Background: There is paucity of literature on the prognostic value of tissue oxygen saturation (StO2) and regional cerebral oxygen saturation (rSO2) in neurological patients with sepsis. In this preliminary study, we investigated the prognostic value of StO2 and rSO2 in a group of neurological patients and correlated StO2 and rSO2 with hemodynamic and metabolic parameters. Materials and Methods: This preliminary, prospective observational study was conducted in 45 adult neurological patients admitted to intensive care unit. Once a diagnosis of sepsis or septic shock was established, parameters of oxygenation (StO2, rSO2, central venous oxygen saturation [ScvO2]), serum lactate, illness severity scores (Acute Physiology and Chronic Health Evaluation score, Sequential Organ Failure Assessment score, Glasgow Coma Scale) were recorded at 0, 6, 12, 24, 36, and 48 hours, and once daily thereafter. Outcomes were in-hospital mortality attributable to sepsis and the Glasgow outcome score at hospital discharge. Results: There was a moderately positive correlation between StO2 and rSO2 at baseline (r=0.599; P=0.001). StO2, illness severity scores and serum lactate, but not rSO2, were significantly different between survivors (n=29) and nonsurvivors (n=16) at baseline and during the first 48 hours. An rSO2 of 62.5% had a sensitivity of 83% and specificity of 67% to differentiate survivors and nonsurvivors of septic shock at 48 hours. StO2 had a higher correlation with ScvO2 and serum lactate than rSO2. Conclusions: StO2 prognosticates survival and favorable/unfavorable outcomes in neurological patients with sepsis. The role of rSO2 in predicting survival in milder form of sepsis is doubtful. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Sonia Bansal, MD, DNB, PDF, Department of Neuroanaesthesia and Neurocritical Care, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560029, India (e-mail: itz.sonia77@gmail.com). Received February 13, 2018 Accepted October 4, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved
https://ift.tt/2zpqaVr
Τετάρτη 21 Νοεμβρίου 2018
Predictive Factors for Hypotension Associated With Supine-to-Prone Positional Change in Patients Undergoing Spine Surgery
Background: Positional change during general anesthesia can cause hypotension. The objective of this retrospective study was to determine predictive factors for hypotension associated with supine-to-prone positional change in spinal surgery patients. Materials and Methods: Data on demographics, current medications, comorbidity, intraoperative mean arterial pressure (MAP), heart rate, pulse pressure variation, tidal volume, peak inspiratory pressure, and propofol and remifentanil effect-site concentrations were collected from 179 patients undergoing elective spine surgery. Hypotension associated with supine-to-prone positional change was defined as >20% reduction in MAP during positional change. Results: Hypotension associated with supine-to-prone positional change was observed in 16 (8.9%) patients. The median (interquartile range) effect-site concentration of remifentanil (5.3 [4.0 to 8.5] vs. 4.0 [3.1 to 4.0] ng/mL, P
https://ift.tt/2OZnaUV
https://ift.tt/2OZnaUV
Opioidergic Regulation of Emotional Arousal: A Combined PET–fMRI Study
Abstract
Emotions can be characterized by dimensions of arousal and valence (pleasantness). While the functional brain bases of emotional arousal and valence have been actively investigated, the neuromolecular underpinnings remain poorly understood. We tested whether the opioid and dopamine systems involved in reward and motivational processes would be associated with emotional arousal and valence. We used in vivo positron emission tomography to quantify μ-opioid receptor and type 2 dopamine receptor (MOR and D2R, respectively) availability in brains of 35 healthy adult females. During subsequent functional magnetic resonance imaging carried out to monitor hemodynamic activity, the subjects viewed movie scenes of varying emotional content. Arousal and valence were associated with hemodynamic activity in brain regions involved in emotional processing, including amygdala, thalamus, and superior temporal sulcus. Cerebral MOR availability correlated negatively with the hemodynamic responses to arousing scenes in amygdala, hippocampus, thalamus, and hypothalamus, whereas no positive correlations were observed in any brain region. D2R availability—here reliably quantified only in striatum—was not associated with either arousal or valence. These results suggest that emotional arousal is regulated by the MOR system, and that cerebral MOR availability influences brain activity elicited by arousing stimuli.https://ift.tt/2FyB3Kb
Alterations in Schizophrenia-Associated Genes Can Lead to Increased Power in Delta Oscillations
Abstract
Genome-wide association studies have implicated many ion channels in schizophrenia pathophysiology. Although the functions of these channels are relatively well characterized by single-cell studies, the contributions of common variation in these channels to neurophysiological biomarkers and symptoms of schizophrenia remain elusive. Here, using computational modeling, we show that a common biomarker of schizophrenia, namely, an increase in delta-oscillation power, may be a direct consequence of altered expression or kinetics of voltage-gated ion channels or calcium transporters. Our model of a circuit of layer V pyramidal cells highlights multiple types of schizophrenia-related variants that contribute to altered dynamics in the delta-frequency band. Moreover, our model predicts that the same membrane mechanisms that increase the layer V pyramidal cell network gain and response to delta-frequency oscillations may also cause a deficit in a single-cell correlate of the prepulse inhibition, which is a behavioral biomarker highly associated with schizophrenia.https://ift.tt/2qY267v
Guselkumab: A Review in Moderate to Severe Plaque Psoriasis
Abstract
Guselkumab (Tremfya®) is a human immunoglobulin G1 λ (IgG1λ) monoclonal antibody (mAb) that blocks the interleukin-23 (IL-23)-mediated signalling pathway and is the first in its class to be approved in adults with moderate to severe plaque psoriasis in several countries, including the USA and EU. In the VOYAGE trials, guselkumab was superior to placebo and to adalimumab at week 16 in terms of the proportion of patients achieving an Investigator Global Assessment (IGA) score of 0/1 and ≥ 90% improvement from baseline in Psoriasis Area and Severity index score (PASI 90 response), with benefits of guselkumab over adalimumab maintained at week 24. To date, the beneficial effects of guselkumab treatment in these trials were maintained for up to 2 years. Inadequate responders to ustekinumab who were then randomized to guselkumab in NAVIGATE showed better responses than those randomized to ustekinumab between weeks 28–40, with a significantly greater mean number of visits at which patients had IGA 0/1 and ≥ 2-grade improvement in IGA score, as well as higher proportions of patients achieving PASI 90 and PASI 100 at week 52. Treatment with guselkumab improved health-related quality of life (HR-QOL) and patient-reported outcomes in all trials and was generally well tolerated. Guselkumab, administered by subcutaneous injection, is a useful new option for patients with moderate to severe plaque psoriasis.
https://ift.tt/2OUYhJO
Chilean Registry for Neuroendocrine Tumors: A Latin American Perspective
Abstract
Neuroendocrine tumors (NETs) are relatively rare and highly heterogeneous neoplasms. Despite this, recent studies from North America and Central Europe have suggested an increase in incidence. In Latin America, NET data are scarce and scattered with only a few studies reporting registries. Our goal was to establish a NET registry in Chile. Here, we report the establishment and our first 166 NET patients. We observed a slight preponderance of males, a median age at diagnosis of 53 years and a median overall survival of 110 months. As anticipated, most tumors were gastroenteropancreatic (GEP). Survival analyses demonstrated that non-GEP or stage IV tumors presented significantly lower overall survival (OS). Similarly, patients with surgery classified as R0 had better OS compared to R1, R2, or no surgery. Furthermore, patients with elevated chromogranin A (CgA) or high Ki67 showed a trend to poorer OS; however, these differences did not reach statistical significance (log-rank test p = 0.07). To the best of our knowledge, this is the first report of a NET registry in Chile. Median OS in our registry (110 months) is in line with other registries from Argentina and Spain. Other variables including age at diagnosis and gender were similar to previous studies; however, our data indicate a high proportion of small-bowel NETs compared to other cohorts, reflecting the need for NET regional registries. Indeed, these registries may explain regional discrepancies in incidence and distribution, adding to our knowledge on this seemingly rare, highly heterogeneous disease.
https://ift.tt/2FyGhW4
Prevalence of allergic and nonallergic rhinitis in a rural area of northern China based on sensitization to specific aeroallergens
Most epidemiologic studies reporting prevalence of allergic rhinitis (AR) and nonallergic rhinitis (NAR) have assessed solely self-reported prevalence, without confirmation by objective measures. Furthermore, ...
https://ift.tt/2BqTegH
The diagnosis of hereditary angioedema with C1 inhibitor deficiency: a survey of Canadian physicians and laboratories
Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease resulting in random and unpredictable attacks of swelling. The swelling in C1-INH-HAE is a result of impaired ...
https://ift.tt/2KvFDI5
Streptococcus pyogenes bacteremia and toxic shock syndrome related to Strongyloides stercoralis hyperinfection: a case report
We describe a patient with Strongyloides stercoralis hyperinfection associated with Streptococcus pyogenes and with streptococcal toxic shock syndrome. To the best of our knowledge this association has not been p...
https://ift.tt/2DROdQC
Thyroid® High-Impact Articles
FREE ACCESS through December 5, 2018.
Latest Impact Factor: 7.557
The Official Journal of: American Thyroid Association®
Read now:
Mutated Thyroid Hormone Transporter OATP1C1 Associates with Severe Brain Hypometabolism and Juvenile Neurodegeneration
Petter Strømme, Stefan Groeneweg, Elaine C. Lima de Souza, Chantal Zevenbergen, Anette Torgersbråten, Asbjørn Holmgren, Ebrar Gurcan, Marcel E. Meima, Robin P. Peeters, W. Edward Visser, Linda Høneren Johansson, Almira Babovic, Henrik Zetterberg, Heike Heuer, Eirik Frengen, Doriana Misceo, and Theo J. Visser
Metal Coordinated Poly-Zinc-Liothyronine Provides Stable Circulating Triiodothyronine Levels in Hypothyroid Rats
Rodrigo R. Da Conceição, Gustavo W. Fernandes, Tatiana L. Fonseca, Barbara M.L.C. Bocco, and Antonio C. Bianco
Response to Lenvatinib in Children with Papillary Thyroid Carcinoma
Priya Mahajan, Jonathan Dawrant, Albert Kheradpour, Norma M. Quintanilla, Monica E. Lopez, Robert C. Orth, Ioanna Athanassaki, and Rajkumar Venkatramani
Comprehensive Transcriptomic and Genomic Profiling of Subtypes of Follicular Variant of Papillary Thyroid Carcinoma
Young Shin Song, Jae-Kyung Won, Seong-Keun Yoo, Kyeong Cheon Jung, Min Joo Kim, Su-Jin Kim, Sun Wook Cho, Kyu Eun Lee, Ka Hee Yi, Jeong-Sun Seo, and Young Joo Park
Diagnostic Performance of Ultrasound-Based Risk-Stratification Systems for Thyroid Nodules: Comparison of the 2015 American Thyroid Association Guidelines with the 2016 Korean Thyroid Association/Korean Society of Thyroid Radiology and 2017 American Congress of Radiology Guidelines
Eun Ju Ha, Dong Gyu Na, Won-Jin Moon, Young Hen Lee, and Nami Choi
The post <i>Thyroid<sup>®</sup></i> High-Impact Articles appeared first on American Thyroid Association.
https://ift.tt/2OW13P9
Thyroid® High-Impact Articles
FREE ACCESS through December 5, 2018.
Latest Impact Factor: 7.557
The Official Journal of: American Thyroid Association®
Read now:
Mutated Thyroid Hormone Transporter OATP1C1 Associates with Severe Brain Hypometabolism and Juvenile Neurodegeneration
Petter Strømme, Stefan Groeneweg, Elaine C. Lima de Souza, Chantal Zevenbergen, Anette Torgersbråten, Asbjørn Holmgren, Ebrar Gurcan, Marcel E. Meima, Robin P. Peeters, W. Edward Visser, Linda Høneren Johansson, Almira Babovic, Henrik Zetterberg, Heike Heuer, Eirik Frengen, Doriana Misceo, and Theo J. Visser
Metal Coordinated Poly-Zinc-Liothyronine Provides Stable Circulating Triiodothyronine Levels in Hypothyroid Rats
Rodrigo R. Da Conceição, Gustavo W. Fernandes, Tatiana L. Fonseca, Barbara M.L.C. Bocco, and Antonio C. Bianco
Response to Lenvatinib in Children with Papillary Thyroid Carcinoma
Priya Mahajan, Jonathan Dawrant, Albert Kheradpour, Norma M. Quintanilla, Monica E. Lopez, Robert C. Orth, Ioanna Athanassaki, and Rajkumar Venkatramani
Comprehensive Transcriptomic and Genomic Profiling of Subtypes of Follicular Variant of Papillary Thyroid Carcinoma
Young Shin Song, Jae-Kyung Won, Seong-Keun Yoo, Kyeong Cheon Jung, Min Joo Kim, Su-Jin Kim, Sun Wook Cho, Kyu Eun Lee, Ka Hee Yi, Jeong-Sun Seo, and Young Joo Park
Diagnostic Performance of Ultrasound-Based Risk-Stratification Systems for Thyroid Nodules: Comparison of the 2015 American Thyroid Association Guidelines with the 2016 Korean Thyroid Association/Korean Society of Thyroid Radiology and 2017 American Congress of Radiology Guidelines
Eun Ju Ha, Dong Gyu Na, Won-Jin Moon, Young Hen Lee, and Nami Choi
The post <i>Thyroid<sup>®</sup></i> High-Impact Articles appeared first on American Thyroid Association.
https://ift.tt/2OW13P9
Association between atopic dermatitis and extra-cutaneous bacterial and mycobacterial infections: A systematic review and meta-analysis
Atopic dermatitis was found to be associated with increased odds of ear infection, strep throat, urinary tract infection, and multiple other extra-cutaneous infections. Risk of infection should be incorporated into clinical decision-making of atopic dermatitis patients.
https://ift.tt/2DBfWEl
Erratum to “Surgical outcomes in the treatment of temporal bone cerebrospinal fluid leak: A systematic review” [Auris Nasus Larynx 45 (2018) 903–910]
The publisher regrets that the abstract was missing in the original publication of this article.
https://ift.tt/2QaEPxn
Combined Karapandzic-Abbé/Estlander/Stein Flap For Subtotal and Total Lower Lip Reconstruction
Background: Lower lip reconstruction remains a challenging task due to multi-functional and high aesthetic requirements that have to be achieved for successful outcome. This is particularly true to near-total lower lip defects, encompassing over 70% of lower lip loss due to cancer, trauma or burns. Despite the fact that numerous flaps and their modifications have been described over the past century, only a few valuable techniques and concepts withstood the test of time for sub-total lower lip defects, each having their own drawbacks.
https://ift.tt/2BqFv9H
“Radiological Morphometric Analysis of the Zygomatic Arch: Application of Osteosynthesis on the Upper Arch Border for Rigid Fixation”
This study was designed to introduce a novel method of applying osteosynthetic materials to the upper zygomatic arch border for fracture fixation through a temporal incision, and analyze the radiologic morphometric dimensions of the arch to verify its validity.
https://ift.tt/2Kpwy3s
Temporal Trends in Immediate Post-Mastectomy Breast Reconstruction
Breast reconstruction after mastectomy offers significant improvements in quality of life for breast cancer (BC) patients. To improve access to post-mastectomy breast reconstruction (PMBR) for BC patients in the U.S., the Women's Health and Cancer Rights Act (WHCRA) was implemented in 1999, mandating coverage of PMBR by all insurers. Prior to WHCRA, post mastectomy breast reconstruction (PMBR) was variably covered by insurers as it was primarily viewed as a cosmetic procedure. The objectives of this study were to explore whether the incidence of PMBR has changed over time and whether patient age, receipt of radiation therapy, or tumor grade has an effect on the incidence of reconstruction over time.
https://ift.tt/2BoYPUF
Cancer Stem Cells within Moderately Differentiated Head and Neck Cutaneous Squamous Cell Carcinoma Express Components of the Renin-angiotensin System
To investigate expression of components of the renin-angiotensin system (RAS): pro-renin receptor (PRR), angiotensin converting enzyme (ACE), angiotensin II receptor 1 (ATIIR1) and angiotensin II receptor 2 (ATIIR2) by the cancer stem cell (CSC) subpopulations in moderately differentiated head and neck cutaneous squamous cell carcinoma (MDHNCSCC).
https://ift.tt/2KoNZkA
Sub-muscular Plane for Augmentation Mammoplasty Patients Increases Silicone Gel Implant Rupture Rate
Breast augmentation is one of the most common aesthetic procedures performed worldwide. One of the worst associated complications is implant rupture, a topic that will be addressed in the present study. The risk of developing silicone gel breast implant rupture following breast augmentation is associated with multiple factors, including: older generation implant, increased implant age, implant type, specific manufacturer, severe capsular contracture (Baker grade III or IV), and the presence of local symptoms.
https://ift.tt/2BqMbVl
Functional outcomes of upper eyelid blepharoplasty: a systematic review.
Various functional outcomes after upper blepharoplasty are reported in the literature. We systematically reviewed the literature to assess the objective and subjective functional effects of upper blepharoplasty.
https://ift.tt/2Kt9jWc
Impact of Incidental Findings in Preoperative CTA imaging for Autologous Breast Reconstruction
CT angiography (CTA) can be performed pre-operatively for perforator mapping in autologous breast reconstruction. The full impact of incidental CTA findings on breast reconstruction remains unclear.
https://ift.tt/2BoX0az
A retrospective comparison of 3M™ Micropore™ with other common dressings in cosmetic breast surgery
Surgical site infection has considerable cost implications for healthcare providers. Evidence suggests that the use of Micropore™ tape as a dressing for surgical incisions may be associated with reduced/comparable rates of infection in surgical wounds. 3M™ Micropore™ tape is significantly cheaper than conventional wound dressings. The purpose of this study was to compare differences in the rate of wound healing problems including superficial incisional surgical site infection (SSI) and wound healing problems following cosmetic breast procedures between Micropore™ tape and other common wound dressings.
https://ift.tt/2Kp3Gbr
Incidence of second primary cancers after radiotherapy combined with platinum and/or cetuximab in head and neck cancer patients
Abstract
Purpose
The second primary cancer (SPC) incidence after treatment with platinum-based chemotherapy and cetuximab in combination with radiotherapy has not been previously reported. Our aim was to compare SPC risk following radiotherapy in combination with these agents for the treatment of head and neck squamous cell carcinoma (HNSCC).
Methods
The charts of 296 cases treated for loco-regionally advanced HNSCC between 2009 and 2015 were retrospectively reviewed for patient, tumor, and procedural characteristics. All patients were planned to undergo radiotherapy either with platinum compounds (group: Platinum) or monoclonal antibody cetuximab (group: Cetuximab). A third group of patients switched from platinum compounds to cetuximab due to toxicity (group: Switch). Treatment groups were evaluated for the incidence of SPC with log-rank test. Possible confounders were investigated with multivariate Cox's proportional hazards model. All tests were two-sided, and a p < 0.05 was set to indicate statistical significance.
Results
Median follow-up was 36 months. Platinum, Cetuximab, and Switch groups consisted of 158, 101, and 37 patients, respectively. Three-year overall survival in the whole cohort was 70%. The rate of SPC was comparable between Platinum (9.2%) and Cetuximab (11.5%) groups (p = 0.98), whereas the patients in the Switch group were exposed to a significantly higher incidence of SPC (23.3%) in 3 years (p = 0.01). The multivariate model indicated Switch to be the only variable correlating with an increased risk for SPC.
Conclusions
The Switch strategy may expose the patients to an increased risk of developing SPC. The use of switch should be advocated with caution until robust pre-clinical and clinical data are available.
https://ift.tt/2TuQ9Dv
Improving Dermatologic Care for Sexual and Gender Minority Patients Through Routine Data Collection
This Viewpoint explores the routine collection of sexual orientation and gender identity data in dermatology settings to address health disparities faced by sexual and gender minority patients.
https://ift.tt/2KrVLKE
https://ift.tt/2KrVLKE
Pricing a Year of Progression-Free Survival
What is a reasonable price for society to pay to give a patient with cancer 1 extra year of life without tumor growth?
https://ift.tt/2BpJBiu
https://ift.tt/2BpJBiu
Economic Evaluation of Talimogene Laherparepvec Plus Ipilimumab vs Ipilimumab Alone for Unresectable Melanoma
This economic evaluation assesses the cost-effectiveness of talimogene laherparepvec plus ipilimumab combination therapy vs ipilimumab monotherapy in patients with advanced unresectable melanoma from the perspective of public and private US payers.
https://ift.tt/2KqqI1E
https://ift.tt/2KqqI1E
Herpes-Associated Erythema Multiforme
This case report describes the occurrence of herpes-associated erythema multiforme.
https://ift.tt/2Bp3zcZ
https://ift.tt/2Bp3zcZ
Metastatic Calcinosis Cutis Associated With a Selective FGFR Inhibitor
This case report describes metastatic calcinosis cutis associated with selective FGFR inhibitor therapy.
https://ift.tt/2Km5Ybc
https://ift.tt/2Km5Ybc
α-Gal Syndrome vs Chronic Urticaria
This cohort study assesses the use of a blood test to distinguish galactose-α-1,3-galactose (α-gal) allergy from chronic urticaria.
https://ift.tt/2Bq6AtA
https://ift.tt/2Bq6AtA
Use of Dapsone in the Treatment of Chronic Idiopathic and Autoimmune Urticaria
This medical record review evaluates the efficacy and safety of dapsone as second-line therapy in patients with chronic spontaneous urticaria.
https://ift.tt/2KqqF5Y
https://ift.tt/2KqqF5Y
Association of Phenotypic Characteristics and UV Radiation Exposure With Risk of Melanoma
This population-based cohort study uses data from the Norwegian Women and Cancer study to investigate the association between phenotypic characteristics, pattern of UV radiation exposure, and risk of melanoma on different body sites.
https://ift.tt/2BnvuKf
https://ift.tt/2BnvuKf
Association of Hospital Volume With Laryngectomy Outcomes in Patients With Larynx Cancer
This cross-sectional study of patients with a diagnosis of larynx cancer characterizes the hospital volume-outcome association specifically for laryngectomy surgery and identifies a minimum hospital volume threshold associated with improved outcomes.
https://ift.tt/2zfOf0X
https://ift.tt/2zfOf0X
Surgical Volumes and Outcomes
Practice makes perfect. Three words, easily conceptualized, and second nature for any surgeon. It is not surprising that an established and growing body of literature describes improved outcomes when complex surgery is performed by hospitals and surgeons who do those procedures frequently. Luft et al published the foundational study in 1979, reporting on 8 complex operations in almost 1 million patients. For some operations, they found a negative association between the number of procedures performed in a hospital and mortality rates. That general finding has been reproduced using a wide range of data sources for a variety of high-risk operations, including those done for head and neck cancer.
https://ift.tt/2OWroMO
https://ift.tt/2OWroMO
Secondary Endolymphatic Hydrops Associated With Spontaneous Intracranial Hypotension
This case report describes a woman in her 40s who presented with spontaneous intracranial hypotension associated with cerebrospinal fluid leakage.
https://ift.tt/2zfO6dV
https://ift.tt/2zfO6dV
Flat-Panel CT-Guided Place-Pitch Mapping and Speech and Pitch Perception in Cochlear Implant Users
This cohort study evaluates the association between image-based place-pitch mapping using flat-panel computed tomography with speech and pitch perception in individuals with cochlear implants.
https://ift.tt/2OWVhg7
https://ift.tt/2OWVhg7
A Rare Case of a Nasopharyngeal Mass
A man in his 50s with a history of chronic hepatitis C, hypothyroidism, and alcoholism presented to the outpatient clinic complaining of nasal congestion and epistaxis; nonenhanced computed tomography of the paranasal sinuses revealed a soft-tissue mass extending from the nasopharynx into the left sphenoid sinus with erosion of the sphenoid sinus floor and the clivus. What is your diagnosis?
https://ift.tt/2zfNXan
https://ift.tt/2zfNXan
Confluence Model of Sexual Aggression in College Males: Examining Polyvictimization
Violence and Gender, Ahead of Print.
https://ift.tt/2AbccWP
Association of serum ghrelin with weight gain during pregnancy in overweight and normal women
Abstract
Purpose
Despite the fact that the ghrelin hormone plays pivotal role in the process of weight gain, its correlation with weighing during pregnancy has not been elucidated. Hence, the present study was conducted to evaluate the correlation between plasma ghrelin levels and gestational weight gain in overweight and normal women.
Methods
This prospective cohort study was conducted in 27 overweight and 18 normal body mass index (BMI) pregnant women referring to Tehran health care centers. Weight gain during all trimesters of pregnancy was measured and the blood samples were collected at 8–12 (first trimester) and 16–20 weeks (second trimester) of pregnancy. The plasma total ghrelin concentration was measured by ELISA method.
Results
The overweight pregnant women exhibited significantly lower weight gain at the second (p = 0.002), third trimesters (p = 0.005) as well as total weighing during pregnancy (p = 0.001) compared to the normal BMI pregnant women. There was no significant difference in plasma ghrelin levels between the groups from the first to the second trimesters of pregnancy (p > 0.05). Moreover, no correlation was found between ghrelin levels and gestational weight gain in the overweight and normal groups.
Conclusions
Our results indicate that the increased level of serum ghrelin could not be considered as a key mediator for weight gain difference during pregnancy of overweight women.
https://ift.tt/2Ae1jn2
Outcomes in Patients Treated With Carfilzomib, Lenalidomide, and Dexamethasone for Multiple Myeloma
This 5-year follow-up of a phase 2 clinical trial assesses long-term durability of minimal residual disease–negative remission and time to disease progression among patients with newly diagnosed multiple myeloma who received triplet-based induction therapy with lenalidomide maintenance therapy.
https://ift.tt/2DNEefr
https://ift.tt/2DNEefr
Circulating Tumor Cells and Radiotherapy Benefit in Early Breast Cancer
To the Editor Goodman et al recently described a consistent benefit from radiotherapy (RT) in terms of survival and distant disease control after breast-conserving surgery (BCS), but not mastectomy, in 2 cohorts of patients with breast cancer (BC) harboring any circulating tumor cells (CTCs). Speers and Rugo emphasize that the lack of benefit from RT in patients with CTC-negative status is probably owing to the study being underpowered to detect small benefits, and the findings should not be regarded as contradictory to abundant randomized evidence of the benefit of RT. We agree and value the identification of a predictive biomarker of RT benefit.
https://ift.tt/2S74hRL
https://ift.tt/2S74hRL
Second Solid Cancers After Hematopoietic Stem Cell Transplantation in European Patients
This cohort study examines patient data in the European Society for Blood and Marrow Transplantation Registry for causes of death, risk factors, and overall survival rates among patients who received a second cancer diagnosis after being treated with stem cell transplant.
https://ift.tt/2DNEdbn
https://ift.tt/2DNEdbn
Body Composition and Overall Survival in Patients With Nonmetastatic Breast Cancer
To the Editor Cann et al conducted an interesting study to evaluate the associations of 3 body composition measures with overall survival (OS) in patients with nonmetastatic breast cancer. Comparing patients with and without sarcopenia, the authors report a hazard ratio (HR) of 1.41 (95% CI, 1.18-1.69). Although a statistically significant association between sarcopenia and OS was established, a 40% increase in the HR for sarcopenia is difficult to interpret clinically. The hazard cannot be interpreted as a risk (ie, the chance or likelihood of an event occurring). Moreover, without the background hazard function as a benchmark in patients without sarcopenia, a 40% increase might not amount to a clinically meaningful difference. Furthermore, when the HR is not constant over time, it is unclear how to interpret the observed HR.
https://ift.tt/2S0IJGq
https://ift.tt/2S0IJGq
Body Composition and Overall Survival in Patients With Nonmetastatic Breast Cancer—Reply
In Reply McCaw et al propose using restricted mean survival time (RMST) as an alternative to the Cox proportional hazards models we used to examine the influence of body composition on survival in patients with breast cancer. While we agree that RMST presents an alternative method of interpreting data with less restrictions about model fit, there are several reasons why we chose the approach used. First, our article is an epidemiological study examining body composition risk factors for survival, not a randomized clinical trial. Thus, it is unlikely that a clinician would ever inform a patient with low muscle or excess adiposity that she had 6 fewer months to live compared with a patient with normal weight or normal muscle, especially because it is unknown if losing adiposity or gaining muscle will change a patient's survival. Mean differences generated from RMST may be more appropriate for patients who need to make informed decisions about treatment. Our study is meant to generate new hypotheses for potential future clinical trials and to help clinicians understand the underlying mechanisms regarding the role of body composition to survival. Thus, presenting relative risks for this purpose is informative. Additionally, other studies on this topic have used statistical approaches similar to the approach we used so that results can easily be compared.
https://ift.tt/2DNEbAh
https://ift.tt/2DNEbAh
Circulating Tumor Cells and Radiotherapy Benefit in Early Breast Cancer—Reply
In Reply We thank Drs Tsoutsou and Vozenin for their insightful comments regarding our recent article detailing the potential for using circulating tumor cell (CTC) status as a predictive biomarker for benefit of radiotherapy among patients with early-stage breast cancer.
https://ift.tt/2S6r5RI
https://ift.tt/2S6r5RI
Rechallenge for Patients With RAS and BRAF Wild-Type mCRC With Resistance to Cetuximab and Irinotecan
This multicenter, phase 2, single-arm trial assesses the activity of cetuximab plus irinotecan as third-line treatment for patients with RAS and BRAF wild-type metastatic colorectal cancer who were initially sensitive to and then resistant to first-line irinotecan- and cetuximab-based therapy.
https://ift.tt/2DNE8V7
https://ift.tt/2DNE8V7
Combination Immunotherapy in the First-line Treatment of Advanced Renal Cell Carcinoma
This narrative review discusses the rationale and results of clinical trials in immunotherapy-based combination therapy for patients with advanced renal cell carcinoma.
https://ift.tt/2S41VmA
https://ift.tt/2S41VmA
Dysmorphic Short Stature: Radiological Diagnosis of Trichorhinophalangeal Syndrome
Trichorhinophalangeal syndrome (TRPS), a type of skeletal dysplasia, is characterized by a triad of dysmorphic (bulbous nose and large ears); ectodermal (thin and sparse hair); and skeletal (short stature and cone-shaped epiphyses) findings, and this combination is helpful for early diagnosis and appropriate follow-up. A 14-year-old boy presented with short stature and distinctive facial features, and following the first clinical and biological evaluation, no precise diagnosis was reached. Progressive bilateral development of noninflammatory and painless deformity of his second finger required a radiological exam that highlighted the key elements (cone-shaped epiphyses) for final diagnosis. This case illustrates the difficulties to early recognition of TRPS when the clinical presentation is not complete and radiological findings are missing.
https://ift.tt/2DAPvyv
Editorial Board
Publication date: January 2019
Source: Archives of Oral Biology, Volume 97
Author(s):
https://ift.tt/2DEOHJh
Proteomics of the acid-soluble fraction of whole and major gland saliva in burning mouth syndrome patients
Publication date: Available online 20 November 2018
Source: Archives of Oral Biology
Author(s): Tiziana Cabras, Barbara Manconi, Massimo Castagnola, Maria Teresa Sanna, Morena Arba, Shikha Acharya, Jörgen Ekström, Anette Carlén, Irene Messana
Abstract
OBJECTIVE
In the present study the salivary proteome of burning mouth syndrome patients and healthy subjects was characterized by a top-down proteomic approach and compared to highlight possible qualitative and quantitative differences that may give suggestions about the causes of this pathology which are still unknown.
MATERIALS AND METHODS
Resting and stimulated whole saliva, stimulated parotid and submandibular/sublingual saliva samples were collected from burning mouth syndrome patients (n = 16) and age- and gender-matched healthy subjects (n = 14). An equal volume of 0.2% trifluoroacetic acid was added to each sample immediately after collection and the supernatants were analysed by liquid chromatography coupled to electrospray-ionisation mass spectrometry. Proteins and peptides were quantified using a label-free approach measuring the extracted ion current peak areas of the main salivary proteins and peptides.
RESULTS
The quantitation of the main salivary proteins and peptides revealed a higher concentration of cystatin SN in resting saliva of burning mouth syndrome patients with respect to healthy controls and no other conspicuous changes.
CONCLUSIONS
The reported data showed that the salivary protein profile was not affected, in composition and relative abundance, by the burning mouth syndrome, except for the cystatin SN, a protein up-regulated in several pathological conditions, that might be considered potentially indicative of the disease.
https://ift.tt/2Qdxayq
Peptides from rice endosperm protein restrain periodontal bone loss in mouse model of periodontitis
Publication date: Available online 20 November 2018
Source: Archives of Oral Biology
Author(s): Hikaru Tamura, Tomoki Maekawa, Hisanori Domon, Takumi Hiyoshi, Daisuke Yonezawa, Kosuke Nagai, Akihito Ochiai, Masayuki Taniguchi, Koichi Tabeta, Takeyasu Maeda, Yutaka Terao
Abstract
Objective
Food-derived peptides have been reported to exhibit antibacterial activity against periodontal pathogenic bacteria. However, no effect has been shown on inflammation and bone resorption in periodontal pathology. The overall objective of the current study was to investigate how rice peptides influence biological defense mechanisms against periodontitis-induced inflammatory bone loss, and identify their novel functions as a potential anti-inflammatory drug.
Design
The expression of inflammatory and osteoclast-related molecules was examined in mouse macrophage-derived RAW 264.7 cell cultures using qPCR. Subsequently, the effect of these peptides on inflammatory bone loss in mouse periodontitis was examined using a mouse model of tooth ligation. Briefly, periodontal bone loss was induced for 7 days in mice by ligating the maxillary second molar and leaving the contralateral tooth un-ligated (baseline control). The mice were microinjected daily with the peptide in the gingiva until the day before euthanization. One week after the ligation, TRAP-positive multinucleated cells (MNCs) were enumerated from five random coronal sections of the ligated sites in each mouse.
Results
Rice peptides REP9 and REP11 significantly inhibited transcription activity of inflammatory and osteoclast-related molecules. Local treatment with the rice peptides, in mice subjected to ligature-induced periodontitis, inhibited inflammatory bone loss, explaining the decreased numbers of osteoclasts in bone tissue sections.
Conclusion
Therefore, these data suggested that the rice peptides possess a protective effect against periodontitis.
https://ift.tt/2DCgOJ2
Leptin Stimulates DMP-1 and DSPP Expression in Human Dental Pulp via MAPK 1/3 and PI3K Signaling Pathways
Publication date: Available online 20 November 2018
Source: Archives of Oral Biology
Author(s): Jenifer Martín-González, Antonio Pérez-Pérez, Daniel Cabanillas-Balsera, Teresa Vilariño-García, Victor Sánchez-Margalet, Juan José Segura-Egea
Abstract
Introduction
: To investigate the physiological function of leptin in human dental pulp, and to determine the specific pathways implicated in its effect.
Methods
Twenty-seven dental pulp samples were obtained from human third molars. Pulp samples were treated with or without human recombinant leptin. Leptin functional effect was analyzed in terms of regulation of the synthesis levels of DSPP and DMP-1, determined by immunoblot.
Results
Leptin stimulated DMP-1 and DSPP synthesis in all human dental pulp specimens. The stimulatory effect of leptin on DMP-1 and DSPP synthesis was partially prevented by blocking mitogen-activated protein kinase (MAPK 1/3) and phosphatidylinositol 3 kinase (PI3K) pathways, respectively.
Conclusions
The present study demonstrates the functional effect of leptin in human dental pulp stimulating the expression of DMP-1 and DSPP, both proteins implicated in dentinogenesis. Leptin stimulates DSPP expression via PI3K pathway and DMP-1 synthesis via MAPK 1/3 pathway. These results support the role of leptin in pulpal reparative response, opening a new research line that could have translational application to the clinic in vital pulp therapy procedures.
https://ift.tt/2Qapug9
Betamethasone suppresses the inflammatory response in LPS-stimulated dental pulp cells through inhibition of NF-κB
Publication date: Available online 20 November 2018
Source: Archives of Oral Biology
Author(s): Dan Wang, Ning-Xin Zhu, Man Qin, Yuan-Yuan Wang
Abstract
Objective
This study aimed to investigate the anti-inflammatory effect of betamethasone on LPS-stimulated human dental pulp stem cells (DPSCs) and its associated mechanism. The osteo-/odontogenic differentiation and osteoclast effect of betamethasone on DPSCs and stem cells from human exfoliated deciduous teeth (SHED) were evaluated.
Design
The proliferative effect of betamethasone on DPSCs was analyzed using a cholecystokinin octapeptide assay. The anti-inflammatory effect of betamethasone was investigated using quantitative polymerase chain reaction (qPCR) and ELISA. The anti-inflammatory mechanism was explored using qPCR, Western blot, and immunofluorescence staining. Glucocorticoid receptor antagonist mifepristone was applied to verify the anti-inflammatory mechanism of betamethasone. The osteo-/odontogenic differentiation and osteoclast effect of betamethasone on DPSCs and SHED were detected by qPCR.
Results
1 μg L-1 betamethasone was found to have the strongest effect on DPSCs proliferation. The expression of pro-inflammatory cytokines and mediators, as well as prostaglandin E2 (PGE2) were significantly decreased following treatment with betamethasone in LPS- stimulated DPSCs. They were also decreased in response to an NF-κB inhibitor, Bay 11-7082. Betamethasone and Bay 11-7082 significantly inhibited the expression of p-p65 and promoted the nuclear exclusion of p65. The anti-inflammatory effect of betamethasone was clearly reversed by adding mifepristone. Gene expression associated with osteo-/odontogenic differentiation was significantly up-regulated in betamethasone and osteogenic media (OM) treated groups. The ratio of the receptor activator of nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) at the mRNA level was suppressed in DPSCs and elevated in SHED.
Conclusions
Betamethasone has an anti-inflammatory effect on LPS- stimulated DPSCs through a blockade of NF-κB activation and exhibits an osteo-/odonto-inductive effect on DPSCs and SHED. Although betamethasone displays an osteoclast effect on SHED.
https://ift.tt/2DAKR3x
Molecular mechanism of the ichthyosis pathology of Chanarin–Dorfman syndrome: stimulation of PNPLA1-catalyzed ω-O-acylceramide production by ABHD5
Publication date: Available online 20 November 2018
Source: Journal of Dermatological Science
Author(s): Yusuke Ohno, Atsuki Nara, Shota Nakamichi, Akio Kihara
Abstract
Background
ABHD5 mutations cause Chanarin–Dorfman syndrome accompanied by ichthyosis. ω-O-Acylceramide (acylceramide) is essential for skin permeability barrier formation. Acylceramide production is impaired in Abhd5 knockout mice. The transacylase PNPLA1 catalyzes the final step of acylceramide production: transfer of linoleic acid in triglyceride to ω-hydroxyceramide.
Objective
We aimed to elucidate the role of ABHD5 in acylceramide production and the molecular mechanism of the ichthyosis symptoms of Chanarin–Dorfman syndrome.
Methods
We investigated how ABHD5 influences acylceramide production using an acylceramide-producing cell system. The effects of ABHD5 and PNPLA1 expression on the morphology of lipid droplets were examined by indirect immunofluorescent microscopy and immunoelectron microscopy.
Results
When ABHD5 was expressed in the acylceramide-producing cell system, acylceramide synthesis by PNPLA1 was enhanced. Dispersed localization of PNPLA1 was observed by immunofluorescent microscopy in HeLa cells under lipid droplet-forming conditions. Co-expression with ABHD5 caused PNPLA1 to localize on the lipid droplet membranes or their periphery. This staining pattern was observed in cells where PNPLA1 and ABHD5 were expressed at low levels. In contrast, lipid droplets disappeared in cells where PNPLA1 and ABHD5 were highly expressed. Immunoelectron microscopic analyses suggested that lipid droplets underwent morphological changes, transforming into vesicles or becoming incorporated into the endoplasmic reticulum. ABHD5 mutations found in Chanarin–Dorfman syndrome patients reduced ABHD5's ability to promote PNPLA1-dependent acylceramide production.
Conclusion
ABHD5 enhances PNPLA1-catalyzed acylceramide production. We speculate that ABHD5 retains triglycerides in the endoplasmic reticulum, and presents them to PNPLA1 to promote substrate recognition.
https://ift.tt/2DELmKf
Type 2 diabetes treatment and progression of chronic kidney disease in Italian family practice
Abstract
Aims
Progressive chronic kidney disease represents a dreadful complication of type 2 diabetes mellitus (T2DM). We tested the pattern of use and the renal effects of old glucose-lowering drugs in T2DM patients cared for by Italian general practitioners (GPs).
Methods
Data of 2606 T2DM patients were extracted from the databases of GPs, who do not have access to the most recent glucose-lowering drugs in Italy. The rate of kidney function decline was calculated by CKD-EPIcr, based on two consecutive creatinine values.
Results
Metformin was used in 55% of cases, either alone or with sulfonylureas/repaglinide, across the whole spectrum of CKD (from 66% in stage G1 to only 8% in G4). Sulfonylurea use peaked at 21–22% in stage G2–G3a, whereas repaglinide use significantly increased from 8% in G1 to 22% in G4. The median rate of CKD decline was − 1.64 mL/min/1.73 m2 per year; it was higher in G1 (− 3.22 per year) and progressively lower with CKD severity. 826 cases (31.7%) were classified as fast progressors (eGFR decline more negative than − 5 mL/min/1.73 m2 per year). The risk of fast progressing CKD was associated with increasing BMI, albuminuria, and sulfonylurea use, alone (OR, 1.47; 95% confidence interval, 1.16–1.85), or in association with metformin (OR, 1.40; 95% CI 1.04–1.88). No associations were demonstrated for metformin, cardiovascular and lipid lowering drug use.
Conclusion
In the setting of Italian family practice, sulfonylurea use is associated with progressive CKD in patients with T2DM. Metformin, at doses progressively reduced according to CKD stages, as recommended by guidelines, is not associated with fast progression.
https://ift.tt/2qXzUBy
Special section on intensity-modulated radiation therapy for head and neck cancer (IMRT)
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Vincent Grégoire, Wai Tong Ng
https://ift.tt/2R07emV
The impact of treatment package time on survival in surgically managed head and neck cancer in the United States
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Alexander N. Goel, Mariana I. Frangos, Govind Raghavan, Stephanie L. Lazaro, Belicia Tang, Dinesh K. Chhetri, Jennifer L. Long, Maie A. St. John
Abstract
Objectives
Delays in the initiation of postoperative radiation have been associated with worse outcomes; however, the effect of the overall treatment package time (interval from surgery through the completion of radiation) remains undefined. The purpose of this study was to determine the impact of package time on survival and to evaluate this effect among different subgroups of head and neck cancer patients.
Patients and methods
In this observational cohort study, the National Cancer Database was used to identify 35,167 patients with resected nonmetastatic head and neck cancer who underwent adjuvant radiation from 2004 to 2014. Kaplan-Meier survival estimates and multivariate Cox regression analyses were performed to determine the effect of treatment package time on overall survival.
Results
Median package time was 96 days (interquartile range, 85–112 days). After adjusting for covariates, package times of 11 weeks or less were associated with improved survival (adjusted hazard ratio (aHR), 0.90; 95% confidence interval, 0.83–0.97) compared to an interval of 12–13 weeks, whereas package times of more than 14 weeks were associated with worse survival (aHR, 1.14, 1.14, and 1.22 for 14–15, 15–17, and >17 weeks, respectively). A significant interaction was identified between package time and disease site, nodal status, and stage. Specifically, patients with oropharyngeal tumors, advanced stage (III or IV) disease, or nodal involvement experienced more pronounced increases in mortality risk with delays in treatment time.
Conclusions
Treatment package time independently impacts survival. This effect may be strongest for patients with oropharyngeal tumors or advanced stage disease.
https://ift.tt/2PIgyzq
Macrophages in the microenvironment of head and neck cancer: potential targets for cancer therapy
Publication date: January 2019
Source: Oral Oncology, Volume 88
Author(s): Diane Evrard, Petr Szturz, Annemilaï Tijeras-Raballand, Lucile Astorgues-Xerri, Chloé Abitbol, Valérie Paradis, Eric Raymond, Sébastien Albert, Béatrix Barry, Sandrine Faivre
Abstract
The microenvironment of solid tumors has become a promising target for future therapies modulating immune cells. Patients with advanced head and neck cancer, which still portends a poor outcome, are particularly in need of innovative approaches. In oral squamous cell carcinoma, high density of tumor-associated macrophages (TAMs) appears consistently associated with poor prognosis, whereas data are currently limited for other head and neck sites. Several approaches to block TAMs have been investigated, including TAMs inactivation by means of the colony stimulating factor 1 (CSF-1)/CSF-1 receptor (CSF-1R) inhibitors or strategies to reprogram TAMs from M2 protumoral phenotype toward M1 antitumoral phenotype. This review focuses on both prognostic and therapeutic aspects related to TAMs in head and neck carcinomas.
Graphical abstract
https://ift.tt/2R0lLPH
Surgical deroofing in the treatment of patients with auricular pseudocyst
Publication date: Available online 20 November 2018
Source: Auris Nasus Larynx
Author(s): Yoon Jae Lee, Jin Geun Kwon, Hyun Ho Han
Abstract
Objective
An auricular pseudocyst is a fluid filled cavity, characterized by a lack of epithelium, in the intra-cartilaginous space. Clinically, it presents as a painless lump on the upper anterior surface of the ear. Various treatment methods have been discussed in the literature, including aspiration, incision and drainage, or steroid injection. However, these approaches are associated with a high rate of recurrence and results are often esthetically unsatisfactory; therefore, a need for improved treatment approaches remains.
Methods
From March, 2015, to June, 2017, 15 patients with auricular pseudocyst were treated with surgical deroofing followed by local contour pressure dressing with a simple bolster. In addition, the structure of the auricular pseudocyst was assessed at a microscopic level.
Results
Patients were followed up for a mean period of 12 months, during which time there were no reports of postoperative complications or recurrence. The results were cosmetically excellent in all patients and no cartilage deformity was seen. Considering the composition of pseudocysts seen on microscopic evaluation, deroofing to remove the anterior leaflet and removal of debris from the posterior leaflet is an appropriate treatment modality.
Conclusion
This reliable and simple approach may be recommended as first line treatment for auricular pseudocysts to avoid recurrence and complications associated with other treatment modalities, such as cartilage deformity, skin depigmentation, and scarring.
https://ift.tt/2PJxHIX
Mast cells as protectors of health
Publication date: Available online 20 November 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Anne Dudeck, Martin Köberle, Oliver Goldmann, Nicole Meyer, Jan Dudeck, Stefanie Lemmens, Manfred Rohde, Nestor González Roldán, Kirsten Dietze-Schwonberg, Zane Orinska, Eva Medina, Sven Hendrix, Martin Metz, Ana Claudia Zenclussen, Esther von Stebut, Tilo Biedermann
Abstract
Mast cells (MC), well known for their effector functions in Th2 skewed allergic and also autoimmune inflammation, become increasingly acknowledged for their role in protection of health. It is now clear that they are also key modulators of immune responses at interface organs like skin or gut. MC can prime tissues for adequate inflammatory responses and cooperate with dendritic cells in T cell activation. They also regulate harmful immune responses in trauma and help to successfully orchestrate pregnancy. This review focusses on the beneficial effects of mast cells on tissue homeostasis and elimination of toxins or venoms. MC can enhance pathogen clearance in many bacterial, viral, and parasite infections, e.g. by TLR2 triggered degranulation, secretion of antimicrobial cathelicidins, recruiting neutrophils or by providing extracellular DNA traps. The role of MC in tumors is more ambiguous, however, encouraging new findings show they can change the tumor microenvironment towards anti-tumor immunity when adequately triggered. Uterine tissue remodeling by α-chymase (MCP-5) is crucial for successful embryo implantation. MCP-4 and the tryptase MCP-6 emerge to be protective in CNS trauma by reducing inflammatory damage and excessive scar formation, thereby protecting axon growth. Last but not least, we see proteases like carboxypeptidase A released by FcεRI activated MC detoxify an increasing number of venoms and endogenous toxins. A better understanding of the plasticity of MC will help to improve these advantageous effects, and hint on ways to cut down detrimental MC actions.
https://ift.tt/2Acmbv5
Inter-laboratory variability in multiplexed pneumococcal antibody testing
Publication date: Available online 20 November 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): David C. LaFon, Moon H. Nahm
Summary
This pragmatic, updated assessment of variability among pneumococcal antibody assays suggests that variability may now be greater than previously reported, and potentially influential in clinical decision making.
https://ift.tt/2Tx7Xxy
Impact of Ixekizumab Treatment on Itch and Psoriasis Area and Severity Index in Patients with Moderate-to-Severe Plaque Psoriasis: An Integrated Analysis of Two Phase III Randomized Studies
Abstract
Introduction
We evaluated baseline itch and its impact on the efficacy of ixekizumab (IXE) in clearing psoriasis and improving quality-of-life measures, and we explored the relationship between itch and psoriatic skin improvement.
Methods
Data were analyzed from two double-blind, randomized, controlled phase III studies (UNCOVER-2/3) comparing etanercept (ETN), IXE, and placebo (PBO) in patients with moderate-to-severe plaque psoriasis. Long-term analysis included UNCOVER-3 data from week 0 to week 156.
Results
At week 12, a clinically meaningful improvement in itch [Itch Numeric Rating Scale (NRS) reduction ≥ 4] was seen in 70.0%, 88.6%, and 90.8% of the IXE-treated patients in the baseline Itch NRS 4–6, 7–8, and 9–10 groups, respectively (all itch severity groups p < 0.001 versus ETN and PBO). Also, 68.9%, 67.1%, and 73.6% of the IXE-treated patients in the baseline Itch NRS 4–6, 7–8, and 9–10 groups, respectively, showed an improvement of ≥ 90.0% in the Psoriatic Area and Severity Index (PASI) at week 12 as compared to the baseline (PASI 90) (all itch severity groups p < 0.001 versus ETN and PBO). For most patients, itch reduction preceded psoriatic plaque improvement. Sustained effects of IXE on itch and PASI were observed during 3 years of treatment.
Conclusions
Regardless of baseline itch severity, IXE treatment provided a rapid improvement in itch followed by clinically meaningful improvements in psoriasis.
Funding
Eli Lilly and Company.
Trial registration
ClinicalTrials.gov identifiers, NCT01597245 and NCT01646177.
https://ift.tt/2zlyVQd
The Number Interval Position Effect (NIPE) in the mental bisection of numerical intervals might reflect the influence of the decimal-number system on the Gaussian representations of numerosities: a combined developmental and computational-modelling study
Publication date: Available online 20 November 2018
Source: Cortex
Author(s): Francesca Rotondaro, Michela Ponticorvo, Onofrio Gigliotta, Mario Pinto, Michele Pellegrino, Simone Gazzellini, Pasquale Dolce, Orazio Miglino, Fabrizio Doricchi
Abstract
Healthy adults show typical error biases when they mentally bisect number intervals without exact calculations. For a given number interval length, the bisection bias is in fact modulated by the position that the interval occupies within a ten. For intervals positioned at the beginning of tens the error bias is directed toward values that are higher than those of the true interval midpoint whereas for intervals at the end of tens the direction of the error bias is reversed toward values that are lower than that of the true midpoint (Doricchi et al., 2009; Rotondaro et al., 2015). This effect has been defined Number Interval Position Effect (NIPE). The NIPE recurs over consecutive tens and it is not found when intervals are bisected through exact calculations. For this reasons we have hypothesised that the NIPE reflects the influence that the habit of counting in tens has on the neural representations of numerosities that humans share with other species. Here, in a developmental study we demonstrate that children from preschool to fifth-grade display a NIPE that is comparable to that of healthy adults. Then, through a computational-modelling study we investigated whether the NIPE might reflect specific patterns in the Gaussian representations of numerosities that are found in the parietal and pre-frontal neuronal populations of macaque monkeys and that underlie approximate numerosity estimations also in humans. The findings of computational simulations suggest that the NIPE might reflect the influence that the learning and use of the decimal numerical system has on the phylogenetically and ontogenetically older representation of numerosities that humans share with other species. These changes in the representation of numerosities have an influence on approximate numerical estimations even when these, like in the case of the mental bisection of number intervals, are elicited by numerical symbols or words.
https://ift.tt/2PGmmt3
Evaluation of body composition using dual-energy X-ray absorptiometry in patients with non-functioning adrenal incidentalomas and an intermediate phenotype: Is there an association with metabolic syndrome?
Abstract
Purpose
Metabolic syndrome (MS) and sarcopenia are associated with increased cardiovascular risk. No studies using dual-energy x-ray absorptiometry (DXA) have evaluated association between body composition (BC) changes and MS in adrenal incidentaloma (AI). Our aim was to analyse BC in non-functioning AI (NFAI) and intermediate phenotype (IP) relative to controls and to correlate with cortisol levels.
Methods
Cross-sectional study with 44 NFAI (serum cortisol ≤ 50 nmol/L after the overnight 1 mg dexamethasone suppression test), 27 IP (cortisol 51–138 nmol/L), and 41 controls (normal adrenal on imaging examination) using DXA. Autonomic cortisol secretion (cortisol > 138 nmol/L) was excluded from the study. BC data were compared using criteria for MS (World Health Organization, National Cholesterol Education Program-Adult Treatment Panel-III, American Association of Clinical Endocrinologists (AACE), and International Diabetes Federation).
Results
There was no significant difference in clinical data and body mass index (BMI) among the three groups. Waist circumference (WC) was larger in AI vs. controls (p < 0.01). Waist-to-hip ratio was higher in NFAI vs. controls and waist-to-height ratio was higher in IP vs. controls (p = 0.03 and p = 0.02, respectively). The frequency of MS was higher in AI vs. controls. BC was not different among the groups. Patients with AI there was a significant association of MS with both an increase in total fat and body fat index (all criteria), and a significant difference between MS and smaller BMI-adjusted lean mass (AACE, p = 0.036). No correlation of cortisol after 1 mg dexamethasone test with BC or MS. AI and WC were independently associated with MS.
Conclusions
AI presented high frequency of MS and was independently associated with MS. Possible deleterious effects of cortisol secretion seem to initially affect the muscular system.
https://ift.tt/2OWPBT5
Potassium Iodide for Cutaneous Inflammatory Disorders: A Monocentric, Retrospective Study
Objectives: Potassium iodide (KI) is a medication that has been used for decades in dermatology and it is mentioned as a treatment option in all major dermatology textbooks. Yet, there is little recent information on its efficacy. In our study, we wanted to retrospectively evaluate the therapy response to KI in our patients. Methods: The hospital information system was searched for patients treated with KI at the Department of Dermatology (University Hospital Zurich) in the last 20 years (January 1, 1998 to December 31, 2017). A total of 52 patients were found and, subsequently, 35 patients were included in our study. Results: KI was prescribed for the following skin conditions: erythema nodosum, disseminated granuloma anulare, necrobiosis lipoidica, nodular vasculitis, cutaneous sarcoidosis, and granulomatous perioral dermatitis/ rosacea. The median duration of KI intake was 5 ± 7.7 weeks (range 1–26). The global assessment of efficacy by the treating physician showed an improvement of disease in about a third of all patients. No response was seen in 14 patients and 9 even had a progression of disease. An adverse event was documented in 16 cases. Conclusions: Our findings show that an improvement was reached in only about a third of all cases. High response rates with only mild side effects (in 16 out of 35 patients) were observed.
Dermatology
https://ift.tt/2QZ00Qb
Dermatology
https://ift.tt/2QZ00Qb
An alphavirus-based therapeutic cancer vaccine: from design to clinical trial
Abstract
Cancer immunotherapy has greatly advanced in recent years. Most immunotherapeutic strategies are based on the use of immune checkpoint blockade to unleash antitumor immune responses or on the induction or adoptive transfer of immune effector cells. We aim to develop therapeutic vaccines based on recombinant Semliki Forest virus vectors to induce tumor-specific effector immune cells. In this review, we describe our ongoing work on SFV-based vaccines targeted against human papillomavirus- and hepatitis C virus-related infections and malignancies, focusing on design, delivery, combination strategies, preclinical efficacy and product development for a first-in-man clinical trial with an HPV-specific vaccine.
https://ift.tt/2DNO5BV
Highlights from 2017: impactful topics published in the Annals of Nuclear Medicine
Abstract
The aim of the review is to highlight articles published in 2017 in the Annals of Nuclear Medicine, an official peer-reviewed journal of the Japanese Society of Nuclear Medicine. Among all published manuscripts during the past year, we conducted a subjective selection of the most relevant topics. Fourteen fascinating articles are included in this review, ranging in topic from preclinical to clinical arenas.
https://ift.tt/2KoE66n
18 F-FDGPET/CT in fever of unknown origin and inflammation of unknown origin: a Chinese multi-center study
Abstract
Purpose
To evaluate the clinical value of 18F-FDG-PET/CT for the diagnosis of fever of unknown origin (FUO) and inflammation of unknown origin (IUO) in Chinese population, as well as the characteristics of PET/CT in different category of etiological disease.
Methods
A total of 376 consecutive patients with FUO/IUO who underwent FDG-PET/CT at 12 hospitals were retrospectively studied. FDG uptake was quantitatively and visually evaluated, by using SUVmax and a 4-grade scale respectively. A questionnaire survey to the clinicians was used to evaluate the significance of PET/CT in diagnosing of FUO/IUO. Data analysis included the etiological distribution in the study population, image characteristics in different category of diseases, and clinical significance of PET/CT.
Results
In 376 studied patients, the infectious diseases accounted for 33.0% of patients, rheumatologic diseases for 32.4%, malignancies for 19.1%, miscellaneous causes for 6.6%, and cause unknown for 8.8%. However, the etiological distribution among hospitals was varied. In addition, the etiological disease composition ratio has changed over time in China. On PET/CT examinations, 358 (95.2%) of the patients had a positive finding. Within them, local high uptake lesion was found in 219 cases, and nonspecific abnormal uptake (NAU) was found in 187 cases. FDG uptake in malignant diseases was significantly higher than in other category diseases both on SUVmax and visual scores (t-value range from 4.098 to 5.612, all P value < 0.001). Based on a clinical questionnaire survey, PET/CT provided additional diagnostic information for 77.4% of patients, and 89.6% of patients benefited from PET/CT examination.
Conclusions
FDG PET/CT is a valuable tool for clinical diagnosis of FUO/IUO, and it is of great significance in further investigating the usefulness of PET/CT in non-neoplastic diseases.
https://ift.tt/2KnOICl
FDG PET/CT imaging in detecting and guiding management of invasive fungal infections: a retrospective comparison to conventional CT imaging
Abstract
Purpose
Invasive fungal infections (IFIs) are common in immunocompromised patients. While early diagnosis can reduce otherwise high morbidity and mortality, conventional CT has suboptimal sensitivity and specificity. Small studies have suggested that the use of FDG PET/CT may improve the ability to detect IFI. The objective of this study was to describe the proven and probable IFIs detected on FDG PET/CT at our centre and compare the performance with that of CT for localization of infection, dissemination and response to therapy.
Methods
FDG PET/CT reports for adults investigated at Peter MacCallum Cancer Centre were searched using keywords suggestive of fungal infection. Chart review was performed to describe the risk factors, type and location of IFIs, indication for FDG PET/CT, and comparison with CT for the detection of infection, and its dissemination and response to treatment.
Results
Between 2007 and 2017, 45 patients had 48 proven/probable IFIs diagnosed prior to or following FDG PET/CT. Overall 96% had a known malignancy with 78% being haematological. FDG PET/CT located clinically occult infection or dissemination to another organ in 40% and 38% of IFI patients, respectively. Of 40 patients who had both FDG PET/CT and CT, sites of IFI dissemination were detected in 35% and 5%, respectively (p < 0.001). Of 18 patents who had both FDG PET/CT and CT follow-up imaging, there were discordant findings between the two imaging modalities in 11 (61%), in whom normalization of FDG avidity of a lesion suggested resolution of active infection despite a residual lesion on CT.
Conclusion
FDG PET/CT was able to localize clinically occult infection and dissemination and was particularly helpful in demonstrating response to antifungal therapy.
https://ift.tt/2KoDFsL
FDG PET in response evaluation of bulky masses in paediatric Hodgkin’s lymphoma (HL) patients enrolled in the Italian AIEOP-LH2004 trial
Abstract
Purpose
We present the results of an investigation of the role of FDG PET in response evaluation of bulky masses in paediatric patients with Hodgkin's lymphoma (HL) enrolled in the Italian AIEOP-LH2004 trial.
Methods
We analysed data derived from 703 patients (388 male, 315 female; mean age 13 years) with HL and enrolled in 41 different Italian centres from March 2004 to September 2012, all treated with the AIEOP-LH2004 protocol. The cohort comprised 309 patients with a bulky mass, of whom 263 were evaluated with FDG PET at baseline and after four cycles of chemotherapy. Responses were determined according to combined functional and morphological criteria. Patients were followed up for a mean period of 43 months and for each child we calculated time-to-progression (TTP) and relapse rates considering clinical monitoring, and instrumental and histological data as the reference standard. Statistical analyses were performed for FDG PET and morphological responses with respect to TTP. Multivariate analysis was used to define independent predictive factors.
Results
Overall, response evaluation revealed 238 PET-negative patients (90.5%) and 25 PET-positive patients (9.5%), with a significant difference in TTP between these groups (mean TTP: 32.67 months for negative scans, 23.8 months for positive scans; p < 0.0001, log-rank test). In the same cohort, computed tomography showed a complete response (CR) in 85 patients (32.3%), progressive disease (PD) in 6 patients (2.3%), and a partial response (PR) in 165 patients (62.7%), with a significant difference in TTP between patients with CR and patients with PD (31.1 months and 7.9 months, respectively; p < 0.001, log-rank test). Similarly, there was a significant difference in relapse rates between PET-positive and PET-negative patients (p = 0000). In patients with PR, there was also a significant difference in TTP between PET-positive and PET-negative patients (24.6 months and 34.9 months, respectively; p < 0.0001). In the multivariate analysis with correction for multiple testing, only the PET result was an independent predictive factor in both the entire cohort of patients and the subgroup showing PR on CT (p < 0.01).
Conclusion
After four cycles of chemotherapy, FDG PET response assessment in paediatric HL patients with a bulky mass is a good predictor of TTP and disease outcome. Moreover, in patients with a PR on CT, PET was able to differentiate those with a longer TTP. In paediatric HL patients with a bulky mass and in patients with a PR on CT, response on FDG PET was an independent predictive factor.
https://ift.tt/2KlSGvq
Correction to: Highlights from 2017: impactful topics published in the Annals of Nuclear Medicine
The author names in the original version of this article were inversed. Correct author names were reflected here.
https://ift.tt/2Kq7Sb6
Outcome of patients with early-stage follicular lymphoma staged with 18 F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) and treated with radiotherapy alone
Abstract
Purpose/objective(s)
To evaluate the impact of positron emission tomography (PET) staging on overall survival (OS) and progression-free survival (PFS) in patients with early-stage (stages I and II) follicular lymphoma (ESFL) treated with radiation therapy alone.
Materials/methods
Eighty-five patients with ESFL treated with curative-intent radiation therapy (RT) between December 2000 and May 2011 were identified. Of those, 13 who had no PET staging and 25 who received additional systemic therapy were excluded from the analysis. Thus, we analyzed 47 patients with PET-staged ESFL treated with definitive radiation therapy alone (dose > 23Gy). Tumour features, pre-treatment computed tomography (CT) and PET stage, dose fractionation, and radiation therapy field extent were recorded. The Kaplan–Meier method was used to estimate the OS and PFS. Patterns of failure were assessed as cumulative incidences assuming competing risks.
Results
Median age was 57 years (range 24–83); 43% were females. Most were PET stage 1 (76.6%). Median maximum nodal diameter was 3 cm. Median pre-treatment lactate dehydrogenase (LDH) was 327.5 (range 123–607, upper normal limit = 220). Twenty-six patients (55.3%) had infra-diaphragmatic disease. All received 30–36Gy in 15–24 fractions, with 59.6% treated with involved-field radiation therapy (IFRT) techniques. There was no significant difference in PFS between CT stage I and stage II (HR 1.30 95% CI [0.25–6.72], p = 0.75) with a 5-year PFS of 77% and 78% respectively. However, stage I on PET staging had a significantly better PFS than stage II (HR 4.66 95% CI [1.15–18.8], p = 0.038), with 5-year PFS of 84% and 60% respectively. Ten patients had recurrent disease, with distant disease being the first site of failure in seven patients. Seven-year OS was 91% (95% CI 79–100) for the whole cohort.
Conclusion
FDG-PET should be considered an essential element in the evaluation of patients with ESFL being considered for RT.
https://ift.tt/2BnCwir
Salvage extended field or involved field nodal irradiation in 18 F-fluorocholine PET/CT oligorecurrent nodal failures from prostate cancer
Abstract
Purpose
The concept of metastasis-directed therapy for nodal oligorecurrences with stereotactic body radiotherapy is increasingly accepted. Hence, the comparison between salvage extended field radiotherapy (s-EFRT) and salvage involved field radiotherapy (s-IFRT) in patients with 18F-fluorocholine (FCH) PET/CT+ nodal oligorecurrences from prostate cancer is worthy of investigation.
Methods
Patients with oligorecurrent nodes on FCH PET/CT treated with salvage radiotherapy between 2009 and 2017 in a single tertiary cancer centre were selected for this study. Patients treated with s-IFRT were compared with those treated with s-EFRT. Toxicities and times to failure (TTF) were compared between the two groups.
Results
The study included 62 patients with positive lymph nodes only who underwent FCH PET/CT for a rising PSA level after radical prostatectomy or radiotherapy. Of these patients, 35 had s-IFRT and 27 had s-EFRT. After a median follow-up of 41.8 months (range 5.9–108.1 months), no differences were observed in acute or late gastrointestinal and genitourinary toxicities of grade 2 or more between the two groups. The 3-year failure rates were 55.3% (95% CI 37.0–70.3%) in the s-IFRT group and 88.3% (95% CI 66.9–96.1%) in the s-EFRT group (p = 0.0094). In multivariate analysis of TTF, an interval of >5 years was significantly correlated with better outcomes (HR = 0.33, 95% CI 0.13–0.86, p = 0.023). There was a strong trend toward better outcomes with s-EFRT even after adjusting for concomitant androgen-deprivation therapy (HR = 0.38, 95% CI 0.12–1.27, p = 0.116).
Conclusion
FCH PET-positive node-targeted s-EFRT is feasible with low rates of toxicity and longer TTF, suggesting that oligorecurrent nodal disease diagnosed on FCH PET is unlikely.
https://ift.tt/2Kq7t8A
68 Ga-PSMA-11 PET/CT in recurrent prostate cancer: efficacy in different clinical stages of PSA failure after radical therapy
Abstract
Objectives
The primary objective was the evaluation of Gallium 68 (68Ga)-prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computed tomography (PET/CT) detection rate, for identifying the site of prostate cancer (PCa) relapse (local vs systemic), stratifying the population according to different clinical stages of biochemical recurrence (BCR). Secondary aims were: 1) to evaluate the association of clinical/pathologic features and 68Ga-PSMA-11 PET/CT detection rate, 2) to compare 68Ga-PSMA-11 PET/CT with other imaging procedures, and 3) to evaluate the positive predictive value (PPV) in a per-patient analysis.
Material and methods
This population was enrolled through a prospective, open label, single-center trial performed at the Nuclear Medicine of the University Hospital of Bologna (Eudract: 2015-004589-27 OsSC). The inclusion criteria were: (1) proven PCa, (2) surgery or radiotherapy as definitive therapy, (3) proven BCR, (4) prostate-specific antigen (PSA) 0.2–2 ng/ml, (5) age ≥ 35 years, and 6() willing to sign an informed consent. Three-hundred and thirty-two (332) patients were enrolled between March 2016 and June 2017; mean/median PSA was 0.84/0.61 ng/ml, 97.9% (325/332) of patients received radical prostatectomy and 2.1% (7/332) radiotherapy. Different patterns of BCR were identified by referent physicians as follows: (a) persisting detectable PSA after radical prostatectomy in 13.5% (45/332) of patients (subgroup 1), (b) first-time PSA failure after radical therapy in 44.9% (149/332) (subgroup 2), and (c) PSA increase after salvage or hormonal therapy in 41.6% (138/332) (subgroup 3).
Results
Primary objective: 68Ga-PSMA-11 PET/CT detection rate was 53.6% (CI 95% 48.1%–59.1%). In a patient-based analysis, disease confined to pelvis (prostate bed and/or lymph-nodes) was detected in 24.7% of cases (82/332). The presence of at least one distant lesion was observed in 28.9% of cases (96/332). The detection rate in different subgroups was: subgroup 1 = 64.5%, subgroup 2 = 45.6%, and subgroup-3 = 58.7%. Secondary objectives: 1) PSA (p = 0.041) and PSAdt (p = 0.001) showed association with 68Ga-PSMA-11 PET/CT detection rate, and 2) correlative imaging was available in 73.2% of patients (243/332). When 68Ga-PSMA-11 PET/CT was positive, correlative imaging resulted negative in 83% of cases (108/130). 3) The calculated PPV was 96.2%.
Conclusion
Our data confirmed the efficacy of 68Ga-PSMA-11 PET/CT for detecting local vs systemic disease in PCa patients presenting PSA failure after radical therapy. Furthermore, 68Ga-PSMA-11 PET/CT detection rate is different depending on the clinical stage of BCR, and this information should be taken into consideration by referring physicians.
https://ift.tt/2BnpLUK
18 F-FDG PET/CT is useful for determining survival outcomes of patients with multiple myeloma classified as stage II and III with the Revised International Staging System
Abstract
Purpose
This study evaluated the prognostic role of 18F-FDG PET/CT at baseline in patients with newly diagnosed multiple myeloa (MM) and evaluated the prognostic relevance of 18F-FDG PET/CT for each stage according to the Revised International Staging System (R-ISS).
Method
We retrospectively analyzed the records of 167 patients with newly diagnosed MM. 18F-FDG PET/CT was performed prior to induction therapy in patients with newly diagnosed MM.
Results
In the total cohort, the presence of more than three hypermetabolic focal lesions (FLs) or extramedullary disease (EMD) on baseline PET/CT was associated with significantly inferior progression-free survival (PFS) and overall survival (OS) than other patients. Because most patients (91%) with EMD had more than three FLs, PET/CT positivity was defined as the presence of more than three FLs or the presence of EMD. In multivariate analyses, PET/CT positivity was an independent predictor of PFS and OS in all patients. Fifty-five patients (46.1%) with R-ISS II were PET/CT-positive at baseline and had significantly shorter PFS and OS. PET/CT positivity was also correlated with poor PFS and OS in patients with R-ISS III.
Conclusion
18F-FDG PET/CT was an independent predictor of survival outcomes in patients with newly diagnosed MM. In addition, performing 18F- FDG PET/CT at diagnosis may be useful for determining the survival outcomes of MM patients with R-ISS II and III.
https://ift.tt/2BorNUI
Initial clinical experience performing sialendoscopy for salivary gland protection in patients undergoing 225 Ac-PSMA-617 RLT
Abstract
Purpose
The main side effect of prostate-specific membrane antigen targeting alpha therapy (PSMA TAT) is dry mouth syndrome. Inflammation of the salivary glands and consequent reduced salivary function have been reported in patients after radioiodine therapy. The beneficial effects of sialendoscopy on radiation-induced inflammation in tissue are well known. Thus sialendoscopy with dilatation, saline irrigation and steroid injections (prednisolone) was performed before and after 225Ac-PSMA-617 TAT to reduce inflammatory effects in the salivary glands and to improve or prevent xerostomia.
Methods
Eleven men with metastatic castration-resistant prostate cancer (mean age 68.5 years, range 58–80 years) underwent sialendoscopy, dilatation, saline irrigation and steroid injection of both submandibular and both parotid glands before or after every cycle of 225Ac-PSMA-617 TAT. Sialendoscopy and steroid injection were performed by a senior ENT physician. Quality of life was evaluated using two health-related quality of life (HRQOL) questionnaires, the Xerostomia Questionnaire (XQ) and the Xerostomia Inventory (XI) before and 3 months after the intervention.
Results
In all 11 patients both parotid and both submandibular glands were affected by radiation sialadenitis and sialendoscopy was performed. The patients experienced no complications after sialendoscopy, and showed a significant improvement in HRQOL as measured using the XQ and XI. After sialendoscopy the XQ score decreased significantly from 77.7 ± 13.6 to 42.7 ± 14.8 (p = 0.003) and the XI score decreased from 44.5 ± 6.9 to 25.8 ± 12.8 (p = 0.003). Due to the limited number of patients we only report tendencies.
Conclusion
Sialendoscopy with dilatation, saline irrigation and steroid injection had beneficial effects on salivary gland function and HRQOL in patients undergoing 225Ac-PSMA-617 RLT. However, even with sialadenoscopic support after multiple cycles of TAT, salivary gland function was reduced and xerostomia was present. Therefore, not only inflammation but also the direct effect of radiation is a putative cause of dry mouth. Further research is necessary to determine the main side effects of PSMA TAT.
https://ift.tt/2Klb3k0
68 Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA <0.5 ng/ml. Efficacy and impact on treatment strategy
Abstract
Purpose
The primary aim of this retrospective, single-centre analysis was to assess the performance of 68Ga-PSMA-11 PET/CT in prostate cancer (PCa) patients in early PSA failure after radical prostatectomy (RP). The secondary aim was to assess the potential impact of 68Ga-PSMA-11 PET/CT on treatment strategy.
Methods
68Ga-PSMA-11 PET/CT is performed in our institution within an investigational new drug (IND) trial in PCa patients with biochemical recurrence (BCR). The records of all patients enrolled between March 2016 and July 2017 were evaluated. These records were retrospectively analysed according to the following inclusion criteria: (a) RP as primary therapy, (b) proven BCR, ©) PSA levels in the range 0.2–0.5 ng/ml at the time of the 68Ga-PSMA-11 PET/CT investigation, and (d) no salvage radiotherapy (S-RT) performed after recurrence. The performance of 68Ga-PSMA-11 PET/CT was evaluated in terms of detection rate on a per-patient and a per-region basis (local vs. distant lesions). We further performed an intention-to-treat (ITT) analysis. The patient cohort was grouped into three subpopulations, blinded to the 68Ga-PSMA-11 PET/CT results, according to the patients' characteristics and different patterns of treatment: (1) S-RT (with or without systemic treatment), (2) stereotactic body radiotherapy (SBRT) (with or without systemic treatment), and (3) systemic treatment. The treatment strategy was re-evaluated for each patient taking into consideration the 68Ga-PSMA-11 PET/CT images.
Results
We enrolled 119 PCa patients (mean age 66 years, range 44–78 years) with a mean PSA level at the time of 68Ga-PSMA-11 PET/CT of 0.34 ng/ml (median 0.32 ng/ml, SD ±0.09, range 0.20–0.50 ng/ml). 68Ga-PSMA-1 1 PET/CT was positive in 41 of the 119 patients, resulting in an overall detection rate of 34.4%. 68Ga-PSMA-11 uptake was observed in the prostate bed (3 patients, 2.5%), in the pelvic lymph nodes (21, 17.6%), in the retroperitoneal lymph nodes (4, 3.4%) and in the skeleton (21, 17.6%). Regarding ITT, 81 patients (68.1%) were considered possible candidates for S-RT only in the prostate bed and none of the patients (0%) for SBRT. According to the 68Ga-PSMA-11 PET/CT results, the intended treatment was changed in 36 patients (30.2%). According to the PET/CT results, S-RT was recommended in 70 patients (58.8%), only to the prostate bed in 58 (48.7%) and SBRT in 29 (24.4%). The intended RT planning was modified in 36 (87.8%) of 41 patients with a positive 68Ga-PSMA-11 PET/CT result.
Conclusion
In our patient series with PSA levels <0.5 ng/ml, 68Ga-PSMA-11 PET/CT had a detection rate of 34.4%. In the ITT analysis, 30.2% of patients had a change in the intended treatment. These data support the hypothesis that 68Ga-PSMA-11 PET/CT is a useful procedure in the management of PCa patients showing early recurrence after RP, and should be implemented in routine clinical practice.
https://ift.tt/2BnCA1F
A Rare Cause of Acute Hepatopancreatitis in a Nepalese Teen
Background. Acute pancreatitis (AP) coexisting with acute hepatitis (AH) in children is uncommon. Moreover, a single bacterial cause explaining both the complications is even rarer. Despite familiarity with the usual presentation of enteric fever, atypical presentations can go unnoticed. Case Presentation. A 16-year-old previously healthy male presented to the emergency unit with recurrent swinging pyrexia, abdominal symptoms, and jaundice for a week. Blood work-up revealed deranged liver function tests (LFTs) and elevated pancreatic enzymes. Further assessment with imaging made a diagnosis of AH and AP without necrosis. Blood culture positivity for Salmonella typhi eventually confirmed the diagnosis. Conclusion. This is an uncommon presentation of an infection that is fairly common in our part of globe. Nevertheless, early suspicion and recognition is the key to timely management. Regular follow-ups are required to pick complications up early.
https://ift.tt/2Q9WgxX
Correlates and Outcomes of Low Physical Activity Posttransplant: A Systematic Review and Meta-Analysis
Background Little is known about associations between low physical activity (PA) and its correlates and outcomes in solid organ transplant recipients. This systematic review with meta-analysis examined correlates and outcomes associated with low PA (i.e. not meeting individual study's definition of being physically active) following solid organ transplantation. Methods We searched PubMed, CINAHL, PsycINFO and EMBASE from inception to February 2016 to identify peer-reviewed data-based articles. Articles published in English, German, Spanish, French, Italian, Portuguese, or Dutch that examined correlates or outcomes associated with low PA in adult single, solid organ transplant recipients were included. Studies' quality was assessed using a 14-item checklist. Pooled odds ratios and 95% confidence intervals were computed for correlates and outcomes examined in ≥ 5 studies. Results Of 7,401 publications screened, 34 studies met inclusion criteria and were included in the overall synthesis with 15 included in the meta-analysis. Most focused on renal transplantation (n=18, 53%) and used cross-sectional designs (n=26, 77%). Of 30 correlates examined, [condition-related (n=11), social/economic-related (n=9), patient-related (n=4), healthcare system-related (n=3), and treatment-related (n=3)], only four were examined ≥5 times and included in meta-analyses. None were significantly related to low PA. Of 19 outcomes assessed, only physical health-related quality of life was examined ≥ 5 times. Low PA was significantly associated with low physical health-related quality of life (OR=0.172, 95% CI=0.08, 0.37). Conclusions We found few studies examining most correlates and outcomes related to low PA despite growing evidence that improving PA might be an effective intervention in improving post-transplant outcomes. Address for Correspondence: Sabina De Geest, Institute of Nursing Science, Department of Public Health, University of Basel, Bernoullistrasse 28, Basel, Switzerland, Tel +41 61 2070951, sabina.degeest@unibas.ch Protocol registration: PROSPERO protocol CRD42015003333 Authership contributions: Lut Berben: Participated in research design, performance of the research (design of search strategy, title and abstract screening, full text evaluation, data extraction), data analysis (effect size calculation), and wrote the paper. Sandra J. Engberg: Participated in research design, performance of the research (design of search strategy, full text evaluation, data extraction), data analysis (effect size calculation), participating in writing the paper. Anja Rossmeissl: Participated in research design, performance of the research (design of search strategy, title and abstract screening, full text evaluation, data extraction), and participating in writing the paper. Elisa J. Gordon: Participated in research design, performance of the research (design of search strategy, title and abstract screening, full text evaluation, data extraction), and participating in writing the paper. Fabienne Dobbels: Participated in research design, performance of the research (design of search strategy, title and abstract screening, full text evaluation, data extraction), data analysis (effect size calculation), and critical review of the paper. Christiane Kugler: Participated in research design, performance of the research (design of search strategy, title and abstract screening, full text evaluation, data extraction), data analysis (effect size calculation), and critical review of the paper. Arno Schmidt-Trucksäss: Participated in research design, performance of the research (design of search strategy, title and abstract screening, full text evaluation, data extraction), data analysis (effect size calculation), and critical review of the paper. Mary Lou Klem: Design of search strategy, programming of searches in different databases, feedback on methodology used to conduct the systematic review; critical revision of the paper. Susan M. Sereika: Design of the Access databases for data input, advice on methodology to be used for effect size calculation, review of statistical analyses, and critical revision of the paper. Paolo De Simone: Participated in the design of the study, overall project management and quality control of methodology followed, and critical revision of the paper. Fabienne Dobbels: Participated in the design of the study, overall project management and quality control of methodology followed, and critical revision of the paper. Sabina M. De Geest: Participated in the design of the study, overall project management and quality control of methodology followed, and critical revision of the paper. Disclosure No author states any conflicts of interest. Funding The research has received funding for a consortium meeting from the Brocher Foundation, a Swiss non-profit private foundation. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2PFyz12
https://ift.tt/2PFyz12
Enrichment of cytomegalovirus-induced NKG2C+ Natural Killer cells in the lung allograft
Background In lung transplant recipients, immunosuppressive medications result in impaired antiviral immunity and a propensity for cytomegalovirus (CMV) reactivation within the lung allograft. Natural Killer (NK) cells play a key role in immunity to CMV, with an increase in the proportion of NK cells expressing activating CD94-NKG2C receptors in the blood being a strong correlate of CMV infection. Whether a similar increase in NKG2C+ NK cells occurs in lung transplant recipients following CMV reactivation in the allograft and if such cells contribute to viral control, remains unclear. Methods In this pilot study, we longitudinally assessed the frequency and phenotype of NKG2C+ NK cells in the blood and bronchoalveolar lavage (BAL) of lung transplant recipients and stratified recipients based on their risk of developing CMV disease. Results We observed an increase in the proportion of NKG2C+ NK cells in the blood and BAL of CMV high-risk patients, coincident with both the cessation of anti-viral prophylaxis and subsequent detection of actively replicating CMV in the blood and/or lung allograft. Additionally, these NKG2C+ NK cells expressed killer-cell immunoglobulin-like receptors (KIR) distinct from those of other NK subsets and BAL NKG2C+ NK cells possessed an activated phenotype. Finally, the frequency of NKG2C+ NK cells in the BAL may be inversely correlated with CMV blood titers. Conclusions Monitoring the phenotype of NK cells post-lung transplant may be a useful biomarker for monitoring patient levels of CMV immunity. # Joint senior authors * Corresponding author: Lucy C. Sullivan, Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, 3000, Australia Email: lcsull@unimelb.edu.au Authorship: Conceived and designed experiments: L.C.S., A.J.B., G.P.W. Performed the experiments: C.M.H., J.M.L.W., A.K., L.C.S. Analyzed the data: C.M.H, L.C.S., S.S. Contributed reagents/materials/analysis tools: Y.C., B.L., G.I.S., G.P.W. Wrote the paper: L.C.S., C.M.H., S.S., G.I.S., G.P.W. Disclosures: The authors declare no conflicts of interest Funding: National Health and Medical Research Council (NHMRC) Program Grant (A.G.W.), NHMRC Project Grant (L.C.S. and G.P.W.). We acknowledge the Margaret Pratt Foundation and the Lungitude Foundation for ongoing support. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2QZVl0p
https://ift.tt/2QZVl0p
Report of the 24th Annual Congress of the International Liver Transplantation Society
The 24th Joint Annual Congress of the International Liver Transplantation Society (ILTS) in association with European Liver and Intestine Transplant Association (ELITA) and Liver Intensive Care Group of Europe (LICAGE) was held in Lisbon, Portugal from May 23-26, 2018. More than 1200 participants from over 60 countries including surgeons, hepatologists, anesthesiologists and critical care intensivists, radiologists, pathologists, organ procurement personnel and research scientists, came together with the common aim of improving care and outcomes for liver transplant recipients. Over 600 scientific abstracts were presented. The principal themes were living donation, use of marginal liver donors, machine preservation, disease-specific immunosuppressive regimen, malignancies, and advances in pediatric liver transplantation and liver transplant anaesthesia. This report presents excerpts from invited lectures, and select abstracts from scientific sessions, which add to current knowledge, and will drive clinical practice and future research. * Eleonora De Martin and Amelia Hessheimer are co-first authors Corresponding Author and Reprint Requests: Prashant Bhangui, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Sector 38, Gurugram, Delhi NCR, India. Email: pbhangui@gmail.com AUTHORSHIP PAGE Eleonora De Martin - Participated in study design, data collection, writing of the paper Amelia Hessheimer - Participated in study design, data collection, writing of the paper Ryan Chadha - Participated in study design, data collection, writing of the paper Gokhan Kabacam - Participated in study design, data collection, writing of the paper Jeremy Raganayagam - Participated in study design, data collection, writing of the paper Varvara Kirchner - Participated in study design, data collection Marit Kalisvaart - Participated in study design, data collection Irene Scalera - Participated in study design, data collection Mamatha Bhat - Participated in study design, data collection Alan Contreras - Participated in study design, data collection Prashant Bhangui - Participated in study design, writing of the paper, critical appraisal Disclosure: The authors declare no conflicts of interest. Funding or Grants: None to declare Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2R0htYi
https://ift.tt/2R0htYi
Young people with biliary atresia requiring liver transplantation: a distinct population requiring specialist care
Background Young people born with biliary atresia are an emerging population for adult hepatologists with 40-45% of children entering adolescence with their native liver intact. For those requiring liver transplantation during adolescence, disparity on the waiting list and post liver transplantation outcome for young adults compared to younger and older age groups has stimulated discussion regarding the optimal timing of listing. In this study we review our experience of young people with biliary atresia requiring liver transplantation during adolescence and young adulthood. Methods Retrospective, single centre review of patients with biliary atresia requiring liver transplantation > 11 years. Results Thirty-six young people (16 male) underwent liver transplantation between 1991-2014 at a median age of 16.6 (IQR 14.2,19.5) years. The commonest indications for listing were refractory cholangitis (31%), synthetic failure (25%) and variceal bleeding (14%). Patients listed by the adult team (n=14) waited longer than those listed by the paediatric team (10 (IQR 7.7,24.6) vs 5.8 (IQR 4.0,15.1) months (p
https://ift.tt/2PFys5C
https://ift.tt/2PFys5C
Human Atrial Natriuretic Peptide in Cold Storage of Donation after Circulatory Death Rat Livers: An Old but New Agent for Protecting Vascular Endothelia?
Background Current critical shortage of donor organs has increased the use of donation after circulatory death (DCD) livers for transplantation, despite higher risk for primary non-function or ischemic cholangiopathy. Human atrial natriuretic peptide (hANP) is a cardiovascular hormone that possesses protective action to vascular endothelia. We aimed to clarify the therapeutic potential of hANP in cold storage of DCD livers. Methods Male Wistar rats were exposed to 30-minute warm ischemia in situ. Livers were then retrieved and cold-preserved for 6 hours with or without hANP supplementation. Functional and morphological integrity of the livers was evaluated by oxygenated ex vivo reperfusion at 37°C. Results hANP supplementation resulted in significant reduction of portal venous pressure (12.2 ± 0.5 vs. 22.5 ± 3.5 mmHg, P
https://ift.tt/2R1B4Y8
https://ift.tt/2R1B4Y8
The effects of oxygenation on ex vivo kidneys undergoing Hypothermic Machine Perfusion
Background Supplemental oxygenation of the standard Hypothermic Machine Perfusion (HMP) circuit has the potential to invoke favourable changes in metabolism, optimising cadaveric organs prior to transplantation. Methods Eight pairs of porcine kidneys underwent 18 hours of either oxygenated (HMP/O2) or aerated (HMP/Air) HMP in a paired DCD model of transplantation. Circulating perfusion fluid was supplemented with the metabolic tracer universally labelled glucose ([U-13C] glucose). Perfusate, end-point renal cortex and medulla samples underwent metabolomic analysis using 1D and 2D NMR experiments in addition to GC-MS. Analysis of 13C labelled metabolic products was combined with adenosine nucleotide levels and differences in tissue architecture. Results Metabolomic analysis revealed significantly higher concentrations of universally labelled lactate in the cortex of HMP/Air vs HMP/O2 kidneys (0.056 mM vs. 0.026 mM, p
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https://ift.tt/2PFyjPC
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