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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Dendritic spine loss in epileptogenic Type II focal cortical dysplasia: Role of enhanced classical complement pathway activation

alexandrossfakianakis shared this article with you from Inoreader Dendritic spine loss in epileptogenic Type II focal cortical dysplasia: Role of enhanced classical complement pathway activation via Brain Pathology Abstract Dendritic spines are the postsynaptic sites for most excitatory glutamatergic synapses. We previously demonstrated a severe spine loss and synaptic reorganization in human neocortices presenting Type II focal cortical dysplasia (FCD), a developmental malformation and frequent cause of drug-resistant focal epilepsy. We extend the findings, investigating the potential role of complement components C1q and C3 in synaptic pruning imbalance. Data from Type II FCD were compared with those obtained in focal epilepsies with different etiologies. Neocortical tissues were collected from 20 subjects, mainly adults with a mean age at surgery of 31 years, admitted to epilepsy surgery with a neuropathological diagnosis of: cryptogenic, temporal lobe epilepsy with hippocampal sclerosis, and Type IIa/b FCD. Dendritic spine density quantitation, evaluated in a previous paper using Golgi impregnation, was available in a subgroup. Immunohistochemistry, in situ hybridization, electron microscopy, a nd organotypic cultures were utilized to study complement/microglial activation patterns. FCD Type II samples presenting dendritic spine loss were characterized by an activation of the classical complement pathway and microglial reactivity. In the same samples, a close relationship between microglial cells and dendritic segments/synapses was found. These features were consistently observed in Type IIb FCD and in 1 of 3 Type IIa cases. In other patient groups and in perilesional areas outside the dysplasia, not presenting spine loss, these features were not observed. In vitro treatment with complement proteins of organotypic slices of cortical tissue with no sign of FCD induced a reduction in dendritic spine density. These data suggest that dysregulation of the complement system plays a role in microglia-mediated spine loss. This mechanism, known to be involved in the removal of redundant synapses during development, is likely reactivated in Type II FCD, particularly in Type IIb; loc al treatment with anticomplement drugs could in principle modify the course of disease in these patients. View on Web

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Epstein–Barr virus‐positive diffuse large B‐cell lymphoma onset as familial hemophagocytic lymphohistiocytosis in an infant

alexandrossfakianakis shared this article with you from Inoreader Epstein–Barr virus‐positive diffuse large B‐cell lymphoma onset as familial hemophagocytic lymphohistiocytosis in an infant via Pediatric Blood & Cancer View on Web

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Imaging of pediatric calvarial and skull base tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee/ASPNR White Paper

alexandrossfakianakis shared this article with you from Inoreader Imaging of pediatric calvarial and skull base tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee/ASPNR White Paper via Pediatric Blood & Cancer Abstract A standardized imaging protocol for pediatric oncology patients is essential for accurate and efficient imaging, while simultaneously promoting collaborative understanding of pathologies and radiologic assessment of treatment response. The objective of this article is to provide standardized pediatric imaging guidelines and parameters for evaluation of tumors of the pediatric orbit, calvarium, skull base, and temporal bone. This article was drafted based on current scientific literature as well as consensus opinions of imaging experts in collaboration with the Children's Oncology Group Diagnostic Imaging Committee, Society of Pediatric Radiology Oncology Committee, and American Society of Pediatric Neuroradiology. View on Web

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Clinical severity of Omicron sub‐variants BA.1, BA.2 and BA.5 in a population‐based cohort study in British Columbia, Canada

alexandrossfakianakis shared this article with you from Inoreader Clinical severity of Omicron sub‐variants BA.1, BA.2 and BA.5 in a population‐based cohort study in British Columbia, Canada via Journal of Medical Virology Abstract The SARS-CoV-2 variant Omicron emerged in late 2021. In British Columbia (BC), Canada, and globally, three genetically distinct sub-variants of Omicron, BA.1, BA.2 and BA.5, emerged and became dominant successively within an 8-month period. SARS-CoV-2 sub-variants continue to circulate in the population, acquiring new mutations that have the potential to alter infectivity, immunity and disease severity. Here, we report a propensity-matched severity analysis from residents of BC over the course of the Omicron wave, including 39,237 individuals infected with BA.1, BA.2 or BA.5 based on paired high-quality sequence data and linked to comprehensive clinical outcomes data between Dec. 23, 2021 and August 31, 2022. Relative to BA.1, BA.2 cases were associated with a 15% and 28% lower risk of hospitalization and Intensive Care Unit (ICU) admission (aHRhospital=1.17; 95%CI=1.096-1.252; aHRICU=1.368; 95%CI=1.152-1.624), whereas BA.5 infections were associated with a 1 8% higher risk of hospitalization (aHRhospital=1.18; 95%CI=1.133-1.224) after accounting for age, sex, co-morbidities, vaccination status, geography and social determinants of health. Phylogenetic analysis revealed no specific sub-clades associated with more severe clinical outcomes for any Omicron sub-variant. In summary, BA.1, BA.2 and BA.5 sub-variants were associated with differences in clinical severity, emphasizing how variant-specific monitoring programs remain critical components of patient and population-level public health responses as the pandemic continues. This article is protected by copyright. All rights reserved. View on Web

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HTLV‐1 persistent infection and ATLL oncogenesis

alexandrossfakianakis shared this article with you from Inoreader HTLV‐1 persistent infection and ATLL oncogenesis via Journal of Medical Virology Abstract Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus; whereas HTLV-1 mainly persists in the infected host cell as a provirus, it also causes a malignancy called adult T-cell leukemia/lymphoma (ATLL) in about 5% of infection. HTLV-1 replication is in most cases silent in vivo and viral de novo infection rarely occurs; HTLV-1 rather relies on clonal proliferation of infected T cells for viral propagation as it multiplies the number of the provirus copies. It is mechanistically elusive how leukemic clones emerge during the course of HTLV-1 infection in vivo and eventually cause the onset of ATLL. This review summarizes our current understanding of HTLV-1 persistence and oncogenesis, with the incorporation of recent cutting-edge discoveries obtained by high-throughput sequencing. This article is protected by copyright. All rights reserved. View on Web

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Imaging of pediatric hematopoietic stem cell transplant recipients: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

alexandrossfakianakis shared this article with you from Inoreader Imaging of pediatric hematopoietic stem cell transplant recipients: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper via Pediatric Blood & Cancer Abstract Imaging in hematopoietic stem cell transplantation patients is not targeted at evaluating the transplant per se. Rather, imaging is largely confined to evaluating peri-procedural and post-procedural complications. Alternatively, imaging may be performed to establish a baseline study for comparison should the patient develop certain post-procedural complications. This article looks to describe the various imaging modalities available with recommendations for which imaging study should be performed in specific complications. We also provide select imaging protocols for different indications and modalities for the purpose of establishing a set minimal standard for imaging in these complex patients. View on Web

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the Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM‐Pt)

alexandrossfakianakis shared this article with you from Inoreader The Portuguese version of the Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM‐Pt): translation, cultural adaptation, and multicenter validation study in professional orchestra musicians via Pain Practice Abstract Objectives We aim to assess the validity and reliability of the Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM) and to add to its cross-cultural adaptation process by translating, culturally adapting and validating the MPIIQM into European Portuguese language in the population of Portuguese musicians. Methods A Portuguese version of the MPIIQM (MPIIQM-Pt) was created through a process of forward and back translation, pilot testing and cultural adaptation by expert panel evaluation. The psychometric evaluation was performed in a validation sample of 134 musicians, at baseline and after seven days. Results The high degree of internal consistency and the substantial test-retest reliability coefficients were demonstrated for each subscale (α = 0,896 and ICC = 0,997 for "pain intensity", and α = 0,879 and ICC = 0,999 for "pain interference", respectively). Exploratory factor analysis indicated two-factor structure (pain intensity and interference) that explained 75,5% of the variance. Both convergent and divergent validity are well demonstrated, confirming more than 90% of the previously defined hypotheses regarding correlations with other measures. Discussion MPIIQM-Pt is the first validated questionnaire to evaluate pain among Portuguese musicians. It showed excellent psychometric properties, both in terms of internal consistency, test-retest reliability, factor analysis, and construct validity. Therefore, it is a valid and reliable tool suitable for both research and clinical practice purposes. MPIIQM-Pt will allow the development of more robust studies on pain among musicians and the improved assessment and monitoring of pain in this population, filling an important gap in this field of Pain Medicine. View on Web

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Rehabilitation of long‐term mandibular defects by whole‐process digital fibula flap combining with implants: a case report

alexandrossfakianakis shared this article with you from Inoreader Rehabilitation of long‐term mandibular defects by whole‐process digital fibula flap combining with implants: a case report via Journal of Prosthodontics Abstract Currently, the gold standard and workhorse in mandibular reconstruction is the free vascularized fibula flap. Particularly for patients who have had mandibulectomy for a long time, it is still difficult to precisely reconstruct the mandibular contour and successfully restore the patient's chewing function and aesthetics. For the restoration and rehabilitation of long-term mandibular abnormalities, 3D virtual surgical planning and 3D-printed surgical guides are essential. Digital design and manufacturing were used to improve the accuracy of prostheses, and facilitate occlusal reconstruction. Therefore, equipped with the methods of 3D virtual surgical planning, 3D printed surgical guides, free vascularized fibular flap, and immediate dental implants, this clinical report provides a feasible solution for mandibular reconstruction. This article is protected by copyright. All rights reserved View on Web

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