Transabdominal two-cavity approach for radical nephrectomy combined with inferior vena cava thrombectomy for malignant thrombus caused by renal cell carcinoma: a case series

Advanced renal cell carcinoma in some cases causes malignant intravascular thrombus with the potential for growth into the inferior vena cava or even the right atrium. Renal cell carcinoma is accompanied by ma...

https://ift.tt/2Rcp5H2

Monoclonal gammopathy in prostate carcinoma: a case report and review of literature

Monoclonal gammopathy is commonly associated with plasma cell dyscrasia. However, monoclonal gammopathy without bone marrow plasmacytosis in prostate carcinoma has rarely been reported. The association between...

https://ift.tt/2OQcdtx

The physician and hereditary angioedema friend or foe: 62-year diagnostic delay and iatrogenic procedures

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease characterized by episodes of acute subcutaneous swelling, and/or recurrent severe abdominal pain. The dise...

https://ift.tt/2z2nEUc

Nine year follow-up of a rare case of angioedema due to acquired C1-inhibitor deficiency with late onset and good response to attenuated androgen

Angioedema due to acquired deficiency of C1-inhibitor (C1-INH-AAE) is a rare disease sharing some clinical and laboratory similarities with hereditary angioedema, but with late onset and no positive family his...

https://ift.tt/2Sin0ea

Practicalities of a reduced volume formulation of a C1-INH concentrate for the treatment of hereditary angioedema: real-life experience

Hereditary angioedema (HAE) due to C1 esterase inhibitor (C1-INH) deficiency is characterized by recurrent swelling attacks that can be life-threatening if left untreated. Prompt treatment is vital during acut...

https://ift.tt/2z1NkjJ

Apremilast as therapeutic option in a HIV positive patient with severe psoriasis

Dermatologic Therapy, EarlyView.


https://ift.tt/2EE7R3Q

Apremilast as therapeutic option in a HIV positive patient with severe psoriasis

Dermatologic Therapy, EarlyView.


https://ift.tt/2EE7R3Q

Stromal interleukin-33 promotes regulatory T cell-mediated immunosuppression in head and neck squamous cell carcinoma and correlates with poor prognosis

Abstract

Regulatory T cells (Tregs) mediate immunosuppressive signals that can contribute to the progression of head and neck squamous cell carcinoma (HNSCC). Interleukin-33 (IL-33) is defined as an 'alarmin', an endogenous factor that is expressed during tissue and cell damage, which has been shown to promote Treg proliferation in non-lymphoid organs. However, the interaction between IL-33 and Tregs in the HNSCC tumor microenvironment remains uncertain. In this study, we examined IL-33⁺ and Foxp3⁺ cells by immunohistochemistry in 68 laryngeal squamous cell cancer patients, followed by functional analysis of IL-33 in Tregs. In addition, the suppressive function of Tregs was assessed by cell proliferation assays. The level of stromal IL-33 was significantly upregulated in advanced versus early stage HNSCC patients and positively correlated with Foxp3⁺ Treg infiltration as well as a poor prognosis. ST2 is regarded as the only receptor of IL-33. Infiltrated ST2-expressing Tregs were responsive to IL-33, and the percentage of Tregs was increased upon IL-33 stimulation. Functional investigation demonstrated that IL-33 increased the proportion of Foxp3⁺GATA3⁺ Tregs and improved the suppressive functions of Tregs by inducing IL-10 and TGF-β1 as well as decreasing the proliferation of responder T cells. Blockade of ST2 abrogated the immunosuppression caused by IL-33. Our data demonstrate that stromal IL-33 both expands the Treg population and enhances their functions in the tumor microenvironment. Furthermore, stromal IL-33 has prognostic value for tumor progression. Thus, stromal IL-33 is a potential target for future HNSCC immunotherapy.

https://ift.tt/2PQopXG

Eating disorders in premenstrual dysphoric disorder: a neuroendocrinological pathway to the pathogenesis and treatment of binge eating

Abstract

Background

This case report details the presentation, treatment and post-operative outcome of an adult female with co-occurring binge eating disorder and premenstrual dysphoric disorder (PMDD).

Case presentation

The patient, self-presenting for treatment, reported having struggled with severe, debilitating physical and psychological PMDD symptoms for nearly a decade. After having taken part in a number of unsuccessful first- and second line treatments in primary and secondary care, the patient was referred to tertiary care at the Department of Gynecology at Oslo University Hospital in Norway. Chemical menopause using a gonadotropin-releasing hormone (GnRH) agonist was induced, predicting the desired response (i.e. resolution of PMDD symptoms) to bilateral salpingo-oophorectomy (BSO). At three- and six months post BSO follow-up, the patient reported complete resolution of all reported PMDD symptoms including marked increase in appetite (i.e. hyperphagia), specific food cravings and auxiliary binge eating.

Conclusions

To our knowledge, this is the first case documenting the recovery from an eating disorder following surgical ovarian suppression. Our findings lend supports to existing studies linking binge eating to hormonal changes in the mid-luteal phase of the menstrual cycle, and may help advance new treatment options for a selected, severely impaired group of females struggling with excessive appetite and binge eating due to fluctuations in ovarian activity.

https://ift.tt/2Rg7SfX

Symptom Expression in Patients with Advanced Cancer Admitted to an Acute Supportive/Palliative Care Unit With and Without Delirium

AbstractAim.The aim of this study was to investigate the relationship between delirium and symptom expression in patients with advanced cancer admitted to an acute supportive/palliative care unit (ASPCU).Methods.A consecutive sample of patients with advanced cancer who were admitted to an ASPCU was prospectively assessed for a period of 10 months. The Edmonton Symptom Assessment Scale (ESAS) and the MDAS (Memorial Delirium Assessment Scale) were measured at admission (T0) and after 7 days of palliative care (T7).Results.Two hundred forty‐six patients had complete data regarding MDAS measurements, at either T0 and T7. Of these, 75 (30.5%) and 63 patients (25.6%) had delirium at T0 and after a week of palliative care (T7), with a decrease in the frequency of delirium of 4.9% (from 30.5% to 25.6%); that means that 16% of patients with delirium improved their cognitive status after initiation of palliative care. Intensities of pain, depression, poor well‐being, and global ESAS were significantly higher in patients with delirium. Patients who did not have delirium at T0 but developed delirium during admission after 1 week of palliative care had a higher level of symptom expression for pain, weakness, nausea, anxiety, dyspnea, appetite, and consequently global ESAS. Patients who did not develop delirium at any time had a relevant decrease in intensity of all ESAS items after 1 week of palliative care. The decrease of symptom intensity was significant for pain, insomnia, appetite, poor well‐being, and global ESAS in patients with delirium either at T0 and T7, although these differences were less relevant than those observed in patients without delirium. In patients with delirium at T0 who improved their cognitive function at T7 (no delirium), significant changes were found in most ESAS items.Conclusion.Symptom expression is amplified in patients with delirium, whereas patients without delirium may be more responsive to palliative treatments with a significant decrease in intensity of ESAS items.Implications for Practice.Symptom expression is amplified in patients with cancer who have delirium, whereas patients without delirium may be more responsive to palliative treatments with a significant decrease in symptom intensity.

https://ift.tt/2Ar4VmU

Effect of Lanreotide Depot/Autogel on Urinary 5‐Hydroxyindoleacetic Acid and Plasma Chromogranin A Biomarkers in Nonfunctional Metastatic Enteropancreatic Neuroendocrine Tumors

AbstractBackground.Urinary 5‐hydroxyindoleacetic acid (5‐HIAA) is an established biomarker in neuroendocrine tumors and carcinoid syndrome; however, its role in nonfunctional neuroendocrine tumors is not defined. We present post hoc data on urinary 5‐HIAA and plasma chromogranin A (CgA) from the CLARINET study.Methods.Patients with well‐ or moderately differentiated, nonfunctioning, locally advanced or metastatic enteropancreatic neuroendocrine tumors were randomized to deep subcutaneous lanreotide depot/autogel 120 mg or placebo once every 28 days for 96 weeks. Tumor response, evaluated centrally (RECIST 1.0), and progression‐free survival (PFS) were assessed by treatment and biochemical response, defined as (a) baseline >upper limit of normal (ULN, 41.6 μmol per day 5‐HIAA; 98.1 μg/L CgA) and (b) ≥50% decrease from baseline and to ≤ULN value on study.Results.Forty‐eight percent (82 of 171; lanreotide, n = 45; placebo, n = 37) and 66% (129 of 195; lanreotide, n = 65; placebo, n = 64) of randomized patients had 5‐HIAA and CgA > ULN at baseline. Among patients with >ULN baseline values who did not progress after 96 weeks of treatment, significantly greater reductions in 5‐HIAA and CgA were observed in lanreotide‐treated versus placebo‐treated patients throughout the study (all p < .05). PFS was significantly prolonged among 5‐HIAA responders versus nonresponders (median not reached vs. 16.2 months, p < .0001; hazard ratio [HR] = 0.21, 95% confidence interval [CI], 0.09–0.48) and CgA responders versus nonresponders (median not reached vs. 16.2 months, p = .0070; HR = 0.30, 95% CI, 0.12–0.76), regardless of treatment arm. PFS was also significantly prolonged among lanreotide‐treated 5‐HIAA responders versus nonresponders (p = .0071) but was not significantly different among placebo‐treated 5‐HIAA responders versus nonresponders. There were no significant differences in PFS between lanreotide‐treated CgA responders versus nonresponders or between placebo‐treated CgA responders versus nonresponders.Conclusions.The 5‐HIAA findings are noteworthy because they occurred in patients with nonfunctioning enteropancreatic neuroendocrine tumors. Monitoring 5‐HIAA and CgA may be useful when treating patients with nonfunctional neuroendocrine tumors.Implications for Practice.Current guidelines focus only on the monitoring of 5‐hydroxyindoleacetic acid (5‐HIAA) in the diagnosis and management of functional neuroendocrine tumors with carcinoid syndrome. The current post hoc analysis of patients with nonfunctional enteropancreatic neuroendocrine tumors in the CLARINET study demonstrated that measuring and following both 5‐HIAA and chromogranin A as biomarkers of disease progression may be useful in the management of patients with nonfunctional neuroendocrine tumors.

https://ift.tt/2POY0cC

Cases from the irAE Tumor Board: A Multidisciplinary Approach to a Patient Treated with Immune Checkpoint Blockade Who Presented with a New Rash

AbstractImmune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigms for a broad spectrum of malignancies. Because immune checkpoint inhibitors rely on immune reactivation to eliminate cancer cells, they can also lead to the loss of immune tolerance and result in a wide range of phenomena called immune‐related adverse events (irAEs). At our institution, the management of irAEs is based on multidisciplinary input obtained at an irAE tumor board that facilitates expedited opinions from various specialties and allows for a more uniform approach to these patients. In this article, we describe a case of a patient with metastatic urothelial carcinoma who developed a maculopapular rash while being treated with a programmed death‐ligand 1 inhibitor. We then describe the approach to management of dermatologic toxicities with ICIs based on the discussion at our irAE Tumor Board.Key Points. Innocuous symptoms such as pruritis or a maculopapular rash may herald potentially fatal severe cutaneous adverse reactions (SCARs); therefore, close attention must be paid to the symptoms, history, and physical examination of all patients.Consultation with dermatology should be sought for patients with grade 3 or 4 toxicity or SCARs and prior to resumption of immune checkpoint inhibitors for patients with grade 3 or higher toxicity.A multidisciplinary immune‐related adverse events (irAE) tumor board can facilitate timely input and expertise from various specialties, thereby ensuring a streamlined approach to management of irAEs.

https://ift.tt/2As7DbY

Conflicts of Interest, Baselga, and Clinical Trialists

https://ift.tt/2PT8mbD

Flap Reconstruction of Sarcoma Defects in the Setting of Neoadjuvant and Adjuvant Radiation

J reconstr Microsurg
DOI: 10.1055/s-0038-1675147

Purpose Limb-sparing treatment of extremity soft tissue sarcomas requires wide resections and radiation therapy. The resulting complex composite defects necessitate reconstructions using either muscle or fasciocutaneous flaps, often in irradiated wound beds. Methods A retrospective chart review was performed of all limb-sparing soft tissue sarcoma resections requiring immediate flap reconstruction from 2012 through 2016. Results Forty-four patients with 51 flaps were identified: 25 fasciocutaneous and 26 muscle-based flaps. Mean defect size, radiation treatment, and follow-up length were similar between groups. More often, muscle-based flaps were performed in younger patients and in the lower extremity. Seventeen flaps were exposed to neoadjuvant radiation, 12 to adjuvant radiation, 5 to both, and 17 to no radiation therapy. Regardless of radiation treatment, complication rates were comparable, with 28% in fasciocutaneous and 31% in muscle-based groups (p < 0.775). Muscle-based flaps performed within 6 weeks of undergoing radiotherapy were less likely to result in complications than those performed after greater than 6 weeks (p < 0.048). At time of follow-up, Musculoskeletal Tumor Society scores for fasciocutaneous and muscle-based reconstructions, with or without radiation, showed no significant differences between groups (mean [SD]: 91% [8%] vs. 89% [13%]). Conclusions The similar complication rates and functional outcomes in this study support the safety and efficacy of both fasciocutaneous flaps and muscle-based flaps in reconstructing limb-sparing sarcoma resection defects, with or without radiotherapy.
[...]

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

https://ift.tt/2qaGLak

Actinomyces Orbital Osteomyelitis in the Setting of Multiple Myeloma and Bisphosphonate-Related Osteonecrosis

No abstract available

https://ift.tt/2qadZ9U

Ischemic Optic Neuropathy Secondary to Intravascular Lymphoma

Background: To describe a case of optic neuropathy associated with intravascular lymphoma (IVL). Methods: Case report and review of the literature. Results: A case of asymmetric binocular vision loss is described, preceded by transient vision loss. Associated optic perineural enhancement and enhancing and diffusion-positive cortical lesions were observed on magnetic resonance imaging. Biopsy of the cerebellum revealed exclusively intraluminal neoplastic B-cells consistent with IVL. Conclusions: Patients with IVL may rarely present with optic nerve involvement, presumably due to small vessel occlusion. The presentation may mimic features of anterior ischemic optic neuropathy including an acute onset and disc edema. Although optic nerve enhancement and associated white matter lesions may suggest optic neuritis, enhancement of the optic nerve sheath, as in this case, has a wide differential diagnosis, which includes giant cell arteritis. IVL should be considered in atypical cases of optic neuropathy accompanied by enhancing, diffusion-positive brain lesions that are not within a specific vascular territory. Address correspondence to Marc Dinkin, MD, Weill Cornell Ophthalmology, 1305 York Avenue, 11th Floor, New York, NY 10065; E-mail: mjd2004@med.cornell.edu The authors report no conflicts of interest. © 2018 by North American Neuro-Ophthalmology Society

https://ift.tt/2Rc1Xsi

Inhibitory functions of PD-L1 and PD-L2 in the regulation of anti-tumor immunity in murine tumor microenvironment

Abstract

Although a role of PD-L1 in the suppression of anti-tumor immunity and its value as a predictive biomarker has been suggested by various preclinical and clinical studies, the precise mechanisms how PD-L1 and PD-L2, another ligand of PD-1, regulate anti-tumor immunity in the tumor microenvironment are yet to be fully explored. Here, we address this issue using PD-L1-deficient tumor cells, PD-L1-knockout (KO) mice, anti-PD-L1 monoclonal antibody (mAb), and anti-PD-L2 mAb. Firstly, PD-L1-deficient or competent tumor cells were inoculated into wild-type or PD-L1-KO mice. Results of tumor growth and mouse survival indicated that both tumor- and host-derived PD-L1 are functional to suppress anti-tumor immunity, while the former contributes predominantly than the latter. Experiments using bone marrow (BM) chimeric mice, generated by transferring PD-L1-KO BM cells into wild-type mice or vice versa, further suggested that PD-L1 expressed on BM-derived hematopoietic cells mediates the suppressive effects on anti-tumor immunity. Secondly, anti-PD-L2 mAb treatment demonstrated a profound synergy with anti-PD-L1 mAb therapy, whereas anti-PD-L2 mAb alone hardly induced any anti-tumor effects, suggesting that PD-L2's function becomes evident when the effects of PD-L1 are abrogated by anti-PD-L1 mAb. Consistent with this notion, PD-L2 expression was upregulated on tumor-associated macrophages (TAM) when mice were treated with anti-PD-L1 mAb. Taken together, our study elucidated the importance of PD-L1 associated with tumor cells and non-tumor host cells, particularly BM-derived hematopoietic cells, as well as PD-L2 inducibly expressed on TAM in the suppression of anti-tumor immunity in the tumor microenvironment.

https://ift.tt/2CCo7zM

What to know about microdermabrasion

Microdermabrasion is a cosmetic procedure, during which a dermatologist removes the top layer of skin. The aim is to create a more youthful, even complexion. Learn more here.

https://ift.tt/2EIQD5u

What to know about microdermabrasion

Microdermabrasion is a cosmetic procedure, during which a dermatologist removes the top layer of skin. The aim is to create a more youthful, even complexion. Learn more here.

https://ift.tt/2EIQD5u

Association of Quality of Life With Surgical Excision of Head and Neck Melanoma

This study examines the preoperative and postoperative changes in quality of life as perceived and reported by patients who received surgical treatment for Tis or T1a melanoma of the head and neck.

https://ift.tt/2PUyxyw

Herpetic Whitlow—A Case of Inadvertent Inoculation With Melanoma Viral Therapy

This case report describes an occurrence of herpetic whitlow following inadvertent inoculation with melanoma viral therapy

https://ift.tt/2PfDBR5

Association of Psoriasis With Inflammatory Bowel Disease

This systematic review and meta-analysis of 9 studies comprising more than 7 million patients examines the association between psoriasis and inflammatory bowel disease.

https://ift.tt/2PT4HdA

APOA5 and APOC3 Polymorphisms and Hypertriglyceridemia in Bexarotene-Treated CTCL

This case series study examines the association between APOA5 and APOC3 polymorphisms and triglyceride levels in patients with cutaneous T-cell lymphoma before, during, and after treatment with bexarotene.

https://ift.tt/2PmEzuA

Conflict of interest and citation impact among dermatology guideline authors

https://ift.tt/2Ji2rug

Plasma and brain pharmacokinetics of letrozole and drug interaction studies with temozolomide in NOD- scid gamma mice and sprague dawley rats

Abstract

Purpose

The aromatase inhibitor, letrozole, is being investigated in experimental animal models as a novel treatment for high-grade gliomas (HGGs). To facilitate optimal dosing for such studies, we evaluated the plasma and brain pharmacokinetics (PK) of letrozole in NOD-scid gamma (NSG) mice, which are frequently employed for assessing efficacy against patient-derived tumor cells. Furthermore, we evaluated the potential PK interactions between letrozole and temozolomide (TMZ) in Sprague–Dawley rats.

Methods

NSG mice were administered letrozole (8 mg/kg; i.p) as a single or multiple dose (b.i.d, 10 days). Brain tissue and blood samples were collected over 24 h. Letrozole and TMZ interaction study employed jugular vein-cannulated rats (three groups; TMZ alone, letrozole alone and TMZ + letrozole). Intracerebral microdialysis was performed for brain extracellular fluid (ECF) collection simultaneously with venous blood sampling. Drug levels were measured employing HPLC and PK analysis was conducted using Phoenix WinNonlin^®.

Results

In NSG mice, peak plasma and brain tissue letrozole concentrations (C_max) were 3–4 and 0.8–0.9 µg/ml, respectively. The elimination half-life was 2.6 h with minimal accumulation following multiple dosing. In the drug interaction study, no PK changes were evident when TMZ and letrozole were given in combination. For instance, peak plasma and brain ECF TMZ levels when given alone were 14.7 ± 1.1 and 4.6 ± 0.6 µg/ml, respectively, and 12.6 ± 2.4 and 3.4 ± 0.8 µg/ml, respectively, when given with letrozole.

Conclusions

These results will guide the optimization of dosing regimen for further development of letrozole for HGG treatment.

https://ift.tt/2OJoCPQ

The Prevalence of Soft Tissue Calcifications in the Head and Neck Region Using CBCT Among Egyptian Population

Condition:   Oral Soft Tissue Conditions
Intervention:   Other: presence of soft tissue calcification in head and neck
Sponsors:   Maha Samy Elhadidy;   Cairo University
Not yet recruiting

https://ift.tt/2OJUWCj

The Prevalence of Soft Tissue Calcifications in the Head and Neck Region Using CBCT Among Egyptian Population

Condition:   Oral Soft Tissue Conditions
Intervention:   Other: presence of soft tissue calcification in head and neck
Sponsors:   Maha Samy Elhadidy;   Cairo University
Not yet recruiting

https://ift.tt/2OJUWCj

Histopathology of livers in patients with congenital portosystemic shunts (Abernethy malformation): a case series of 22 patients

Abstract

Congenital portosystemic shunt (CPSS) is a congenital anomaly resulting in partial or complete diversion of the portal blood into the systemic circulation. The literature on the histological changes in livers of patients with CPSS is limited. Liver histology of 22 consecutive patients managed in our institution between 2001 and 2016 was reviewed. Twenty-one patients were children at the time of diagnosis. Thirty-two specimens were available and consisted of three explant livers and 29 biopsy samples from 19 patients. Sixteen samples were from wedge biopsies taken at the time of shunt closure. Thirteen were from core needle biopsies taken during clinical work-up. A variable proportion of portal tracts contained prominent thin-walled channels (PTWCs) and arterio-biliary dyads. The proportion of portal tracts containing triads, arterio-biliary dyads and biliary monads varied considerably in the different samples. Dilated inlet venules, increase in the number of portal arteries or the presence of portal arteries of increased size, deposition of copper-associated protein, sinusoidal dilatation, capillarization and intralobular individual arteries were present. Physiological nuclear vacuolation of periportal hepatocytes was absent in most samples from our paediatric patients. Presence of PTWCs, arterial-biliary dyads, increased arterial profiles in portal tracts and lobule and lack of the physiological periportal vacuolated hepatocytes in children are the most characteristic histological changes of CPSS in the liver periphery.

https://ift.tt/2yvVaTs

Use of Cepstral Analysis for Differentiating Dysphonic from Normal Voices in Children

Publication date: Available online 23 October 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Fatma Esen Aydinli, Esra Özcebe, Önal İncebay

https://ift.tt/2yEDDIP

Is transcanal tympanoplasty an appropriate surgical treatment for congenital middle ear cholesteatoma with ossicular involvement?

Publication date: Available online 23 October 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Hantai Kim, Shin Young Yoo, Yun-Hoon Choung, Hun Yi Park

Abstract

Objectives

The aims of this study are to analyze the clinical characteristics of congenital middle ear cholesteatoma (CMC), to evaluate the treatment results according to the types of surgical approach, and to suggest the appropriate surgical treatment option in each stage.

Methods

One hundred fifteen children (≤15 years old) with surgically confirmed CMC, who underwent surgery at a tertiary hospital during 1994 to 2012 and were followed up more than 2 years, were enrolled in this study. CMC was classified into four stages by the staging system proposed by Potsic. Clinical characteristics of CMC were analyzed and its association with the rate of residual disease was evaluated.

Results

Based on the location of the lesion, posterior-origin CMCs were detected significantly later (5.5 years old, P = 0.018) and more likely to be in the Stage 3 or 4 (P < 0.001). Residual CMCs were observed in 10 out of 115 cases (8.7%) and were more frequent in the Stage 3 or 4 patients (P = 0.007). However, the rate of the residual disease was not statistically different between anterior- and posterior-origin CMCs (P = 0.101). All 58 cases of CMC in the Stage 1 or 2 were successfully removed by transcanal tympanoplasty with only one residual case (1.7%). In the Stage 3 cases, transcanal tympanoplasty was conducted in 24 out of 29 patients, and the residual disease rate was 12.5% (3 out of 24).

Conclusions

The early stages of CMC were likely to be diagnosed at younger age, and the early diagnosis seemed to show better surgical outcomes with less invasive techniques. Transcanal tympanoplasty can be an effective surgical option for CMCs in the Stage 3.

https://ift.tt/2O5cnb8

Effects of Socioeconomic Status on Children with Hearing Loss

Publication date: Available online 23 October 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Blake Smith, Jessica Zhang, Gina Nhu Pham, Keerthana Pakanati, Nikhila Raol, Julina Ongkasuwan, Samantha Anne

Abstract

Objective

Health care disparities are noted between different socioeconomic groups; it is crucial to recognize and correct disparities, if present, that extend to children with hearing loss. The objective of the study is to evaluate the effect of socioeconomic status (SES) on access to hearing rehabilitation and speech and language therapy and outcomes in children with hearing loss.

Methods

Retrospective Chart Review of children diagnosed with hearing loss at 3 tertiary care academic centers from 2010-2012. Two hundred patients were then randomly selected from each institution for analysis. International and self-pay patients were excluded. They were separated into two groups based on SES using insurance coverage as proxy for financial status (private insurance versus Medicaid). Main outcome measures included number of hearing aid evaluations recommended andcompleted, compliance with hearing aids use, diagnosis on speech therapy evaluations, participation in speech therapy, and outcomes noted on the last speech therapy session in patients' medical record at time of study completion.

Results

600 patients were identified by random selection out of total of 3679 patients. 18 were excluded because they were international pay or self-pay. Of 582 patients, 299 (51.4%) had private insurance and 283 (48.6%) had Medicaid. The pure tone average (PTA) at initial diagnosis did not differ between the two populations (left ear p = 0.74, right ear p = 0.68). There was no significant difference in the number of hearing aid evaluations recommended (p = 0.49), hearing aid evaluation completed (p = 0.68), or documented hearing aid compliance (p=0.68) between the two populations. Similarly, there was no significant difference in the presence of speech delay (p = 0.62), the receipt of speech therapy (p=0.49), or speech language outcomes between the two groups (p= 0.45).

Conclusions

This study suggests that despite lower socioeconomic status, in children with hearing loss, Medicaid allows equivalent access to hearing rehabilitation and speech therapy as their privately insured counterparts and children achieve similar speech and language outcomes.

https://ift.tt/2yuYTAj

Dopamine Signaling Modulates the Stability and Integration of Intrinsic Brain Networks

Abstract

Dopaminergic projections are hypothesized to stabilize neural signaling and neural representations, but how they shape regional information processing and large-scale network interactions remains unclear. Here we investigated effects of lowered dopamine levels on within-region temporal signal variability (measured by sample entropy) and between-region functional connectivity (measured by pairwise temporal correlations) in the healthy brain at rest. The acute phenylalanine and tyrosine depletion (APTD) method was used to decrease dopamine synthesis in 51 healthy participants who underwent resting-state functional MRI (fMRI) scanning. Functional connectivity and regional signal variability were estimated for each participant. Multivariate partial least squares (PLS) analysis was used to statistically assess changes in signal variability following APTD as compared with the balanced control treatment. The analysis captured a pattern of increased regional signal variability following dopamine depletion. Changes in hemodynamic signal variability were concomitant with changes in functional connectivity, such that nodes with greatest increase in signal variability following dopamine depletion also experienced greatest decrease in functional connectivity. Our results suggest that dopamine may act to stabilize neural signaling, particularly in networks related to motor function and orienting attention towards behaviorally-relevant stimuli. Moreover, dopamine-dependent signal variability is critically associated with functional embedding of individual areas in large-scale networks.

https://ift.tt/2JdtNl7

Parcellation of the Human Cerebral Cortex Based on Molecular Targets in the Serotonin System Quantified by Positron Emission Tomography In vivo

Abstract

Parcellation of distinct areas in the cerebral cortex has a long history in neuroscience and is of great value for the study of brain function, specialization, and alterations in neuropsychiatric disorders. Analysis of cytoarchitectonical features has revealed their close association with molecular profiles based on protein density. This provides a rationale for the use of in vivo molecular imaging data for parcellation of the cortex with the advantage of whole-brain coverage. In the current work, parcellation was based on expression of key players of the serotonin neurotransmitter system. Positron emission tomography was carried out for the quantification of serotonin 1A (5-HT_1A, n = 30) and 5-HT_2A receptors (n = 22), the serotonin-degrading enzyme monoamine oxidase A (MAO-A, n = 32) and the serotonin transporter (5-HTT, n = 24) in healthy participants. Cortical protein distribution maps were obtained using surface-based quantification. Based on k-means clustering, silhouette criterion and bootstrapping, five distinct clusters were identified as the optimal solution. The defined clusters proved of high explanatory value for the effects of psychotropic drugs acting on the serotonin system, such as antidepressants and psychedelics. Therefore, the proposed method constitutes a sensible approach towards integration of multimodal imaging data for research and development in neuropharmacology and psychiatry.

https://ift.tt/2yyMrzC

Neuronal Distribution Across the Cerebral Cortex of the Marmoset Monkey (Callithrix jacchus)

Abstract

Using stereological analysis of NeuN-stained sections, we investigated neuronal density and number of neurons per column throughout the marmoset cortex. Estimates of mean neuronal density encompassed a greater than 3-fold range, from >150 000 neurons/mm³ in the primary visual cortex to ~50 000 neurons/mm³ in the piriform complex. There was a trend for density to decrease from posterior to anterior cortex, but also local gradients, which resulted in a complex pattern; for example, in frontal, auditory, and somatosensory cortex neuronal density tended to increase towards anterior areas. Anterior cingulate, motor, premotor, insular, and ventral temporal areas were characterized by relatively low neuronal densities. Analysis across the depth of the cortex revealed greater laminar variation of neuronal density in occipital, parietal, and inferior temporal areas, in comparison with other regions. Moreover, differences between areas were more pronounced in the supragranular layers than in infragranular layers. Calculations of the number of neurons per unit column revealed a pattern that was distinct from that of neuronal density, including local peaks in the posterior parietal, superior temporal, precuneate, frontopolar, and temporopolar regions. These results suggest that neuronal distribution in adult cortex result from a complex interaction of developmental/ evolutionary determinants and functional requirements.

https://ift.tt/2JdtzdL

Characteristics and Prognosis of Primary Head and Neck Angiosarcomas: A Surveillance, Epidemiology, and End Results Program (SEER) Analysis of 1250 Cases

Abstract

Head and neck angiosarcomas (HN-AS) are rare malignancies with a poor prognosis relative to other soft tissue sarcomas. To date, the HN-AS literature has been limited to short reports and single-institution experiences. This study evaluated patients registered with the Surveillance, Epidemiology, and End Results (SEER) program who had been diagnosed with a primary HN-AS. Predictors were drawn from demographic and baseline tumor characteristics. Outcomes were survival months and cause of death. Kaplan–Meier analyses were used to estimate overall (OS) and disease-specific survival (DSS) rates. Cox proportional hazards regression models were used for multivariate analyses. A total of 1250 patients (mean age 73.3 years) were identified, and nearly all lesions (93.5%) were cutaneous. Two- and 5-year OS rates were 47.3% (95% CI 44.3–50.3) and 26.5% (95% CI 23.7–29.3), while 2- and 5-year DSS rates were 66.6% (95% CI 63.6–69.6) and 48.3% (95% CI 44.5–52.1). In the univariate analyses, age, race, tumor grade, tumor size, AJCC stage, SEER historic stage, and surgery were significant predictors of both OS and DSS. Multivariate regression revealed that independent predictors of poor OS and DSS were older age [OS: HR 1.04 (95% CI 1.02–1.05), p < 0.01; DSS: HR 1.03 (95% CI 1.01–1.05), p < 0.01], increased tumor size [OS: HR 1.01 (95% CI 1.01–1.01), p < 0.01; DSS: HR 1.01 (95% CI 1.01–1.02), p < 0.01], and distant disease [OS: HR 2.97 (95% CI 1.65–5.34), p < 0.01; DSS: HR 4.99 (95% CI 2.50–9.98), p < 0.01]. Age, tumor size, and disease extent were determinants of HN-AS survival. When all other factors were controlled, lower histologic grade and surgery did not improve the risk of death.

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Nontraumatic Parapharyngeal Haematoma: A Rare Lesion

Nontraumatic haematoma of parapharyngeal space is very rare and may cause dysphagia and dyspnea. The authors present a case report of a 74-year-old woman with sudden nontraumatic neck swelling without dyspnea and with left pharyngeal bulging and endolaryngeal displacement. Parathyroid hormone elevation and imaging exams confirmed bleeding from a parathyroid adenoma. Symptoms and signs resolved after one week of conservative treatment. There are few cases of parapharyngeal haematomas caused by parathyroid adenomas. Most patients can be managed without emergent surgery, but close airway monitoring is fundamental.

https://ift.tt/2D2ufCv

Recommandations diagnostiques et thérapeutiques pour les maladies sexuellement transmissibles : herpès génital

Publication date: Available online 23 October 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): B. Milpied, M. Janier, J. Timsit, N. Spenatto, E. Caumes, O. Chosidow, L. Sentilhes, M.-V. Senat, Groupe infectiologie dermatologique et infections sexuellement transmissibles (GrIDIST) de la Société française de dermatologie et du Collège national des gynécologues obstétriciens français (CNGOF)

Résumé

Traitement de la primo-infection ou du premier épisode clinique d'herpès génital en cours de grossesse

Le traitement de la primo-infection ou du premier épisode clinique d'herpès génital est basé sur l'aciclovir oral, 200 mg × 5/j pendant 5 à 10 jours en fonction de l'état clinique. Concernant le valaciclovir, la posologie recommandée est de 1 g × 2 jours avec une durée de traitement identique à celle proposée pour l'aciclovir.

Traitement de la récurrence herpétique en cours de grossesse

Il n'y a pas d'étude permettant d'évaluer l'efficacité d'un traitement antiviral sur la symptomatologie en cas de récurrence d'herpès génital pendant la grossesse. Le traitement antiviral par aciclovir ou valaciclovir peut cependant être proposé devant une symptomatologie le justifiant (durée et intensité des symptômes). Le valaciclovir pourra être préféré (efficacité d'utilisation même si les données d'innocuité sont plus nombreuses pour l'aciclovir). Le valaciclovir peut être utilisé à la dose de 1cp à 500 mg per os deux fois par jour pendant 5 jours.

Traitement antiviral prophylactique en cas de grossesse

Chez les femmes ayant eu une infection initiale ou une récurrence pendant la grossesse, bien qu'il n'existe pas de bénéfice démontré du traitement prophylactique pour réduire le risque d'herpès néonatal, il est recommandé de proposer une prophylaxie antivirale à partir de 36 SA (semaines d'aménorrhée) afin de réduire le risque de césarienne pour lésion herpétique. Les antiviraux recommandés sont l'aciclovir à la posologie de 400 mg trois fois par jour per os ou le valaciclovir à la posologie de 500 mg deux fois par jour per os jusqu'à l'accouchement.

Summary

Treatment of the initial infection or first clinical episode of genital herpes

An initial infection or first clinical episode of genital herpes is treated with oral aciclovir 200 mg × 5/d for 5 to 10 days depending on clinical status. The recommended dosage for valaciclovir is 1 g × 2/d and treatment duration is identical to that for aciclovir.

Treatment of herpes recurring during pregnancy

There are no studies of the efficacy of antiviral therapy on the symptoms of genital recurring during pregnancy. However, initial anti-viral treatment using aciclovir or valaciclovir may be given where warranted by symptoms (i.e. duration and severity of symptoms). Valaciclovir may be used instead (equivalent efficacy but better safety data for aciclovir). Valaciclovir may be given at a dosage of 1 × 500 mg b.i.d. p.o. for 5 days.

Prophylactic anti-viral treatment during pregnancy

In female patients presenting an initial infection or infection recurring during pregnancy, although there is no demonstrated benefit for prophylactic treatment in reducing the risk of neonatal herpes, anti-viral prophylaxis is recommended after 36 WA (weeks' amenorrhoea) to limit the need for Caesarean section due to herpetic lesions. The recommended antivirals are aciclovir at a dosage of 400 mg t.i.d p.o. or valaciclovir at a dosage of 500 mg b.i.d. p.o. until delivery.

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Ulcérations buccales aphtoïdes inaugurales d’une maladie inflammatoire chronique de l’intestin induite par le sécukinumab

Publication date: Available online 23 October 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): X. Grimaux, S. Leducq, P. Goupille, A. Aubourg, E. Miquelestorena-Standley, M. Samimi

Résumé

Introduction

Le sécukinumab, anticorps monoclonal humanisé ciblant l'interleukine 17A, a été associé à la survenue de maladies inflammatoires digestives. Nous rapportons le cas d'une patiente ayant développé des ulcérations buccales inaugurales d'une maladie inflammatoire chronique intestinale (MICI) induite par le sécukinumab. Cette patiente avait eu six ans auparavant des ulcérations buccales similaires au cours d'un traitement par tocilizumab (ciblant l'IL6R), suggérant un lien immunologique entre les deux épisodes.

Observation

Une femme de 36 ans avait une spondylarthrite ankylosante réfractaire. En 2010, elle avait présenté des ulcérations buccales au cours d'un traitement par tocilizumab. En 2011, le tocilizumab avait été arrêté et l'aphtose résolutive. En 2016, l'introduction du sécukinumab s'accompagnait d'une récidive d'ulcérations buccales aphtoïdes puis d'une iléo-pancolite. Une corticothérapie, puis un traitement par ustékinumab, permettaient une évolution partiellement favorable.

Discussion

Cette patiente a développé une maladie inflammatoire chronique intestinale au cours d'un traitement par sécukinumab, précédée par des ulcérations buccales aphtoïdes. Elle avait développé, six ans auparavant, des ulcérations buccales similaires au cours d'un traitement ciblant l'IL6R. L'IL6 est une cytokine pléiotrope qui peut activer la voie Th17. Ainsi, le tocilizumab a pu induire un effet « anti-IL17-like » expliquant la survenue de lésions buccales aphtoïdes possiblement en lien avec une maladie inflammatoire digestive a minima.

Conclusion

La survenue d'ulcérations buccales au cours d'un traitement par sécukinumab peut être inaugurale d'une maladie inflammatoire chronique intestinale. La notion d'aphtose préalable, notamment au cours de traitements biologiques antérieurs, devrait faire discuter le rapport bénéfices/risques de la prescription d'un anti-IL17.

Summary

Background

Secukinumab, a humanized monoclonal antibody targeting interleukin 17A, has been associated with the development of inflammatory bowel diseases. We report a case of a female patient developing recurrent oral ulcers prior to inflammatory bowel disease induced by secukinumab. The patient had developed similar oral ulcers 6 years earlier while on tocilizumab (targeting IL6R), suggesting an immunological link between the two episodes.

Patients and methods

A 36-year-old female patient had refractory spondylarthrosis. In 2010, she had presented oral aphthous ulcers during treatment with tocilizumab. In 2011, tocilizumab was stopped and the ulcers resolved. In 2016, secukinumab was introduced and led to recurrence of oral aphthous ulcers followed by ileitis-pancolitis. Corticosteroids and ustekinumab resulted in partial remission.

Discussion

The patient developed inflammatory bowel disease during treatment with secukinumab, preceded by recurrent oral aphthous ulcers. She had presented similar oral ulcers 6 years earlier while on a treatment targeting IL6R. IL6 is a pleiotropic cytokine that may activate the Th17 pathway. Thus, tocilizumab could have induced an "anti-IL17-like" effect, accounting for the occurrence of oral aphthous ulcers, possibly related to mild inflammatory bowel disease.

Conclusion

The occurrence of oral ulcers during treatment with secukinumab may herald inflammatory bowel disease. In patients with a previous history of recurrent aphthous stomatitis, especially where induced by previous biologics, consideration must be given to the risk-benefit ratio of prescribing an anti-IL17 antibody.

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Comparative Effects of Sodium Bicarbonate and Intravenous Lipid Emulsions on Reversing Bupivacaine-Induced Electrophysiological Toxicity in a Porcine Experimental Model

BACKGROUND: Bupivacaine cardiotoxicity mainly manifests as inhibition of the cardiac sodium channel, which slows conduction, particularly at the ventricular level. Experimental studies have demonstrated that intravenous lipid emulsions (ILEs) can reduce the cardiotoxic effects of bupivacaine, but the extent of these effects is controversial. Sodium bicarbonate (B) represents the standard treatment of toxicity related to sodium channel–blocking drugs. The aim of this study was to compare the effects of ILEs and B on the speed of recovery from bupivacaine-induced effects on the electrocardiographic parameters. METHODS: Bupivacaine 4 mg/kg was administered to 24 anesthetized pigs. Three minutes after delivering the bupivacaine bolus, the animals were given the following: ILE 1.5 mL/kg followed by 0.25 mL/kg/min (ILE group) and B 2 mEq/kg followed by 1 mEq/kg/h (B group). Controls (C group) were given saline solution, 50 mL followed by 1 mL/kg/h. Electrophysiological parameters were evaluated in sinus rhythm and during right ventricular pacing at several time intervals up to 30 minutes. Data were analyzed as the area under the curve (AUC) for the first 10 minutes (AUC10) or 30 minutes (AUC30). RESULTS: Bupivacaine increased the sinus cycle length, PR interval, and QRS duration. AUC30 of the sinus rhythm QRS duration after antidote administration was significantly different among the 3 groups (P = .003). B group experienced faster recovery from intoxication than the C group (AUC10, P = .003; AUC30, P = .003) or the ILE group (AUC10, P = .018). During the first minute, 50% of the B group (versus 0% of the ILE and C groups) had recovered >30% of QRS duration (P = .011). The trend toward faster recovery in the ILE group than in the C group did not reach significance (AUC10, P = .23; AUC30, P = .06). Effects on the paced QRS duration at a rate of 150 bpm were more intense but with similar results (B versus C group: AUC10, P = .009; AUC30, P = .009; B versus ILE: AUC10, P = .015; AUC30, P = .024). The recovery process of the paced QRS tended to be slower for all antidotes. CONCLUSIONS: In a closed-chest swine model, B was an effective treatment for electrophysiological alterations caused by established bupivacaine toxicity. At clinical doses, B ameliorated bupivacaine electrocardiographic toxicity faster than ILE. Use-dependent effects of bupivacaine are prominent and delay the effects of both antidotes, but B produces faster recovery than ILE. Accepted for publication September 19, 2018. Funding: Supported by a research grant from the Ministry of Economy, Industry, and Competitiveness of Spain, and Fondos Fondo Europeo de Desarrollo Regional. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Matilde Zaballos, MD, PhD, Department of Anesthesiology, Hospital General Universitario Gregorio Marañón, C/Tellez, No. 52, 3º D, Madrid 28007, Spain. Address e-mail to mati@plagaro.net. © 2018 International Anesthesia Research Society

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Objective Epidural Space Identification Using Continuous Real-Time Pressure Sensing Technology: A Randomized Controlled Comparison With Fluoroscopy and Traditional Loss of Resistance

BACKGROUND: Performance of epidural anesthesia and analgesia depends on successful identification of the epidural space (ES). While multiple investigations have described objective and alternative methodologies to identify the ES, traditional loss of resistance (LOR) and fluoroscopy (FC) are currently standard of care in labor and delivery (L&D) and chronic pain (CP) management, respectively. While FC is associated with high success, it exposes patients to radiation and requires appropriate radiological equipment. LOR is simple but subjective and consequently associated with higher failure rates. The purpose of this investigation was to compare continuous, quantitative, real-time, needle-tip pressure sensing using a novel computer-controlled ES identification technology to FC and LOR for lumbar ES identification. METHODS: A total of 400 patients were enrolled in this prospective randomized controlled noninferiority trial. In the CP management arm, 240 patients scheduled to receive a lumbar epidural steroid injection had their ES identified either with FC or with needle-tip pressure measurement. In the L&D arm, 160 female patients undergoing lumbar epidural catheter placements were randomized to either LOR or needle-tip pressure measurement. Blinded observers determined successful ES identification in both arms. A modified intention-to-treat protocol was implemented, with patients not having the procedure for reasons preceding the intervention excluded. Noninferiority of needle-tip pressure measurement regarding the incidence of successful ES identification was claimed when the lower limit of the 97.27% confidence interval (CI) for the odds ratio (OR) was above 0.50 (50% less likely to identify the ES) and P value for noninferioirty <.023. results: demographics were similar between procedure groups with a mild imbalance in relation to gender when evaluated through standardized difference. noninferiority of needle-tip pressure measurement was demonstrated fc where pain management patients presented success rate es identification both methodologies ci p=".021" for and l experienced noninferior the novel technology vs or using priori delta conclusions: objective lumbar continuous quantitative real-time compuflo epidural computer controlled anesthesia system resulted rates compared lor cp respectively. benefits this may include nonexposure radiation contrast medium consequently reduced health care costs. accepted publication september funding: clinical trial funded by milestone scientific livingston nj. conflicts interest: see disclosures at end article. number: nct02378727 clinicaltrials.gov. reprints will not be available from authors. address correspondence ralf e. gebhard md department anesthesiology university miami miller school medicine nw ave c-300 fl e-mail rgebhard international research society>

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Distraction-Free Induction Zone: A Quality Improvement Initiative at a Large Academic Children’s Hospital to Improve the Quality and Safety of Anesthetic Care for Our Patients

BACKGROUND: Noise in the operating room may cause distractions during critical periods and impair reliable communication between staff. Even momentary inefficiency while administering anesthesia can lead to errors and serious consequences for the patient. Distractions to an anesthesia provider during critical periods such as induction and emergence are a patient safety issue. Because of concerns regarding unacceptable noise levels and distractions during induction of general anesthesia, our institution developed a quality improvement initiative, the "Distraction-Free Induction Zone." The specific aim of this project was to decrease the percentage of cases with a distraction, described as music, unnecessary conversations, or loud noises, occurring during induction of general anesthesia in pediatric otolaryngology operating rooms from 61% to 15%. METHODS: To complete this quality improvement initiative, a multidisciplinary team used improvement science methods, including The Model for Improvement with interventions tested via Plan-Do-Study-Act cycles. We used tools such as the Key Driver Diagram, Pareto Charts, Process Flow Chart, and Plan-Do-Study-Act worksheets. Data were manually collected and entered weekly in an Excel spreadsheet. Statistical process control methods, including a run chart and a P-control chart, were used for data analysis. Our measure was a composite measure in which observation of 1 of the 3 distractions during induction of general anesthesia categorized the case as a case with a distraction. RESULTS: We tested and implemented several interventions via Plan-Do-Study-Act cycles in which 3 main interventions collectively were associated with an observed decrease in distractions during induction of general anesthesia. These included educating the perioperative staff present in the operating room to help them understand that distractions to anesthesia providers represent a patient safety issue, the operating room circulating nurse taking responsibility to pause any music on arrival to the operating room, and the anesthesiologist reminding the staff in the operating room of induction time and/or asking for quiet during induction if a distraction occurs. The percentage of cases with a distraction during induction of general anesthesia in our pediatric otolaryngology operating rooms decreased from 61% to 15% by April 15, 2017 and to 10% by June 5, 2017. CONCLUSIONS: Using improvement science methods, we observed a decrease in distractions during induction of general anesthesia, improved a process, and encouraged change in culture at a large academic children's hospital to enhance the quality and safety of the anesthetic care we provide our patients. Accepted for publication September 19, 2018. Funding: None. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Christy J. Crockett, MD, Department of Anesthesiology, Vanderbilt University Medical Center, 2200 Children's Way, Suite 3116, Nashville, TN 37232. Address e-mail to christy.crockett@vumc.org. © 2018 International Anesthesia Research Society

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In Reply: Encouraging a Bare Minimum While Striving for the Gold Standard A Response to the Updated WHO-WFSA Guidelines

No abstract available

https://ift.tt/2JczbVs

Encouraging a Bare Minimum While Striving for the Gold Standard: A Response to the Updated WHO-WFSA Guidelines

No abstract available

https://ift.tt/2ywCSkW

Dexmedetomidine-Mediated Prevention of Renal Ischemia-Reperfusion Injury Depends in Part on Cholinergic Anti-Inflammatory Mechanisms

BACKGROUND: Organ ischemia-reperfusion injury often induces local and systemic inflammatory responses, which in turn worsen organ injury. These inflammatory responses can be regulated by the central nervous system, particularly by the vagal nerve and nicotinic acetylcholine receptors, which are the key components of cholinergic anti-inflammatory pathway. Activation of the cholinergic anti-inflammatory pathway can suppress excessive inflammatory responses and be a potential strategy for prevention of ischemia-reperfusion injury of organs including the kidney. METHODS: Vagal nerve activity, plasma acetylcholine, catecholamine and inflammatory mediators, renal tissue injury, and cell death were measured in mice with bilateral renal ischemia/reperfusion with or without treatment with dexmedetomidine (Dex), an α2-adrenergic receptor agonist. RESULTS: Dex significantly increased the discharge frequency of the cervical vagal nerve by up to 142 Hz (mean) (P

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Ophthalmologic Anesthesia: Seeing the Forest for the Trees

No abstract available

https://ift.tt/2yxD1UZ

Perioperative Management and In-Hospital Outcomes After Minimally Invasive Repair of Pectus Excavatum: A Multicenter Registry Report From the Society for Pediatric Anesthesia Improvement Network

BACKGROUND: There are few comparative data on the analgesic options used to manage patients undergoing minimally invasive repair of pectus excavatum (MIRPE). The Society for Pediatric Anesthesia Improvement Network was established to investigate outcomes for procedures where there is significant management variability. For our first study, we established a multicenter observational database to characterize the analgesic strategies used to manage pediatric patients undergoing MIRPE. Outcome data from the participating centers were used to assess the association between analgesic strategy and pain outcomes. METHODS: Fourteen institutions enrolled patients from June 2014 through August 2015. Network members agreed to an observational methodology where each institution managed patients based on their institutional standards and protocols. There was no requirement to standardize care. Patients were categorized based on analgesic strategy: epidural catheter (EC), paravertebral catheter (PVC), wound catheter (WC), no regional (NR) analgesia, and intrathecal morphine techniques. Primary outcomes, pain score and opioid consumption by postoperative day (POD), for each technique were compared while adjusting for confounders using multivariable modeling that included 5 covariates: age, sex, number of bars, Haller index, and use of preoperative pain medication. Pain scores were analyzed using repeated-measures analysis of variance with Bonferroni correction. Opioid consumption was analyzed using a multivariable quantile regression. RESULTS: Data were collected on 348 patients and categorized based on primary analgesic strategy: EC (122), PVC (57), WC (41), NR (120), and intrathecal morphine (8). Compared to EC, daily median pain scores were higher in patients managed with PVC (POD 0), WC (POD 0, 1, 2, 3), and NR (POD 0, 1, 2), respectively (P

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In Response

No abstract available

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Surveying the Literature: Synopsis of Recent Key Publications

No abstract available

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Pharmacokinetics of Cefazolin and Vancomycin in Infants Undergoing Open-Heart Surgery With Cardiopulmonary Bypass

BACKGROUND: Gram-positive bacteria account for nearly three-quarters of all surgical site infections. Antibiotic prophylaxis against these bacteria with cephalosporins or, in select circumstances, with vancomycin is considered standard of care for prevention of surgical site infections. There is little evidence to describe the optimal dosing regimen for surgical site infection prophylaxis in infants undergoing cardiac surgery, and a great deal of institutional variability exists in dosing prophylactic antibiotics. We designed this study to describe an optimal dose regimen for cephalosporin and vancomycin based on pharmacokinetic evidence for infant open-heart surgery on cardiopulmonary bypass. METHODS: Two separate cohorts of infants undergoing cardiac surgery with cardiopulmonary bypass were evaluated. Plasma concentrations of vancomycin (cohort 1, N = 10) and cefazolin (cohort 2, N = 10) were measured, and mixed-effects pharmacokinetic models were constructed for each drug. Simulations of various dosing regimens were performed to describe an appropriate dosing regimen necessary to maintain antibiotic concentrations above the susceptibility cutoff for staphylococci. RESULTS: Both cefazolin and vancomycin plasma concentration versus time profiles were characterized by a 2-compartment model. Subject weight was a significant covariate for V1 for vancomycin. Subject age was a significant covariate for V1 for cefazolin. Cardiopulmonary bypass did not influence concentration versus time profiles. Simulations demonstrated that a 1-hour vancomycin infusion (15 mg·kg−1), repeated every 12 hours and a 10-minute infusion of cefazolin (30 mg·kg−1), repeated every 4 hours maintained plasma concentrations above 4 μg·mL−1 and 16 μg·mL−1, for vancomycin and cefazolin, respectively. Both concentrations are above the minimum inhibitory concentration 90 for most susceptible staphylococci. CONCLUSIONS: Prophylactic treatment of vancomycin 15 mg·kg−1 infused >1 hour with 12-hour redosing and cefazolin 30 mg·kg−1 infused >10 minutes with 4-hour redosing will maintain serum levels of each antibiotic above the susceptibility cut-offs for susceptible staphylococci in infants undergoing cardiac surgery. Cefazolin levels may be adequate for some, but not all, Gram-negative bacteria. The effect of cardiopulmonary bypass on pharmacokinetics is negligible. Accepted for publication September 19, 2018. Funding: None. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Clinical Trials Registry: NCT01619982. Reprints will not be available from the authors. Address correspondence to Jerry Ingrande, MD, MS, Department of Anesthesiology, University of California, San Diego School of Medicine, 402 Dickinson St, Hillcrest, CA 92103. Address e-mail to jingrande@ucsd.edu. © 2018 International Anesthesia Research Society

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KDF1 is a novel candidate gene of non-syndromic tooth agenesis

Publication date: Available online 23 October 2018

Source: Archives of Oral Biology

Author(s): Binghui Zeng, Hui Lu, Xue Xiao, Xinlin Yu, Sijie Li, Ling Zhu, Dongsheng Yu, Wei Zhao

Abstract

Objective

Tooth agenesis (TA) is featured by congenital loss of teeth, and can be divided into two subtypes, non-syndromic TA (NSTA) and syndromic TA (STA). Although 12 candidate genes of NSTA have been revealed, the genetic basis of NSTA needs to be further studied. We noticed an overlap of candidate genes between NSTA and STA, and hypothesized that some candidate genes of STA may be new candidate genes of NSTA.

Methods

Sanger sequencing, whole exome sequencing, bioinformatics analyses and immunohistochemical staining were performed to reveal the genetic basis of the patients in a family with NSTA.

Results

No pathogenic mutation was found in the 12 candidate genes of NSTA. We screened the variants of 76 STA candidate genes and identified a novel pathogenic mutation c.G908C (p.R303 P) inKeratinocyte Differentiation Factor 1 (KDF1). This mutation was cosegregated with the disease in the family. Bioinformatics analyses predicted the mutation to be pathogenic. Immunohistochemical staining of kdf1 in developing tooth germs indicated that kdf1 expression is important for the development of teeth.

Conclusions

This study identifiedKDF1 as a novel candidate gene for NSTA. STA candidate genes may be a promising source of new NSTA genes.

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Reduced ADAM8 Levels upon Non-surgical Periodontal Therapy in Patients with Chronic Periodontitis

Publication date: Available online 23 October 2018

Source: Archives of Oral Biology

Author(s): Tanawat Nimcharoen, Win Pa Pa Aung, Anupong Makeudom, Thanapat Sastraruji, Sakornrat Khongkhunthian, Benyapha Sirinirund, Suttichai Krisanaprakornkit, Pattanin Montreekachon

Abstract

Objective

To determine effect of non-surgical periodontal treatment on a disintegrin and metalloproteinase 8 (ADAM8) levels in gingival crevicular fluid (GCF) of patients with chronic periodontitis (CP) in comparison with those of patients with gingivitis and to find correlations between ADAM8 levels and clinical parameters.

Design

Twenty-two and eleven patients with CP and gingivitis, respectively, were examined for four clinical parameters, probing depth, clinical attachment level, gingival and plaque indices. GCF from the selected gingivitis or peri

odontitis sites with distinct severities was sampled by Periopaper strips. The non-surgical treatments, including scaling and/or root planing and oral hygiene instruction, were provided for all patients. Clinical measurements and GCF sampling were repeated at three months after the treatments. ADAM8 concentrations were analyzed by ELISA and normalized by GCF volumes or total protein amounts.

Results

All patients exhibited significant improvement of almost every clinical parameter after treatment, whereas the median ADAM8 concentrations were significantly decreased at the moderate and severe periodontitis sites of patients with CP (p < 0.05). Moreover, the significantly positive correlations between ADAM8 concentrations and four clinical parameters were found in both moderate and severe groups (p < 0.05).

Conclusion

ADAM8 concentrations were decreased by non-surgical periodontal therapy in patients with chronic periodontitis at the moderate and severe sites and were correlated with four clinical parameters, implying that GCF ADAM8 levels reflect inflammatory and bone-resorbing activities in the periodontal pocket.

https://ift.tt/2CzJlhA

Effect of non-surgical periodontal therapy on salivary metabolic fingerprint of generalized chronic periodontitis using nuclear magnetic resonance spectroscopy

Publication date: Available online 23 October 2018

Source: Archives of Oral Biology

Author(s): Federica Romano, Gaia Meoni, Valeria Manavella, Giacomo Baima, Giulia Maria Mariani, Stefano Cacciatore, Leonardo Tenori, Mario Aimetti

ABSTRACT

Objective

Metabolomic analysis of saliva proved its accuracy in discriminating patients with generalized chronic periodontitis (GCP) from healthy subjects by identifying specific molecular signatures of the disease. There is lack of investigations concerning the effect of periodontal treatment on individual metabolic fingerprints. Therefore, the aim of this study was to determine whether non-surgical periodontal therapy could change salivary metabolomic profile in GCP to one more similar to periodontal health.

Design

Unstimulated whole saliva of 32 controls and 19 GCP patients were obtained prior to and 3 months after conventional staged non-surgical periodontal therapy. Metabolic profiling was performed using Nuclear Magnetic Resonance (NMR) spectroscopy, followed by univariate and multivariate paired approaches to assess the changes introduced by the therapy.

Results

In GCP group, periodontal treatment led to an improvement in all clinical parameters (p < 0.001). The accuracy of the multivariate model in discriminating the metabolomic profile of each GCP patient at two time points was 92.5%. Despite the almost perfect separation of the spectra in the metabolic space, the univariate analysis failed to identify significant variations in single metabolite content. The post-treatment metabolic profile of GCP patients could not be assimilated to that of healthy controls who exhibited different levels of lactate, pyruvate, valine, proline, tyrosine, and formate.

Conclusions

Based on these data, NMR-spectroscopic analysis revealed that, despite significant changes in the overall metabolomic fingerprint after non-surgical therapy, GCP patients maintained a distinctive metabolic profile compared to healthy individuals.

https://ift.tt/2Apw0al

Characteristics and Prognosis of Primary Head and Neck Angiosarcomas: A Surveillance, Epidemiology, and End Results Program (SEER) Analysis of 1250 Cases

Abstract

Head and neck angiosarcomas (HN-AS) are rare malignancies with a poor prognosis relative to other soft tissue sarcomas. To date, the HN-AS literature has been limited to short reports and single-institution experiences. This study evaluated patients registered with the Surveillance, Epidemiology, and End Results (SEER) program who had been diagnosed with a primary HN-AS. Predictors were drawn from demographic and baseline tumor characteristics. Outcomes were survival months and cause of death. Kaplan–Meier analyses were used to estimate overall (OS) and disease-specific survival (DSS) rates. Cox proportional hazards regression models were used for multivariate analyses. A total of 1250 patients (mean age 73.3 years) were identified, and nearly all lesions (93.5%) were cutaneous. Two- and 5-year OS rates were 47.3% (95% CI 44.3–50.3) and 26.5% (95% CI 23.7–29.3), while 2- and 5-year DSS rates were 66.6% (95% CI 63.6–69.6) and 48.3% (95% CI 44.5–52.1). In the univariate analyses, age, race, tumor grade, tumor size, AJCC stage, SEER historic stage, and surgery were significant predictors of both OS and DSS. Multivariate regression revealed that independent predictors of poor OS and DSS were older age [OS: HR 1.04 (95% CI 1.02–1.05), p < 0.01; DSS: HR 1.03 (95% CI 1.01–1.05), p < 0.01], increased tumor size [OS: HR 1.01 (95% CI 1.01–1.01), p < 0.01; DSS: HR 1.01 (95% CI 1.01–1.02), p < 0.01], and distant disease [OS: HR 2.97 (95% CI 1.65–5.34), p < 0.01; DSS: HR 4.99 (95% CI 2.50–9.98), p < 0.01]. Age, tumor size, and disease extent were determinants of HN-AS survival. When all other factors were controlled, lower histologic grade and surgery did not improve the risk of death.

https://ift.tt/2O3HQu7

Cervical Spine Movement in a Cadaveric Model of Severe Spinal Instability: A Study Comparing Tracheal Intubation With 4 Different Laryngoscopes

Background: This study compared the Macintosh blade direct laryngoscope, Glidescope, C-Mac d-Blade, and McGrath MAC X-blade video laryngoscopes in 2 cadaveric models with severe cervical spinal instability. We hypothesized that the Glidescope video laryngoscope would allow for intubation with the least amount of cervical spine movement. Our secondary endpoints were glottic visualization and intubation success. Methods: In total, 2 fresh cadavers underwent maximal surgical destabilization from the craniocervical junction to the cervicothoracic junction by a neurosurgical spine specialist, with subsequent neutral positioning of the heads with surgical head fixation devices. On each cadaver, 8 experienced anesthesiologists performed four intubations with the 4 laryngoscopes in random order. Lateral radiographic measurements determined vertebral displacement during intubation. Results: Cervical spine displacements were not significantly different amongst video laryngoscopes. Cormack-Lehane Grade 1 views were achieved with all attempts with each of the 3 video laryngoscopes; intubation attempts with the Macintosh blade achieved only grade 3 or grade 4 views. Intubation was successful every time with a video laryngoscope but only during 1 of 16 intubation attempts with the Macintosh blade. Conclusions: In a cadaveric model with maximally destabilized cervical spines, cervical spine movement was observed during attempted laryngoscopy using each of 3 video laryngoscopes, although there was no significant difference between the laryngoscopes. Given cervical spine displacement occurred, these video laryngoscopes do not prevent cervical spine motion during laryngoscopy. However, with improved glottic visualization and intubation success, video laryngoscopes are superior to the Macintosh blade in both cervical spine safety and intubation efficacy in the model studied. Supported by Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center. The authors have no conflicts of interest to disclose. Address correspondence to: Jia W. Romito, MD, Department of Anesthesiology & Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9068 (e-mail: Jia.Romito@utsouthwestern.edu). Received March 5, 2018 Accepted September 19, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

https://ift.tt/2PQi52c

The clinical usage and definition of autoantibodies in immune-mediated liver disease: A comprehensive overview

Publication date: Available online 23 October 2018

Source: Journal of Autoimmunity

Author(s): Benedetta Terziroli Beretta-Piccoli, Giorgina Mieli-Vergani, Diego Vergani

Abstract

Autoimmune serology is key to the diagnosis and management of autoimmune liver diseases. Its correct use in clinical practice requires a basic knowledge of the laboratory techniques used for autoantibody detection. Indirect immunofluorescence (IIF) on triple rodent tissue is still the gold standard screening procedure for liver-relevant autoantibodies, while HEp2 cells and human ethanol-fixed neutrophils are used as substrates to characterize nuclear reactivities and to detect anti-neutrophil cytoplasm antibody, respectively. Assays based on purified or recombinant antigens are increasingly used, having the main advantage of being observer-independent and the disadvantage of detecting only autoantibodies whose antigenic target has been identified. The AIH-specific anti-soluble liver antigen antibody cannot be detected by IIF and a molecular-based assay should be used at the screening level. Since autoantibodies may be present in the context of viral hepatitides and other inflammatory liver diseases it is important to exclude these conditions before diagnosing autoimmune liver disease. Anti-nuclear antibody (ANA), most often with a homogeneous IIF pattern on HEp2 cells, characterizes type 1 autoimmune hepatitis (AIH), and is found in association with anti-smooth muscle antibody in about half of the cases. Two IIF ANA patterns are specific for primary biliary cholangitis, namely the rim-like/membranous pattern, and the multiple nuclear dots pattern. Anti-liver kidney microsomal antibody type 1 is the serological hallmark of type 2 AIH, often in association with anti-liver cytosol type 1 antibody. Atypical perinuclear anti-neutrophil antibody, referred to as perinuclear anti-neutrophil nuclear antibody, is frequently detected in primary sclerosing cholangitis, in AIH type 1 and in inflammatory bowel diseases. The anti-asiaglycoprotein receptor antibody is liver-specific but not disease-specific, and reliable commercial assays for its detection are lacking. Anti-mitochondrial antibody is the hallmark of primary biliary cholangitis (PBC), being disease-specific and present in about 95% of the PBC patients. Its incidental detection presages the future development of PBC.

https://ift.tt/2ResOE7

Autoimmune sclerosing cholangitis: Evidence and open questions

Publication date: Available online 23 October 2018

Source: Journal of Autoimmunity

Author(s): Benedetta Terziroli Beretta-Piccoli, Diego Vergani, Giorgina Mieli-Vergani

Abstract

Juvenile sclerosing cholangitis is a rare chronic hepatobiliary disorder characterized by inflammation of the intra- and/or extrahepatic bile ducts, bile duct dilatation, narrowing and obliteration, and, histologically, by inflammatory bile duct damage leading to periductular fibrosis. The diagnosis is based on endoscopic retrograde cholangiopancreatography or magnetic resonance cholangiopancreatography. In children, it may be associated to a variety of systemic and hepatic conditions: thus, the term "primary" sclerosing cholangitis should be reserved for the rare cases without a known cause. Small duct disease is diagnosed in the presence of histological features diagnostic of sclerosing cholangitis and normal cholangiography. Autoimmune sclerosing cholangitis (ASC) is a form of sclerosing cholangitis with strong autoimmune features overlapping with those of autoimmune hepatitis (AIH). It is a well-recognized nosological entity in paediatrics, where it accounts for the majority of sclerosing cholangitis cases. It is as prevalent as AIH in children, is equally frequent in males and females, half of the patients have concomitant inflammatory bowel disease, virtually all patients have raised immunoglobulin G levels and positive anti-nuclear and/or anti-smooth muscle antibodies. Half of the ASC patients respond well to standard immunosuppressive treatment for AIH with the addition of ursodeoxycholic acid, but the transplant rate is higher than in AIH, and post-transplant recurrence is frequent. A number of open questions remain: are ASC and AIH distinct entities or different manifestations of the same condition? What is the role of histology? Is small duct disease a specific entity? What is the relationship between ASC and adult primary sclerosing cholangitis? What is the role of inflammatory bowel disease? In addition, validated diagnostic criteria for ASC are needed.

https://ift.tt/2q85sV1

Endoscopic transnasal transseptal pituitary surgery

Publication date: Available online 23 October 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): V. Favier, J. Boetto, C. Cartier, F. Segnarbieux, L. Crampette

Abstract

Pituitary surgery is performed via a transsphenoidal approach in the vast majority of cases according to various methods that have changed over the years. A microscopic transseptal approach via a sublabial mucosal incision or a nasal mucosal incision has also been extensively used. An endoscopic transnasal approach was first described in the 1990's, followed by the concept of a microscopic transseptal approach and an endoscopic strictly endonasal approach. We use an entirely endoscopic transseptal transsphenoidal approach via an incision in the nasal mucosa for both access and tumour resection. This procedure has a number of advantages: strictly midline approach to the sella turcica, large operative field, no interference between instruments and a low rate of nasal complications.

https://ift.tt/2EQHJmG

Bee venom improves diabetic wound healing by protecting functional macrophages from apoptosis and enhancing Nrf2, Ang-1 and Tie-2 signaling

Publication date: November 2018

Source: Molecular Immunology, Volume 103

Author(s): Wael N. Hozzein, Gamal Badr, Badr M. Badr, Ahmed Allam, Ahmad Al Ghamdi, Mohammed A. Al-Wadaan, Noori S. Al-Waili

Abstract

Impaired wound healing is a serious complication of diabetes that negatively affects the patient's socioeconomic life. Multiple mechanisms contribute to impaired diabetic wound healing including deficient recruitment of wound macrophages/neutrophils and impaired neovascularization. Bee venom (BV) has been used as an anti-inflammatory agent for the treatment of several diseases. Nevertheless, the impacts of BV on the diabetic wound healing have been poorly studied. In the present study, we investigated the molecular mechanisms underlying BV treatment on diabetic wound healing in a type I diabetic mouse model. Three experimental groups were used: group 1, non-diabetic control mice; group 2, vehicle-diabetic mice; and group 3, BV-treated diabetic mice. We found that the diabetic mice exhibited impaired wound closure characterized by a significant decrease in collagen and β-defensin-2 (BD-2) expression compared to control non-diabetic mice. The impairment of diabetic wound healing is attributed to increased ROS levels and abolished antioxidant enzymes activity in the wounded tissues. Additionally, wounded tissue in diabetic mice revealed aberrantly decreased levels of Ang-1 and Nrf2 (the agonist ligands of Tie-2) followed by a marked reduction in the phosphorylation of Tie2 and downstream signaling eNOS, AKT and ERK. Impaired diabetic wound healing was also characterized by a significant reduction in activities of total antioxidant enzymes followed by a marked reduction in the levels of CCL2, CCL3 and CXCL2; which led to impaired recruitment and functions of wound macrophages/neutrophils; and significant reduction in the expression of CD31, a marker for neovascularization and angiogenesis of the injured tissue. Interestingly, BV treatment significantly enhanced wound closure in diabetic mice by increasing collagen and BD-2 expression and restoring the levels of Ang-1 and Nrf2 and hence enhancing the Tie-2 downstream signaling. Most importantly, treatment of diabetic mice with BV significantly restored the activities of wounded tissue antioxidant enzymes and the levels of chemokines, and subsequently rescued wound macrophages from mitochondrial membrane potential-induced apoptosis. Our findings reveal the immune-enhancing effects of BV for improving healing process of diabetic wounds and provide the first insight concerning the underlying molecular mechanisms.

Graphical abstract

https://ift.tt/2ApDolX

Role of myeloid regulatory cells (MRCs) in maintaining tissue homeostasis and promoting tolerance in autoimmunity, inflammatory disease and transplantation

Abstract

Myeloid cells play a pivotal role in regulating innate and adaptive immune responses. In inflammation, autoimmunity, and after transplantation, myeloid cells have contrasting roles: on the one hand they initiate the immune response, promoting activation and expansion of effector T-cells, and on the other, they counter-regulate inflammation, maintain tissue homeostasis, and promote tolerance. The latter activities are mediated by several myeloid cells including polymorphonuclear neutrophils, macrophages, myeloid-derived suppressor cells, and dendritic cells. Since these cells have been associated with immune suppression and tolerance, they will be further referred to as myeloid regulatory cells (MRCs). In recent years, MRCs have emerged as a therapeutic target or have been regarded as a potential cellular therapeutic product for tolerance induction. However, several open questions must be addressed to enable the therapeutic application of MRCs including: how do they function at the site of inflammation, how to best target these cells to modulate their activities, and how to isolate or to generate pure populations for adoptive cell therapies. In this review, we will give an overview of the current knowledge on MRCs in inflammation, autoimmunity, and transplantation. We will discuss current strategies to target MRCs and to exploit their tolerogenic potential as a cell-based therapy.

https://ift.tt/2PkvRgD

Allergological work‐up with half‐dose challenge in iodinated contrast media hypersensitivity

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Jdl3LR

HPV-positives Oropharynxkarzinom – eine Gefahr für den Partner?

Zusammenfassung

Es wird über eine Kasuistik von einem metachron auftretenden HPV-positiven Oropharynxkarzinom bei einem Ehepaar im Kontext mit anderen Studien berichtet, sodass die Frage nach der Notwendigkeit einer Screeninguntersuchung und einer intensivierten Überwachung der Lebensgefährten von erkrankten Personen oder der Ergreifung von Präventionsmaßnahmen aufgeworfen wird. Die aktuelle Datenlage suggeriert ein potenzielles Risiko für den Lebensgefährten einer erkrankten Person, es kann jedoch bzgl. der Häufigkeit des konkordant auftretenden HPV-positiven Oropharynxkarzinoms aufgrund der nur spärlich erfassten Fälle keine genaue Aussage getroffen werden. Weitere epidemiologische Studien könnten sich als nützlich erweisen.

https://ift.tt/2q9xUFS

Characteristics and Prognosis of Primary Head and Neck Angiosarcomas: A Surveillance, Epidemiology, and End Results Program (SEER) Analysis of 1250 Cases

Abstract

Head and neck angiosarcomas (HN-AS) are rare malignancies with a poor prognosis relative to other soft tissue sarcomas. To date, the HN-AS literature has been limited to short reports and single-institution experiences. This study evaluated patients registered with the Surveillance, Epidemiology, and End Results (SEER) program who had been diagnosed with a primary HN-AS. Predictors were drawn from demographic and baseline tumor characteristics. Outcomes were survival months and cause of death. Kaplan–Meier analyses were used to estimate overall (OS) and disease-specific survival (DSS) rates. Cox proportional hazards regression models were used for multivariate analyses. A total of 1250 patients (mean age 73.3 years) were identified, and nearly all lesions (93.5%) were cutaneous. Two- and 5-year OS rates were 47.3% (95% CI 44.3–50.3) and 26.5% (95% CI 23.7–29.3), while 2- and 5-year DSS rates were 66.6% (95% CI 63.6–69.6) and 48.3% (95% CI 44.5–52.1). In the univariate analyses, age, race, tumor grade, tumor size, AJCC stage, SEER historic stage, and surgery were significant predictors of both OS and DSS. Multivariate regression revealed that independent predictors of poor OS and DSS were older age [OS: HR 1.04 (95% CI 1.02–1.05), p < 0.01; DSS: HR 1.03 (95% CI 1.01–1.05), p < 0.01], increased tumor size [OS: HR 1.01 (95% CI 1.01–1.01), p < 0.01; DSS: HR 1.01 (95% CI 1.01–1.02), p < 0.01], and distant disease [OS: HR 2.97 (95% CI 1.65–5.34), p < 0.01; DSS: HR 4.99 (95% CI 2.50–9.98), p < 0.01]. Age, tumor size, and disease extent were determinants of HN-AS survival. When all other factors were controlled, lower histologic grade and surgery did not improve the risk of death.

https://ift.tt/2O3HQu7

Head and neck cancer organoids established by modification of the CTOS method can be used to predict in vivo drug sensitivity

Publication date: December 2018

Source: Oral Oncology, Volume 87

Author(s): Noriaki Tanaka, Abdullah A. Osman, Yoko Takahashi, Antje Lindemann, Ameeta A. Patel, Mei Zhao, Hideaki Takahashi, Jeffrey N. Myers

Abstract

Objectives

Currently there are no standard biomarkers of head and neck squamous cell carcinoma (HNSCC) response to therapy. This is, due to a lack of adequate predictive tumor models. To this end, we established cancer organoid lines from individual patient's tumors, and characterized their growth characteristics and response to different drug treatments with the objective of using these models for prediction of treatment response.

Materials and Methods

Forty-three patients' samples were processed to establish organoids. To analyze the character of these organoids, immunohistochemistry, Western blotting, drug sensitivity assays, clonogenic survival assays, and animal experiments were performed. The HPV status and TP53 mutational status were also confirmed in these lines.

Results

HNSCC organoids were successfully established with success rate of 30.2%. Corresponding two-dimensional cell lines were established from HNSCC organoids at higher success rate (53.8%). These organoids showed similar histological features and stem cell, epithelial and mesenchymal marker expression to the original tumors, thus recapitulating many of the characteristics of the original tumor cells. The cisplatin and docetaxel IC50 were determined for HNSCC organoids and the corresponding 2D cell lines using drug sensitivity and clonogenic survival assays. Responses to drug treatment in vivo were found to be similar to the IC₅₀ calculated from organoids by drug sensitivity assays in vitro.

Conclusion

We established novel in vitro HNSCC cancer organoid lines retaining many properties of the original tumors from they were derived. These organoids can predict in vivo drug sensitivity and may represent useful tools to develop precision treatments for HNSCC.

https://ift.tt/2z1JGGm

Study on the correlation between age and changes in mosquito bite response

The Journal of Dermatology, EarlyView.


https://ift.tt/2RdBB9n

Diagnostic accuracy of F-18 FDG PET or PET/CT for detection of lymph node metastasis in clinically node negative head and neck cancer patients; A systematic review and meta-analysis

Publication date: Available online 23 October 2018

Source: American Journal of Otolaryngology

Author(s): Seong-Jang Kim, Kyoungjune Pak, Keunyoung Kim

Abstract

Objective

The purpose of the current study was to investigate the diagnostic performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) or positron emission tomography/computed tomography (PET/CT) for the detection of cervical lymph node (LN) metastasis in clinically node negative head and neck squamous cell cancer (cN0 HNSCC) patients through a systematic review and meta-analysis.

Methods

The PubMed and EMBASE database, from the earliest available date of indexing through April 30, 2018, were searched for studies evaluating the diagnostic performance of F-18 FDG PET or PET/CT for the detection of LN metastasis in cN0 HNSCC patients. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR−), and constructed summary receiver operating characteristic (SROC) curves.

Results

Across 18 studies (1044 patients), the pooled sensitivity for F-18 FDG PET or PET/CT for the detection of LN metastasis was 0.58 and a pooled specificity of 0.87 for patient based analysis. Neck side based analysis showed the pooled sensitivity of 0.67 and a pooled specificity of 0.85. Level based study demonstrated the pooled sensitivity of 0.53 and a pooled specificity of 0.97 (95% CI; 0.95–0.98). In meta-regression analysis, no definite variable was the source of the study heterogeneity.

Conclusion

The current meta-analysis showed the low sensitivity and moderate specificity of F-18 FDG PET/CT for the detection of cervical LN metastasis in cN0 HNSCC patients. Level based analysis of F-18 FDG PET or PET/CT has a high specificity and NPV for the detection of cervical metastatic LN detection.

https://ift.tt/2PgvEeu

Palmar crease xanthomas in familial hypercholesterolemia

International Journal of Dermatology, EarlyView.


https://ift.tt/2NZfRM9

Treatment of primary non-metastatic melanoma at high-volume academic facilities is associated with improved long-term patient survival

Publication date: Available online 23 October 2018

Source: Journal of the American Academy of Dermatology

Author(s): Shayan Cheraghlou, George O. Agogo, Michael Girardi

Abstract

Background

Previous studies of cancer care have demonstrated improved long-term patient outcomes for those treated at high-volume centers. The influence of treatment center characteristics on outcomes for primary non-metastatic melanoma is not currently established.

Objective

We aimed to investigate the association of cancer treatment center case volume and academic affiliation on long-term patient survival for cases of primary non-metastatic melanoma.

Methods

US adult melanoma cases diagnosed from 2004-2014 in the NCDB were identified. Hospitals were grouped by yearly case volume quartile: bottom quartile, middle quartiles, and top quartile.

Results

Facility case volume was significantly associated with long-term patient survival (p<0.0001). Five-year survival was 76.8%, 81.9%, and 86.4% respectively for patients treated at institutions in the bottom, middle, and top quartiles of case volume respectively. On multivariate analysis, treatment at both middle-quartile (HR 0.834;95% CI 0.778-0.895) and top-quartile (HR 0.691;95% CI 0.644-0.741) volume centers was associated with improved survival relative to bottom-quartile volume hospitals. Academic affiliation was associated with improved outcomes for top-quartile but not middle-quartile volume facilities.

Limitations

Disease-specific survival was not available.

Conclusions

Treatment at a high-volume facility is associated with improved long-term patient survival for melanoma. High-volume academic centers have improved patient outcomes compared to other high-volume centers.

https://ift.tt/2ywzGWf

2B4 and CD48: A powerful couple of the immune system

Publication date: Available online 24 October 2018

Source: Clinical Immunology

Author(s): Hadas Pahima, Pier Giorgio Puzzovio, Francesca Levi-Schaffer

Abstract

The signaling lymphocytic activation molecule (SLAM) family of receptors (SLAMF) is a group of receptors belonging to the CD2 family. It is composed of several members expressed on many hematopoietic cells. Most of the receptors interact in a homophilic fashion with neighboring cells. Their distribution and binding properties, together with their ability to function as both activating and inhibitory receptors, put them as key players in the immune system regulation. Several SLAM family receptors have been extensively investigated. This review mainly focuses on CD244 (2B4 or SLAMF4,) and CD48, particularly as expressed by the key cells of allergy, mast cells and eosinophils.

https://ift.tt/2Re6UAT

SLAMF6 in health and disease: Implications for therapeutic targeting

Publication date: Available online 23 October 2018

Source: Clinical Immunology

Author(s): Burcu Yigit, Ninghai Wang, Roland W. Herzog, Cox Terhorst

https://ift.tt/2q9ZKlA

A comprehensive understanding of the gut mucosal immune system in allergic inflammation

Publication date: Available online 23 October 2018

Source: Allergology International

Author(s): Daisuke Tokuhara, Yosuke Kurashima, Mariko Kamioka, Toshinori Nakayama, Peter Ernst, Hiroshi Kiyono

Abstract

Despite its direct exposure to huge amounts of microorganisms and foreign and dietary antigens, the gut mucosa maintains intestinal homeostasis by utilizing the mucosal immune system. The gut mucosal immune system protects the host from the invasion of infectious pathogens and eliminates harmful non-self antigens, but it allows the cohabitation of commensal bacteria in the gut and the entry of dietary non-self antigens into the body via the mucosal surface. These physiological and immunological activities are regulated by the ingenious gut mucosal immune network, comprising such features as gut-associated lymphoid tissue, mucosal immune cells, cytokines, chemokines, antimicrobial peptides, secretory IgA, and commensal bacteria. The gut mucosal immune network keeps a fine tuned balance between active immunity (against pathogens and harmful non-self antigens) and immune tolerance (to commensal microbiota and dietary antigens), thus maintaining intestinal healthy homeostasis. Disruption of gut homeostasis results in persistent or severe gastrointestinal infection, inflammatory bowel disease, or allergic inflammation. In this review, we comprehensively introduce current knowledge of the gut mucosal immune system, focusing on its interaction with allergic inflammation.

https://ift.tt/2PlAeb8

Complex congenital cardiac anomalies in the setting of right isomerism in a 31-month-old infant: a case report

Congenital cardiac defects are not rare among neonates. Prompt assessment for life-threatening anomalies is essential for rapid management decisions and positive outcomes. Extracardiac anomalies can occur in c...

https://ift.tt/2D1lPv0

Proctalgia and constipation secondary to hypertrophic polyglucosan inclusion body myopathy of the internal anal sphincter: a case report

Hereditary polyglucosan inclusion body myopathy of the internal anal sphincter is a rare cause of proctalgia fugax and constipation. Treatment options are explored.

https://ift.tt/2PTxT4b

Direct infant UV light exposure is associated with eczema and immune development

Publication date: Available online 23 October 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Kristina Rueter, Anderson P. Jones, Aris Siafarikas, Ee-Mun Lim, Natasha Bear, Paul S. Noakes, Susan L. Prescott, Debra J. Palmer

Background

Suboptimal vitamin D levels during critical periods of immune development have emerged as an explanation for higher rates of allergic diseases associated with industrialization and residing at higher latitudes.

Objective

We sought to determine the effects of early postnatal vitamin D supplementation on infant eczema and immune development.

Methods

By using a double-blind randomized controlled trial, newborn infants were randomized to receive vitamin D supplementation (400 IU/d) or a placebo until 6 months of age. Some infants also wore personal UV dosimeters to measure direct UV light (290-380 nm) exposure. Infant vitamin D levels were measured at 3 and 6 months of age. Eczema, wheeze, and immune function outcomes were assessed at 6 months of age.

Results

At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater for the vitamin D–supplemented group than the placebo group, but there was no difference in eczema incidence between groups. Infants with eczema were found to have had less UV light exposure (median, 555 Joules per square meter [J/m²; interquartile range, 322-1210 J/m²]) compared with those without eczema (median, 998 J/m² [interquartile range, 676-1577 J/m²]; P = .02). UV light exposure was also inversely correlated with IL-2, GM-CSF, and eotaxin production to Toll-like receptor ligands.

Conclusion

This study is the first to demonstrate an association between greater direct UV light exposures in early infancy with lower incidence of eczema and proinflammatory immune markers by 6 months of age. Our findings indicate that UV light exposure appears more beneficial than vitamin D supplementation as an allergy prevention strategy in early life.

Graphical abstract

https://ift.tt/2PRQuOh

Endocrine Pathology Society Hubert Wolfe Award for 2018: Call for Nominations

https://ift.tt/2PS7rrU

Asymptomatic perianal papules in a 75‐year‐old man

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2R91AOZ

Red crateriform tumour on the scalp

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2AqILRZ

Asymptomatic perianal papules in a 75‐year‐old man

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2R91AOZ

Red crateriform tumour on the scalp

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2AqILRZ

Dermoscopy of folliculosebaceous cystic hamartoma

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2O2VzS2

Delayed angioedema of the unilateral tongue associated with angiotensin II receptor blocker in a patient with polypharmacy

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2OL7pWl

Volume outlier benchmark proposal for Australian Mohs surgery

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2O2YEBJ

Effects of CYP2D6 * 10 polymorphism on tamoxifen pharmacokinetics in patients with breast cancer in Asia: a meta-analysis

Abstract

Purpose

Insufficient serum metabolite concentrations of tamoxifen can compromise treatment efficacy in patients with breast cancer. The purpose of this meta-analysis was to explore correlations between cytochrome P450 (CYP) 2D6*10 gene polymorphisms and serum concentrations of tamoxifen and its active metabolites in patients with breast cancer in Asia.

Methods

The study included a systematic literature search for cohort studies published before March 2018 in English databases (PubMed, Embase, Cochrane Library, and Web of Science) and Chinese databases (Chinese National Knowledge Infrastructure and Wan Fang database). The meta-analysis was performed using RevMan 5.3 software. Pooled means and standard deviations were calculated with 95% confidence intervals. Publication bias and sensitivity analyses were also performed using STATA 14.0.

Results

In total, 7 studies and 552 patients were included in the meta-analysis. Serum concentrations of endoxifen were significantly different in each CYP2D6*10 genotype group (p < 0.05). The CC genotype was associated with higher concentrations of 4-OH-TAM than the CT/TT genotype (p < 0.05). However, there were no statistically significant between-group differences in serum concentrations of TAM (p > 0.05). Publication bias and sensitivity analyses confirmed that the meta-analysis results were stable and reliable.

Conclusions

CYP2D6*10 polymorphisms influence the pharmacokinetics of tamoxifen in patients with breast cancer in Asia.

https://ift.tt/2z142j0

Dermoscopy of folliculosebaceous cystic hamartoma

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2O2VzS2

Delayed angioedema of the unilateral tongue associated with angiotensin II receptor blocker in a patient with polypharmacy

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2OL7pWl

Volume outlier benchmark proposal for Australian Mohs surgery

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2O2YEBJ

Children with unilateral cochlear nerve canal stenosis have bilateral cochleovestibular anomalies

The Laryngoscope, EarlyView.


https://ift.tt/2PTiIrS

Safety and efficacy of Early injection laryngoplasty in pediatric patients

The Laryngoscope, EarlyView.


https://ift.tt/2D29yqq