Dynamics of Plasma Cytokines in a Patient with Deficiency of Interleukin-36 Receptor Antagonist Successfully Treated with Anakinra

Generalized pustular psoriasis (GPP) is an autoinflammatory disease characterized by abrupt-onset episodes of erythematous skin plaques with countless pustules, fever, marked neutrophilia and increased acute phase reactants (APR).¹ Loss-of-function mutations in the IL36RN gene, encoding for interleukin (IL)-36 receptor antagonist (IL-36Ra), have been described in a significant proportion of GPP patients.^2,3 Previous studies have shown in vitro and ex vivo enhanced production of pro-inflammatory cytokines (IL-1, IL-6 and IL-8) and successful outcomes with anti-IL-1 drugs in patients carrying IL36RN mutations.^1,2 However, little is known about the correlation of plasma cytokines, inflammatory markers and clinical follow-up, before and after treatment with anti-IL-1 drugs.

This article is protected by copyright. All rights reserved.

http://ift.tt/2yJNrTx

Comment on: A Visual Literacy Course for Dermatology Trainees

We would like to congratulate Griffin and colleagues on their report of an innovative training programme in visual literacy for dermatology registrars (residents).¹ Our experience of visual literacy training for registrars in South London resonates with that of the Manchester group, and we would like to add to this by describing our observation of some additional qualitative benefits which may be derived from such training. Training similar to that described by the Griffin et al was delivered to 10 dermatology registrars at the Dulwich Picture Gallery in London, England from September 2016 – January 2017 in 5 one hour sessions. Baseline and post-course assessments, scored on the unique accurate observations method described by Huang et al,² were carried out and demonstrated an increase in the number of unique accurate observations per image following the course compared to pre-course assessment.

This article is protected by copyright. All rights reserved.

http://ift.tt/2hI0zgC

Safe Administration of An Anti-PD-1 Antibody to Kidney-transplant Patients: 2 Clinical Cases and Review of the Literature

Antiprogrammed cell-death protein 1 (PD-1) antibodies have revolutionized therapy of metastatic melanoma and other tumors, but some subgroups of patients such as immunosuppressed patients after solid-organ transplantation, have regularly been excluded from clinical studies. We report 2 cases of kidney-transplant patients who received an anti-PD-1 antibody to treat metastatic melanoma. Treatment was tolerated well with no relevant adverse events and stable kidney functions, but the melanoma progressed in both patients. Factors potentially affecting risk of allograft rejection and response to treatment, for example, immunosuppressive regimen and therapeutic sequence, are discussed on the basis of current literature. Further studies are necessary to determine the risk of allograft rejection and the therapeutic benefit of anti-PD-1 antibodies for organ-transplanted patients, in particular as these checkpoint inhibitors have become therapeutic standard in a variety of tumors other than melanoma.

http://ift.tt/2gDIWij

Relationship Between PD-L1 Expression and CD8+ T-cell Immune Responses in Hepatocellular Carcinoma

As PD-1/PD-L1 immune checkpoint inhibitors exhibited promising clinical outcomes in various types of solid tumors, PD-1/PD-L1 blockades have been explored for the treatment of hepatocellular carcinoma (HCC). However, the association of PD-L1 with antitumor immunoregulation is not clearly defined in HCC. Here, we evaluated the characteristics of PD-L1 expression, CD8+ T-cell infiltration and their relationship in HCC. A total of 411 resected tumor specimens from HCC patients were immunostained for PD-L1 and CD8. Only 78 (19%) cases showed ≥5% membranous PD-L1 expression on tumor cells, although a significantly positive correlation was found between PD-L1 expression and CD8+ T-cell densities. Moreover, patients with higher tumor PD-L1 expression also showed a higher hepatitis B virus load, which was also related to increased CD8 infiltration. Survival analysis suggested that both tumor and stroma PD-L1 status did not significantly affect overall survival or recurrence-free survival in patients. Although high CD8+ T-cell density was overall associated with better overall survival and recurrence-free survival, its favorable prognostic value was eliminated by high tumor PD-L1 expression. Further flow cytometric and enzyme-linked immunosorbent assay (ELISA) results from the coculture of HCC cell lines with specific CD8+ cytotoxic T lymphocytes (CTLs) demonstrated that CD8+ CTLs remarkably upregulated PD-L1 expression on tumor cell lines by HLA class-I specificity, and the overexpression of tumor PD-L1 impaired interferon-γ secretion by CD8+ CTLs in a negative feedback regulation mechanism. In conclusion, our findings reveal an interaction between PD-L1 expression and CD8+ T-cell immunity in HCC, although PD-L1 is not a prognostic factor for the patients.

http://ift.tt/2gDIMHJ

DCOne as an Allogeneic Cell-based Vaccine for Multiple Myeloma

Multiple myeloma (MM) is characterized by progressive immune dysregulation, loss of myeloma-specific immunity, and an immunosuppressive milieu that fosters disease growth and immune escape. Accordingly, cancer vaccines that reverse tumor-associated immune suppression represent a promising therapeutic avenue of investigation. We examined the potential of an allogeneic cellular vaccine to generate immune responses against MM tumor cells. The DCOne vaccine is comprised of a human myeloid leukemia cell line differentiated into a fully functional dendritic cell, expressing a range of tumor-associated antigens that are also known targets in MM. We found that the myeloma-specific antigens expressed by the DCOne vaccine can traffic via extracellular vesicles to surrounding antigen-presenting cells, thus stimulating autologous T-cell responses. Indeed, coculture of peripheral blood mononuclear cells from patients with MM with the DCOne vaccine resulted in the expansion of activated CD8+ T cells expressing interferon-γ and perforin, with no significant change in the percentage of CD4+ T cells producing interleukin-10. Further, coculture of patient's tumor cells with peripheral blood mononuclear cells and DCOne induced cytotoxic T-lymphocyte-mediated killing of autologous MM cells. These findings demonstrate that the allogeneic DCOne vaccine can induce T-cell activation and myeloma-specific immunity via cross presentation of antigens by native antigen-presenting cells.

http://ift.tt/2gECDLs

Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States: An Expanded Access Program

KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody, for patients with advanced melanoma before its regulatory approval. Patients with unresectable stage III/IV melanoma that progressed after standard-of-care therapy, including ipilimumab and, if BRAFV600 mutant, a BRAF inhibitor, were eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by immune-related response criteria by investigator review. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the United States, 979 patients enrolled between April and September 2014. Of the 947 evaluable patients, 621 (65.6%) remained on treatment and transitioned to receive commercial pembrolizumab following approval by the Food and Drug Administration, whereas 326 (34.4%) discontinued, most commonly for disease progression (39.6%) or death (26.4%). Objective response rate was 14.5% (95% confidence interval, 12.2%–16.8%) in the treated population (n=947) and 22.1% (95% confidence interval, 18.8%–25.5%) in patients who had ≥1 response assessment reported (n=619). Twelve patients achieved complete response. One hundred eighty-one (19.1%) patients experienced ≥1 treatment-related AE, most commonly general disorders (8.0%), skin/subcutaneous tissue disorders (7.3%), and gastrointestinal disorders (6.4%); 29 (3.1%) patients experienced ≥1 grade 3/4 treatment-related AE. Immune-mediated AEs were also reported. There were no treatment-related deaths. The safety and efficacy observed in this expanded access program were consistent with those previously reported for similar populations and support the use of pembrolizumab for patients with advanced melanoma.

http://ift.tt/2gDIGzR

Nivolumab-associated Nephrotic Syndrome in a Patient With Renal Cell Carcinoma: A Case Report

Introduction: Immune checkpoint inhibitors have taken an important place in the treatment of different types of malignancies. These drugs are known to have specific immune-mediated adverse events. We describe a case of severe nephrotic syndrome secondary to treatment with nivolumab in a patient with renal cell carcinoma. Case Presentation: A 62-year-old man was treated with nivolumab for papillary renal cell carcinoma type 2 for 8 weeks when he was admitted to the hospital with a severe nephrotic syndrome and acute kidney injury. Renal biopsy showed focal segmental glomerulosclerosis. Treatment with high-dose corticosteroids had insufficient effect, but the addition of mycophenolate mofetil resulted in remission of the nephrotic syndrome and recovery of renal function. Proteinuria subsequently relapsed during corticosteroid tapering. Conclusions: The time course in this patient strongly suggests that the nephrotic syndrome occurred as an adverse drug reaction to nivolumab treatment. If during nivolumab treatment renal insufficiency, hypoalbuminemia, or proteinuria develops, further analysis for a possible nephrotic syndrome is warranted for early detection and treatment of this life-threatening complication.

http://ift.tt/2gECzeG

The Effect of a Pediatric Intensive Care Severity-Tiered Pathway for Status Asthmaticus on Quality Measures and Outcomes

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


http://ift.tt/2xFvUM7

Longitudinal melanonychia due to voriconazole therapy during treatment of chromoblastomycosis

http://ift.tt/2giIlpy

A feasibility study for a triple-blind randomized controlled trial investigating the effects of oral isotretinoin on mood and quality of life in patients with acne vulgaris

Summary

Isotretinoin is used in the treatment of severe acne vulgaris (AV), but has controversially been associated with depression and suicide. Large prospective studies have failed to translate this clinically. We undertook a feasibility study to investigate the parameters of a triple-blind, randomized controlled trial (RCT) assessing the effect of oral isotretinoin on quality of life (QoL) and mood in patients with AV. Patients meeting the inclusion criteria were randomized for 2 weeks to isotretinoin or doxycycline. Participants completed verified depression and QoL screening questionnaires at baseline and week 2. In total, 194 patients with AV were screened, with 48 meeting the inclusion criteria and 13 of these being willing to participate. The follow-up rate was 92% and questionnaire response rate was 96%. To our knowledge, this is the first study to demonstrate a successful design for a triple-blind RCT investigating the effects of isotretinoin on mood in patients with AV.

http://ift.tt/2ynKRkQ

Unstable Thyroid Function in Older Adults Is Caused by Alterations in Both Thyroid and Pituitary Physiology and Is Associated with Increased Mortality

Thyroid , Vol. 0, No. 0.


http://ift.tt/2ylui7i

87th Annual Meeting of the American Thyroid Association

Thyroid Oct 2017, Vol. 27, No. S1: P-1-A-156.


http://ift.tt/2z6tB0B

Short Call Abstracts

Thyroid Oct 2017, Vol. 27, No. S1: A-166-A-188.


http://ift.tt/2yjUXRP

Short Call Author Abstract Index

Thyroid Oct 2017, Vol. 27, No. S1: A-189-A-191.


http://ift.tt/2z6tzWx

Abstract Author Index

Thyroid Oct 2017, Vol. 27, No. S1: A-157-A-165.


http://ift.tt/2yn38P1

Carcinoma análogo del secretor mamario de glándulas salivales: a propósito de un caso clínico

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Carlota Rovira, Xavier León, Celina P. Vásquez, Montserrat López




http://ift.tt/2xEUb4K

Análisis de supervivencia libre de recaída audiométrica en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Nieves Mata-Castro, Raimon García-Chilleron, Javier Gavilanes-Plasencia, Rafael Ramírez-Camacho, Alfredo García-Fernández, José Ramón García-Berrocal
ObjetivoDescribir los resultados en términos de supervivencia libre de recaída audiométrica y el ritmo de recaída en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides.MétodoEstudio retrospectivo de pacientes, con recaídas audiométricas, en seguimiento desde 1995 hasta 2014, en 2 centros de la Comunidad de Madrid.ResultadosSe evaluaron 31 pacientes con una media de edad de 48,52 años (14,67 DE) de los cuales el 61,3% fueron mujeres. La mayoría de las hipoacusias fueron fluctuantes (48,4%). Solo el 16,1% de los pacientes presentaban enfermedad autoinmune sistémica. Existe una correlación positiva moderada entre ser mujer y presentar afectación sistémica (coeficiente de correlación de Spearman=0,356). La tasa relativa de incidencia de recaída en el primer año en nuestra serie fue de 2,01 recaídas/año con un IC95% (1,32-2,92). El tiempo de supervivencia medio del evento (recaída audiométrica) fue de 5,25 meses (DE 0,756). Con el análisis multivariante, la única variable que consiguió significación estadística fue la edad, con una hazard ratio de 1,032 (IC95%; 1,001-1,063, p=0,043)ConclusionesLa enfermedad inmunomediada del oído interno es una enfermedad crónica con recaídas. La mitad de los pacientes tratados exclusivamente con corticoides recaen antes de los 6 meses de seguimiento. Además, si un paciente no ha presentado recaída, tiene más riesgo de recaer cada año que pasa. El análisis de la supervivencia libre de recaída audiométrica permitirá comparar el efecto de tratamientos futuros y su capacidad para reducir el ritmo de recaídas.ObjectiveTo describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids.MethodRetrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid.ResultsWe evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient=0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043).ConclusionsImmune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses.



http://ift.tt/2kN72vH

Vértigo y mareo en el hospital: frecuentación, flujo y características de los pacientes

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Carmen Bécares Martínez, Marta M. Arroyo Domingo, Aurora López Llames, Jaime Marco Algarra, María M. Morales Suárez-Varela
Introducción y objetivosLos síntomas de vértigo y mareo son frecuentes en la población, se presentan como manifestación de un amplio abanico de enfermedades y habitualmente es difícil realizar un diagnóstico de certeza. El objetivo general de este estudio es obtener la información para evaluar estos síntomas en el entorno hospitalario. Los objetivos específicos son: estimar el peso global que representan estos síntomas en las derivaciones al hospital; conocer las características de los pacientes derivados y detallar el flujo de las consultas.MétodosEstudio descriptivo observacional. Se buscaron las propuestas de consulta realizadas en 2011 y 2012 al hospital por el síntoma de vértigo. Se analizaron características demográficas y clínicas de los pacientes, y administrativas de las derivaciones.ResultadosSe analizaron un total de 558 propuestas correspondientes a 494 pacientes. El vértigo supuso el 0,5% del total de las derivaciones realizadas desde Atención Primaria al hospital. El 63% de la muestra han sido mujeres, con una edad media de 58 años. El 88% de los pacientes fue valorado por Otorrinolaringología y el 24% por Neurología. Un 30,8% consultó en 3 o más ocasiones por el síntoma. El 16% fue valorado por enfermedad psiquiátrica en el hospital.ConclusionesEl vértigo como síntoma supone una carga significativa en el ámbito hospitalario. Los pacientes que lo presentan consultan en múltiples ocasiones y son valorados en distintas especialidades. En ciertos casos, el flujo de pacientes puede resultar excesivamente dinámico e ineficaz. En nuestro entorno, Otorrinolaringología es el principal receptor de pacientes con síntomas de vértigo y mareo.Introduction and objectivesVertigo and dizziness as symptoms are frequent in the population. They are present in a wide range of pathologies and it is usually difficult to make an accurate diagnosis. The general objective of this study is to obtain the information to evaluate vertigo and dizziness in the hospital setting. The specific objectives are: to estimate the burden of these symptoms at the hospital; to study patients' conditions and to detail the flow of these patients inside the hospital.MethodsObservational descriptive study. We made a search of the referral proposals made in 2011 and 2012 to the hospital because of vertigo symptoms. The patients' demographic and clinical characteristics, and the administrative details of the referrals were analysed.ResultsA total of 558 proposals were analysed corresponding to 494 patients. Vertigo accounted for 0.5% of all referrals made from Primary Care to the hospital. Sixty-three percent of the sample were women; the average age was 58 years. Eighty-eight percent of the patients were evaluated by Otorhinolaryngology, 24% by Neurology. Thirty point eight percent consulted on 3 or more occasions for the symptom. Sixteen percent were assessed for psychiatric conditions in the hospital.ConclusionsVertigo as a symptom is a significant burden in the hospital setting. The patients who suffer it consult on several occasions and are assessed by different specialties. This implies in some cases an excessive and ineffective flow of patients. In our setting, otorhinolaryngology is the main department to treat vertigo and dizziness patients.



http://ift.tt/2kOzGwD

Significado pronóstico de la extensión extranodal en pacientes con carcinomas escamosos de cabeza y cuello cN0 con metástasis ganglionares ocultas

Publication date: Available online 13 October 2017
Source:Acta Otorrinolaringológica Española
Author(s): Joan Lop, Antoni Rigó, Alberto Codina, Julia de Juan, Miquel Quer, Xavier León
Introducción y objetivosLa presencia de extensión extranodal en adenopatías metastásicas de pacientes con carcinoma escamoso de cabeza y cuello es un reconocido factor de mal pronóstico. Sin embargo, pocos estudios analizan específicamente su significado en pacientes sin evidencia clínica de extensión ganglionar en el momento del diagnóstico inicial.Material y métodosEstudio retrospectivo de 348 pacientes con carcinoma escamoso de cabeza y cuello cN0 tratados con un vaciamiento cervical electivo. Se evaluó la presencia de metástasis ganglionares ocultas con extensión extranodal y se analizó su impacto sobre la supervivencia.ResultadosEl porcentaje de pacientes con metástasis ganglionares ocultas fue del 33%. De estos, un 23,5% presentaron al menos una adenopatía metastásica con extensión extranodal. Existieron diferencias significativas en la supervivencia específica en función del estatus ganglionar. La supervivencia a los 5 años para los pacientes sin afectación ganglionar patológica fue del 90%, para aquellos con metástasis ganglionares ocultas sin extensión extranodal, del 71,2%, y para los pacientes con metástasis ganglionares ocultas con extensión extranodal, del 25,9% (p=0,0001). En un estudio multivariante la presencia de metástasis ganglionares ocultas con extensión extranodal fue el factor relacionado de forma más importante con la supervivencia. La incorporación de la extensión extranodal como criterio de clasificación histopatológico en la octava edición del TNM mejoró la capacidad pronóstica en relación con las ediciones anteriores.ConclusionesLa presencia de adenopatías metastásicas con extensión extranodal es un factor de mal pronóstico en pacientes con carcinoma escamoso de cabeza y cuello sin evidencia clínica de afectación regional en el momento del diagnóstico de la enfermedad.Introduction and objectivesExtranodal extension in nodal metastases is an independent adverse prognostic factor in head and neck squamous cell carcinoma patients. However, few studies specifically address the subgroup of patients with no clinical evidence of nodal disease.Material and methodsWe retrospectively analysed data from 348 head and neck squamous cell carcinoma patients without any previous treatment and lacking clinical or radiological evidence of neck node metastases during the initial workup, treated with an elective neck dissection between 1992-2014. The incidence of occult metastatic neck nodes with extranodal extension and the impact of extranodal extension in survival were evaluated.ResultsThe proportion of patients with occult neck node metastases was 33%. Of these, 23.5% had at least one metastatic neck node with extranodal extension. There were significant differences in the disease-specific survival rate according to neck node status. Five-year disease-specific survival for patients without histopathological metastases was 90%, for patients with occult neck node metastases without extranodal extension it was 71.2%, and for patients with occult neck node metastases with extranodal extension it was 25.9% (P=.0001). The multivariate analysis revealed that the presence of occult node metastases with extranodal extension was the factor with strongest impact on survival. The inclusion of the extranodal extension as a criterion of histopathological evaluation in the 8th TNM classification edition improves the prognostic capacity compared to previous TNM editions.ConclusionsAppearance of metastatic neck nodes with extranodal extension is an adverse prognostic factor in head and neck squamous cell carcinoma patients without clinical evidence of regional disease during the initial workup of the tumour.



http://ift.tt/2xEU5tU

Postoperative care after tonsillectomy: what's the evidence?.

Purpose of review: The purpose of this review is to evaluate the current literature regarding postoperative management after tonsillectomy in children. Recent findings: Controversy remains regarding the ideal medication regimen to manage pain after tonsillectomy. Acetaminophen and ibuprofen are routinely used, although concerns of more severe postoperative hemorrhage with ibuprofen remain. Narcotics are prescribed commonly, but with extreme caution in children with severe obstructive sleep apnea. Although not always utilized by the authors, additional adjunctive medications such as perioperative dexamethasone, ketamine, and local infiltration of lidocaine into tonsillar pillars may decrease postoperative pain. Systematic reviews have shown that dexamethasone does not increase risk of posttonsillectomy bleeding. Summary: Adenotonsillectomy is one of the most common procedures performed on children and may have significant morbidity from postoperative pain and bleeding. Managing pain remains challenging and the optimal treatment regimen has not been definitively identified. Many medications and alternative therapies have been studied and suggest possible benefit. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2yiDqvX

Innate sensing of cancer's non-immunologic hallmarks

Ruth Seelige | Stephen Searles | Jack D Bui

http://ift.tt/2yfChVF

Ethical Challenges with Treating Non-Adherent Patients in a Group Practice Setting

http://ift.tt/2xEpc8Y

Omalizumab Response in Patients with Chronic Idiopathic Urticaria: Insights from the XTEND-CIU Study

http://ift.tt/2kNXgcK

Adams-Oliver Syndrome With Moyamoya Disease for Cerebral Revascularisation Surgery.

No abstract available

http://ift.tt/2yKKcuZ

GSK Shingles Vaccine Shingrix Gets First Okay in Canada

Shingrix, given in two doses 2 to 6 months apart, is for adults aged 50 years and older. It was shown to achieve ≥90% efficacy in clinical trials.
International Approvals

http://ift.tt/2yiUUWf

THE 2017 13TH ANNUAL DAVID W. KENNEDY, MD, LECTURE The evolution of outcomes in sinus surgery for chronic rhinosinusitis: past, present, and future

Abstract

This is an edited transcript from the 2017 13th Annual David W. Kennedy, MD, Lecture, presented to the American Rhinologic Society during the 63rd Annual Meeting.

http://ift.tt/2xDAJp8

A validated model for the 22-item Sino-Nasal Outcome Test subdomain structure in chronic rhinosinusitis

Background

Previous studies have identified subdomains of the 22-item Sino-Nasal Outcome Test (SNOT-22), reflecting distinct and largely independent categories of chronic rhinosinusitis (CRS) symptoms. However, no study has validated the subdomain structure of the SNOT-22. This study aims to validate the existence of underlying symptom subdomains of the SNOT-22 using confirmatory factor analysis (CFA) and to develop a subdomain model that practitioners and researchers can use to describe CRS symptomatology.

Methods

A total of 800 patients with CRS were included into this cross-sectional study (400 CRS patients from Boston, MA, and 400 CRS patients from Reno, NV). Their SNOT-22 responses were analyzed using exploratory factor analysis (EFA) to determine the number of symptom subdomains. A CFA was performed to develop a validated measurement model for the underlying SNOT-22 subdomains along with various tests of validity and goodness of fit.

Results

EFA demonstrated 4 distinct factors reflecting: sleep, nasal, otologic/facial pain, and emotional symptoms (Cronbach's alpha, >0.7; Bartlett's test of sphericity, p < 0.001; Kaiser-Meyer-Olkin >0.90), independent of geographic locale. The corresponding CFA measurement model demonstrated excellent measures of fit (root mean square error of approximation, <0.06; standardized root mean square residual, <0.08; comparative fit index, >0.95; Tucker-Lewis index, >0.95) and measures of construct validity (heterotrait-monotrait [HTMT] ratio, <0.85; composite reliability, >0.7), again independent of geographic locale.

Conclusion

The use of the 4-subdomain structure for SNOT-22 (reflecting sleep, nasal, otologic/facial pain, and emotional symptoms of CRS) was validated as the most appropriate to calculate SNOT-22 subdomain scores for patients from different geographic regions using CFA.

http://ift.tt/2kM5YYZ

Clinical Validation of ThyroidPrint: A Gene Expression Signature for Diagnosis of Indeterminate Thyroid Nodules

Condition:   Indeterminate Thyroid Cytology
Intervention:   Diagnostic Test: In vitro Diagnostic
Sponsors:   Pontificia Universidad Catolica de Chile;   Geneprodx
Recruiting

http://ift.tt/2i8SHZw

Hypochlorous acid is anti-pruritic and anti-inflammatory in a mouse model of atopic dermatitis

Abstract

Background

It has been reported that topical hypochlorous acid (HOCl) formulations lead to relief of itch in human patients with atopic dermatitis, however the specific anti-pruritic mechanism of action remains unclear.

Objective

To confirm itch relief and reduction of lesions in a mouse model of atopic dermatitis and to elucidate possible HOCl's mode of action.

Methods

In this study, the effects of topical administration of HOCl hydrogel (0.05%) on atopic dermatitis-like lesions in NC/Nga mice model as well as in vitro effects of HOCl on dorsal root ganglia neurons and mouse bone marrow derived dendritic cells (mBMDC) were investigated. NC/Nga mice were sensitized with house dust mite allergen and treated topically with HOCl hydrogel both preventively as well as therapeutically against established lesions. Allergen challenge was continued during HOCl hydrogel application.

Results

Treatment with HOCl hydrogel prevented the development of lesions and scratching bouts during the whole observation period. When administered after full development of lesions, HOCl reduced lesions and scratching behaviour to a similar extent as a positive control 0.1% betamethasone dipropionate ointment. The reduced inflammatory response by HOCl treatment was demonstrated by reduced secretion of inflammatory cytokines in affected skin tissue from NC/Nga mice. In addition, HOCl significantly reduced IL-12 production in mBMDC. The diminished scratching behaviour was confirmed by impaired response to several pruritogens in dorsal root ganglia neurons excised from NC/Nga mice after termination of the studies. The response to the stimuli was also reduced by pre-incubation of sensory neurons from untreated BALB/c mice with 0.0001% HOCl.

Conclusions and Clinical Relevance

These data indicate a direct reduction of sensory response by HOCl, leading to significantly reduced itch and inflammation in vivo.

This article is protected by copyright. All rights reserved.

http://ift.tt/2g8yM97

Enhancing antibiotic stewardship by tackling ‘spurious’ penicillin allergy

Abstract

Approximately 90-99% of patients with a label of penicillin allergy (PenA) are not allergic when comprehensively investigated. An inaccurate label of PenA has major public health implications – longer hospital stay, more frequent hospital admissions, greater use of fluoroquinolones, glycopeptides, cephalosporins and other expensive antibiotics resulting in significantly higher costs to the health service and predisposing to Clostridium difficile, meticillin-resistant Staphylococcus aureus infections and vancomycin resistant enterococcus.

We describe lessons learnt from recent studies regarding possible reasons contributing to an inaccurate label of PenA as well as propose a concerted multidisciplinary approach to address this important public health problem. Given the unmet need for allergy services in the UK and several other countries and knowledge gaps regarding PenA amongst health care professionals, we describe the potential role for a computerised clinical decision support system to enable nonspecialists rapidly identify and de-label 'low risk' hospitalised patients with a label of PenA thereby obviating the need for allergy tests. This approach however needs rigorous evaluation for feasibility, safety, patient & physician acceptability, cost effectiveness and its compatibility with information technology systems currently employed in the health service.

This article is protected by copyright. All rights reserved.

http://ift.tt/2yf2Ha6

Trichodysplasia spinulosa associated with HIV infection: clinical response to acitretin and valganciclovir

http://ift.tt/2kQb0Uz

Stevens–Johnson syndrome induced by modafinil

http://ift.tt/2kQaW7h

Prognostic significance of standardized uptake value on F18-FDG PET/CT in patients with extranodal nasal type NK/T cell lymphoma: A multicenter, retrospective analysis

Publication date: Available online 12 October 2017
Source:American Journal of Otolaryngology
Author(s): Kyoungjune Pak, Bum Soo Kim, Keunyoung Kim, In Joo Kim, Sungmin Jun, Young Jin Jeong, Hye Kyung Shim, Sung-Dong Kim, Kyu-Sup Cho
ObjectivesThe purpose of this study was to evaluate the value of parameters assessed with F18-flurodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in predicting relapse free survival and overall survival in patients with extranodal nasal type NK/T cell lymphoma.MethodsThirty-six patients with extranodal nasal type NK/T cell lymphoma, and who underwent PET/CT prior to curative treatment, were enrolled at five institutions. Volumes of interest covering the entire tumor volume were delineated on PET/CT images, and the maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using thresholds of 40% of SUVmax. Furthermore, we compared the difference in F18-FDG avidity according to Epstein-Barr virus (EBV) infection status.ResultsThe SUVmax (p=0.041) and SUVmean (p=0.049) in patients who died were higher than the respective values of those who survived. A higher TLG (>45.8) was associated with relapse free survival (HR 7.856, p=0.034). Ann Arbor stage (III–IV, HR 14.12, p=0.004), and a higher SUVmax (>12.6, p=0.024) and SUVmean (>6.4, p=0.024) were associated with poor survival. However, neither the MTV nor the TLG (volumetric parameters) were significant predictors of death. The PET parameters SUVmax (p=0.181), SUVmean (p=0.237), MTV (p=0.636), and TLG (p=0.469) did not differ significantly between patients with and without EBV infections.ConclusionsHigh TLG was the only significant predictive factor on relapse free survival. The SUVmax and SUVmean measured by F18-FDG PET/CT could be significant prognostic factors in patients with extranodal nasal type NK/T cell lymphoma.



http://ift.tt/2ykF0wQ

Activation of cannabinoid receptor 1 is involved in protection against mitochondrial dysfunction and cerebral ischaemic tolerance induced by isoflurane preconditioning

Abstract

Background

Isoflurane preconditioning (IPC) induces cerebral ischaemic tolerance, but the mechanism remains poorly understood. The aim of this study was to determine changes in mitochondrial function in the brain after IPC, and whether the cannabinoid receptor 1 (CB1R) could be involved in the mechanism of mitochondrial protection mediated by IPC.

Methods

Adult male Sprague–Dawley rats were pretreated with isoflurane 2% for 1 h day⁻¹, for 5 days consecutively, and then subjected to 120 min right middle cerebral artery occlusion. Cannabinoid receptor 1 expression in the cellular and mitochondrial membrane was measured. The CB1R agonist HU-210 was administered alone, or the antagonists AM251 and SR141716A were given to the animals before each preconditioning. Neurological scores, infarct volume, apoptosis, and mitochondrial function were examined after middle cerebral artery occlusion.

Results

Expression of CB1R on cellular and mitochondrial membranes was increased 6 h after preconditioning. Both IPC and HU-210 administration before middle cerebral artery occlusion improved neurological outcomes and reduced infarct volume. Isoflurane preconditioning increased the expression of the anti-apoptotic proteins Bcl-2 and Bcl-X_L and reduced apoptosis in neurones. Isoflurane preconditioning and HU-210 also markedly preserved the activity of respiratory chain complexes, reduced mitochondrial radical generation, preserved mitochondrial membrane potential, and inhibited mitochondrial permeability transition pore opening. Cannabinoid receptor 1 antagonists abolished the improvement in mitochondrial function and the neuroprotective effects induced by IPC.

Conclusions

Our results indicate that IPC elicits brain ischaemic tolerance and mitochondrial protection by activating the CB1R, which provides a new mechanism for IPC-induced neuroprotection against cerebral ischaemia.

http://ift.tt/2zkBJeN

Early pitfalls in establishing the British Journal of Anaesthesia

'Those who do not remember the past are condemned to repeat it.'George Santayana (1863-1952)

http://ift.tt/2z47bNy

Effectiveness of enhanced pulse oximetry sonifications for conveying oxygen saturation ranges: a laboratory comparison of five auditory displays

Abstract

Background

Anaesthetists monitor auditory information about a patient's vital signs in an environment that can be noisy and while performing other cognitively demanding tasks. It can be difficult to identify oxygen saturation (SpO2) values using existing pulse oximeter auditory displays (sonifications).

Methods

In a laboratory setting, we compared the ability of non-clinician participants to detect transitions into and out of an SpO2 target range using five different sonifications while they performed a secondary distractor arithmetic task in the presence of background noise. The control sonification was based on the auditory display of current pulse oximeters and comprised a variable pitch with an alarm. The four experimental conditions included an Alarm Only condition, a Variable pitch only condition, and two conditions using sonifications enhanced with additional sound dimensions. Accuracy to detect SpO2 target transitions was the primary outcome.

Results

We found that participants using the two sonifications enhanced with the additional sound dimensions of tremolo and brightness were significantly more accurate (83 and 96%, respectively) at detecting transitions to and from a target SpO2 range than participants using a pitch only sonification plus alarms (57%) as implemented in current pulse oximeters.

Conclusions

Enhanced sonifications are more informative than conventional sonification. The implication is that they might allow anaesthetists to judge better when desaturation decreases below, or returns to, a target range.

http://ift.tt/2zl4KXO

Drug safety in paediatric anaesthesia

British Journal of Anaesthesia, 2017; 118(5): 670–9, DOI 10.1093/bja/aex072

http://ift.tt/2z61n67

Is postspinal hypotension a sign of impaired cardiac performance in the elderly? An observational mechanistic study

Abstract

Background

We have previously reported that stroke volume is reduced in a majority of elderly patients undergoing surgical repair of hip fracture before and after intrathecal injection of anaesthetic. We aimed to investigate these observations further in a prospective study of elderly patients undergoing elective hip or knee arthroplasty under spinal anaesthesia.

Methods

Patients ≥65 yr undergoing elective arthroplasty were monitored with LiDCOplus™ preoperatively (baseline), before and continuously for 45 min after spinal anaesthesia. Postspinal hypotension was defined as systolic blood pressure (bp) < 100 mm Hg or > 30% decrease from baseline. Associations between post-spinal hypotension and haemodynamic changes before (i.e. between baseline and before injection) spinal anaesthesia were analysed by logistic regression analysis.

Results

Twenty patients with a mean age of 74 (range 66–89) yr were included. Stroke volume index decreased by 14% (95% CI 9.3%–19%) before spinal anaesthesia. When patients were categorised according to post-spinal hypotension (Y/N) the patterns of haemodynamic changes differed. In the hypotensive patients, cardiac index progressively decreased whereas it increased initially in the non-hypotensive patients. Reduction of cardiac index from baseline before spinal anaesthesia was associated with increased risk of hypotension: OR 0.79 (95% CI 0.60, 0.91). The predictive value of reduced cardiac index was good (AUC under ROC curve 0.91).

Conclusions

A decrease in cardiac output from baseline before spinal anaesthesia and an inability to increase it after induction may be important features of postspinal hypotension in elderly patients.

http://ift.tt/2zl4Z58

Low end-tidal CO 2 as a real-time severity marker of intra-anaesthetic acute hypersensitivity reactions

Abstract

Background

Prompt diagnosis of intra-anaesthetic acute hypersensitivity reactions (AHR) is challenging because of the possible absence and/or difficulty in detecting the usual clinical signs and because of the higher prevalence of alternative diagnoses. Delayed epinephrine administration during AHR, because of incorrect/delayed diagnosis, can be associated with poor prognosis. Low end-tidal CO₂ (etCO₂) is known to be linked to low cardiac output. Yet, its clinical utility during suspected intra-anaesthetic AHR is not well documented.

Methods

Clinical data from the 86 patients of the Neutrophil Activation in Systemic Anaphylaxis (NASA) multicentre study were analysed. Consenting patients with clinical signs consistent with intra-anaesthetic AHR to a neuromuscular blocking agent were included. Severe AHR was defined as a Grade 3–4 of the Ring and Messmer classification. Causes of AHR were explored following recommended guidelines.

Results

Among the 86 patients, 50% had severe AHR and 69% had a confirmed/suspected IgE-mediated event. Occurrence and minimum values of arterial hypotension, hypocapnia and hypoxaemia increased significantly with the severity of AHR. Low etCO₂ was the only factor able to distinguish mild [median 3.5 (3.2;3.9) kPa] from severe AHR [median 2.4 (1.6;3.0) kPa], without overlap in inter-quartile range values, with an area under the receiver operator characteristic curve of 0.92 [95% confidence interval: 0.79–1.00]. Among the 41% of patients who received epinephrine, only half received it as first-line therapy despite international guidelines.

Conclusions

An etCO₂ value below 2.6 kPa (20 mm Hg) could be useful for prompt diagnosis of severe intra-anaesthetic AHR, and could facilitate early treatment with titrated doses of epinephrine.

Clinical trial registration

NCT01637220.

http://ift.tt/2z6rppM

Changes in platelet Bax levels contribute to impaired platelet response to thrombin after cardiopulmonary bypass: prospective observational clinical and laboratory investigations

Abstract

Background

Anucleate platelets can undergo apoptosis in response to various stimuli, as do nucleated cells. Cardiopulmonary bypass (CPB) causes platelet dysfunction and can also activate platelet apoptotic pathways. We therefore evaluated time-dependent changes in blood platelet Bax (a pro-apoptotic molecule) levels and platelet dysfunction after cardiac surgery.

Methods

We assessed blood samples obtained from subjects having on-pump or off-pump coronary artery bypass graft surgery (n=20 each). We also evaluated the in vitro effects of platelet Bax increase in eight healthy volunteers.

Results

Thrombin-induced platelet calcium mobilisation and platelet-surface glycoprotein Ib (GPIb) expression were lowest at weaning from CPB and did not recover on postoperative day one. On-pump surgery increased platelet expression of Bax, especially the oligomerised form, along with translocation of Bax from the cytosol to mitochondria and platelet-surface tumour necrosis factor-alpha (TNF-α)–converting enzyme (TACE) expression. In contrast, mitochondrial cytochrome c expression was reduced. While similar in direction, the magnitude of the observed changes was smaller in patients having off-pump surgery. In vitro, a cell-permeable Bax peptide increased platelet Bax expression to the same extent seen during bypass and produced similar platelet changes. These apoptotic-like changes were largely reversed by Bcl-xL pre-administration, and were completely reversed by combined application of inhibitors that stabilise outer mitochondrial membrane permeability and TACE.

Conclusions

CPB increases platelet Bax expression, which contributes to reduced platelet-surface GPIb expression and thrombin-induced platelet calcium changes. These changes in platelet apoptotic signalling might contribute to platelet dysfunction after CPB.

Clinical trial registration

UMIN Clinical Trials Registry (number UMIN000006033).

http://ift.tt/2zl4iZC

Outcomes of pediatric delayed facial palsy after head trauma

Publication date: Available online 13 October 2017
Source:Auris Nasus Larynx
Author(s): Liping Li, Peng Xu, Aiyan Jin, Wenna Zuo, Xiaoming Su, Hongqin Wang, Yefeng Li, Xue Jiang
ObjectiveTo analyze clinical outcomes of delayed facial palsy after head trauma in the pediatric population.MethodsA total of 45 pediatric cases with delayed facial palsy after head trauma were conservatively or surgically treated in our hospital between January 2009 and January 2015, and they were followed up for one year after the corresponding treatment. The clinical data were collected and the outcomes of facial nerve were analyzed.ResultsDuring the one-year follow-up, 33 cases (82.5%) completely recovered, and 5 cases (12.5%) recovered to Grade II among the 40 cases accepting conservative treatment. For the 5 surgically treated cases, 4 cases (80.0%) recovered to Grade I or Grade II, and one case recovered to Grade III.ConclusionThe outcomes of pediatric delayed facial palsy after head trauma were generally satisfactory.



http://ift.tt/2z6e15e

A Herald of Plasma Cell Myeloma: A Report of Malignant Plasma Cells Identified in Parathyroid Adenoma and a Review of Non-parathyroid Malignancies in Parathyroid Glands

Abstract

Involvement of the parathyroid glands by non-parathyroid neoplasia is an infrequent event. Rare cases of metastases to the parathyroid gland have been reported in parathyroidectomies and autopsies of patients with known solid or hematopoietic malignancies. Here, we present a case of atypical clonal plasma cells incidentally identified within a parathyroid adenoma resected for hyperparathyroidism and hypercalcemia, which served as the sentinel event for a subsequent diagnosis of plasma cell myeloma. To our knowledge, this is the only reported case of a hematopoietic malignancy involving a parathyroid adenoma and the only reported case of malignant hematopoietic cells initially detected in parathyroidectomy.

http://ift.tt/2ymk7kC

Treatment of pediatric anogenital condyloma acuminata with sinecatechins ointment

http://ift.tt/2g7PVQ2

Local hyperthermia therapy for refractory cutaneous Mycobacterium marinum infection

http://ift.tt/2gg1lF2

Spontaneous closure of ventricular septal perforation following percutaneous coronary intervention for acute myocardial infarction

We report on an 84-year-old woman with anteroseptal acute myocardial infarction. Emergency coronary angiography revealed the occlusion of proximal left anterior descending artery without collateral circulation, and percutaneous coronary intervention was performed. Two drug eluting stents were implanted, and the procedure was concluded with thrombolysis in myocardial infarction grade 3 without complications. Postoperatively, no murmur was audible on auscultation and no shunt flow was observed on transthoracic echocardiography (TTE), and normal blood pressure was maintained. On day 2, however, the patient's vital signs deteriorated to a state of shock and systolic murmur appeared at the apical region. TTE showed a left-to-right shunt in the apical septal region, and ventricular septal perforation was diagnosed. Although emergency surgery was considered, the patient's vital signs improved the following day. The disappearance of the cardiac murmur and the shunt was confirmed. The clinical course was uneventful thereafter, and the patient was discharged.

http://ift.tt/2wSv6ij

Worsening Guillain-Barre syndrome: harbinger of IRIS in HIV?

We report an HIV patient aged 38 years with acute inflammatory demyelinating polyradiculoneuropathy subtype of Guillain-Barré syndrome (GBS) as the only manifestation of seroconversion and worsening of GBS being the harbinger of immune reconstitution inflammatory syndrome (IRIS). To date, only 5 cases of GBS during IRIS are reported. They manifested either during the third week or later after starting highly active antiretroviral therapy (HAART). Our patient witnessed worsening weakness by fifth day after starting HAART, even before the occurrence of Pneumocystis jirovecii pneumonia, cautioning one of the impending serious complications of IRIS and helped us initiate steroids at an early date.

http://ift.tt/2yhti3Q

Disfiguring facial pyoderma vegetans with an excellent outcome

We describe a case of disfiguring facial pyoderma vegetans in order to highlight the challenges in managing this rare skin condition and review the literature.

A 54-year-old woman presented to dermatology clinic with a 3-month history of a left-sided facial lesion, which had been treated as an infected sebaceous cyst. The lesion had dramatically increased in size in the weeks prior to presentation. There was a history of Crohn's disease and ileal adenocarcinoma, both of which were in remission. A clinical diagnosis of pyoderma vegetans was made and the patient responded well to immunosuppressive therapy with oral ciclosporin. Carbon dioxide (CO₂) laser resurfacing to residual scarring contributed to an excellent cosmetic result.

http://ift.tt/2wSiasE

Non-progressing cancer patients have persistent B cell responses expressing shared antibody paratopes that target public tumor antigens

Publication date: Available online 12 October 2017
Source:Clinical Immunology
Author(s): Jeff DeFalco, Michael Harbell, Amy Manning-Bog, Gilson Baia, Alexander Scholz, Beatriz Millare, May Sumi, Danhui Zhang, Felix Chu, Christine Dowd, Patricia Zuno-Mitchell, Dongkyoon Kim, Yvonne Leung, Shuwei Jiang, Xiaobin Tang, Kevin S. Williamson, Xiaomu Chen, Sean M. Carroll, Gregg Espiritu Santo, Nicole Haaser, Ngan Nguyen, Eldar Giladi, David Minor, Yann Chong Tan, Jeremy B. Sokolove, Lawrence Steinman, Tito A. Serafini, Guy Cavet, Norman M. Greenberg, Jacob Glanville, Wayne Volkmuth, Daniel E. Emerling, William H. Robinson
There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size. Recombinant antibodies from clonal families bound non-autologous tumor tissue and cell lines, and families possessing immunoglobulin paratope sequence motifs shared across patients exhibited increased rates of binding. We identified antibodies that caused regression of, and durable immunity toward, heterologous syngeneic tumors in mice. Our findings demonstrate convergent functional anti-tumor antibody responses targeting public tumor antigens, and provide an approach to identify antibodies with diagnostic or therapeutic utility.



http://ift.tt/2ykA8I0

Gain-of-function variants in NLRP1 protect against the development of diabetic kidney disease: NLRP1 inflammasome role in metabolic stress sensing?

Publication date: Available online 12 October 2017
Source:Clinical Immunology
Author(s): Jaine Soares, Fernanda Pereira Fernandes, Thiago Andrade Patente, Maria B. Monteiro, Maria C. Parisi, Daniel Giannella-Neto, Maria L. Corrêa-Giannella, Alessandra Pontillo
Although inflammasome plays a well-known role in animal models of renal injury, limited studies in humans are available, and its participation in diabetic kidney disease (DKD) remains unknown. Aim of this study was to elucidate the contribution of inflammasome genetics in the development of DKD in type-1 diabetes (T1D).The association of functional variants in inflammasome genes with DKD was assessed by multivariate analysis in a retrospective and in a prospective cohort.NLRP1 rs2670660 and rs11651270 polymorphisms were significantly associated with a decrease risk to develop DKD (padj<0.01), and rs11651270 also with a lower risk of new renal events during follow-up (padj=0.01). Supporting these findings, diabetes metabolites (glycated albumin and high glucose) were able to modulate NLRP1 expression.This study is the first to suggest a protective role of NLRP1 in DKD, highlighting an emerging role of NLRP1 as a homeostatic factor against metabolic stress.



http://ift.tt/2ggMsCt

Generalized pustular psoriasis triggered by Zika virus infection

Summary

Zika virus is an emerging arbovirus, which is expanding in epidemic proportions through tropical and subtropical areas of the world. Although Zika is linked to a number of congenital and neurological complications, there is scarce knowledge on the impact of ZIKV infection in human skin. We report the case of a 68-year old woman who presented with generalized pustular psoriasis after a preceding and otherwise uneventful episode of ZIKV infection. Based on recent experimental data on the biology of ZIKV infection in the cutaneous environment, we speculate that ZIKV may have directly triggered the development of generalized pustular psoriasis by stimulation of keratinocyte-derived mediators of inflammation and a polyfunctional T-cell driven immune reaction in the cutaneous milieu.

http://ift.tt/2kLScpk

Lymphopenia and fumaric acid esters for psoriasis: a retrospective case series prompted by the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) recommendations

http://ift.tt/2xCseup

Pemphigus vulgaris complicated by extensive keloid scarring

http://ift.tt/2kMLDTd

Novel Program of Using Village Health Workers in Early Detection and Awareness of Head and Neck Cancers: Audit of a Community Screening Program

Abstract

Head and neck cancers together (oral cavity, pharynx and larynx) are sixth commonest worldwide and are the commonest cancers in developing countries. The Cancer Project was started in Kheda/Anand, Gujarat, a harvest land of tobacco. The objective of this programme was to indoctrinate the most vulnerable and the least tended upon; the basics of head and neck cancers via the medium of their own kins. Voluntary village health workers were educated and trained to pick up the early signs of head and neck cancers. Oral self examination was taught to them and they went to peripheral villages to screen the population. They would refer suspicious cases to tertiary healthcare centre. The population was enlightened upon the basics of preventable measures, treatment options and rehabilitation facilities for head and neck cancer patients. Knowledge, attitude and practice analysis was done in the population which showed widespread disbelief and false practices. A population of 26,10,432 was surveyed in 1862 villages of which 10,522 (1.1%) individuals successfully quit the habit. The minimally educated workers referred 3309 suspicious individuals to higher centre of which 1890 (57.11%) tested positive for cancer. A lot of resource is put in research and development of rapid diagnosis and complete cure; however such a minimally costing program may help the most in primordial, primary and secondary level of prevention. Such programs should be advocated on the global platform on lines of Breast Self Examination.

http://ift.tt/2ylGw1Q

Audiological findings in a de novo mutation of ANKRD11 gene in KBG syndrome: Report of a case and review of the literature

Publication date: Available online 12 October 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Pier Marco Bianchi, Alessandra Bianchi, Maria Cristina Digilio, Filippo Maria Tucci, Emanuela Sitzia, Giovanni Carlo De Vincentiis
KBG syndrome is a rare genetic disorder, due to a mutation of ANKRD11, characterized by specific craniofacial dysmorphism, short stature and macrodontia of upper central incisors, intellectual disability and skeletal anomalies. We report a de novo mutation of ANKRD11 gene in a 7-years old girl, affected by KBG syndrome with bilateral conductive hearing loss. The aim of this article was to review the audiological findings of this syndrome.



http://ift.tt/2kJc5gC

Novel Program of Using Village Health Workers in Early Detection and Awareness of Head and Neck Cancers: Audit of a Community Screening Program

Abstract

Head and neck cancers together (oral cavity, pharynx and larynx) are sixth commonest worldwide and are the commonest cancers in developing countries. The Cancer Project was started in Kheda/Anand, Gujarat, a harvest land of tobacco. The objective of this programme was to indoctrinate the most vulnerable and the least tended upon; the basics of head and neck cancers via the medium of their own kins. Voluntary village health workers were educated and trained to pick up the early signs of head and neck cancers. Oral self examination was taught to them and they went to peripheral villages to screen the population. They would refer suspicious cases to tertiary healthcare centre. The population was enlightened upon the basics of preventable measures, treatment options and rehabilitation facilities for head and neck cancer patients. Knowledge, attitude and practice analysis was done in the population which showed widespread disbelief and false practices. A population of 26,10,432 was surveyed in 1862 villages of which 10,522 (1.1%) individuals successfully quit the habit. The minimally educated workers referred 3309 suspicious individuals to higher centre of which 1890 (57.11%) tested positive for cancer. A lot of resource is put in research and development of rapid diagnosis and complete cure; however such a minimally costing program may help the most in primordial, primary and secondary level of prevention. Such programs should be advocated on the global platform on lines of Breast Self Examination.

http://ift.tt/2ylGw1Q

Late recanalization of basilar artery occlusion in a previously healthy 17-month-old child

Endovascular treatment of acute ischemic stroke in children is increasingly being reported, although the time window for intervention is unclear. We describe a previously healthy 17-month-old child who presented with vertebral artery thrombosis and cerebellar stroke requiring posterior fossa decompression. She later progressed to basilar artery thrombosis treated with mechanical thrombectomy 50 hours after clinical decline. At 3 month follow-up, the patient had a modified Rankin Scale score of 0.

http://ift.tt/2yecnSp

Ruptured aneurysm of the artery of Adamkiewicz: is conservative management the standard of treatment in the current era?

Spinal aneurysms are rare lesions, and their natural history is not well known. In particular, aneurysms arising from the artery of Adamkiewicz (AA) are an extremely rare phenomenon, and given the lack of solid evidence its management remains unclear. We present the case of a 54-year-old woman with spinal subarachnoid hemorrhage. A spinal angiogram demonstrated a fusiform aneurysm arising from the AA. Based on the location, the absence of evident collateral circulation to the anterior spinal artery, and the available literature supporting spontaneous thrombosis, we opted for conservative management. Fifteen days after the diagnosis, a spinal angiogram demonstrated complete occlusion of the aneurysm with no visualization of the AA. At 10-month follow-up, the patient was able to walk without assistance. Management should be done on a case-by-case basis with the goal of preserving spinal cord perfusion. Similar to previous articles, our report reinforces conservative management as a valid strategy.

http://ift.tt/2zlLN7C

Intracavitary ultrasound (ICARUS): a neuroendoscopic adaptation of intravascular ultrasound for intracerebral hemorrhage evacuation

Neurosurgeons performing intracerebral hemorrhage evacuation procedures have limited options for monitoring hematoma evacuation and assessing residual hematoma burden intraoperatively. Here, we report the successful neuroendoscopic adaptation of intravascular ultrasound, referred to here as intracavitary ultrasound (ICARUS), in two patients. Pre-evacuation ICARUS demonstrated dense hematomas in both patients. Post-evacuation ICARUS in patient 1 demonstrated significant reduction in clot burden and two focal hyperechoic regions consistent with pockets of hematoma not previously seen with the endoscope or burr hole ultrasound. These areas were directly targeted and resected with the endoscope and suction device. Post-evacuation ICARUS in patient 2 showed significant reduction of hematoma volume without indication of residual blood. ICARUS findings were confirmed on intraoperative DynaCT and postoperative CT 24 hours later. ICARUS is feasibly performed in a hematoma cavity both before and after hematoma aspiration. ICARUS may provide additional information to the operating surgeon and assist in maximizing hematoma removal.

http://ift.tt/2yg0Q50

Flanking the fenestration: circumferential limb-to-limb stent-assisted coiling of a basilar artery fenestration aneurysm

A man aged 61 years with a history of a ruptured basilar fenestration aneurysm underwent unassisted coiling in 1997 and repeat intervention for a recurrence at the aneurysm mouth in 2011. At repeat intervention, the decision was made to intentionally leave some filling at the base to preserve the parent vessels. Stent-assisted coil embolization, although technically feasible, was not pursued given the relative risks of the procedure. In 2017, the patient returned for repeat surveillance and further coil compaction was found at the aneurysm base. With the advent of more compliant woven stents deliverable through 0.017 microcatheters, stent-assisted coiling was possible. This case demonstrates hereto unseen agility afforded by novel low-profile stents allowing a circumferential approach to a basilar artery fenestration aneurysm and resultant limb-to-limb stent-assisted coiling. Techniques described here may be extended to more common anatomic variants that require stent-assisted coiling.

http://ift.tt/2zlfoh9

Prolapsed antrochoanal polyp: an unusual cause of acute adult respiratory distress

Here we describe an adult male who presented with acute dyspnoea and airway occlusion. Nasoendoscopy revealed a large antrochoanal polyp extending from his maxillary sinus to the level of the epiglottis. The patient underwent a successful semi-emergency polypectomy following initial stabilisation with medication.

http://ift.tt/2zliP7V

Unexpected early radiographic findings associated with a ruptured blister-like carotid wall aneurysm

A 33-year-old man presented with aneurysmal subarachnoid hemorrhage from a ruptured, blister-type sidewall internal carotid artery (ICA) aneurysm. Balloon-assisted coiling was performed with residual neck. He subsequently developed severe vasospasm requiring intra-arterial therapies on multiple occasions, during which it was noted that despite widespread vasospasm, a focal segment of the ICA at the site of the aneurysm showed no significant spasm, suggesting underlying vessel abnormality. He was discharged without deficit and scheduled for flow diversion given concern over this potentially pathologic segment of vessel. At time of scheduled flow diversion 6 weeks later, a de novo unstable-appearing 6 mm stalk-like pseudoaneurysm was identified in this segment. Both aneurysms and the diseased vessel were successfully treated with Pipeline stenting, with excellent clinical and angiographic result. This case highlights the need for close angiographic follow-up when there is a heterogeneous vasospastic response in arterial segments adjacent to a ruptured aneurysm.

http://ift.tt/2ygcrkg

Juvenile Trabecular Ossifying Fibroma

Abstract

Benign fibro-osseous lesions within the maxillofacial region represent a heterogeneous group of benign entities with overlapping histologic features. Ossifying fibroma, the rarest of these entities, represents a true neoplasm. Juvenile ossifying fibroma (JOF) is considered an aggressive rapidly growing sub-type. It tends to occur in the first or second decades of life. Based on histological and clinical features it can further be classified into two variants, namely juvenile trabecular ossifying fibroma (JTOF) and juvenile psammomatoid ossifying fibroma (JPOF). JTOF features a proliferation of cellular fibroblastic tissue admixed with woven bone trabeculae with varying histologic presentations. Correlation with clinical and radiographic features is essential to differentiate it from other fibro-osseous lesions. A case of JTOF of the mandible is exemplified in this Sine Qua Non Radiology-Pathology article.

http://ift.tt/2xD15mp

Neuroimaging of Cavernous Malformations

Abstract

Purpose of Review

Cerebral cavernous malformations (CCMs) are common vascular abnormalities often discovered on imaging as an incidental finding. The most common clinical presentations of CCMs include seizure, headache, focal neurological deficits, and intracranial hemorrhage. This article discusses the most recent guidelines including imaging diagnostic criteria and radiographic standards of CCMs and reviews the utility of currently available imaging techniques.

Recent Findings

Gradient echo T2*-weighted imaging and susceptibility-weighted imaging are the recommended imaging protocols for evaluation of suspected CCMs. Diffusion tensor imaging-based tractography provides visualization of the eloquent white matter tracks in the brain. This imaging is increasingly used in clinical practice to assist in selecting the optimal surgical approach, especially for brainstem lesions. Quantitative susceptibility mapping and dynamic contrast-enhanced quantitative perfusion are presently considered experimental. Its proposed value might prove helpful in the future to monitor disease activity and response to treatments.

Summary

The choice of imaging modality of CCMs depends on the goals the clinician expects to achieve, such as establishing the initial diagnosis, follow-up and monitoring disease activity, preoperative, intraoperative, and postoperative evaluation, or research and experimental work on patients with CCM.

http://ift.tt/2ykajI4

Role of transoesophageal echocardiography in renal cell carcinoma: a brief review

Transoesophageal echocardiography (TOE) is regularly used in cardiac and also increasingly in non-cardiac surgeries. It has a leading role in the perioperative management of renal cell carcinoma with tumour extension into inferior vena cava. We report two cases in which TOE was of immense help for patient management. This report highlights the two cases where intraoperative TOE was of immense help to establish diagnosis, to modify surgical plan, to guide the surgeon during clamp placement, to monitor cardiac function, to rule out tumour embolism and to confirm the complete removal of tumour thrombus.

http://ift.tt/2g92JWy

So near, yet so far: access to safe abortion services remains elusive for poor women in India

In this case study, we describe our experiences with a woman employed as a housemaid who sought unsafe abortion services from a private doctor. This was her sixth pregnancy, after previously giving birth to one son and two daughters and undergoing two induced abortions. Her husband remained opposed to the use of contraception. Initially, she had sought medical termination of pregnancy through a government hospital but was denied because of procedural delays, specifically the non-availability of an ultrasonography report consequent to a lack of proof of identity (ie, the AADHAAR card, a unique identification card for recording biometric and demographic data in India). She finally sought the services of an unqualified private physician and received oral abortifacient agents. Consequently, she was required to seek treatment for bleeding per vaginum from the dispensary staff at a government hospital. We note that many such incidents occur in our daily practice but remain unnoticed and undocumented. Although this patient was eligible for sterilisation (ie, tubectomy), her husband was uncooperative. This case illustrates the lack of decision-making power experienced by Indian women who have a low societal status.

http://ift.tt/2yeRqqr

Iron deficiency anaemia in a coeliac: a cause for concern?

A 70-year-old woman with a 15-year history of coeliac disease was admitted for treatment and investigation of symptomatic anaemia. Of note, she was recently commenced on aspirin therapy for retinal artery occlusion. This followed a normal gastro-duodenoscopy, colonoscopy and CT abdomen as workup for iron deficiency anaemia. On this occasion, the patient was further investigated with small bowel capsule endoscopy. This revealed an ulcerated lesion in her proximal jejunum suspicious for malignancy, namely lymphoma. A biopsy of the lesion confirmed adenomatous changes and high-grade dysplasia without malignant changes. Given the endoscopic appearances of the lesion, she was further evaluated with a small bowel MRI. This revealed a 3 cm lesion with associated lymphadenopathy but no distant metastases. She proceeded to resection of her small bowel which confirmed an invasive adenocarcinoma of her proximal jejunum. She is currently undergoing adjuvant chemotherapy on an outpatient basis.

http://ift.tt/2g5JPjg

Transient global amnesia following a whole-body cryotherapy session

Whole-body cryotherapy (WBC), which consists of a short exposure to very cold and dry air in special 'cryo-chambers', is believed to reduce inflammation and musculoskeletal pain as well as improve athletes' recovery. This is the case of a 63-year-old male, who presented with transient global amnesia (TGA) after undertaking a WBC session. TGA is a clinical syndrome characterised by a sudden onset of anterograde amnesia, sometimes coupled with a retrograde component, lasting up to 24 hours without other neurological deficits. Even though the patient completely recovered, as expected, in 24 hours, this case highlights that WBC is potentially not as risk free as thought to be initially. To conclude, before WBC can be medically recommended, well-conducted studies investigating the possible adverse events are required.

http://ift.tt/2yfmqq8

Patients with common variable immunodeficiency paradoxically have increased rates of autoimmune disorders

Common variable immunodeficiency (CVID), characterised by disordered B cell function, is one of the most common primary immunodeficiency disorders. Patients with CVID are at lifelong risk of recurrent infections, particularly of the respiratory and gastrointestinal tracts. Paradoxically, given their immunocompromised state, patients with CVID are also at significantly increased risk of autoimmune disorders, which are seen in almost 25% of cases. The authors report a 24-year-old female patient with CVID, manifested as severe hypogammaglobulinaemia with recurrent sinopulmonary infections and enterocolitis, who presented with transaminitis, chronic diarrhoea and haematemesis. No infectious aetiologies were identified. She was diagnosed with coeliac disease after a small bowel biopsy and positive response to gluten-free diet. Haematemesis was attributed to portal hypertension due to liver cirrhosis, which was confirmed via liver biopsy. Coeliac disease can be a cause of diarrhoea in patients with immunodeficiency disorders and is often underdiagnosed. It can also be the underlying source of liver disease and is an often under-recognised cause of cirrhosis. The case presented emphasises the paradoxical and challenging relationship that patients with CVID face between immunodeficiency and autoimmune disorders, and also highlights that coeliac disease is an under-recognised cause of liver disease.

http://ift.tt/2g7CX4Q

Post laser-assisted in situ keratomileusis keratomycotic malignant glaucoma

We report a case of a 24-year-old male patient with post-laser assisted in situ keratomileusis (LASIK) culture-proven mycotic keratitis who developed pupillary block glaucoma on day 19 of medical management. The case was initially managed with multiple Nd-Yag peripheral iridotomy along with systemic and topical antiglaucoma medications. However, an emergency therapeutic penetrating keratoplasty (TPK) with lens extraction was done in view of persistently raised intraocular pressure (IOP) and seclusio pupillae. On postoperative day 1, IOP was 10 mm Hg with graft clarity 2 plus and deep anterior chamber with no evidence of residual infection or recurrence. Pupillary block glaucoma can occur in cases of post-LASIK mycotic keratitis, which may necessitate emergency TPK.

http://ift.tt/2yfmpT6

Isolated left ventricular non-compaction (LVNC) and recurrent strokes: to anticoagulate or not to anticoagulate, that is the question

Isolated left ventricular non-compaction (LVNC) is an uncommon primary cardiomyopathy associated with significant risk of thromboembolic stroke. We report a case of a 69-year-old man with a medical history of ischaemic stroke who presented with a stroke for the second time, and during stroke workup transthoracic echo was suggestive of increased apical trabeculation. He underwent cardiac MRI study to evaluate the left ventricular structure, which revealed LVNC cardiomyopathy, which we believe is the main culprit of his recurrent strokes. Given the high risk of stroke recurrence, antiplatelets followed by anticoagulation for secondary prevention were initiated. This case demonstrates the association between LVNC and recurrent stroke, with a literature review trying to address the dilemma facing the clinician to decide on anticoagulation in such patients.

http://ift.tt/2g8ZoXi

The preventive effects of dexmedetomidine on endotoxin-induced exacerbated post-incisional pain in rats

Abstract

Purpose

Low-grade endotoxin (lipopolysaccharide; LPS) exposure may contribute to the development of exaggerated acute postoperative pain. In the present study, we investigated the possible impact of intraoperative administration of dexmedetomidine (DEX) on LPS-induced postoperative hyperalgesia in a rat incisional pain model.

Methods

The surgical and sham-surgical animals were randomly divided into saline-treated control, 5.0 mg/kg LPS-treated, 10 µg/kg DEX-treated, and 5.0 mg/kg LPS + 10 µg/kg DEX-treated groups. In the surgical animals, a 1-cm-long plantar incision was made through the skin and fascia under isoflurane anesthesia. The sham-surgical rats were only anesthetized. All treatments were administered by a single intraperitoneal (i.p.) injection 60 min before surgery. Acute postoperative pain was assessed using the Rat Grimace Scale (RGS) one day before surgery (baseline) and at 2 h post incision. In another experiment, the involvement of the α₂-adrenergic receptor was tested using atipamezole, an α₂-adrenergic receptor antagonist.

Results

In the sham-surgical animals, the RGS did not increase at 2 h after sham surgery compared with the corresponding baseline values in all groups. In the surgical rats, however, the postoperative RGS value of the LPS group was significantly higher than the control group, indicating LPS-induced postoperative hyperalgesia. Administration of intraoperative DEX could prevent the development of such LPS-induced exacerbated post-incisional pain. In addition, the preventive effects of intraoperative DEX were inhibited by pretreatment with atipamezole.

Conclusion

Our findings indicate that intraoperative DEX treatment can prevent LPS-induced exacerbated post-incisional pain via the α₂-adrenergic receptor signaling pathway.

http://ift.tt/2xE1QjS

Beta-blockers and perioperative outcomes in vascular surgery

http://ift.tt/2kMdIdp

The Ethical Conundrum of Supervising Physician Assistants at a Distant Site

http://ift.tt/2yHYDzS

The Emboldened Medical Student:Ethical Dilemmas in a University Clinic

http://ift.tt/2hEOxVt

A systematic review of safety and efficacy of systemic corticosteroids in atopic dermatitis

Systemic corticosteroids are often used to treat atopic dermatitis (AD). However, few studies assessed the safety and efficacy of systemic corticosteroids in AD.

http://ift.tt/2hFzKK7

“Arrow” Mark for Orientation in Paramedian Forehead Flap

http://ift.tt/2yHYEDW

Rigid Bronchoscopy in Pediatric Patients

Abstract

Aspiration of foreign-bodies remains a major life-threatening situation in children and have always been a source of interest and confusion to otolaryngologists due to their varied presentations. These conditions if not promptly diagnosed and managed can prove to be fatal, but the current mortality is only one percent compared to pre bronchoscopy era (Rothman and Boeckman in Ann Otol Rhinol Laryngol 89:434–436, 1980). Peak incidence of this condition is in early childhood due to child's habit of putting small objects in mouth to determine their taste and texture and chew while teething. This is a study conducted retrospectively from 2012 to 2017 in a teritiary care center. It includes a total of 70 cases of foreign body in airway who underwent rigid bronchoscopy under general anaesthesia. The patients were all in paediatric age group but mostly between 6 months to 3 years. The youngest patient was 3 months old and the oldest 12 years old. Male children (70%, n = 49) were more common than female children (30%, n = 21) with a male to female ratio of 2.33:1. A definite history of foreign body aspiration was given in only 70% cases, but the most common symptom were cough (100%) and breathlessness (80%). Organic foreign bodies (76.36%, n = 42) were more common when compared to inorganic foreign bodies. Foreign body most commonly impacted in Right main bronchus (49.09%, n = 27) followed by Left main bronchus (31.42%) and lastly the trachea (19.49%). Even though the mortality in patients of foreign body aspiration is low, it is essential to have proper cooperation between the otolaryngologists, paediatrician and the radiologist for rapid diagnosis and prompt management. It is advised to have a second look to check all the bronchopulmonary segments. Life saving steps are Prompt referral, early diagnosis and vigilant management.

http://ift.tt/2ylyu9a

Changing perspectives in atopic dermatitis

Publication date: Available online 12 October 2017
Source:Allergologia et Immunopathologia
Author(s): E. Serra-Baldrich, J.O. de Frutos, I. Jáuregui, J.C. Armario-Hita, J.F. Silvestre, L. Herraez, A. Martín-Santiago, A. Valero, J. Sastre
Atopic dermatitis (AD) is a multifaceted disease that involves a complex interplay between the skin and the immune system. The course of the disease depends strongly on the genetic background of the patient and on yet poorly-defined environmental factors. Changes in lifestyle could be behind the dramatic rise in the prevalence of AD across continents; including hygienic conditions, food, social habits, skin microbiome or exposure to a number of allergens. Although AD typically develops in childhood and disappears after a few years, in a relatively large number of patients it continues into adulthood. Adult AD can also appear de novo but it is often underdiagnosed and its treatment can be challenging. New, highly effective drugs are being developed to manage moderate and severe forms of the disease in adults. In this review, we highlight the most recent developments in diagnostic tools, current insights into the mechanistic basis of this disease, and therapeutic innovations.



http://ift.tt/2z5kbCO

Low efficacy of atopy patch test in predicting tolerance development in non-IgE-mediated cow's milk allergy

Publication date: Available online 12 October 2017
Source:Allergologia et Immunopathologia
Author(s): T.A. Gonzaga, F.A. Alves, M.F.A. Cheik, C.P. de Barros, E.R.M.A. Rezende, G.R.S. Segundo
BackgroundThe food atopy patch (APT) test has been used in previous studies to help the diagnosis of non-IgE mediated food allergies (FA). The aim of this study was to evaluate the efficacy of different cow's milk APT preparations to predict oral tolerance in children with previous non-IgE-mediated cow's milk allergy (CMA) diagnosis.MethodsThirty-two patients non-IgE-mediated CMA diagnosed by oral food challenge (OFC) were enrolled to perform APT with three different cow's milk preparations (fresh, 2% in saline solution, 2% in petrolatum) and comparing with a new OFC after at least three months of diet exclusion.ResultsOnly six (18.7%) subjects presented positive OFC to cow's milk. No differences in gender, onset symptoms age, OFC age, Z-score, and exclusion period were found between positive and negative OFC patients. Preparations using fresh milk and powdered milk in petrolatum presented sensitivity equal to zero and specificity 92.3% and 96.1%. The preparation using powdered milk in saline solution showed sensitivity and specificity of 33.3% and 96.1%. Two patients presented typical IgE symptoms after OFC.ConclusionCow's milk APT presented a low efficacy to predict tolerance in patients with previous non-IgE-mediated CMA and should not be used in clinical routine. The presence of typical IgE reactions after OFC hallmark the necessity of previous IgE-mediated investigation for this patient group.



http://ift.tt/2zkk9I6

Rigid Bronchoscopy in Pediatric Patients

Abstract

Aspiration of foreign-bodies remains a major life-threatening situation in children and have always been a source of interest and confusion to otolaryngologists due to their varied presentations. These conditions if not promptly diagnosed and managed can prove to be fatal, but the current mortality is only one percent compared to pre bronchoscopy era (Rothman and Boeckman in Ann Otol Rhinol Laryngol 89:434–436, 1980). Peak incidence of this condition is in early childhood due to child's habit of putting small objects in mouth to determine their taste and texture and chew while teething. This is a study conducted retrospectively from 2012 to 2017 in a teritiary care center. It includes a total of 70 cases of foreign body in airway who underwent rigid bronchoscopy under general anaesthesia. The patients were all in paediatric age group but mostly between 6 months to 3 years. The youngest patient was 3 months old and the oldest 12 years old. Male children (70%, n = 49) were more common than female children (30%, n = 21) with a male to female ratio of 2.33:1. A definite history of foreign body aspiration was given in only 70% cases, but the most common symptom were cough (100%) and breathlessness (80%). Organic foreign bodies (76.36%, n = 42) were more common when compared to inorganic foreign bodies. Foreign body most commonly impacted in Right main bronchus (49.09%, n = 27) followed by Left main bronchus (31.42%) and lastly the trachea (19.49%). Even though the mortality in patients of foreign body aspiration is low, it is essential to have proper cooperation between the otolaryngologists, paediatrician and the radiologist for rapid diagnosis and prompt management. It is advised to have a second look to check all the bronchopulmonary segments. Life saving steps are Prompt referral, early diagnosis and vigilant management.

http://ift.tt/2ylyu9a