Coltiviruses and Seadornaviruses in North America, Europe, and Asia

Neurotropic virus disease is often misdiagnosed as Japanese encephalitis

Global Positioning System measurements of strain accumulation and slip transfer through the restraining bend along the Dead Sea fault system in Lebanon

Approximately 4 yr of campaign and continuous Global Positioning System (GPS) measurements across the Dead Sea fault system (DSFS) in Lebanon provide direct measurements of interseismic strain accumulation along a 200-km-long restraining bend in this continental transform fault. Late Cenozoic transpression within this restraining bend has maintained more than 3000 m of topography in the Mount Lebanon and Anti-Lebanon ranges. The GPS velocity field indicates 4-5 mm yr-1 of relative plate motion is transferred through the restraining bend to the northern continuation of the DSFS in northwestern Syria. Near-field GPS velocities are generally parallel to the major, left-lateral strike-slip faults, suggesting that much of the expected convergence across the restraining bend is likely accommodated by different structures beyond the aperture of the GPS network (e.g. offshore Lebanon and, possibly, the Palmyride fold belt in SW Syria). Hence, these geodetic results suggest a partitioning of crustal deformation involving strike-slip displacements in the interior of the restraining bend, and crustal shortening in the outer part of the restraining bend. Within the uncertainties, the GPS-based rates of fault slip compare well with Holocene-averaged estimates of slip along the two principal strike-slip faults: the Yammouneh and Serghaya faults. Of these two faults, more slip occurs on the Yammouneh fault, which constitutes the primary plate boundary structure between the Arabia and Sinai plates. Hence, the Yammouneh fault is the structural linkage that transfers slip to the northern part of the transform in northwestern Syria. From the perspective of the regional earthquake hazard, the Yammouneh fault is presently locked and accumulating interseismic strain

Diagnostic accuracy of cervical cancer screening strategies for high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) among women living with HIV: A systematic review and meta-analysis

BACKGROUND: We systematically reviewed the diagnostic accuracy of cervical cancer screening and triage strategies in women living with HIV (WLHIV). METHODS: Cochrane Library, Embase, Global Health and Medline were searched for randomised controlled trials, prospective or cross-sectional studies published from database inception to 15 July 2022 reporting diagnostic accuracy of tests in cervical cancer screening and triage of screen-positive WLHIV. Studies were included if they reported the diagnostic accuracy of any cervical cancer screening or triage strategies for the detection of histologically-confirmed high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) among WLHIV. Summary data were extracted from published reports. Authors were contacted for missing data where applicable. Sensitivity and specificity estimates for CIN2/3+ were pooled using models for meta-analysis of diagnostic accuracy data. Study quality was assessed using the QUADAS-2 tool for the quality assessment of diagnostic accuracy studies. PROSPERO registration:CRD42020189031. FINDINGS: In 38 studies among 18,737 WLHIV, the majority (n=19) were conducted in sub-Saharan Africa. The pooled prevalence was 12.0% (95%CI:9.8-14.1) for CIN2+ and 6.7% (95%CI:5.0-8.4) for CIN3+. The proportion of screen-positive ranged from 3-31% (visual inspection using acetic acid[VIA]); 2-46% (high-grade squamous intraepithelial lesions, and greater [HSIL+] cytology); 20-64% (high-risk[HR]-HPV DNA). In 14 studies, sensitivity and specificity of VIA were variable limiting the reliability of pooled estimates. In 5 studies where majority had histology-confirmed CIN2+, pooled sensitivity was 56.0% (95%CI:45.4-66.1; I2=65%) for CIN2+ and 65.0% (95%CI:52.9-75.4; I2 =42%) for CIN3+; specificity for <CIN2 was 73.8% (95%CI:59.8-84.2, I2=94%). Cytology was similarly variable (sensitivity of ASCUS+ for CIN2+ range: 58-100%; specificity: 9-96%). In 28 studies, sensitivity of tests targeting 14-HR-HPV types was high (91.6%, 95%CI:88.1-94.1; I2=45% for CIN2+ and 92.5%, 95%CI:88.4-95.2; I2=32%) for CIN3+); but specificity for <CIN2 was low (62.2% (95%CI:57.9-66.4;I2=92%). Restriction to 8-HR-HPV increased specificity (65.8%; Relative specificity[RSpec] vs. 14-HR-HPV=1.17; 95%CI:1.10-1.24) with no significant change in sensitivity (CIN2+:85.5%; Relative Sensitivity[RSens]=0.94, 95%CI: 0.89-1.00; CIN3+:90%; RSens=0.96, 95%CI:0.89-1.03). VIA triage of 14-HR-HPV positive women decreased sensitivity for CIN2+ compared to HPV-DNA test alone (64.4% vs. 91.6%; RSens=0.68, 95%CI:0.62-0.75). INTERPRETATION: HPV-DNA based approaches consistently showed superior sensitivity for CIN2+/CIN3+ compared to VIA or cytology. The low specificity of HPV-DNA based methods targeting up to 14-HR-HPV could be improved significantly by restricting to 8-HR-HPV with only minor losses in sensitivity, limiting requirement for triage for which optimal approaches are less clear. FUNDING: World Health Organisation; National Cancer Institute; European Union's Horizon 2020 and Marie Skłodowska-Curie Actions programme

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Anti-CTLA-4 Monoclonal Antibodies Induced Hypophysitis: Case Report and Literature Review

Treatment with Anti-CTLA-4 Monoclonal Antibodies (mAb) has become a common choice in advanced melanoma and is under evaluation for many other types of cancer. These antibodies inhibit the interaction between CTLA-4 (Cytotoxic T Lymphocyte-Associated Antigen 4) receptors on the T cell surface and the antigen presenting cell surface molecules B7, leading to the activation or enhancement of T cell immune responses. The oncologic beneficial effects of Anti-CTLA-4 mAb are marred by many immune related adverse effects, including Ipilimumab-Induced Hypophysitis (IIH). We, herein, report an illustrative case with a literature review. Based on this research, the incidence of IIH was between 1.75% and 13%. Presenting symptoms were predominantly headache and fatigue. Pituitary enlargement was the main radiologic sign on MRI. The thyrotrophic and adrenocorticotropic axes were the most commonly affected followed by gonadotropic, somatotropic and lactotropic axes, respectively. Time to hypophysitis onset varied between 5 and 40 weeks after starting ipilimumab and treatment withdrawal due to hypophysitis was largely variable. Finally, thyrotropin and gonadotropin axes recovered more frequently than other anterior pituitary axes

Association des analogues du GLP-1 et des inhibiteurs du SGLT2 : de nouvelles perspectives ?

Type 2 diabetes therapy has expanded considerably over the last decade. Two anti-diabetic therapeutic groups, which are GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 inhibitors (sodium-glucose co-transporter-2), have shown efficacy not only on glycemic control but also on weight and other parameters that will be detailed in this article. Cardiovascular safety studies for two of these molecules were shown for the first time to decrease overall and cardiovascular mortality. The combination of these two therapeutic classes provides a logical solution due to their different mechanisms of action. The DURATION-8 study designed to demonstrate the benefits of this combination will also be discussed in this article

Restoration of adrenal function after bilateral adrenal damage due to heparin-induced thrombocytopenia (HIT): a case report

Patients with bilateral adrenal damage due to heparin-induced thrombocytopenia usually need lifelong steroid substitution. So far, no data exists about the natural evolution of such a condition, especially about adrenal function recovery and the real need for lifelong steroids

Programmed cell death-1 and programmed cell death ligand-1 antibodies-induced dysthyroidism

Background: Monoclonal antibodies blocking the programmed cell death-1 (PD-1) or its ligand (PD-L1) are a group of immune checkpoints inhibitors (ICIs) with proven antitumor efficacy. However, their use is complicated by immune-related adverse events (irAEs), including endocrine adverse events (eAEs). Purpose: We review the incidence, time to onset and resolution rate of dysthyroidism induced by PD-1/PD-L1 Ab, and the clinical, biological and radiological findings. We aim to discuss the potential mechanisms of PD-1/PD-L1 Ab-induced dysthyroidism, and to propose a management algorithm. Methods: We performed a literature search of available clinical trials regarding PD-1/PD-L1 Ab in the PubMed database. We selected all English language clinical trials that included at least 100 patients. We also present selected case series or reports, retrospective studies and reviews related to this issue. Findings: In patients treated with PD-1 Ab, hypothyroidism occurred in 2–10.1% and hyperthyroidism occurred in 0.9–7.8%. When thyroiditis was reported separately, it occurred in 0.34–2.6%. Higher rates were reported when PD-1 Ab were associated with other ICI or chemotherapy. The median time to onset of hyperthyroidism and hypothyroidism after PD-1 Ab initiation was 23–45 days and 2–3.5 months, respectively. Regarding PD-L1 Ab, hypothyroidism occurred in 0–10% and hyperthyroidism in 0.5–2% of treated patients. The average time to onset of dysthyroidism after PD-L1 Ab was variable and ranged from 1 day after treatment initiation to 31 months. Conclusion: Dysthyroidism occurs in up to 10% of patients treated with PD-1/PD-L1 Ab. Hypothyroidism and reversible destructive thyroiditis are the most frequent endocrine adverse events (eAE) in PD-1/PD-L1 treated patients. Immune and non-immune mechanisms are potentially involved, independently of the presence of thyroid antibodies