Application of the laboratory risk indicator for necrotizing fasciitis score for patients with hand infection in Mexican population

Background: Necrotizing fasciitis (NF) is a severe form of soft tissue infection, early diagnosis, and surgical intervention are direct factors in mortality, it may arise from many infectious aetiologies, at our hospital in Mexico city, it is not uncommon that hand infection patients progress to NF, that in many cases its recognition and treatment may also be delayed, resulting in fatal outcomes. Wong et al in 2004 introduced a laboratory risk indicator for necrotizing fasciitis (LRINEC score) that utilizes common laboratory values of patients with clinical infection and stratifies them by their risk of developing NF, so the aim of our study was to validate this tool in Mexican population. Methods: We reviewed all patients with an initial diagnosis of hand infection admitted at the emergency department of our hospital in Mexico City, from April 2020 to March 2022 and examined the LRINEC score at admission, post-debridement, and at the end of the hospitalization to evaluate its usefulness in our population. Results: The LRINEC score at cut-off ≥6 reported sensitivity for the diagnosis of NF of 35.71% (95% CI 12.76-64.86%), specificity of 100% (95% CI 78.2-100%), positive predictive value of 100% (95% CI 71-100%), and negative predictive value of 62.5% (95% CI 53.01-71.12%). Conclusions: The LRINEC score is a useful tool to distinguish NF from other soft tissue infections, but it is not helpful for early recognition of NF alone, LRINEC score could predict worse hospital outcomes in patients with NF and identify the high-risk patients.

Frecuencia de prolongación del intervalo QTc en adultos infectados con VIH de Paraguay en 2020

Introduction: the prolonged QTc interval predisposes to serious arrhythmias. Various medications, including antiretrovirals, can prolong it. The objectives were to determine the demographic, clinical characteristics and the frequency of the prolonged QTc interval in patients with HIV. Methods: we conducted a prospective, observational study with a control group. Men and women, over 18 years of age, with HIV infection, who attended the National Hospital (Itauguá, Paraguay) during 2020, were included. Medical students acted as a control group. All subjects who did not give their consent and those with arrhythmias were excluded. Demographic, clinical, laboratory variables and 12-channel electrocardiogram at rest were measured. The study was approved by the Ethics Committee of the Universidad Privada del Este (Paraguay). Results: 39 HIV patients and 39 healthy controls entered the study. The mean age of the cases was 37 ± 11 years, being 59% male. The most frequent comorbidity in the cases was obesity (7.6%). The mean values ​​of urea, creatinine, K, Ca and Mg in the cases were in the normal range. Prolonged QTc was detected in 18% of the cases and in 0% of the controls. The subjects with the electrocardiographic alteration were all on antiretroviral and multiple antibiotic treatment known to be associated with prolonged Qtc. Conclusion: the frequency of prolonged QTc in HIV patients was 18% and in healthy controls it was 0%. Regular monitoring of the electrocardiogram is recommended in HIV patients receiving drugs that prolong the QT interval.Introducción: el intervalo QTc prolongado predispone a arritmias graves. Diversos medicamentos, entre ellos los antirretrovirales, pueden prolongarlo. Los objetivos fueron determinar las características demográficas, clínicas y la frecuencia del intervalo QTc prolongado en pacientes con VIH. Métodos: estudio observacional, prospectivo, con grupo control. Se incluyeron varones y mujeres, mayores de 18 años, portadores de infección por VIH, que acudieron al Hospital Nacional (Itauguá, Paraguay) durante 2020. Actuaron como grupo control los estudiantes de Medicina. Se excluyeron todos los sujetos que no dieron su consentimiento y los portadores de arritmias. Se midieron variables demográficas, clínicas, laboratoriales y electrocardiograma de 12 canales en reposo. El estudio contó con la aprobación del Comité de Ética de la Universidad Privada del Este (Paraguay). Resultados: ingresaron al estudio 39 pacientes con VIH y 39 controles sanos. La edad media de los casos fue 37 ± 11 años, siendo 59% del sexo masculino. La comorbilidad más frecuente en los casos fue la obesidad (7,6%). Los valores medios de urea, creatinina, K, Ca y Mg en los casos se hallaban en rango normal. Se detectó 18% de QTc prolongado en casos y 0% en los controles. Estos sujetos con alteración electrocardiográfica se hallaban todos en tratamiento antirretroviral y antibiótico múltiple de conocida asociación con QTc prolongado. Conclusión: la frecuencia de QTc prolongado en pacientes con VIH fue del 18% y en controles sanos fue del 0%. Se recomienda el control periódico del electrocardiograma en pacientes con VIH en tratamiento con fármacos que prolongan el intervalo QT

p62/SQSTM1 Fuels Melanoma Progression by Opposing mRNA Decay of a Selective Set of Pro-metastatic Factors

Modulators of mRNA stability are not well understood in melanoma, an aggressive tumor with complex changes in the transcriptome. Here we report the ability of p62/SQSTM1 to extend mRNA half-life of a spectrum of pro-metastatic factors. These include FERMT2 and other transcripts with no previous links to melanoma. Transcriptomic, proteomic, and interactomic analyses, combined with validation in clinical biopsies and mouse models, identified a selected set of RNA-binding proteins (RBPs) recruited by p62, with IGF2BP1 as a key partner. This p62-RBP interaction distinguishes melanoma from other tumors where p62 controls autophagy or oxidative stress. The relevance of these data is emphasized by follow-up analyses of patient prognosis revealing p62 and FERMT2 as adverse determinants of disease-free survival.M.S.S. is funded by grants from the Spanish Ministry of Economy and Innovation (SAF2014-56868-R; SAF2017-89533-R), the Asociación Española Contra el Cáncer (AECC), TV’13-20131430 (Marato de TV3), the Worldwide Cancer Research, an Established Investigator Award by the Melanoma Research Alliance (MRA), and a L'Oreal-Paris USA-MRA Team Science Award for Women in Scientific Research. M.S.S. also acknowledges a donation from “Fundación Causa Alexandra”, Spain. P.K. was a recipient of a predoctoral fellowship from Fundación La Caixa. E.R.-F. was funded by Fundación Mutua Madrileña (FMM-2013) and was a recipient of a fellowship from ‘‘Fundación Científica de la Asociación Española Contra el Cáncer”. The CNIO Proteomics Unit belongs to ProteoRed, PRB2-ISCIII, supported by grant PT13/0001. J.M. is also supported by Ramon y Cajal Programme (MINECO) RYC-2012-10651. J.L.R.-P. is funded by FIS 2014/173711/02568 and CIBERONC, and P.L.O.-R. by FIS 11/17592014/01784, from the Spanish Ministry of Health

Inter-Rater Variability in the Evaluation of Lung Ultrasound in Videos Acquired from COVID-19 Patients

12 páginas, 7 figuras, 1 tablaLung ultrasound (LUS) allows for the detection of a series of manifestations of COVID-19, such as B-lines and consolidations. The objective of this work was to study the inter-rater reliability (IRR) when detecting signs associated with COVID-19 in the LUS, as well as the performance of the test in a longitudinal or transverse orientation. Thirty-three physicians with advanced experience in LUS independently evaluated ultrasound videos previously acquired using the ULTRACOV system on 20 patients with confirmed COVID-19. For each patient, 24 videos of 3 s were acquired (using 12 positions with the probe in longitudinal and transverse orientations). The physicians had no information about the patients or other previous evaluations. The score assigned to each acquisition followed the convention applied in previous studies. A substantial IRR was found in the cases of normal LUS (κ = 0.74), with only a fair IRR for the presence of individual B-lines (κ = 0.36) and for confluent B-lines occupying 50% (κ = 0.50). No statistically significant differences between the longitudinal and transverse scans were found. The IRR for LUS of COVID-19 patients may benefit from more standardized clinical protocols.This research was partially funded by CDTI (Spanish acronym: Centre for Industrial Tech- nological Development), funding number COI-20201153. Partially supported by the Google Cloud Research Credits program with the funding number GCP19980904, by the project RTI2018-099118- A-I00 founded by MCIU/AEI/FEDER UE and by the European Commission–NextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global)

Adenylyl Cyclase Plays a Regulatory Role in Development, Stress Resistance and Secondary Metabolism in Fusarium fujikuroi

The ascomycete fungus Fusarium fujikuroi (Gibberella fujikuroi MP-C) produces secondary metabolites of biotechnological interest, such as gibberellins, bikaverin, and carotenoids. Production of these metabolites is regulated by nitrogen availability and, in a specific manner, by other environmental signals, such as light in the case of the carotenoid pathway. A complex regulatory network controlling these processes is recently emerging from the alterations of metabolite production found through the mutation of different regulatory genes. Here we show the effect of the targeted mutation of the acyA gene of F. fujikuroi, coding for adenylyl cyclase. Mutants lacking the catalytic domain of the AcyA protein showed different phenotypic alterations, including reduced growth, enhanced production of unidentified red pigments, reduced production of gibberellins and partially derepressed carotenoid biosynthesis in the dark. The phenotype differs in some aspects from that of similar mutants of the close relatives F. proliferatum and F. verticillioides: contrary to what was observed in these species, ΔacyA mutants of F. fujikuroi showed enhanced sensitivity to oxidative stress (H2O2), but no change in heavy metal resistance or in the ability to colonize tomato tissue, indicating a high versatility in the regulatory roles played by cAMP in this fungal group

HTLV-1 infection in solid organ transplant donors and recipients in Spain

HTLV-1 infection is a neglected disease, despite infecting 10-15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

Marine Biodiversity in the Caribbean: Regional Estimates and Distribution Patterns

This paper provides an analysis of the distribution patterns of marine biodiversity and summarizes the major activities of the Census of Marine Life program in the Caribbean region. The coastal Caribbean region is a large marine ecosystem (LME) characterized by coral reefs, mangroves, and seagrasses, but including other environments, such as sandy beaches and rocky shores. These tropical ecosystems incorporate a high diversity of associated flora and fauna, and the nations that border the Caribbean collectively encompass a major global marine biodiversity hot spot. We analyze the state of knowledge of marine biodiversity based on the geographic distribution of georeferenced species records and regional taxonomic lists. A total of 12,046 marine species are reported in this paper for the Caribbean region. These include representatives from 31 animal phyla, two plant phyla, one group of Chromista, and three groups of Protoctista. Sampling effort has been greatest in shallow, nearshore waters, where there is relatively good coverage of species records; offshore and deep environments have been less studied. Additionally, we found that the currently accepted classification of marine ecoregions of the Caribbean did not apply for the benthic distributions of five relatively well known taxonomic groups. Coastal species richness tends to concentrate along the Antillean arc (Cuba to the southernmost Antilles) and the northern coast of South America (Venezuela – Colombia), while no pattern can be observed in the deep sea with the available data. Several factors make it impossible to determine the extent to which these distribution patterns accurately reflect the true situation for marine biodiversity in general: (1) highly localized concentrations of collecting effort and a lack of collecting in many areas and ecosystems, (2) high variability among collecting methods, (3) limited taxonomic expertise for many groups, and (4) differing levels of activity in the study of different taxa

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality