.3% among males and 24.8% among females) scored above the DEPS-R cut-off score for DEB. As for depression and anxiety, the prevalence in the whole sample was 6.2% and 19.0%, respectively. The prevalence was generally higher in females than males across all psychopathology measures. HbA1c was significantly associated with the DEPS-R total score (p < .01) among females, but not with depression and anxiety. Mean DEPS-R score decreased with increasing age, and when our previous reported data from children and adolescents are included, a peak prevalence in DEB in adolescence and young adult age is demonstrated.

Conclusions

The results of this study point to the need for increased awareness of psychological comorbidity among adults with type 1 diabetes, in particular young adult females. Screening is recommended to secure early detection and subsequent intervention for these individuals.



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Anti‐inflammatory and antiradical effects of a 2% diosmin cream in a human skin organ culture as model

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2x1dgvu

Minimally invasive approaches to axillary osmidrosis treatment: A comparison between superficial liposuction with automatic shaver curettage, subcutaneous laser treatment, and microwave‐based therapy with a modified technique

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2O6ds3h

Anti‐inflammatory and antiradical effects of a 2% diosmin cream in a human skin organ culture as model

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2x1dgvu

Minimally invasive approaches to axillary osmidrosis treatment: A comparison between superficial liposuction with automatic shaver curettage, subcutaneous laser treatment, and microwave‐based therapy with a modified technique

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2O6ds3h

Lead exposure from households and school settings: influence of diet on blood lead levels

Abstract

Lead is known as a potent toxicant to human health, particularly for children while their central nervous system is developing. The aim of this study was to investigate the associations between blood lead levels (BLLs) and lead exposure in the children's diet, home, and school environments. A cross-sectional study was conducted with 153 children aged 1–4 years, in four day care centers (DCCs), where a high prevalence of lead exposure was previously found. Lead determination by graphite furnace atomic absorption spectrometry (GF-AAS) was performed for venous blood, drinking water collected in the DCCs, and the 24-h diet (n = 64). Environmental screenings were conducted to evaluate lead concentrations in the tableware, buildings, and playground items in all DCCs and children's homes (n = 18) by using a field-portable X-ray fluorescence analyzer (FP-XRF). The BLL mean was 2.71 μg dL−1. Means for 24-h lead concentrations in the diet were 1.61 and 2.24 μg kg−1 of body weight (BW) in two DCCs. Lead concentrations in the water supply were lower than 2 μg L−1. More than 11% of the DCCs' environmental analyses presented lead concentrations higher than or equal to 1 mg cm−2, as defined by the USEPA. The diet was not found to be a risk factor for lead exposure, but households and DCC settings raised concern. Children's exposure to lead in DCC environments, where they spend the most part of their weekdays, appeared to be relevant.

Graphical abstract



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Adsorption of basic and reactive dyes from aqueous solution onto Intsia bijuga sawdust-based activated carbon: batch and column study

Abstract

The adsorption behavior of basic, methylene blue (MB), and reactive, remazol brilliant violet 5R (RBV), dyes from aqueous solution onto Intsia bijuga sawdust-based activated carbon (IBSAC) was executed via batch and column studies. The produced activated carbon was characterized through Brunauer-Emmett-Teller (BET) surface area and pore structural analysis, proximate and ultimate, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). Batch studies were performed to investigate the effects of contact time, initial concentration, and solution pH. The equilibrium data for both MB and RBV adsorption better fits Langmuir model with maximum adsorption capacity of 434.78 and 212.77 mg/g, respectively. Kinetic studies for both MB and RBV dyes showed that the adsorption process followed a pseudo-second-order and intraparticle diffusion kinetic models. For column mode, the breakthrough curves were plotted by varying the flow rate, bed height, and initial concentration and the breakthrough data were best correlated with the Yoon-Nelson model compared to Thomas and Adams-Bohart model. The adsorption activity of IBSAC shows good stability even after four consecutive cycles.



https://ift.tt/2oWpSzH

Roles of hydrophobic and hydrophilic fractions of dissolved organic matter in sorption of ketoprofen to biochars

Abstract

Hydrophobic acid (HoA) and hydrophilic neutral (HiN) are two major fractions of dissolved organic matter (DOM). Their role in the sorption of ketoprofen (KTP) to wheat straw-derived biochars pyrolyzed at 300 °C (WS300) and 700 °C (WS700) was investigated to further probe the mechanisms responsible. WS700 has much higher pore volume and specific surface area (SSA) than WS300. Loading of HoA and HiN resulted in surface coverage of biochars. HoA with larger molecular size led to more pore blockage of biochars than HiN. Higher HoA binding affinity also caused a stronger competition with KTP on biochars. These factors reduced the accessibility of sorption sites for KTP, and significantly inhibited KTP sorption to biochar of lower SSA (i.e., WS300) by HoA. Water solubility (Sw) of KTP was slightly enhanced (3%) in the presence of HoA. In contrast, the presence of HiN reduced (22%) Sw of KTP. The decreased Sw of KTP by HiN exerted a more dominant influence than its competitive and loading effects, thus led to apparent enhanced sorption of KTP, especially to biochar of higher SSA (i.e., WS700). The results demonstrated the diverse effects of HoA and HiN on KTP sorption, which is helpful in understanding pharmaceutical-DOM-biochar interactions and environmental behaviors of pharmaceuticals.



https://ift.tt/2MlUWCa

Utilization of freshwater mussel ( Lamellidens marginalis ) for the isolation of proteins through pH shift processing: characterization of isolates

Abstract

Study was conducted to use underutilized freshwater mussel (Lamellidens marginalis) for the recovery of proteins using pH shift method and to study the functionality and characteristics of the recovered isolates. From the pH range tested (pH 2.0–13.0), maximum protein yields were obtained during solubilization at pH 2.0 and pH 13.0 (p < 0.05). During the protein recovery process, pH 13.0 was found to have minimal effect on proteins resulting in higher protein yields compared to pH 2.0. Isolates obtained by both acidic and alkaline solubilization processes had low stability and poor gel network. Total lipid content, total myoglobin, and pigment contents were reduced significantly (p < 0.05) during pH shift processing, resulting in whiter protein isolates and protein gels. All the essential amino acids were present in the isolates recovered by acid and alkaline solubilization, indicating the complete recovery of amino acids. No microbial counts were observed in any of the isolates prepared using acid and alkaline-aided processing. Acid and alkaline solubilization (pH shift) process was found to be promising for the recovery of proteins from underutilized freshwater mussel thus by reducing the supply demand gap.



https://ift.tt/2oWwuhr

Air pollution control and flue gas desulfurization residues from Polish copper smelting facility as adsorbents of Pb(II) and Cu(II) from aqueous solutions

Abstract

This study aimed at evaluation of air pollution control residues (APCR) and flue gas desulfurization residues (FGDR) from copper foundry in Southwestern Poland as adsorbents of Cu(II) and Pb(II) from simulated wastewater. Studies of the impact of pH and adsorbent dose, as well as sorption isotherms, and kinetic and thermodynamic studies were conducted in a series of batch experiments. The maximum adsorption capacities were equal to 42.9 mg g−1 Cu(II) and 124.4 mg g−1 Pb(II) for APCR and 98.8 mg g−1 Cu(II) and 124.7 mg g−1 Pb(II) for FGDR, which was comparable to mineral adsorbents examined in other studies. Adsorption isotherms followed the Langmuir model, except for Pb(II) for FGDR, which followed Freundlich model. Sorption kinetics for both materials was properly expressed by pseudo-second-order equation. Mean adsorption energy parameter suggested that the adsorption might have occurred via physical bonding. Thermodynamic study revealed that adsorption was spontaneous and endothermic for Cu(II) and not spontaneous and exothermic for Pb(II), with lower temperature favoring the process. The results suggested that both materials had high affinity towards Cu(II) and Pb(II) ions and could be conducted industrial scale research for consideration as potential adsorbents from aqueous solutions.



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Interaction Between Lactate and Uric Acid is Associated With a Higher Prevalence of Metabolic Syndrome: A Community-Based Study

05-2018-0214-dia_10-1055-a-0672-0908-1.j

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0672-0908

Background Increased blood lactate or uric acid (UA) levels are associated with an increased risk of metabolic syndrome (MS). The aim of this study was to investigate the effect of an interactive association between blood lactate and UA levels on MS. Methods This community-based cross-sectional study included 2584 Chinese subjects aged ≥ 18 years. Participants were classified into 3 groups based on lactate or UA level tertiles or into 9 groups based on a combination of lactate and UA level tertiles. Results The serum high-sensitivity C-reactive protein (hs-CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) levels and odds ratios (ORs) for MS increased across the blood lactate or UA level tertiles (all P for trend<0.05). Interactions between lactate and UA with hs-CRP level, HOMA-IR level, and ORs for MS (P<0.05 for all interactions) were also observed. The adjusted ORs for MS in participants in the third tertile of lactate and UA levels, in the third tertile of lactate levels and first tertile of UA levels, and in the first tertile of lactate levels and third tertile of UA levels were 6.02 (95% CI 2.87–12.64, P<0.001), 2.92 (95% CI 1.39–6.10, P=0.005), and 2.70 (95% CI 1.23–5.96, P=0.014), respectively, compared with those in the first tertiles of both lactate and UA levels. Conclusion The interaction between lactate and UA is associated with a higher prevalence of MS in the Chinese population.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Inherited Forms of Primary Hyperaldosteronism: New Genes, New Phenotypes and Proposition of A New Classification

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0713-0629

Primary aldosteronism is a common cause of endocrine hypertension. It results from the excess production of aldosterone by the adrenal cortex and is related to increased morbidity and mortality. Most cases of PA are sporadic but inherited patterns of the disease have been reported in the literature. Four forms of familial hyperaldosteronism (FH-I- FH-IV) are currently recognized, and the genetic basis has been clarified in recent years. In FH-I patients, aldosterone excess is produced by a CYP11B1/CYP11B2 fusion gene and it is suppressed by glucocorticoid treatment. FH-II is caused by mutations in the inwardly rectifying chloride channel CLCN2. FH-III is caused by mutations in KCNJ5, a gene coding for an inward rectifier K+ channel and mutations in the T-type calcium channel subunit CACNA1H cause FH-IV. In this review we summarize the knowledge on inherited forms of primary aldosteronism, the genetic alterations that cause them and the implications it may have for the classification. Based on current evidence, we propose the term "familial hyperaldosteronism" to refer only to inherited forms of primary aldosteronism with a known genetic basis.
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© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
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Sarcopenia – Endocrinological and Neurological Aspects

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0672-1007

Sarcopenia in geriatric patients is often associated with or even caused by changes of the endocrine and nervous system. The multifactorial pathogenesis of sarcopenia and additional multimorbidity in geriatric patients makes it difficult to study distinct pathogenic pathways leading to sarcopenia. Patients suffering from diabetes, Cushing's syndrome, chronic kidney disease, Klinefelter's syndrome or motor neuron diseases, such as amyotrophic lateral sclerosis for example are known to have impaired muscle property and reduced physical performance. These patients are typically younger and suffer from conditions caused by a known molecular disease mechanism and a peculiar sarcopenic phenotype. Therefore, these sequelae can serve as prototypic disease models to study isolated endocrinological and neurodegenerative causes for sarcopenia. This review focuses on diseases whose etiopathogenesis of muscle impairment is known. The idea is to use these diseases as proof of principles to develop a classification algorithm of sarcopenia in the elderly to make a more mechanism-oriented therapy be possible.
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© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text



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Selected trace elements and metals in groundwater within Permian sediments near Olkusz (Zn-Pb ore mining region, S Poland)

Abstract

The extensive mining of Zn-Pb ores in the Olkusz region resulted in significant changes of both water table level and chemical composition of water in all aquifers in the area. This was caused by intensive dewatering of mining excavations and development of a thick aeration zone reaching 150 m in a central part of the area. That created favorable conditions for oxidation of metal sulfides occurring in the ore-bearing dolomites (Middle Triassic) and started the process of forming readily soluble hydroxysulphates which then migrated to lower aquifers, including the Permian. As a result of those processes, various metals and other elements toxic to the water environment appeared in leaks observed in mine galleries. Changes in concentrations of selected elements (Fe, Mn, Zn, Pb, Cu, Ba, Ni, Co, As, Cr, Hg, Tl, Ag, Cd, B) in mine waters over the period of the last nearly 50 years were described. Water samples were collected from exploratory boreholes, piezometers, and wells located in investigated area inflows and seepages occurring in shafts and drifts excavated in Permian conglomerates. Mean concentrations of metals (Pb, Cd, Cr, Hg, Tl) and other toxic elements were surprisingly low; Pb, 3.94 μg/L; Cd, 0.2 μg/L; Cr, up to 2.26 μg/L; Hg, 0.25 μg/L; Tl, 3.59 μg/L; and As, 6.31 μg/L. However, the observed concentrations varied significantly over time, reaching respectively up to 190 μg Pb/L, 60 μg Cd/L, 15.6 μg Cr/L, 2.67 μg Hg/L, 81.3 μg Tl/L, and 155 μg As/L.



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Inhibiting IDO pathways to treat cancer: lessons from the ECHO-301 trial and beyond

Abstract

With immunotherapy enjoying a rapid resurgence based on the achievement of durable remissions in some patients with agents that derepress immune function, commonly referred to as "checkpoint inhibitors," enormous attention developed around the IDO1 enzyme as a metabolic mediator of immune escape in cancer. In particular, outcomes of multiple phase 1/2 trials encouraged the idea that small molecule inhibitors of IDO1 may improve patient responses to anti-PD1 immune checkpoint therapy. However, recent results from ECHO-301, the first large phase 3 trial to evaluate an IDO1-selective enzyme inhibitor (epacadostat) in combination with an anti-PD1 antibody (pembrolizumab) in advanced melanoma, showed no indication that epacadostat provided an increased benefit. Here we discuss several caveats associated with this failed trial. First is the uncertainty as to whether the target was adequately inhibited. In particular, there remains a lack of direct evidence regarding the degree of IDO1 inhibition within the tumor, and previous trial data suggest that sufficient drug exposure may not have been achieved at the dose tested in ECHO-301. Second, while there is a mechanistic rationale for the combination tested, the preclinical data were not particularly compelling. More efficacious combinations have been demonstrated with DNA damaging modalities which may therefore be a more attractive alternative. Third, as a highly selective IDO1 inhibitor, epacadostat was advanced aggressively despite preclinical genetic evidence of tumors bypassing IDO1 blockade. Indeed, a well-grounded literature starting in 2011 points to targeting strategies that account for both IDO and tryptophan 2,3-dioxygenase as more appealing directions to pursue, including dual inhibitors and inhibitors of nodal downstream effector pathways such as aryl hydrocarbon receptor blockade. Overall, the clinical readout from a single trial with significant limitations is by no means a definitive test for the field. While biomarker information yet to be gleaned from ECHO-301 may yet reveal useful information regarding IDO1 pathway drugs, better rationalized compounds and better rationalized trial designs will be important in the future to accurately gauge medical impact.



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Perspectives on interferon-alpha in the treatment of Polycythemia vera and related Myeloproliferative neoplasms: minimal residual disease and cure?

Abstract

The first clinical trials of the safety and efficacy of interferon-alpha2 (IFN-alpha2) were performed about 30 years ago. Since then, several single-arm studies have convincingly demonstrated that IFN-alpha2 is a highly potent anti-cancer agent in several cancer types but unfortunately not being explored sufficiently due to a high toxicity profile when using non-pegylated IFN-alpha2 or high dosages or due to competitive drugs, that for clinicians at first glance might look more attractive. Within the hematological malignancies, IFN-alpha2 has only recently been revived in patients with the Philadelphia-negative myeloproliferative neoplasms—essential thrombocytosis, polycythemia vera, and myelofibrosis (MPNs)—and in patients with chronic myelogenous leukemia (CML) in combination with tyrosine kinase inhibitors. In this review, we tell the IFN story in MPNs from the very beginning in the 1980s up to 2018 and describe the perspectives for IFN-alpha2 treatment of MPNs in the future. The mechanisms of actions are discussed and the impact of chronic inflammation as the driving force for clonal expansion and disease progression in MPNs is discussed in the context of combination therapies with potent anti-inflammatory agents, such as the JAK1–2 inhibitors (licensed only ruxolitinib) and statins as well. Interferon-alpha2 being the cornerstone treatment in MPNs and having the potential of inducing minimal residual disease (MRD) with normalization of the bone marrow and low-JAK2V617F allele burden, we believe that combination therapy with ruxolitinib may be even more efficacious and hopefully revert disease progression in many more patients to enter the path towards MRD. In patients with advanced and transforming disease towards leukemic transformation or having transformed to acute myeloid leukemia, "triple therapy" is proposed as a novel treatment modality to be tested in clinical trials combining IFN-alpha2, DNA-hypomethylator, and ruxolitinib. The rationale for this "triple therapy" is given, including the fact that even in AML, IFN-alpha2 as monotherapy may revert disease progression. We envisage a new and bright future with many more patients with MPNs obtaining MRD on the above therapies. From this stage—and even before—vaccination strategies may open a new horizon with cure being the goal for some patients.



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Usage of the HINTS exam and neuroimaging in the assessment of peripheral vertigo in the emergency department

Abstract

Background

Dizziness is a common presenting symptom in the emergency department (ED). The HINTS exam, a battery of bedside clinical tests, has been shown to have greater sensitivity than neuroimaging in ruling out stroke in patients presenting with acute vertigo. The present study sought to assess practice patterns in the assessment of patients in the ED with peripherally-originating vertigo with respect to utilization of HINTS and neuroimaging.

Methods

A retrospective cohort study was performed using data pertaining to 500 randomly selected ED visits at a tertiary care centre with a final diagnostic code related to peripherally-originating vertigo between January 1, 2010 - December 31, 2014.

Results

A total of 380 patients met inclusion criteria. Of patients presenting to the ED with dizziness and vertigo and a final diagnosis of non-central vertigo, 139 (36.6%) received neuroimaging in the form of CT, CT angiography, or MRI. Of patients who did not undergo neuroimaging, 17 (7.1%) had a bedside HINTS exam performed. Almost half (44%) of documented HINTS interpretations consisted of the ambiguous usage of "HINTS negative" as opposed to the terminology suggested in the literature ("HINTS central" or "HINTS peripheral").

Conclusions

In this single-centre retrospective review, we have demonstrated that the HINTS exam is under-utilized in the ED as compared to neuroimaging in the assessment of patients with peripheral vertigo. This finding suggests that there is room for improvement in ED physicians' application and interpretation of the HINTS exam.



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Spontaneous reduction of acute cecal herniation through the foramen of Winslow

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Abstract
This is the case of a 70-year-old woman who presented to the emergency department complaining of 2 hours of acute-onset epigastric pain. She had experienced this pain once before which had spontaneously resolved. Axial imaging demonstrated the cecum in an abnormal position within the lesser sac, as well as compression of the inferior vena cava and portal vein. She was taken emergently to the operating room for laparotomy, where a free-floating cecum and ascending colon was identified without ischemia, and a right hemicolectomy was performed. Foramen of Winslow hernias are rare internal hernias with a high rate of strangulation and bowel ischemia, requiring urgent surgical intervention. Operative treatment depends on the type of herniated viscera. Spontaneous reduction is not well documented.

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Are morphologic and topographic alterations of the mandibular fossa after fixed functional treatment detectable on tomograms? Visual classification and morphometric analysis

Abstract

Aim

The goal was to evaluate if changes in morphology and topography of the mandibular fossa after Functional Mandibular Advancer (FMA) treatment are detectable on tomograms. Furthermore, the suitability of digital tomograms (DT) over magnetic resonance imaging (MRI) for this particular question was investigated.

Materials and methods

In all, 25 patients (14 female, 11 male) with a skeletal class II malocclusion received treatment with a FMA. DTs were available prior to (T1) and after (T2) FMA treatment. A total of 50 temporomandibular joints were investigated. The mandibular fossae were evaluated metrically and visually regarding treatment-induced alterations. A p < 0.05 was set as the level for statistical significance for all tests. Results were compared to the results of a recent MRI study.

Results

Visual inspection of all 50 joints in the DT at T1 and T2 revealed no alterations of the fossa shape in the sagittal plane; 24 patients showed identical morphology of right and left joints. The metrical analysis revealed no significant changes regarding width, depth and ratio thereof between T1 and T2. There also were no bilateral differences. Another 18 different distance measurements between porion, mandibular fossa, articular eminence and pterygoid fossa showed no significant changes. There was no detectable proof of a fossa shift.

Conclusions

No changes in the sagittal plane, mandibular fossa, the articular tubercle, or a possible fossa shift were found in the DT of class II patients after FMA treatment. DT and MRI measurements and the visual inspection revealed identical findings; thus, DT appears to be a valuable research tool for sagittal analysis of mandibular fossa changes.



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Radiosurgery of vestibular schwannoma: prognostic factors for hearing outcome using 3D-constructive interference in steady state (3D-CISS)

Abstract

Purpose

Stereotactic radiosurgery (SRS) is an effective treatment for vestibular schwannoma (VS). Three-dimensional (3D) constructive interference in steady state (CISS) is the preferred magnetic resonance imaging (MRI) sequence for evaluating signal changes in the inner ear endolymph. Previous studies demonstrated a correlation between pretreatment cochlear signal intensity in 3D-CISS and posttherapeutic hearing outcomes. The purpose of our study was to compare 3D-CISS sequences before and after primary SRS of unilateral VSs to evaluate the effect of radiosurgery on the 3D-CISS signal intensities of cochlea and sacculus/utriculus.

Methods

We retrospectively reviewed 47 patients with unilateral VS treated with SRS. The neuroradiological MRI datasets were analysed to evaluate the signal intensity of the inner ear structure, tumour size, Koos grade, tumour volume, and infiltration of the cochlear aperture before therapy and at follow-up. The differences in these signal intensities before SRS and at follow-up were correlated with clinical symptoms, cochlear radiation dose, tumour volume and infiltration of the cochlear aperture.

Results

No differences were found between signal intensities in cochlea and utriculus/sacculus before and after SRS and no correlation with clinical symptoms, cochlear radiation dose, tumour volume, Koos grade or infiltration of the cochlear aperture (all p > 0.05).

Conclusion

Our study supports the theory of a complex interaction causing alteration of the endolymph protein concentration and not a direct dependency on the SRS. Use of modern dosing schemes will have a positive impact on clinical outcome with preservation of hearing in patients with VS.



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Modelling the relationship between poverty, environment, and institutions: a panel data study

Abstract

The paper examines the relationship between poverty and CO2 emission. We contribute by using a global panel data of 146 countries over the period 1996–2014 and by focusing on the role of institution in poverty and environmental degradation nexus. The main findings are that the non-linearity relationship between poverty and CO2 emission could prompt a further increase in the poverty and environmental degradation. However, an increase in the institutional quality leads to a reduction in poverty and more protection to the environment. The main policy recommendation is that all countries need to improve their institutional framework so that reduction of poverty and environmental degradation can occur.



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Ecological degradation of an inland river basin and an evaluation of the spatial and distance effect on willingness to pay for its improvement

Abstract

Improvements in the ecological attributes of inland rivers have been projected to provide considerable non-market benefits, and the monetary valuation of these attributes has steadily increased over the past several decades. The present study addresses the spatial heterogeneity of the public's preference for ecological attributes and the distance-decay effect of willingness to pay (WTP) to improve various attributes of the river basin. The results revealed that spatial heterogeneity exists among the individuals; for example, the respondents of Liangzhou County prefer a large improvement in the natural landscape, forest coverage, and eco-tourism and are willing to pay 491.89, 369.32, and 338.37 yuan per year, respectively, for one unit improvement in these ecological attributes. Similarly, the respondents of Jinchang County value and are willing to pay 447.60, 431.81, and 318.18 yuan for one unit improvement in tourism, forest coverage, and natural landscape, respectively. Furthermore, the results from the random parameter logit model show a significant distance-decay effect of the household WTP for ecological attributes. For example, the respondents living within 5 km of the river are willing to pay more money, that is, 832.61, 365.62, and 353.05 yuan per year for improving the natural landscape, water quantity, and grass cover, respectively. As the distance from the river increases, the corresponding WTP decreases, meaning that the respondents (users) living near the Shiyang River Basin are willing to pay more for ecological attribute improvement than those living far away from the river.



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Topical Selenium Sulfide for the Treatment of Hyperkeratosis

Abstract

Hyperkeratosis presents as thickened skin. It can be congenital or acquired. Typically, it affects the palms and soles; the distribution of epidermal involvement is either diffuse, focal, or punctate. Microscopically, the pathologic signature of hyperkeratosis is marked orthokeratosis of the stratum corneum. Topical treatments provide the mainstay of therapy for hyperkeratosis. These include keratolytics (such as urea, salicylic acid, and lactic acid) and retinoids; physical debridement, topical corticosteroids, and phototherapy (using topical psoralen and ultraviolet A phototherapy) are other local therapeutic modalities. Selenium is a non-metallic essential element; its water-insoluble salt, selenium sulfide, is an active ingredient that is used (in either a foam, lotion, or shampoo) to treat not only seborrheic dermatitis but also tinea versicolor. Three individuals with hyperkeratosis involving their palms and/or soles are described; the hyperkeratosis was successful treated with topical selenium sulfide in either a 2.5% lotion/shampoo or a 2.75% foam. The response to topical selenium sulfide was not only rapid but also complete and sustained; none of the patients experienced any adverse events secondary to the therapy. In conclusion, we recommend that topical selenium sulfide be added to the therapeutic armamentarium for congenital or acquired hyperkeratosis—particularly for those patients with involvement of their palms and soles.



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Impaired glucagon secretion in patients with fulminant type 1 diabetes mellitus

Abstract

Purpose

Fulminant type 1 diabetes mellitus (FT1DM), characterized by rapid and almost complete destruction of pancreatic β-cells, is a newly identified subtype of type 1 diabetes mellitus. Although, the pathophysiology of this condition remains still unclear, histological evidence suggests that not only β-cells but also α-cells of pancreatic islets are reduced in number in FT1DM. However, the ability of glucagon secretion in patients with this condition has remained largely uncharacterized. We therefore examined glucagon secretion in patients with FT1DM and compared that with patients with other types of diabetes mellitus.

Methods

Fasting glucagon levels as well as glucagon secretion induced by intravenous administration of arginine were measured in hospitalized 83 patients with diabetes mellitus, including 4 with FT1DM, 18 with type 1 diabetes mellitus (T1DM), 40 with type 2 diabetes mellitus (T2DM), 5 with slowly progressive insulin-dependent diabetes mellitus (SPIDDM), and 16 with pancreatic diabetes mellitus (PDM).

Results

The area under the curve for serum glucagon levels after arginine infusion in FT1DM patients was significantly smaller than that in T1DM, T2DM, or SPIDDM patients but was similar to that in PDM patients. The fasting serum glucagon level of FT1DM patients was lower than that of T1DM or T2DM patients but did not significantly differ from that of SPIDDM or PDM patients.

Conclusions

These results suggest that glucagon secretion is impaired in patients with FT1DM.



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Cervical Lymph Node Fine-Needle Aspiration and Needle-Wash Thyroglobulin Reflex Test for Papillary Thyroid Carcinoma

Abstract

Fine-needle aspiration (FNA) cytology coupled with needle-wash thyroglobulin (FNA-Tg) testing is recommended for cervical lymph node (LN) biopsies in patients with a history of papillary thyroid carcinoma (PTC). However, the procedure has not been standardized with the assay for FNA-Tg testing. A standard operating procedure (SOP) has been generated at our facility for cervical LN FNAs with Tg reflex testing on patients with a history of PTC. The procedure requires FNA cytology to be reviewed first, and all cases not positive for PTC are reflexed for FNA-Tg testing with the Beckman Access thyroglobulin assay. The thyroglobulin cutoff value is ≤ 1.0 ng/mL. From 2016 to 2017, 117 patients, including 71 women and 46 men, were identified as having a history of PTC. Patients' clinical characteristics were collected from medical records. A total of 143 LN biopsies were investigated for these patients. The results show that four out of 11 (36.4%) non-diagnostic LNs and five out of five (100%) atypical/suspicious LNs tested positive for FNA-Tg. Among these nine patients with positive thyroglobulin testing, LN metastases were proven histologically for all nine patients, and two patients were treated with LN ablation. Out of 68 LNs positive for PTC, three had FNA-Tg results. FNA-Tg testing was ordered for unknown reasons on two positive LNs (> 5000 ng/mL thyroglobulin) from one patient. The third LN was tested due to non-classic morphology, and the result was less than the cutoff value. Three patients with negative LN biopsies were tested to have elevated (> 1.0 ng/mL) thyroglobulin levels. One patient (FNA-Tg ng/mL) was proven to have multiple metastatic LNs through follow-up surgery. However, no positive LN was identified for the other two patients who had FNA-Tg level of 4.1 ng/mL and 37 ng/mL respectively. This is likely due to contamination, as these two patients had intact thyroids. In our practice, the FNA-Tg test is a very useful adjunct test to LN FNA specimens with a non-positive diagnosis in patients with a history of PTC. Furthermore, FNA-Tg testing increases diagnostic sensitivity among non-diagnostic and atypical/suspicious LNs. However, FNA-Tg testing should not substitute conventional cytology due to the following reasons: (1) false-negative thyroglobulin lab results; (2) PTC with loss of thyroglobulin expression; (3) LN metastasis from other origins; and (4) false-positive thyroglobulin testing due to blood contamination in patients who are not completely athyrotic.



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Takayasu's aorto-arteritis: Not your regular lesion for angioplasty

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Navdeep Singh, Vivek Athwani, Vikas Bansal, Shaveta Kundra

Annals of Pediatric Cardiology 2018 11(3):312-314

We report a case of a 6-year-old female child with Takayasu's aorto-arteritis (TA) with severe coarctation of the aorta which resulted in an aortic dissection post-ballooning. This happened despite ensuring that markers for disease activity were negative, with appropriate corticosteroid therapy started before the procedure, and using a low-profile, low-pressure, and slightly undersized balloon for dilating the stenotic segment. It required immediate endovascular stenting to tide over the crisis. Following the procedure, she became normotensive with well-palpable lower limb pulses.

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Repaired congenital heart disease and our social milieu

AnnPediatrCard_2018_11_3_233_240837_i1.j

Krishna S Iyer

Annals of Pediatric Cardiology 2018 11(3):233-234



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Is transposition a defect of laterality?

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Robert H Anderson, John Stickley

Annals of Pediatric Cardiology 2018 11(3):235-236



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Anomalous origin of the right coronary artery from the pulmonary artery associated with an aortopulmonary window

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Padebettu Subramanya Seetharama Bhat, Chandana Nirmala Chandrashekar, Divya Mallikarjun, SL Girish Gowda

Annals of Pediatric Cardiology 2018 11(3):325-327

Anomalous origin of the right coronary artery (RCA) from the pulmonary artery is a rare entity that causes chronic left-to-right shunting of blood from the RCA, through the coronary collaterals into the pulmonary artery. This results in persistent myocardial ischemia and ventricular dysfunction. Association of this anomaly with an aortopulmonary window worsens the condition further due to an additional shunt. We encountered a combination of these two anomalies along with an ostium secundum atrial septal defect in a 10-month-old baby who presented with excessive crying and failure to thrive. Evaluation by transthoracic echocardiography and cardiac computed tomography scan confirmed the diagnosis. Intrapulmonary baffle was done using a pericardial patch to connect the RCA origin to ascending aorta through the aortopulmonary window, similar to Takeuchi procedure. Concomitantly, ostium secundum atrial septal defect was also closed.

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Transposition of the great arteries: A laterality defect in the group of heterotaxy syndromes or an outflow tract malformation?

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Rana S Al-Zahrani, Samaher H Alharbi, Rawan M A Tuwaijri, Bayan T Alzomaili, Alaa Althubaiti, Talat Mesud Yelbuz

Annals of Pediatric Cardiology 2018 11(3):237-249

Background/Aim: Transposition of the great arteries (TGA) is traditionally classified as a "conotruncal heart defect", implying that TGA evolves from abnormal development of the outflow tract (OFT) of the embryonic heart. However, recently published genetic data suggest that TGA may be linked to laterality gene defects rather than OFT gene defects. The aim of our study was to clarify whether there is any statistically significant link between TGA and clinically diagnosed laterality defects (heterotaxy). Methods: Retrospective cross-sectional analysis of 533 patients diagnosed with TGA at our cardiac center over a period of 13 years (2002-2015). Hospital informatics and digital data recording systems were used for collecting patients' data and all patients were reviewed to check the echocardiograms for verification of the diagnosis, type (TGA, congenitally corrected TGA (ccTGA), and levo-position of the great arteries (LGA)), complexity of TGA, and all other variables (e.g., abdominal organ arrangement, cardiac position, presence or absence of other cardiac defects). Results: Of 533 TGA patients, 495 (92.9%) had the usual arrangement of the internal organs, 21 (3.9%) had mirror-imagery, 7 (1.3%) had left and 10 (1.8%) had right isomerism. 444 (83.3%) patients had TGA. The number of patients who had usual visceral arrangement in each TGA type was: 418 (94.1%) in TGA, 49 (92.4%) in ccTGA, and 28 (77.7%) in LGA. 6 (1.4%) TGA patients, 4 (11.1%) patients with LGA were found to have right isomerism, while no ccTGA patient presented with this asymmetry. 4 (0.9%) TGA patients, 1 (1.9%) ccTGA patient and 2 (5.6%) patients with LGA had left isomerism. Heterotaxy (mirror-imagery, left and right isomerism) was more associated with LGA than TGA or ccTGA with a statistically significant difference (P value of 0.001). Conclusion: In contrast to recently published genetic data, our morphological data do not disclose a significant link between TGA and heterotaxy.

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Endovascular management of vein of Galen aneurysmal malformation in a neonate

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Siddharthan Deepti, Rajnish Juneja, Leve Joseph Devarajan Sebastian

Annals of Pediatric Cardiology 2018 11(3):304-307

A term baby presented on the 7th day of life in cardiogenic shock due to vein of Galen aneurysmal malformation. A successful embolization of the malformation was performed through transarterial route on day 12 of life after a period of initial stabilization.

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Validation of the accuracy of handheld echocardiography for diagnosis of congenital heart disease

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Sulafa Ali, Tajudeen Bushari

Annals of Pediatric Cardiology 2018 11(3):250-254

Background: Handheld echocardiography (HHE) has been increasingly used for rheumatic heart disease screening and in adult emergency room settings. Aims: This study aimed to validate the accuracy of HHE in the diagnosis of congenital heart disease (CHD). Settings and Design Methodology: This is a prospective study carried out at three pediatric cardiology outpatient clinics in Khartoum, Sudan. All patients with suspected CHD were evaluated by clinical examination followed by HHE, performed using a modified segmental approach. Then, a complete study was performed using a standard echocardiography machine. The results were then compared using appropriate statistical tools. Results: A total of eighty cases were included with the following diagnoses either in isolation or combination: ventricular septal defect (n = 23), atrial septal defect (n = 10), pulmonary stenosis (n = 7), tetralogy of Fallot (n = 7), patent ductus arteriosus (n = 6), atrioventricular septal defect (n = 6), transposition of the great arteries (n = 6), and other diagnoses (n = 15). Agreement between HHE and SE was excellent both for visualizing heart segments (κ =77%–100% with a mean of 92.9%) and for diagnosis of CHD (κ =66%–100% with a mean of 91.7%). The sensitivity of HHE was 69.2%–100% (mean = 90.2%) and specificity was 98.5%–100% (mean = 99.3%). Conclusion: This study supports extending the utility of HHE in children for screening of CHD in addition to its current role in rheumatic heart disease screening.

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Neonatal supraventricular extrasystole as early clinical debut of cardiac rhabdomyoma

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Roger Esmel-Vilomara, Amparo Castellote, Luz Santana, Dimpna Calila Albert

Annals of Pediatric Cardiology 2018 11(3):318-321

We are reporting the case of a newborn with a diagnosis of frequent supraventricular extrasystoles, up to 25% of beats at Holter monitoring, and partial response to beta-blockers. Initial echocardiographic studies were normal until the identification of a right atrial mass at 4 months of life. Given the progressive growth of the mass and the suspicion of myxoma or thrombus in the magnetic resonance study, surgical resection of the tumor was performed. The surgical specimen was histologically diagnostic of rhabdomyoma. Currently, the patient remains asymptomatic after a 6-year follow-up period. A single rhabdomyoma is described, located in an atypical situation, near the crista terminalis, and diagnosed from frequent extrasystoles which appeared before the echocardiographic resolution was able to identify it. Magnetic resonance showed nondiagnostic tissue enhancement characteristics.

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Predictors of abnormal electrocardiograms in the pediatric emergency department

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Shiv Gandhi, Miranda Lin, Sharon R Smith, Jesse J Sturm

Annals of Pediatric Cardiology 2018 11(3):255-260

Background: Electrocardiograms (ECGs) are ordered in the pediatric emergency room for a wide variety of chief complaints. Objectives: Criteria are lacking as to when physicians should obtain ECGs. This study uses a large retrospective cohort of 880 pediatric emergency department (ED) patients to highlight objective criteria including significant medical history and specific vital sign abnormalities to guide clinicians as to which patients might have an abnormal ECG. Methods: Retrospective review of Pediatric ED charts in all patients aged < 18 years who had ECG performed during ED stay. Pediatric ED physician interpretation of the ECG, clinical data on vital signs and past medical history was collected from the medical record for analysis. Results: Of 880 ECGs performed in the ED, 17.4% were abnormal. When controlled for medical history and demographic differences, abnormal ECGs were associated with age-adjusted abnormal ED vital signs including increased heart rate (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.1–3.09) and increased respiratory rate (OR 1.74, CI 1.42–2.62). In a logistic regression analysis, certain chief complaints and history components were less likely to have abnormal ECGs including complaints of chest pain (OR 0.38, CI 0.18–0.80) and known history of gastrointestinal or respiratory condition (i.e., asthma) (OR 0.48, CI 0.29–0.79). Conclusions: In this cohort of patients, those with a chief complaint of chest pain or known respiratory conditions and normal age-adjusted vital signs in the ED have low likelihood of an abnormal ECG.

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Professor Ivatury Mritunjay Rao

AnnPediatrCard_2018_11_3_330_240836_i1.j

Krishna Subramony Iyer

Annals of Pediatric Cardiology 2018 11(3):330-331



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Native aortic coarctation in neonates and infants: Immediate and midterm outcomes with balloon angioplasty and surgery

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Supratim Sen, Sandeep Garg, Suresh G Rao, Snehal Kulkarni

Annals of Pediatric Cardiology 2018 11(3):261-266

Background: Native aortic coarctation in young infants can be treated surgically or with balloon angioplasty, although the latter approach remains controversial. We sought to compare midterm outcomes of balloon and surgical coarctoplasty at our center and to review the current practices in literature. Methods: The study design was a retrospective record review. Patients with coarctation aged <1 year who underwent balloon or surgical coarctoplasty at our center (January 2010–January 2016) with >6-month post-procedure follow-up were studied. Patients with significant arch hypoplasia or interruption, long-segment coarctation, and associated intracardiac lesions were excluded from the study. Clinical, echocardiographic, and procedural details were recorded at initial presentation and follow-up. Need for reintervention was noted. Results: Out of a total of 75 patients, 28 underwent balloon (Group A) and 47 underwent surgical coarctoplasty (Group B). There were two deaths in Group B (mortality 4.2%) and none in Group A. In neonates, 63.6% of Group A and 17.4% of Group B patients required reintervention (P = 0.007). Beyond the neonatal age, 29.4% of Group A and 41.6% of Group B patients required reintervention (not statistically significant). On univariate analysis, residual coarctation on predischarge echocardiogram was the only significant predictor of reintervention (P = 0.04). On Kaplan–Meier analysis, with neonatal presentation, freedom from reintervention in Group B was significantly higher than Group A (P = 0.028). Conclusion: In neonates with native aortic coarctation, surgery unequivocally yields better immediate and midterm results and is the preferred treatment modality. In older infants, balloon coarctoplasty has good early and midterm outcomes with acceptable reintervention rates and should be considered a viable alternative to surgery, especially in critical patients with high surgical risk.

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Successful Angiojet® aortic thrombectomy of extracorporeal membrane oxygenation-related thrombus in a newborn

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Maria Elena Gutierrez, Jeffrey A Alten, Mark A Law

Annals of Pediatric Cardiology 2018 11(3):300-303

Thrombosis and systemic embolization are important complications of extracorporeal membrane oxygenation (ECMO). We present a 2.5 kg neonate born at 37.4 weeks with hypoplastic left heart supported on ECMO that developed an acute, occlusive distal aortic thrombus that was emergently managed by transcatheter Angiojet® (Boston Scientific, Boston, MA) thrombectomy. The procedure successfully restored perfusion to the lower extremities with sustained result upon 1-week follow-up. This case highlights the Angiojet® thrombectomy as a treatment option for limb- or organ-threatening acute thrombus in even the most complex ECMO patients.

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Early outcomes of modification of end to side repair of coarctation of aorta with arch hypoplasia in neonates and infants

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Anil Kumar Dharmapuram, Nagarajan Ramadoss, Sudeep Verma, Goutami Vejendla, Rao Mrutyunjaya Ivatury

Annals of Pediatric Cardiology 2018 11(3):267-274

Background: In coarctation of aorta associated with proximal arch hypoplasia, extended end-to-end anastomosis through a thoracotomy would result in a residual gradient between the origins of the innominate and the left common carotid arteries. To eliminate this, we modified the surgical technique. Patients and Methods: Between March 2012 and May 2017, 50 patients (14 neonates) underwent repair of coarctation of aorta through a thoracotomy. The age ranged from 6 days to 2 years (median 2 months) and the weight from 1.8 to 8.0 kg (median 4.3 kg). A total of 15 patients (Group A) underwent repair by the extended end-to-end anastomosis. Among them, two patients developed early restenosis at the proximal arch requiring surgical reintervention. Hence, in the second half of the study, 35 patients (Group B) who were identified to have significant hypoplasia of the proximal arch underwent a modified end-to-side anastomosis of the descending aorta to the proximal arch incorporating the distal ascending aorta in the anastomosis and leaving the left subclavian artery end of the isthmus as an end-on vessel. Results: One neonate in Group B died due to a cause not related to the repair. All the other patients in Group B are doing well without a residual gradient during a median follow-up of 23 months. There were no airway issues related to extensive mobilization of the aorta. Conclusion: End-to-side anastomosis of the descending aorta to the proximal arch and side of the ascending aorta is possible through a thoracotomy and can be achieved with good outcome in neonates and infants.

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Morphology of intramural ventricular septal defects: Clinical imaging and autopsy correlation

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Neil D Patel, Richard W Kim, Suwanna Pornrattanarungsi, Pierre C Wong

Annals of Pediatric Cardiology 2018 11(3):308-311

An intramural ventricular septal defect (IVSD) is a type of interventricular communication that can occur following biventricular repair of a conotruncal malformation. There have been no previous reports depicting the actual pathologic anatomy of this defect. We describe two cases of IVSDs with their clinical imaging and postmortem pathology.

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Modified technique for uncommon coarctation of the aorta with arch hypoplasia

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Brijesh Parayaru Kottayil, Praveen R Bayya, Luis Baquero, Amitabh C Sen, Raman K Kumar

Annals of Pediatric Cardiology 2018 11(3):275-277

A true presubclavian coarctation of the aorta with arch hypoplasia without major intracardiac anomaly can result in a surgical dilemma. Theoretically, one can avoid repair through median sternotomy using selective cerebral perfusion and its sequelae since no major intracardiac repair is needed. Repair through thoracotomy is technically challenging if arch reconstruction is required and precise surgical planning is required to avoid spinal hypoperfusion and to maintain cerebral perfusion. Moreover, inadequate repair often has resulted in hypoplastic aortic arch or residual coarctation on follow-up requiring future intervention. We have employed a modified surgical repair through thoracotomy avoiding cardiopulmonary bypass to address presubclavian coarctation of the aorta with diffuse arch hypoplasia with theoretically less chance for future stenosis.

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Balloon angioplasty for supravalvular aortic stenosis as an early complication following arterial switch operation

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Kaitlin Carr, Osamah Aldoss, Bijoy Thattaliyath, Manish Bansal

Annals of Pediatric Cardiology 2018 11(3):315-317

Supravalvular aortic stenosis as an early complication of transposition of the great artery repair is rare with few cases reported. Furthermore, transcatheter intervention is uncommon as surgical re-intervention has been traditionally done. We describe two cases of supravalvular aortic stenosis at the anastomotic site as an early complication of the arterial switch operation. Both patients underwent balloon angioplasty of the supravalvular aorta with improvement in postangioplasty gradients and angiographic appearance. Both patients at short-term follow-up had persistent improved gradient without need for further intervention.

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Descending aortic translocation procedure for relief of bronchial compression in left aortic arch and right descending aorta

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Roy Varghese, Ronak Sheth, Sivakumar Kothandam

Annals of Pediatric Cardiology 2018 11(3):278-281

Compression of the left bronchus by a right-sided descending aorta arising from a left aortic arch constitutes an exceedingly rare form of vascular ring. This manuscript describes the surgical technique that involves translocation of the descending aorta directly to the proximal ascending aorta, thereby relieving the bronchial compression.

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Total anomalous pulmonary venous connection masking an aortopulmonary window: A rare combination of defects

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Shyamajit Samaddar, Dheeraj Bhatt, Munish Guleria, Dinesh Kumar Yadav, Anubhav Gupta

Annals of Pediatric Cardiology 2018 11(3):322-324

The association of aortopulmonary (AP) window with total anomalous pulmonary venous connection (TAPVC) has so far not been reported. We report a unique case of an 8-month-old child who presented with congestive cardiac failure and severe pulmonary arterial hypertension. Initial echocardiography revealed supracardiac TAPVC. Cardiac computed tomography showed the presence of Type I AP window along with the TAPVC. In the presence of severe pulmonary hypertension and dilated right ventricle, AP window may easily be missed if not actively looked for.

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Rationale and design of long-term outcomes and vascular evaluation after successful coarctation of the aorta treatment study

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Jose D Martins, Justin Zachariah, Elif Seda Selamet Tierney, Uyen Truong, Shaine A Morris, Shelby Kutty, Sarah D de Ferranti, Jonathan Rhodes, Marta Antonio, Maria Guarino, Boban Thomas, Diana Oliveira, Kimberlee Gauvreau, Nuno Jalles, Tal Geva, Miguel Carmo, Ashwin Prakash

Annals of Pediatric Cardiology 2018 11(3):282-296

Background: Coarctation of the aorta (CoA) can be treated using surgery, balloon angioplasty, or stent implantation. Although short-term results are excellent with all three treatment modalities, long-term cardiovascular (CV) morbidity and mortality remain high, likely due to persistently abnormal vascular function. The effects of treatment modality on long-term vascular function remain uncharacterized. The goal of this study is to assess vascular function in this patient population for comparison among the treatment modalities. Methods: We will prospectively assess vascular Afunction in large and small arteries fusing multiple noninvasive modalities and compare the results among the three groups of CoA patients previously treated using surgery, balloon angioplasty, or stent implantation after frequency matching for confounding variables. A comprehensive vascular function assessment protocol has been created to be used in 7 centers. Our primary outcome is arterial stiffness measured by arterial tonometry. Inclusion and exclusion criteria have been carefully established after consideration of several potential confounders. Sample size has been calculated for the primary outcome variable. Conclusion: Treatment modalities for CoA may have distinct impact on large and small arterial vascular function. The results of this study will help identify the treatment modality that is associated with the most optimal level of vascular function, which, in the long term, may reduce CV risk.

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Coronary-to-pulmonary artery collaterals in pulmonary atresia

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Deepa Sasikumar, Bijulal Sasidharan, Anoop Ayyappan, Arun Gopalakrishnan, Kavasseri M Krishnamoorthy

Annals of Pediatric Cardiology 2018 11(3):328-329

A 2-month-old baby with ventricular septal defect and pulmonary atresia was found to have coronary-to-pulmonary artery collaterals. Cardiac computed tomography confirmed the coronary collaterals and showed the absence of other systemic to pulmonary artery collaterals. Although these collaterals do not cause coronary ischemia, it is important to delineate them by accurate imaging to plan the appropriate surgical strategy.

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Impaired glucagon secretion in patients with fulminant type 1 diabetes mellitus

Abstract

Purpose

Fulminant type 1 diabetes mellitus (FT1DM), characterized by rapid and almost complete destruction of pancreatic β-cells, is a newly identified subtype of type 1 diabetes mellitus. Although, the pathophysiology of this condition remains still unclear, histological evidence suggests that not only β-cells but also α-cells of pancreatic islets are reduced in number in FT1DM. However, the ability of glucagon secretion in patients with this condition has remained largely uncharacterized. We therefore examined glucagon secretion in patients with FT1DM and compared that with patients with other types of diabetes mellitus.

Methods

Fasting glucagon levels as well as glucagon secretion induced by intravenous administration of arginine were measured in hospitalized 83 patients with diabetes mellitus, including 4 with FT1DM, 18 with type 1 diabetes mellitus (T1DM), 40 with type 2 diabetes mellitus (T2DM), 5 with slowly progressive insulin-dependent diabetes mellitus (SPIDDM), and 16 with pancreatic diabetes mellitus (PDM).

Results

The area under the curve for serum glucagon levels after arginine infusion in FT1DM patients was significantly smaller than that in T1DM, T2DM, or SPIDDM patients but was similar to that in PDM patients. The fasting serum glucagon level of FT1DM patients was lower than that of T1DM or T2DM patients but did not significantly differ from that of SPIDDM or PDM patients.

Conclusions

These results suggest that glucagon secretion is impaired in patients with FT1DM.



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Die intraorale Sprachaufnahme – die Perspektive einer neuen Smartphone-basierten Methode zur stimmlichen Rehabilitation

Zusammenfassung

Die stimmliche Rehabilitation nach einer Laryngektomie ist obligat. Das Ziel des Projekts bestand darin, eine Smartphone-basierte Methode zu entwickeln, bei der ein Mikrofon in der Mundhöhle zur Aufnahme der Pseudoflüsterstimme platziert und diese durch eine Spracherkennungssoftware analysiert wird – mit nachfolgender Sprachsynthese. Eine Mikrofonkapsel wurde an 10 extra- und intraoralen Positionen platziert (2-mal vor dem Mund (2 cm und 20 cm Abstand), 5‑mal am harten Gaumen und 3‑mal mandibulär). An diesen Stellen erfolgte bei 8 gesunden Männern die Stimmaufnahme und anschließende Analyse sowie Textausgabe durch eine Spracherkennungssoftware. Dieser Text wurde mit dem Prüfungstext verglichen. Der Mittelwert der intraoralen Erkennungsrate aller Positionen betrug 19,3 % im Vergleich zur extraoralen Rate von 75,2 % (p = 0,01). Intraoral wiesen die Messungen an der Maxilla (22,8 %) im Vergleich zur mandibulären Platzierung (13,5 %) einen Vorteil auf (p = 0,01). Die beste Erkennung war am höchsten Punkt des harten Gaumens mit 31,9 % (p = 0,028) gegeben. Weitere Versuche müssen in Abhängigkeit von der technischen Weiterentwicklung der Smartphones in Bezug auf Verarbeitungsgeschwindigkeit und Spracherkennungsapplikationen durchgeführt werden.



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Are morphologic and topographic alterations of the mandibular fossa after fixed functional treatment detectable on tomograms? Visual classification and morphometric analysis

Abstract

Aim

The goal was to evaluate if changes in morphology and topography of the mandibular fossa after Functional Mandibular Advancer (FMA) treatment are detectable on tomograms. Furthermore, the suitability of digital tomograms (DT) over magnetic resonance imaging (MRI) for this particular question was investigated.

Materials and methods

In all, 25 patients (14 female, 11 male) with a skeletal class II malocclusion received treatment with a FMA. DTs were available prior to (T1) and after (T2) FMA treatment. A total of 50 temporomandibular joints were investigated. The mandibular fossae were evaluated metrically and visually regarding treatment-induced alterations. A p < 0.05 was set as the level for statistical significance for all tests. Results were compared to the results of a recent MRI study.

Results

Visual inspection of all 50 joints in the DT at T1 and T2 revealed no alterations of the fossa shape in the sagittal plane; 24 patients showed identical morphology of right and left joints. The metrical analysis revealed no significant changes regarding width, depth and ratio thereof between T1 and T2. There also were no bilateral differences. Another 18 different distance measurements between porion, mandibular fossa, articular eminence and pterygoid fossa showed no significant changes. There was no detectable proof of a fossa shift.

Conclusions

No changes in the sagittal plane, mandibular fossa, the articular tubercle, or a possible fossa shift were found in the DT of class II patients after FMA treatment. DT and MRI measurements and the visual inspection revealed identical findings; thus, DT appears to be a valuable research tool for sagittal analysis of mandibular fossa changes.



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Haploidentical Stem Cell Transplantation: A Gateway to Infrequent Availability of HLA-Matched Related Donors

Haploidentical stem cell transplantation provides a plausible alternative for the patients when a fully matched donor is unavailable. Historically, the decision of considering haploidentical transplant has remained elusive; however, with the recent advances, the consideration of haploidentical grafts as a treatment option has become more apparent for both allografting for diseases and engraftment failure. We are reporting here an anecdotal case of a successful haploidentical engraftment in a patient with the prior graft failure of an HLA-matched related donor. Since the patient was severely alloimmunized, desensitization protocol was utilized before the haploidentical transplant, and the patient after 8 months of her second allogeneic transplantation is doing great with successful engraftment, no relapse, and no graft-versus-host disease (GVHD). Numerous reports pertinent to haploidentical graft have shown favorable outcomes in the graft placement, a decline in the rate of GVHD, and an improvement in the morbidity and mortality in affected individuals. Based on the current reports, haploidentical transplantation might be more feasible and has meaningful implications in the situations where matched donors are infrequent.

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CT-guided interstitial HDR-brachytherapy for recurrent glioblastoma multiforme: a 20-year single-institute experience

Abstract

Purpose

To report our results of computed tomography-guided interstitial high-dose-rate (HDR) brachytherapy (BRT) in the treatment of patients with recurrent inoperable glioblastoma multiforme (GBM).

Patients and methods

Between 1995 and 2014, 135 patients were treated with interstitial HDR BRT for inoperable recurrent GBM located within previously irradiated volumes. Patient's median age was 57.1 years (14–82 years). All patients were pretreated with surgery, postoperative external beam radiation therapy (EBRT) and systemic chemotherapy (ChT). The median recurrent tumor volume was 42 cm3 (2–207 cm3). The prescribed HDR dose was median 40 Gy (30–50 Gy) delivered in twice-daily fractions of 5.0 Gy over consecutive days. No repeat surgery or ChT was administered in conjunction with BRT. Survival from BRT, progression-free survival (PFS), toxicity as well as the impact of several prognostic factors were evaluated.

Results

At a median follow-up of 9.2 months, the median overall survival following BRT and the median PFS were 9.2 and 4.6 months, respectively. Of the prognostic variables evaluated in univariate analysis, extent of surgery at initial diagnosis, tumor volume at recurrence, as well as time from EBRT to BRT reached statistical significance, retained also in multivariate analysis. Eight patients (5.9%) developed treatment-associated complications including intracerebral bleeding in 4 patients (2.9%), symptomatic focal radionecrosis in 3 patients (2.2%), and severe convulsion in 1 patient (0.7%).

Conclusions

For patients with recurrent GBM, interstitial HDR BRT is an effective re-irradiation method for even larger tumors providing palliation without excessive toxicity.



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Treatment outcomes of radiotherapy for primary spinal cord glioma

Abstract

Purpose

Spinal cord gliomas are rare, and there is no consensus on the optimal radiotherapy (RT) regimen. Herein, we investigated therapeutic outcomes in spinal cord gliomas to obtain clues for the optimal RT regimen.

Methods

We assessed 45 patients who received RT for primary spinal cord non-ependymoma gliomas between 2005 and 2017: 37 (82%) received postoperative RT, 6 (13%) underwent definitive RT without surgery, and 2 (5%) received salvage RT for recurrent tumors. Craniospinal irradiation (CSI; median, 40 Gy) was administered in 4 patients with seeding at diagnosis; all other patients received local RT only (median, 50.4 Gy).

Results

In all 23 failures occurred (20 in patients without initial seeding +3 in patients with initial seeding and CSI; median follow-up, 33 months). The 2‑year overall survival and progression-free survival rates were 74 and 54%, respectively. Overall, 13 (32%) new seeding events outside the local RT field developed either first or subsequently. Tumor grade was significantly associated with survival endpoints (p = 0.009, 0.028) and overall seeding rates (p = 0.042). In grade II tumors, seeding developed in 23%, with a dismal prognosis (median, 10 months after RT). In grade III tumors, seeding developed in 45% with diverse prognosis. In grade IV tumors, seeding developed in 45%. The survival of patients with newly developed seeding was significantly worse than the others (2-year 50%, p < 0.001).

Conclusion

To encompass a considerable rate of progressive disease seeding, aggressive treatment such as pre-emptive application of CSI needs to be considered for high-grade spinal cord gliomas with adverse features. Prophylactic CSI could be an option for survival prolongation and requires prospective validation.



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Novel Facial Cream Containing Carnosine Inhibits Formation of Advanced Glycation End-Products in Human Skin

Background: Accumulation of advanced glycation end-products (AGEs) in skin has been associated with skin aging. Inhibition of glycation of proteins of extracellular matrix may help skin texture and appearance. The objective of the study was to demonstrate the antiglycation activity of topically applied carnosine and novel facial cream (FC) containing carnosine in human skin explants ex vivo. Methods: Glycation was induced in human skin explants by methylglyoxal (MG) in culture media. FC containing carnosine (FC-CARN) or carnosine in aqueous solution (AQ-CARN) was applied topically on skin explants. Levels of AGEs carboxymethyl-lysine (CML) and pentosidine were determined in the epidermis and dermis of skin sections and were used to calculate antiglycation activity. Results: Exposure to MG led to increases in CML and pentosidine in skin explants. Antiglycation effect for AQ-CARN was CML: –64 and –41%, pentosidine: –48 and 42% in epidermis and reticular dermis respectively. Antiglycation effect for FC-CARN was CML: –150 and –122%, pentosidine: –108 and –136%, in epidermis and reticular dermis respectively. Conclusion: Topically applied carnosine protects against the glycation induced by MG. Novel FC-CARN significantly reduced levels of AGEs in both epidermis and reticular dermis in human skin explants.
Skin Pharmacol Physiol 2018;31:324–331

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Tretinoin Loaded Nanoemulsion for Acne Vulgaris: Fabrication, Physicochemical and Clinical Efficacy Assessments

Background and Aim: Acne vulgaris is a common inflammatory skin condition which is treated using Tretinoin (TRE), a widely used retinoid. Nano emulations (NEs) are colloidal nano-sized particles that enhance the therapeutic efficacy of TRE and minimize adverse effects. This study is aimed at developing a TRE-loaded NE (NE-TRE) and at assessing the therapeutic effects of the formulation in acne vulgaris lesions, compared to conventional 0.05% TRE emulsion. Method: The high energy emulsification method was used to make NE-TRE. After obtaining stable NE, particle characterization and physicochemical properties were evaluated under accelerated conditions. Conducting a clinical study, we compared the therapeutic effects of NE-TRE and 0.05% TRE emulsion by comparing the number of acne lesions and porphyrin production in both sides of the face. Results and Conclusion: We successfully developed stable nanoparticles. It was a stable oil-in-water emulsion with particle size of about 150 nm, and containing circular and separated particles. In a pilot clinical study, the number of acne lesions as well as the size and intensity of porphyrin production significantly reduced after topical application of NE-TRE. This formula shows proper efficiency and good loading capacity of TRE in the drug delivery system.
Skin Pharmacol Physiol 2018;31:316–323

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Anatomical accuracy of standard-practice tractography algorithms in the motor system - A histological validation in the squirrel monkey brain

Publication date: Available online 10 September 2018

Source: Magnetic Resonance Imaging

Author(s): Kurt G. Schilling, Yurui Gao, Iwona Stepniewska, Vaibhav Janve, Bennett A. Landman, Adam W. Anderson

Abstract

For two decades diffusion fiber tractography has been used to probe both the spatial extent of white matter pathways and the region to region connectivity of the brain. In both cases, anatomical accuracy of tractography is critical for sound scientific conclusions. Here we assess and validate the algorithms and tractography implementations that have been most widely used - often because of ease of use, algorithm simplicity, or availability offered in open source software. Comparing forty tractography results to a ground truth defined by histological tracers in the primary motor cortex on the same squirrel monkey brains, we assess tract fidelity on the scale of voxels as well as over larger spatial domains or regional connectivity. No algorithms are successful in all metrics, and, in fact, some implementations fail to reconstruct large portions of pathways or identify major points of connectivity. The accuracy is most dependent on reconstruction method and tracking algorithm, as well as the seed region and how this region is utilized. We also note a tremendous variability in the results, even though the same MR images act as inputs to all algorithms. In addition, anatomical accuracy is significantly decreased at increased distances from the seed. An analysis of the spatial errors in tractography reveals that many techniques have trouble properly leaving the gray matter, and many only reveal connectivity to adjacent regions of interest. These results show that the most commonly implemented algorithms have several shortcomings and limitations, and choices in implementations lead to very different results. This study should provide guidance for algorithm choices based on study requirements for sensitivity, specificity, or the need to identify particular connections, and should serve as a heuristic for future developments in tractography.



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Ethyl 2,4-dicarboethoxy pantothenate, a derivative of pantothenic acid, prevents cellular damage initiated by environmental pollutants through Nrf2 activation

Publication date: Available online 9 September 2018

Source: Journal of Dermatological Science

Author(s): Mariko Yokota, Shoichi Yahagi, Hitoshi Masaki

Abstract
Background

Recently, environmental pollutants have become a concern not only for respiratory organs but also for skin-related human health, because skin is localized at the border between the human body and the external environment and is easily influenced by environmental pollutants.

Objective

Here, we investigated the effects of a novel pantothenic acid (PA) derivative, ethyl 2,4-dicarboethoxy pantothenate (EDCEP), on a diesel particulate extract (DPE) as a representative environmental pollutant that generates reactive oxygen species (ROS) through the activation of aryl hydrocarbon receptor (AHR) signaling.

Methods

We characterized the effects of PA and EDCEP on normal human epidermal keratinocytes (NHEKs) exposed to DPE or H2O2 as a general oxidative stress stimulator. Cell viability and intracellular ROS levels were evaluated using the 3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyltetrazolium bromide (MTT) assay and the 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) assay, respectively. Further, we investigated the substantial effects and the underlying mechanism of EDCEP, which elicited a reduction of intracellular ROS.

Results

PA and EDCEP restored the decreases of cell viability induced by DPE and also repressed the up-regulation of CYP1A1 mRNA expression induced by DPE. Interestingly, the effects of PA and EDCEP on intracellular ROS levels showed different responses. EDCEP reduced intracellular ROS levels stimulated by DPE or by exposure to H2O2. EDCEP suppressed the secretion of tumor necrosis factor (TNF-α) and reduced the level carbonylated proteins in reconstructed human epidermal equivalents topically treated with DPE. EDCEP up-regulated the mRNA expression levels of nuclear factor E2-related factor 2 (Nrf2), γ-glutamyl cysteine synthase (γ-GCS), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) and in addition, increased intracellular glutathione (GSH) levels.

Conclusion

EDCEP reduces cellular damage initiated by environmental pollutants by stimulating the intracellular defense system against ROS through the activation of Nrf2, and by interfering with AHR signaling pathway activation.

Graphical abstract

Graphical abstract for this article



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Single and multiple ascending-dose study of glucagon-receptor antagonist RN909 in type 2 diabetes: a phase 1, randomized, double-blind, placebo-controlled trial

Abstract

Purpose

This first-in-human study assessed safety, immunogenicity, pharmacokinetics, and pharmacodynamics of RN909, a monoclonal antibody antagonist of the glucagon receptor, in type 2 diabetes (T2DM) subjects.

Methods

This study enrolled 84 T2DM subjects receiving stable metformin regimens. Forty-four subjects were randomized to receive single escalating doses of RN909 (0.3 to 6 mg/kg subcutaneously (SC), or 1 mg/kg intravenously (IV)), or placebo; 40 subjects were randomized to receive multiple escalating doses (50 to 150 mg SC) or placebo every 4 weeks for 12 weeks.

Results

RN909 was well tolerated; treatment-related elevated liver function tests (LFTs) were observed in 4/33 (12.1%) and 5/32 (15.6%) subjects treated with single and multiple doses, respectively, versus 1/10 (10%) and 0 in the respective placebo groups. RN909 dose-normalized AUCinf increased more than dose-proportionally following single SC doses, and after multiple doses, accumulation ratios ranged from 1.3 to 3.4. The incidence of antidrug antibodies (ADA) was 33% after single doses and 50% after multiple doses. RN909 produced dose-dependent, durable fasting plasma glucose (FPG)-lowering at day 29 (mean change −20.6 to −97.5 mg/dL) and day 85 (mean change; −27.2 to −43.5 mg/dL) after single and multiple doses, respectively. HbA1c also was reduced after single (mean change −0.30% to −1.44%), and multiple doses (−0.83% to −1.56%).

Conclusion

RN909 was well tolerated after single and multiple doses in T2DM subjects, with diarrhea and elevated LFTs the most frequent adverse events. The appearance of ADA did not affect pharmacokinetics or efficacy. Robust lowering of FPG and HbA1c was observed.



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