Mixed Methods EvAluation of the high-volume low-complexity Surgical hUb pRogrammE (MEASURE): a mixed methods study protocol.

INTRODUCTION: The waiting list for elective surgery in England recently reached over 7.8 million people and waiting time targets have been missed since 2010. The high-volume low complexity (HVLC) surgical hubs programme aims to tackle the backlog of patients awaiting elective surgery treatment in England. This study will evaluate the impact of HVLC surgical hubs on productivity, patient care and the workforce. METHODS AND ANALYSIS: This 4-year project consists of six interlinked work packages (WPs) and is informed by the Consolidated Framework for Implementation Research. WP1: Mapping current and future HVLC provision in England through document analysis, quantitative data sets (eg, Hospital Episodes Statistics) and interviews with national service leaders. WP2: Exploring the effects of HVLC hubs on key performance outcomes, primarily the volume of low-complexity patients treated, using quasi-experimental methods. WP3: Exploring the impact and implementation of HVLC hubs on patients, health professionals and the local NHS through approximately nine longitudinal, multimethod qualitative case studies. WP4: Assessing the productivity of HVLC surgical hubs using the Centre for Health Economics NHS productivity measure and Lord Carter's operational productivity measure. WP5: Conducting a mixed-methods appraisal will assess the influence of HVLC surgical hubs on the workforce using: qualitative data (WP3) and quantitative data (eg, National Health Service (NHS) England's workforce statistics and intelligence from WP2). WP6: Analysing the costs and consequences of HVLC surgical hubs will assess their achievements in relation to their resource use to establish value for money. A patient and public involvement group will contribute to the study design and materials. ETHICS AND DISSEMINATION: The study has been approved by the East Midlands-Nottingham Research Ethics Committee 23/EM/0231. Participants will provide informed consent for qualitative study components. Dissemination plans include multiple academic and non-academic outputs (eg, Peer-reviewed journals, conferences, social media) and a continuous, feedback-loop of findings to key stakeholders (eg, NHS England) to influence policy development. TRIAL REGISTRATION: Research registry: Researchregistry9364 (https://www.researchregistry.com/browse-the-registry%23home/registrationdetails/64cb6c795cbef8002a46f115/).

SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?

Introduction: SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical of a different clade. Methods: Here we use high resolution ultra-deep sequencing to analyze SARS-CoV-2 mutant spectra. Results: In 6 out of 11 SARS-CoV-2 isolates from COVID-19 patients, the mutant spectrum of the spike (S)-coding region included two or more amino acids or deletions, that correspond to discordant viral clades. A similar observation is reported for laboratory populations of SARS-CoV-2 USA-WA1/2020, following a cell culture infection in the presence of remdesivir, ribavirin or their combinations. Moreover, some of the clade-discordant genome residues are found in the same haplotype within an amplicon. Discussion: We evaluate possible interpretations of these findings, and reviewed precedents for rapid selection of genomes with multiple mutations in RNA viruses. These considerations suggest that intra-host evolution may be sufficient to generate minority sequences which are closely related to sequences typical of other clades. The results provide a model for the origin of variants of concern during epidemic spread─in particular Omicron lineages─that does not require prolonged infection, involvement of immunocompromised individuals, or participation of intermediate, non-human hosts.

Sudden cardiac death triggered by minimal alcohol consumption in the context of novel PPA2 mutations in 2 unrelated families.

Biallelic variants in PPA2 gene cause a rare but lethal mitochondrial disorder. We describe the first four cases reported in Spain of PPA2 disease in two unrelated families. We have conducted a revision of the clinical history, necropsies, and postmortem genetic testing from probands, and clinical evaluation, genetic testing and blood transcript analysis in family members. All the cases harbored biallelic PPA2 variants in compound heterozygous status. Two brothers from family 1 suffered sudden death after a small first intake of alcohol in 2013 and 2022. The sister remains alive but affected with cardiomyopathy, extensive scar on cardiac imaging, and high sensitivity to alcohol intake. The three siblings carried PPA2 c.290A > G (p.Glu97Gly) novel missense variant and PPA2 c.513C > T (p.Cys171 = ) altering splicing site variant, both probably leading to mRNA degradation based on in-silico and transcript analyses. A teenager from family 2 suffered sudden death after a small intake of alcohol in 2018 and carried PPA2 c.683C > T (p.Pro228Leu) missense and PPA2 c.980_983del (p.Gln327fs) novel frameshift variant, both probably leading to abnormal protein structure. All cases were asymptomatic until adolescence. Furthermore, the sister in family 1 has survived as an asymptomatic adult. PPA2 disease can manifest as cardiac arrest in the young, especially after alcohol exposure. Our results show that PPA2 deficiency can be related to different pathogenicity mechanisms such as abnormal protein structure but also mRNA decay caused by synonymous or missense variants. Strict avoidance of alcohol consumption and early defibrillator implantation might prevent lethal arrhythmias in patients at risk.

Synergism between remdesivir and ribavirin leads to SARS-CoV-2 extinction in cell culture.

BACKGROUND AND PURPOSE: There is a need for effective anti-COVID-19 treatments, mainly for individuals at risk of severe disease such as the elderly and the immunosuppressed. Drug repositioning has proved effective in identifying drugs that can find a new application for the control of coronavirus disease, in particular COVID-19. The purpose of the present study was to find synergistic antiviral combinations for COVID-19 based on lethal mutagenesis. EXPERIMENTAL APPROACH: The effect of combinations of remdesivir and ribavirin on the infectivity of SARS-CoV-2 in cell culture has been tested. Viral populations were monitored by ultra-deep sequencing, and the decrease of infectivity as a result of the treatment was measured. KEY RESULTS: Remdesivir and ribavirin exerted a synergistic inhibitory activity against SARS-CoV-2, quantified both by CompuSyn (Chou-Talalay method) and Synergy Finder (ZIP-score model). In serial passage experiments, virus extinction was readily achieved with remdesivir-ribavirin combinations at concentrations well below their cytotoxic 50 value, but not with the drugs used individually. Deep sequencing of treated viral populations showed that remdesivir, ribavirin, and their combinations evoked significant increases of the number of viral mutations and haplotypes, as well as modification of diversity indices that characterize viral quasi-species. CONCLUSION AND IMPLICATIONS: SARS-CoV-2 extinction can be achieved by synergistic combination treatments based on lethal mutagenesis. In addition, the results offer prospects of triple drug treatments for effective SARS-CoV-2 suppression.

Impact of the Mediterranean Diet on the Gut Microbiome of a Well-Defined Cohort of Healthy Individuals.

A comprehensive understanding of gut microbiota in a clearly defined group of healthy individuals is essential when making meaningful comparisons with various diseases. The Mediterranean diet (MD), renowned for its potential health benefits, and the influence of adherence thereto on gut microbiota have become a focus of research. Our aim was to elucidate the impact of adherence to the MD on gut microbiota composition in a well-defined cohort. In this prospective study, healthy volunteers completed a questionnaire to provide demographic data, medical history, and dietary intake. Adherence was evaluated using the Med-DQI. The V4 region of the 16S rRNA gene was sequenced. Analysis of sequencing data and statistical analysis were performed using MOTHUR software and R. The study included 60 patients (51.7% females). Adherence correlated with alpha diversity, and higher values were recorded in good adherers. Good adherers had a higher abundance of Paraprevotella and Bacteroides (p < 0.001). Alpha diversity correlated inversely with fat intake and positively with non-starch polysaccharides (NSPs). Evenness correlated inversely with red meat intake and positively with NSPs. Predicted functional analysis highlighted metabolic pathway differences based on adherence to the MD. In conclusion, our study adds useful information on the relationship between the MD and the gut microbiome.

Seguimiento Funcional hasta Seis Meses después de Sobrevivir a Cuidados Intensivos: Lecciones aprendidas de un Estudio Chileno Multicéntrico / Functional follow-up six months after surviving intensive care: lessons learned from a Chilean multicenter study

Introducción. Las tasas de retención en los estudios de seguimiento oscilan entre el 32 y 100%, demostrando el desafío que implica realizar estudios longitudinales de sobrevivientes de la unidad de cuidados intensivos (UCI). Objetivo. Identificar las estrategias implementadas y lecciones aprendidas en un estudio prospectivo multicéntrico de seguimiento de sobrevivientes de la UCI durante la pandemia. Métodos. Estudio post-hoc de las lecciones aprendidas mediante encuestas y entrevistas dirigidas a explorar la experiencia de los investigadores y coordinadores del estudio IMPACCT COVID-19, realizado en siete centros chilenos entre octubre 2020 y abril 2021 evaluando el síndrome post-cuidados intensivos de sobrevivientes hasta seis meses después. Resultados. Identificamos ocho lecciones: 1) selección de instrumentos de medición, 2) identificación de centros participantes, 3) aprobación del estudio, 4) financiamiento, 5) capacitación de evaluadores, 6) coordinación/aseguramiento de calidad, 7) reclutamiento y 8) seguimiento de pacientes. Incluso durante el primer año de pandemia, reclutamos 252 pacientes a una tasa de 1,4 pacientes/día con una retención del 48% a los 6 meses de seguimiento. El uso de redes académicas existentes y las estrategias de comunicación entre investigadores, coordinadores y evaluadores fueron aspectos positivos; mientras que la fidelización con evaluadores al egreso de la UCI y con pacientes durante el seguimiento son aspectos que deberían considerarse en futuros estudios. Conclusiones. Se evaluaron más de 250 pacientes en seis meses durante la pandemia, con tasas de retención post UCI acorde a la literatura. Futuros estudios debiesen optimizar los procesos de medición y de seguimiento para minimizar la pérdida de pacientes.

Background. Retention rates of follow-up studies range from 32 to 100%, demonstrating the challenge to conduct longitudinal studies of intensive care unit (ICU) survivors. Objective. To identify the strategies implemented and lessons learned in a multicenter prospective follow-up study of ICU survivors during pandemic times. Methods. Post-hoc study of lessons learned through surveys and interviews aimed at exploring the experience of the researchers and coordinators of the IMPACCT COVID-19 study. The original study was performed in seven Chilean sites between October 2020 and April 2021 evaluating the post-intensive care syndrome of survivors up to six-month follow-up. Results. We identified eight lessons: 1) selection of measurement instruments, 2) identification of participating sites, 3) Study approval, 4) funding, 5) evaluators training, 6) coordination/quality assurance, 7) recruitment, and 8) patient follow-up. Even during the first year of the pandemic, we recruited 252 patients at a rate of 1.4 patients/day with a retention rate of 48% at 6 months of follow-up. The use of existing academic networks and communication strategies between researchers, coordinators and evaluators were positive aspects; while evaluators fidelity at ICU discharge and patient engagement during follow-up are aspects should be considered. Conclusions. More than 250 patients were evaluated in six months during the pandemic, with post-ICU retention rates consistent with the literature. Future studies should optimize measurement and monitoring processes to minimize patient atrition.

Incipient functional SARS-CoV-2 diversification identified through neural network haplotype maps.

Since its introduction in the human population, SARS-CoV-2 has evolved into multiple clades, but the events in its intrahost diversification are not well understood. Here, we compare three-dimensional (3D) self-organized neural haplotype maps (SOMs) of SARS-CoV-2 from thirty individual nasopharyngeal diagnostic samples obtained within a 19-day interval in Madrid (Spain), at the time of transition between clades 19 and 20. SOMs have been trained with the haplotype repertoire present in the mutant spectra of the nsp12- and spike (S)-coding regions. Each SOM consisted of a dominant neuron (displaying the maximum frequency), surrounded by a low-frequency neuron cloud. The sequence of the master (dominant) neuron was either identical to that of the reference Wuhan-Hu-1 genome or differed from it at one nucleotide position. Six different deviant haplotype sequences were identified among the master neurons. Some of the substitutions in the neural clouds affected critical sites of the nsp12-nsp8-nsp7 polymerase complex and resulted in altered kinetics of RNA synthesis in an in vitro primer extension assay. Thus, the analysis has identified mutations that are relevant to modification of viral RNA synthesis, present in the mutant clouds of SARS-CoV-2 quasispecies. These mutations most likely occurred during intrahost diversification in several COVID-19 patients, during an initial stage of the pandemic, and within a brief time period.

Impaired islet function with normal exocrine enzyme secretion is consistent across the head, body, and tail pancreas regions in type 1 diabetes.

Histopathological heterogeneity in human pancreas has been well documented; however, functional evidence at the tissue level is scarce. Herein we investigated in situ glucose-stimulated islet and carbachol-stimulated acinar cell secretion across the pancreas head (PH), body (PB), and tail (PT) regions in no diabetes (ND, n=15), single islet autoantibody-positive (1AAb+, n=7), and type 1 diabetes donors (T1D, <14 months duration, n=5). Insulin, glucagon, pancreatic amylase, lipase, and trypsinogen secretion along with 3D tissue morphometrical features were comparable across the regions in ND. In T1D, insulin secretion and beta-cell volume were significantly reduced within all regions, while glucagon and enzymes were unaltered. Beta-cell volume was lower despite normal insulin secretion in 1AAb+, resulting in increased volume-adjusted insulin secretion versus ND. Islet and acinar cell secretion in 1AAb+ were consistent across PH, PB and PT. This study supports low inter-regional variation in pancreas slice function and potentially, increased metabolic demand in 1AAb+.

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

Background: A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC). Methods: A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained. Results: A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed. Conclusions: The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL.

Analysis of the dermoscopic features of excised melanomas and their relation with tumor thickness in a tertiary hospital in Brazil.

BACKGROUND: Dermoscopy is a non-invasive, cost-effective tool useful in the assessment of pigmented lesions. The aim of this study was to analyze the dermoscopic features in excised melanomas in a tertiary hospital in Brazil and the influence of Breslow thickness on the dermoscopic features observed. METHODS: An observational, cross-sectional study in which dermoscopic images of 43 melanomas were evaluated. The patients were divided into three groups: in situ, thin invasive melanoma (Breslow thickness <1 mm), and thick invasive melanoma (Breslow thickness ≥1 mm). RESULTS: We studied 33 patients with 43 melanomas. Twenty-one (48.8%) were melanoma in situ, 16 (37.2%) were thin melanomas, and 6 (14%) were thick melanomas. The most frequent dermoscopic criteria observed in all cases were atypical pigment network, multiple colors (3 or more), asymmetrical blotches, and peripheral asymmetric dots and globules. There was a statistically significant difference in the three groups regarding the frequency of atypical vessels, white scar areas, blue-white veil, shiny white structures, and radial streaming. The group of invasive melanomas presented with a higher frequency and statistical significance (P < 0.05) of atypical vessels, white scar areas, blue-white veil, and shiny white structures when compared to in situ melanomas. The presence of radial streaming and blue-white veil was more frequent in thick invasive melanomas than in thin invasive melanomas. The presence of a higher number of structures was seen in invasive melanomas, with a median of 5 and 7.5 structures for thin and thick invasive tumors, respectively. CONCLUSIONS: In line with prior data, we identified an association between invasive melanomas and structures linked to fibrosis and tumor vascularity. Specifically, we noted the presence of atypical vessels, scar-like white areas, a blue-white veil, and shiny white structures. Also, a higher number of dermoscopic structures was seen in invasive melanomas. In thicker melanomas, we observed additional findings, including a higher frequency of radial streaming and a blue-white veil.

Fluoride anodic films on stainless-steel fomites to reduce transmission infections.

The growing concern arising from viruses with pandemic potential and multi-resistant bacteria responsible for hospital-acquired infections and outbreaks of food poisoning has led to an increased awareness of indirect contact transmission. This has resulted in a renewed interest to confer antimicrobial properties to commonly used metallic materials. The present work provides a full characterization of optimized fluoride anodic films grown in stainless steel 304L as well as their antimicrobial properties. Antibacterial tests show that the anodic film, composed mainly of chromium and iron fluorides, reduces the count and the percentage of the area covered by 50% and 87.7% for Pseudomonas aeruginosa and Stenotrophomonas maltophilia, respectively. Virologic tests show that the same treatment reduces the infectivity of the coronavirus HCoV-229E-GFP, in comparison with the non-anodized stainless steel 304L.IMPORTANCEThe importance of environmental surfaces as a source of infection is a topic of particular interest today, as many microorganisms can survive on these surfaces and infect humans through direct contact. Modification of these surfaces by anodizing has been shown to be useful for some alloys of medical interest. This work evaluates the effect of anodizing on stainless steel, a metal widely used in a variety of applications. According to the study, the fluoride anodic layers reduce the colonization of the surfaces by both bacteria and viruses, thus reducing the risk of acquiring infections from these sources.

Predictive factors for foot pain in the adult population.

BACKGROUND: Foot pain has been associated to factors like: fat, body mass index, age increased, female gender and the presence of pathologies. Although evidence is limited. The purpose is to determine the predictive factors for foot pain in the adult population. METHODS: From January to December 2021, 457 patients were > 18 years, gave signed informed consent to take part to this cross sectional study. All completed demographic data and various questionnaires related to pain: Foot Function Index, EuroQoL-5D and Visual Analogue Scale (foot pain). Anthropometric measurements were obtained using McPoil platform and foot posture was assessed by the Foot Posture Index (FPI). To determine whether a volume change is a predictive factor for foot pain, a parameter was established: the volumetric index for footwear (VIF). Factors linked to the presence of pain, including the considered VIF variables, were analyzed through multivariable logistic regression. RESULTS: Among the study population, 40.7% were male and 59.3% female. The mean age of 39.06 years and a body mass index of 25.58 Kg/cm2. The logistic regression model had a classification capability of 72.4%, a sensitivity of 72.3% and a specificity of 73%, in which, the predictors considered were the variables found to have a significant association with FFI-pain > 45 points,, showed that younger women, with a higher BMI, higher values of right FPI (pronation), poorer overall perceived health and with problems in walking were more likely to experience foot pain. CONCLUSION: Predictive factors for foot pain in the adult population include gender, age, Body Mass Index, FPI on the right foot, perceived health and mobility. Clinical implication, the presented measure aids physicians in assessing their patients´ foot pain likelihood.

Obstetric pulmonary embolism and long-term cardiovascular symptoms: a cross-sectional study in Western Mexico.

OBJECTIVES: Pulmonary embolism (PE) is an important cause of maternal mortality. There are several guidelines for its diagnosis and management, but there is little information regarding follow-up and frequency of long-term complications. The aim of the study was to determine the frequency of long-term cardiovascular symptoms in patients who had obstetric PE. METHODS: Cross-sectional study including patients who had PE during pregnancy or the puerperium. A telephone interview was conducted at least one year after PE, to determine the frequency of cardiovascular symptoms, general health, and COVID-19 infection, considering the study was conducted during the 2020 pandemic. RESULTS: In five years (2015-2019) there were eleven patients with PE, two died during the acute phase, and the rest (nine) were alive and able to answer our interview. Cardiovascular symptoms were common (6, 67 %), the most frequent were fatigue, edema, and mild dyspnea. Four patients (44 %) had slight limitation of physical activity and one (11 %) had PE recurrence. Of the six symptomatic patients four had obesity and one was overweight. CONCLUSIONS: There is a high frequency of long-term cardiovascular symptoms in patients who had PE during pregnancy or the puerperium. Stronger evidence is needed to design a long-term care pathway after obstetric PE.

Puzzles, challenges, and information reservoir of SARS-CoV-2 quasispecies.

Upon the emergence of SARS-CoV-2 in the human population, it was conjectured that for this coronavirus the dynamic intra-host heterogeneity typical of RNA viruses would be toned down. Nothing of this sort is observed. Here we review the main observations on the complexity and diverse composition of SARS-CoV-2 mutant spectra sampled from infected patients, within the framework of quasispecies dynamics. The analyses suggest that the information provided by myriads of genomic sequences within infected individuals may have a predictive value of the genomic sequences that acquire epidemiological relevance. Possibilities to reconcile the presence of broad mutant spectra in the large RNA coronavirus genome with its encoding a 3' to 5' exonuclease proofreading-repair activity are considered. Indeterminations in the behavior of individual viral genomes provide a benefit for the survival of the ensemble. We propose that this concept falls in the domain of "stochastic thinking," a notion that applies also to cellular processes, as a means for biological systems to face unexpected needs.

Recommendations for the individualised management of atypical hemolytic uremic syndrome in adults.

Background: Despite significant advances in therapeutic management of atypical hemolytic uremic syndrome (aHUS), guidelines are not timely updated and achieving a consensus on management recommendations remains a topic of ongoing discussion. Methods: A Scientific Committee with five experts was set up. A literature review was conducted and publications addressing the classification of aHUS, patient profiles and therapeutic approach were selected. Recommendations were proposed at an initial meeting, evaluated through an online questionnaire and validated during a second meeting. Results: Patients with confirmed or clear suspicion of aHUS should be treated with C5 inhibitors within 24 h of the diagnosis or suspicion of aHUS. Treatment monitoring and the decision to interrupt treatment should be individualised according to the risk of relapse and each patient's evolution. aHUS with a genetic variant or associated with pregnancy should be treated for at least 6-12 months; de novo aHUS associated with kidney transplant until renal function is recovered and genetic variants are ruled out; aHUS associated with malignant hypertension until genetic variants are ruled out; aHUS associated with non-kidney transplant, autoimmune diseases, infection-or drug-induced until the thrombotic microangiopathy is resolved. Patients with a high risk of relapse should be treated for longer than 6-12 months. Conclusion: These recommendations provides physicians who are not familiar with the disease with recommendations for the management of aHUS in adults. The experts who participated advocate early treatment, maintenance for at least 6-12 months and treatment interruption guided by genetic background, trigger factors, risk of relapse and evolution.

Genetic testing in focal segmental glomerulosclerosis: in whom and when?

Background: Genetic causes are increasingly recognized in patients with focal segmental glomerulosclerosis (FSGS), but it remains unclear which patients should undergo genetic study. Our objective was to determine the frequency and distribution of genetic variants in steroid-resistant nephrotic syndrome FSGS (SRNS-FSGS) and in FSGS of undetermined cause (FSGS-UC). Methods: We performed targeted exome sequencing of 84 genes associated with glomerulopathy in patients with adult-onset SRNS-FSGS or FSGS-UC after ruling out secondary causes. Results: Seventy-six patients met the study criteria; 24 presented with SRNS-FSGS and 52 with FSGS-UC. We detected FSGS-related disease-causing variants in 27/76 patients (35.5%). There were no differences between genetic and non-genetic causes in age, proteinuria, glomerular filtration rate, serum albumin, body mass index, hypertension, diabetes or family history. Hematuria was more prevalent among patients with genetic causes. We found 19 pathogenic variants in COL4A3-5 genes in 16 (29.3%) patients. NPHS2 mutations were identified in 6 (16.2%) patients. The remaining cases had variants affecting INF2, OCRL, ACTN4 genes or APOL1 high-risk alleles. FSGS-related genetic variants were more common in SRNS-FSGS than in FSGS-UC (41.7% vs 32.7%). Four SRNS-FSGS patients presented with NPHS2 disease-causing variants. COL4A variants were the most prevalent finding in FSGS-UC patients, with 12 patients carrying disease-causing variants in these genes. Conclusions: FSGS-related variants were detected in a substantial number of patients with SRNS-FSGS or FSGS-UC, regardless of age of onset of disease or the patient's family history. In our experience, genetic testing should be performed in routine clinical practice for the diagnosis of this group of patients.

Six-month post-intensive care outcomes during high and low bed occupancy due to the COVID-19 pandemic: A multicenter prospective cohort study.

INTRODUCTION: The COVID-19 pandemic can be seen as a natural experiment to test how bed occupancy affects post-intensive care unit (ICU) patient's functional outcomes. To compare by bed occupancy the frequency of mental, physical, and cognitive impairments in patients admitted to ICU during the COVID-19 pandemic. METHODS: Prospective cohort of adults mechanically ventilated >48 hours in 19 ICUs from seven Chilean public and private hospitals. Ninety percent of nationwide beds occupied was the cut-off for low versus high bed occupancy. At ICU discharge, 3- and 6-month follow-up, we assessed disability using the World Health Organization Disability Assessment Schedule 2.0. Quality of life, mental, physical, and cognitive outcomes were also evaluated following the core outcome set for acute respiratory failure. RESULTS: We enrolled 252 participants, 103 (41%) during low and 149 (59%) during high bed occupancy. Patients treated during high occupancy were younger (P50 [P25-P75]: 55 [44-63] vs 61 [51-71]; p<0.001), more likely to be admitted due to COVID-19 (126 [85%] vs 65 [63%]; p<0.001), and have higher education qualification (94 [63%] vs 48 [47%]; p = 0.03). No differences were found in the frequency of at least one mental, physical or cognitive impairment by bed occupancy at ICU discharge (low vs high: 93% vs 91%; p = 0.6), 3-month (74% vs 63%; p = 0.2) and 6-month (57% vs 57%; p = 0.9) follow-up. CONCLUSIONS: There were no differences in post-ICU outcomes between high and low bed occupancy. Most patients (>90%) had at least one mental, physical or cognitive impairment at ICU discharge, which remained high at 6-month follow-up (57%). CLINICAL TRIAL REGISTRATION: NCT04979897 (clinicaltrials.gov).

Maternal dietary patterns and acute leukemia in infants: results from a case control study in Mexico.

Background: Childhood cancer is the leading cause of disease-related mortality among children aged 5-14 years in Mexico, with acute leukemia being the most common cancer among infants. Examining the overall dietary patterns allows for a comprehensive assessment of food and nutrient consumption, providing a more predictive measure of disease risk than individual foods or nutrients. This study aims to evaluate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in Mexican infants. Methods: A hospital-based case-control study was conducted, comparing 109 confirmed acute leukemia cases with 152 age-matched controls. All participants (≤24 months) were identified at hospitals in Mexico City between 2010 and 2019. Data on a posteriori dietary patterns and other relevant variables were collected through structured interviews and dietary questionnaires. Multivariate logistic regression was employed to estimate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in infants. Results: The "Balanced & Vegetable-Rich" pattern, characterized by a balanced consumption of various food groups and higher vegetable intake, exhibited a negative association with acute leukemia when compared to the "High Dairy & Cereals" Pattern (adjusted odds ratio [OR] = 0.51; 95% confidence interval [CI]: 0.29, 0.90). We observed that mothers who gave birth to girls and adhered to a healthy dietary pattern during pregnancy exhibited significantly lower odds of their children developing AL compared to those who gave birth to boys [OR = 0.32 (95% CI 0.11, 0.97)]. Our results underscore the significance of maternal nutrition as a modifiable factor in disease prevention and the importance of prenatal health education.