No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection

alexandrossfakianakis shared this article with you from Inoreader No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection via Clinical Infectious Diseases Advance Access Abstract Background IFNL4 genetic variants that are strongly associated with clearance of hepatitis C virus have been linked to risk of certain opportunistic infections (OIs) and cancers, including Kaposi sarcoma, cytomegalovirus infection, and herpes simplex virus infection. As the interferon (IFN) λ family plays a role in response to viral, bacterial, and fungal infections, IFNL4 genotype might affect risk for a wide range of OIs/cancers. Methods We examined associations between genotype for the functional IFNL4 rs368234815 polymorphism and incidence of 16 OIs/cancers among 2310 men with human immunodeficiency virus (2038 white; 272 black) enrolled in the Multicenter AIDS Cohort Study during 1984–1990. Our primary analyses used Cox proportional hazards models adjusted for self-reported racial ancestry to estimate hazard ratios with 95% confidence intervals, comparing participants with the genotypes that generate IFN-λ4 and those with the genotype that abrogates IFN-λ4. We censored follow-up at the introduction of highly effective antiretroviral therapies. Results We found no statistically significant association between IFNL4 genotype and the incidence of Kaposi sarcoma (hazard ratio, 0.92 [95% confidence interval, .76–1.11]), cytomegalovirus infection (0.94 [.71� �1.24]), herpes simplex virus infection (1.37 [.68–2.93]), or any other OI/cancer. We observed consistent results using additive genetic models and after controlling for CD4 cell count through time-dependent adjustment or restriction to participants with a low CD4 cell count. Conclusions The absence of associations between IFNL4 genotype and these OIs/cancers provides evidence that this gene does not affect the risk of disease from opportunistic pathogens. View on Web

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Metformin and Infections: What Is the Next Step in This Decades-Long Story?

alexandrossfakianakis shared this article with you from Inoreader Metformin and Infections: What Is the Next Step in This Decades-Long Story? via Clinical Infectious Diseases Advance Access metforminmedical historyadjunctive therapyinfectious diseases View on Web

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Bartonella quintana transmitted by head lice: an outbreak of trench fever in Senegal

alexandrossfakianakis shared this article with you from Inoreader Bartonella quintana transmitted by head lice: an outbreak of trench fever in Senegal via Clinical Infectious Diseases Advance Access Abstract Background Louse-borne trench fever caused by Bartonella quintana is a neglected public health concern, known to be transmitted from body louse faeces via scratching. No viable B. quintana have ever been isolated from head lice before; therefore, their role as a vector is still poorly understood. Methods In Senegal, the implementation of a permanent local surveillance system in a Point-of-Care laboratory (POC) allows the monitoring of emerging diseases. Here, we used culture as well as molecular and genomic approaches to document an outbreak of trench fever associated with head lice in the village of Ndiop. Head lice and blood samples were collected from febrile patients between November 2010 and April 2015. Genomes of two isolated strains of B. quintana were sequenced and analysed. Results A total of 2,289 blood samples were collected in the 2010-2015 period. From 2010-2013, B. quintana DNA was detected by PCR in 0.25% (4/1,580). In 2014, 228 blood samples were collected, along with 161 head lice from five individuals. B. quintana DNA was detected in 4·4% (10/228) of blood samples, and in lice specimens collected from febrile patients (61·7%, 50/81) and non-febrile patients (61·4%, 43/70). Two B. quintana strains were isolated from blood and head lice from two different patients. Genomic sequence analysis showed 99·98% overall similarity between both strains. Conclusion The presence of live B. quintana in head lice, and the genetic identity of strains from patients' blood and head lice during a localised outbreak in Senegal, supports the evidence of head lice vectorial capacity. View on Web

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Mitotic count is prognostic in IDH-mutant astrocytoma without homozygous deletion of CDKN2A/B. Results of consensus panel review of EORTC trials 26053 and EORTC 22033-26033

alexandrossfakianakis shared this article with you from Inoreader Mitotic count is prognostic in IDH-mutant astrocytoma without homozygous deletion of CDKN2A/B. Results of consensus panel review of EORTC trials 26053 and EORTC 22033-26033 via Neuro-Oncology Advance Access Abstract Background Gliomas with IDH1/2 mutations without 1p19q codeletion have been identified as the distinct diagnostic entity of IDH mutant astrocytoma (IDHmut astrocytoma). Homozygous deletion of Cyclin-dependent kinase 4 inhibitor A/B (CDKN2A/B) has recently been incorporated in the grading of these tumors. The question of whether histologic parameters still contribute to prognostic information on top of the molecular classification, remains unanswered. Here we evaluated consensus histologic parameters for providing additional prognostic value in IDHmut astrocytomas. Methods An international panel of seven neuropathologists scored 13 well-defined histologic features in virtual microscopy images of 192 IDHmut astrocytomas from EORTC trial 22033-26033 (low-grade gliomas) and 263 from EORTC 26053 (CATNON) (1p19q non-codeleted anaplastic glioma). For 192 gliomas the CDKN2A/B status was known. Consensus (agreement ≥ 4/7 panelists) hi stologic features were tested together with homozygous deletion (HD) of CDKN2A/B for independent prognostic power. Results Among consensus histologic parameters, the mitotic count (cut-off of 2 mitoses per 10 high power fields standardized to a field diameter of 0.55 mm and an area of 0.24 mm 2) significantly influences PFS (p = 0.0098) and marginally the OS (p = 0.07). Mitotic count also significantly affects the PFS of tumors with HD CDKN2A/B, but not the OS, possibly due to limited follow-up data. Conclusion The mitotic index (cut-off 2 per 10 40x HPF) is of prognostic significance in IDHmut astrocytomas without HD CDKN2A/B. Therefore, the mitotic index may direct the therapeutic approach for patients with IDHmut astrocytomas with native CDKN2A/B status. View on Web

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Customised acoustic therapy delivered through a web‐based platform – an innovative approach to tinnitus treatment

alexandrossfakianakis shared this article with you from Inoreader Customised acoustic therapy delivered through a web‐based platform – an innovative approach to tinnitus treatment via Clinical Otolaryngology Abstract Objectives Customised acoustic therapy aims to moderate the neural pathways implicated in the pathophysiology of tinnitus. This study aimed to assess the efficacy of customised acoustic therapy administered via a web-based treatment platform. Design Clinical trial with prospective recruitment. 58 participants underwent six weeks of customised acoustic therapy. Setting Treatment was delivered for 2 hours each day using a smartphone, tablet or computer. Treatment was integrated into usual daily activities. Participants Participants with subjective tinnitus were recruited through public and private otolaryngology clinics and electronic and print media. Main Outcomes Measured FiveQ, a novel 5 question tinnitus questionnaire, was measured at baseline and each week of treatment. Statistical analyses, including Wilcoxon, Mann-Whitney and mixed linear regression, were used to assess treatment efficacy and identify factors associated with treatment response. Results 39/58 participants (67.2%) had an improvement in symptom severity scores, 4 had no change (6.9%) and 15 had a decline from baseline (25.9%). Mean FiveQ scores improved by 22.9% from 40.8 (SD=21.4) at baseline to 31.5 (SD=21.3) following 6 weeks of treatment (p<0.001). With the exception of the slight tinnitus group, all other groups (from mild to catastrophic) demonstrated a treatment response. Participants with low frequency tinnitus (<2000 Hertz) had a significantly greater treatment response (p<0.001). Conclusion Customised acoustic therapy administered via a web-based platform demonstrated encouraging efficacy. At least mild symptoms at baseline and low frequency tinnitus were associated with a greater treatment response. Customised acoustic therapy offers accessible and efficacious tinnitus treatment, however longer term clinical studies are required to confirm the observed initial benefit is maintained. View on Web

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Neuroendokrine Tumoren im Kopf-, Halsbereich

alexandrossfakianakis shared this article with you from Inoreader Neuroendokrine Tumoren im Kopf-, Halsbereich via Laryngo-Rhino-Otologie Laryngorhinootologie DOI: 10.1055/a-1976-9641 Hintergrund Neuroendokrine Tumoren (NET) sind benigne oder maligne Neoplasien, die entwicklungsgeschichtlich der Neuralleiste oder paraganglionären Zellen des vegetativen Nervensystems entstammen. Die alte Bezeichnung Karzinoid (karzinomähnlicher Tumor) ist noch sehr verbreitet, jedoch inzwischen obsolet. Lediglich 0,5–2 % aller Neoplasien des Menschen sind neuroendokrine Tumoren, welche überwiegend gastrointestinal oder bronchopulmonal lokalisiert sind. Die Inzidenz beträgt 9.263/100.000. Jedoch ist nur 1 % der Kopf-Hals-Tumore neuroendokriner Genese. Fallzahlstarke Langzeitstudien und Leitlinien zur Diagnose und Therapie im Kopf-Hals Bereich fehlen. Ziel dieser Arbeit ist der wertende Vergleich bekannter Therapiestrategien und daraus folgender Krankheitsverläufe sowie deren Vergleich mit dem Schrifttum anhand eigener Fälle unterschiedlicher Lokalisation und Ausdehnung. Patienten und Methoden In unserer Klinik wurden zwischen 2010 und 2017 14 Patienten mit neuroendokrinen Tumoren im Kopf-Hals-Bereich behandelt. 8 Patienten davon wurden primär operativ mit adjuvanter Radiochemotherapie versorgt. 6 Patienten erhielten eine primäre Radiochemotherapie in kurativer Absicht. 1 Patient erhielt auf Grund des Tumorprogress nach der primären Radiochemotherapie eine weitere Chemotherapie mit palliativer Indikation. Ergebnisse Die Tumorlokalisationen verteilen sich auf den Larynx (n = 7), die Glandula parotis (n = 2) und auf die Nasenhaupt- und -nebenhöhlen (n=5). Von den 8 operierten Patienten konnte in sechs Fällen eine in-sano Resektion (R0) erreicht werden. Die im Kollektiv gemessene Gesamtüberlebensrate beträgt im Mittel 19±6 Monate. Von den 14 untersuchten Patienten erlitten zwei Patienten ein Rezidiv, wovon ein Patient nach 7 Monaten verstarb und ein Patient 32 Monate nach der Nachresektion Rezidiv-frei lebt. In zwei Fällen sprach das NET nicht auf die kombinierte RCT an und die Patienten verstarben jeweils nach sechs und 13 Monaten. Die Überlebenszeit ist abhängig vom T-Stadium des NET sowie vom Erreichen einer R0-Resektion. Die R0-Resektion bietet eine höhere Überlebenswahrscheinlichkeit als die primäre RCT. Schlussfolgerung Patienten mit NET des Kopf-Hals-Bereiches müssen in spezialisierten Zentren interdisziplinär behandelt werden. Zur Erfassung dieser Daten ist eine Tumordatenbank notwendig. Jedoch sind aufgrund der niedrigen Inzidenz keine Studien auf hohem Evidenzniveau zu erwarten. Nach effizienter Diagnosestellung sollte zeitliche Verzögerung unmittelbar im Rahmen einer interdisziplinären Tumorkonferenz eine individuelle auf den Patienten zugeschnittene Therapie erfolgen. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on Web

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enzyme replacement therapy followed by stem cell transplantation in children with Gaucher disease type 1 and 3

alexandrossfakianakis shared this article with you from Inoreader Comprehensive and long‐term outcomes of enzyme replacement therapy followed by stem cell transplantation in children with Gaucher disease type 1 and 3 via Pediatric Blood & Cancer Abstract Background Gaucher disease (GD) is a lysosomal storage disorder, characterized by hepatosplenomegaly, pancytopenia, bone diseases, with or without neurological symptoms. Plasma glucosylsphingosine (lyso-Gb1), a highly sensitive and specific biomarker for GD, has been used for diagnosis and monitoring the response to treatment. Enzyme replacement therapy (ERT) is an effective treatment for the non-neurologic symptoms of GD. Neuronopathic GD (type 2 and 3) accounts for 60%–70% of the Asian affected population. Methods We explored combination therapy of ERT followed by hematopoietic stem cell transplantation (HSCT) and its long-term outcomes in patients with GD type 3 (GD3). Results Four patients with GD3 and one with GD type 1 (GD1) underwent HSCT. The types of donor were one matched-related, one matched-unrelated, and three haploidentical. The age at disease onset was 6–18 months and the age at HSCT was 3.8–15 years in the patients with GD3. The latest age at follow-up was 8–22 years, with a post-HSCT duration of 3–14 years. All patients had successful HSCT. Chronic graft-versus-host disease occurred in one patient. The enzyme activities were normalized at 2 weeks post HSCT. Lyso-Gb1 concentrations became lower than the pathological value. All of the patients are still alive and physically independent. Most of them (4/5) returned to school. None of the patients with GD3 had seizures or additional neurological symptoms after HSCT, but showed varying degrees of cognitive impairment. Conclusions ERT followed by HSCT could be considered as an alternative treatment for patients with GD3 who have a high risk of fatal neurological progression. View on Web

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