Development and validation of a model to predict ceiling of care in COVID-19 hospitalized patients.

BACKGROUND: Therapeutic ceiling of care is the maximum level of care deemed appropiate to offer to a patient based on their clinical profile and therefore their potential to derive benefit, within the context of the availability of resources. To our knowledge, there are no models to predict ceiling of care decisions in COVID-19 patients or other acute illnesses. We aimed to develop and validate a clinical prediction model to predict ceiling of care decisions using information readily available at the point of hospital admission. METHODS: We studied a cohort of adult COVID-19 patients who were hospitalized in 5 centres of Catalonia between 2020 and 2021. All patients had microbiologically proven SARS-CoV-2 infection at the time of hospitalization. Their therapeutic ceiling of care was assessed at hospital admission. Comorbidities collected at hospital admission, age and sex were considered as potential factors for predicting ceiling of care. A logistic regression model was used to predict the ceiling of care. The final model was validated internally and externally using a cohort obtained from the Leeds Teaching Hospitals NHS Trust. The TRIPOD Checklist for Prediction Model Development and Validation from the EQUATOR Network has been followed to report the model. RESULTS: A total of 5813 patients were included in the development cohort, of whom 31.5% were assigned a ceiling of care at the point of hospital admission. A model including age, COVID-19 wave, chronic kidney disease, dementia, dyslipidaemia, heart failure, metastasis, peripheral vascular disease, chronic obstructive pulmonary disease, and stroke or transient ischaemic attack had excellent discrimination and calibration. Subgroup analysis by sex, age group, and relevant comorbidities showed excellent figures for calibration and discrimination. External validation on the Leeds Teaching Hospitals cohort also showed good performance. CONCLUSIONS: Ceiling of care can be predicted with great accuracy from a patient's clinical information available at the point of hospital admission. Cohorts without information on ceiling of care could use our model to estimate the probability of ceiling of care. In future pandemics, during emergency situations or when dealing with frail patients, where time-sensitive decisions about the use of life-prolonging treatments are required, this model, combined with clinical expertise, could be valuable. However, future work is needed to evaluate the use of this prediction tool outside COVID-19.

Pulmonary Matrix-derived Hydrogels from Patients with Idiopathic Pulmonary Fibrosis Induce a Proinflammatory State in Lung Fibroblasts In Vitro.

Idiopathic pulmonary fibrosis (IPF), one of the most common forms of interstitial lung disease, is a poorly understood, chronic, and often fatal fibroproliferative condition with only two FDA-approved medications. Understanding the pathobiology of the fibroblast in IPF is critical to evaluating and discovering novel therapeutics. Using a decellularized lung matrix derived from IPF patients, we generate three-dimensional (3D) hydrogels as in vitro models of lung physiology and characterize the phenotype of fibroblasts seeded into the hydrogels. When cultured in IPF ECM hydrogels, IPF fibroblasts display differential contractility compared to their normal counterparts, lose the classical myofibroblast marker α-smooth muscle actin, and increase expression of proinflammatory cytokines compared to fibroblasts seeded two-dimensionally (2D) on tissue culture dishes. We validate this proinflammatory state in fibroblast-conditioned media studies with monocytes and monocyte-derived macrophages. These findings add to a growing understanding of the lung microenvironment effect on fibroblast phenotypes, shed light on the potential role of fibroblasts as immune signaling hubs during lung fibrosis, and suggest intervention in fibroblast-immune cell crosstalk as a possible novel therapeutic avenue.

Longitudinal Assessment of Left Atrial Remodeling in Patients With Chronic Severe Aortic Regurgitation.

BACKGROUND: There are significant sex and age differences in left ventricular (LV) remodeling that may lead to disparity in outcomes when used to inform the timing of aortic regurgitation (AR) intervention. OBJECTIVES: The aim of this study was to examine whether left atrial (LA) parameters might represent better criteria than LV parameters to inform the timing of AR intervention. METHODS: Using data on patients with moderate to severe or severe AR with serial echocardiography (2010-2016), the longitudinal trends in left atrial volume index (LAVI) and left atrial reservoir strain (LAr) were evaluated by sex and age. The incremental utility of these parameters in predicting adverse events over LV parameters was also determined. RESULTS: In 525 patients (25.7% women) with 1,687 echocardiograms over a median follow-up period of 2.0 years (Q1-Q3: 1.0-3.6 years), there was significant increase in LAVI (1.0 mL/m2 per year [95% CI: 0.76-1.2 mL/m2 per year]) and decrease in LAr (-1.3% per year [95% CI: -1.6% to -0.92%]), without a significant interaction by sex or age category (P for interaction ≥ 0.17). In addition, both LAVI and LAr were significant predictors of adverse events independent of LV parameters. The optimal discriminatory thresholds were 37 mL/m2 for LAVI and 35% for LAr. These thresholds were similar across categories of sex and age. Within the relatively short-term follow-up, surgery was associated with survival benefit among patients with LAVI ≥37 mL/m2 (HR: 0.33 [95% CI: 0.15-0.72]; P = 0.006) but was not statistically significant among patients with LAVI <37 mL/m2 (HR: 0.46 [95% CI: 0.18-1.17]; P = 0.09). Similarly, surgery was associated with survival for the subgroup with LAr ≤35% but not among those with LAr >35%. CONCLUSIONS: Unlike LV remodeling, LA remodeling demonstrates a similar rate of progression between categories of sex and age among patients with AR. In addition, LA parameters provide incremental prognostic value over LV parameters.

Plant-parasitic Nematodes Associated with Grasses Grown for Seed in the Willamette Valley of Oregon.

Plant-parasitic nematodes (PPN) are an understudied pathogen group in the Oregon cool-season grass seed cropping system. In this survey, the PPN associated with annual ryegrass, bentgrass, fine fescue, orchardgrass, perennial ryegrass, and tall fescue were determined. Thirty-seven fields were sampled in the 2022 or 2023 growing season by collecting 10 soil cores in each of six 100-m transects for nematode extraction and visual identification. PerMANOVA testing indicated significant differences in PPN community composition across grass host and sampling time. Pratylenchus and Meloidogyne were the most commonly encountered nematodes, with maximum population densities of 1,984 and 2,496 nematodes/100 g soil, respectively. Sequencing of the COX1 gene region indicated the presence of P. crenatus, P. fallax, P. neglectus, P. penetrans, and P. thornei, with some of these species being detected for the first time on these grass hosts. The only Meloidogyne sp. found in these grasses was M. nassi, based upon sequencing of the ITS gene region. This first-of-its-kind survey indicates the need for further assessment of the impact of these PPNs on yield and stand longevity in cool-season grass seed fields in Oregon.

Stability mapping of bipartite tight-binding graphs with losses and gain: PTPT-symmetry and beyond.

We consider bipartite tight-binding graphs composed by N nodes split into two sets of equal size: one set containing nodes with on-site loss, the other set having nodes with on-site gain. The nodes are connected randomly with probability p. Specifically, we measure the connectivity between the two sets with the parameter α, which is the ratio of current adjacent pairs over the total number of possible adjacent pairs between the sets. For general undirected-graph setups, the non-Hermitian Hamiltonian H(γ,α,N) of this model presents pseudo-Hermiticity, where γ is the loss/gain strength. However, we show that for a given graph setup H(γ,α,N) becomes PT-symmetric. In both scenarios (pseudo-Hermiticity and PT-symmetric), depending on the parameter combination, the spectra of H(γ,α,N) can be real even when it is non-Hermitian. Then we demonstrate, for both setups, that there is a well-defined sector of the γα-plane (which grows with N) where the spectrum of H(γ,α,N) is predominantly real.

Unmasking the Mimic: Radionecrotic Lesion Masquerading as Brain Neoplasia on Magnetic Resonance Imaging.

Corpus callosotomy is a therapeutic approach for drug-resistant epilepsy, with positive outcomes observed in managing atonic seizures. Despite a decline in its usage, radiosurgical callosotomy remains a viable option for drug-resistant epilepsy due to its low risks of post-radiation neoplasia, albeit not with exceptions. Brain radionecrosis is characterized by tissue death and vascular endothelial damage following the procedure. Despite the low risk of intracranial secondary malignancy associated with radiation in some cases, post-radiation lesions might present with distinct characteristics needing a thorough diagnostic approach. Herein, we present a unique case of a patient with focal epilepsy who developed a radionecrotic lesion following radiosurgical callosotomy, affecting the anterior cingulate cortex, and mimicking a central nervous system (CNS) tumor. Molecular imaging techniques, including 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT) and 11C-acetate PET/CT scans, were employed to differentiate the lesion from a tumor. This case underscores the importance of considering radionecrosis as a differential diagnosis in patients who undergo radiosurgical callosotomy presenting with ring-like enhancement lesions on magnetic resonance imaging (MRI).

The consensus of the Asociación Mexicana de Gastroenterología on the diagnosis and treatment of gastroesophageal reflux and gastroesophageal reflux disease in infants.

Gastroesophageal reflux (GER) is a frequent normal phenomenon in children of any age. It is more common in infants, in whom the majority of episodes are short-lived and cause no other symptoms or complications, differentiating it from gastroesophageal reflux disease (GERD). The diagnosis and management of GER and GERD continue to be a challenge for the physician. Therefore, the aim of the Asociación Mexicana de Gastroenterología was to adapt international documents to facilitate their adoption by primary care physicians, with the goal of standardizing quality of care and reducing the number of diagnostic tests performed and inappropriate medication use. The ADAPTE methodology was followed, and the recommendations were approved utilizing the Delphi strategy. The executive committee carried out the review of the guidelines, position papers, and international reviews that met the a priori quality criteria and possible applicability in a local context. The recommendations were taken from those sources and adapted, after which they were approved by the working group. The consensus consists of 25 statements and their supporting information on the diagnosis and treatment of GER and GERD in infants. The adapted document is the first systematic effort to provide an adequate consensus for use in Mexico, proposing a practical approach to and management of GER and GERD for healthcare providers.

Differential accumulation of human ß-amyloid and tau from enriched extracts in neuronal and endothelial cells.

While Aß and Tau cellular distribution has been largely studied, the comparative internalization and subcellular accumulation of Tau and Aß isolated from human brain extracts in endothelial and neuronal cells has not yet been unveiled. We have previously demonstrated that controlled enrichment of Aß from human brain extracts constitutes a valuable tool to monitor cellular internalization in vitro and in vivo. Herein, we establish an alternative method to strongly enrich Aß and Tau aggregates from human AD brains, which has allowed us to study and compare the cellular internalization, distribution and toxicity of both proteins within brain barrier endothelial (bEnd.3) and neuronal (Neuro2A) cells. Our findings demonstrate the suitability of human enriched brain extracts to monitor the intracellular distribution of human Aß and Tau, which, once internalized, show dissimilar sorting to different organelles within the cell and differential toxicity, exhibiting higher toxic effects on neuronal cells than on endothelial cells. While tau is strongly concentrated preferentially in mitochondria, Aß is distributed predominantly within the endolysosomal system in endothelial cells, whereas the endoplasmic reticulum was its preferential location in neurons. Altogether, our findings display a picture of the interactions that human Aß and Tau might establish in these cells.

Riesgo de mortalidad en candidemia en niños oncohematológicos: revisión sistemática / Mortality risk in candidemia in children with cancer and blood disorders: a systematic review

Introducción: La tasa de mortalidad de la candidemia es variable, pero puede estar influenciada por la patología de base, en especial aquella que condiciona la presencia de neutropenia. En niños con patología oncohematológica, son pocos los trabajos que han abordado la mortalidad relacionada a candidemias y sus factores asociados. Las preguntas que promueven esta revisión sistemática, son: ¿Cuáles son las características epidemiológicas, clínicas y de evolución de los pacientes pediátricos oncohematológicos con candidemia? ¿Cuál es la mortalidad relacionada con esta entidad? Materiales y métodos: Revisión sistemática de la literatura. Se utilizaron los siguientes términos de búsqueda: candidemia por Candida spp. y los siguientes filtros humanos, niños y adolescentes y patología oncohematológica. Se revisaron los artículos publicados en inglés, español o francés hasta el 21 de septiembre de 2023. Las referencias bibliográficas de los artículos incluidos se revisaron manualmente para identificar estudios relevantes adicionales. Resultados: Se encontraron 66 artículos. Del análisis cualitativo realizado en sus textos completos, quedaron finalmente 4 estudios que se consideró que cumplían con los criterios de inclusión. Todos los artículos seleccionados sumaron 191 pacientes con diversas patologías oncohematológicas. La presencia de accesos vasculares fue frecuente en esta serie y la no extracción del catéter venoso central fue el factor más prevalente entre los que fallecieron. El agente infectante predominante fue Candida no albicans y la mortalidad osciló entre el 11,3 y el 31% con una mediana de 25%. No fue posible establecer si la especie de Candida influía en la letalidad

Introduction: The mortality rate of candidemia is variable, but may be influenced by underlying diseases, especially those causing neutropenia. In children with cancer and blood disorders, few studies have addressed mortality related to candidemia and its associated factors. The questions that motivated this systematic review were: What are the epidemiological, clinical and outcome characteristics of pediatric cancer patients with candidemia? What is the mortality related to this condition? Materials and methods: Systematic review of the literature. The following search terms were used: Candida spp., candidemia, with the following filters: human, children and adolescents, and cancer and blood disorders. Articles published in English, Spanish, or French up to September 21, 2023 were reviewed. References of included articles were manually reviewed to identify additional relevant studies. Results: 66 articles were identified. From the qualitative analysis carried out on their full texts, 4 studies that were considered to meet the inclusion criteria were finally selected. The selected articles included a total of 191 patients with various types of cancer and blood disorders. The presence of vascular access was common in this series and failure to remove the central venous catheter was the most prevalent factor among those who died. The predominant infectious agent was non-albicans Candida and mortality ranged from 11.3% to 31% with a median of 25%. It was not possible to establish whether Candida species influenced mortality.

Retrospective analysis of regional anaesthesia in hip surgery: A clinical audit.

INTRODUCTION: Total hip arthroplasty is one of the most frequent surgical interventions in the hospital setting. Nonetheless, the ideal method to manage post-operative pain is still unknown. Multimodal analgesia techniques based on regional anaesthesia are amongst the most promising solutions. OBJECTIVES: The aim of this study was to evaluate postoperative pain after total hip arthroplasty according to whether peripheral nerve block was performed (femoral block, fascia iliaca block and pericapsular nerve group block). Intravenous morphine consumption during the patient's stay in the post-anaesthesia care unit was measured, as well as the number of opioid rescues at 24 and 48 h post intervention. As secondary objectives, the prevalence of nerve injury, prolonged quadricipital block, and morphine consumption were established according to other variables of interest. MATERIALS AND METHODS: In this observational retrospective study, data was collected from the electronic medical record of 656 traumatological surgery patients from April 2018 to August 2020, with the following inclusion criteria: over 18 years old, ASA I-III, primary total hip arthroplasty under general anaesthesia or subarachnoid anaesthesia (only with hyperbaric bupivacaine) and use of levobupivacaine for peripheral nerve block. RESULTS: A total of 362 patients were selected. The main surgical indication was coxarthrosis (61.3%), followed by hip fracture (22.6%). Peripheral nerve blocks were performed on 169 patients (66.3% femoral, 27.7% PENG, and 6.0% fascia iliaca). Mean postoperative opioid consumption in PACU was lower in patients in who received a PENG (2.2 mg) or a femoral (3.27 mg) block, compared to those who received neither (6.69 mg). There were no differences in opioid rescues at 24 and 48 h after the procedure. Nerve injury incidence was low (.8%), and not associated with nerve blocks. The incidence of prolonged quadricipital paralysis was also low (1.3%), and was mainly associated with femoral nerve block (75% of cases). CONCLUSIONS: This retrospective study supports the use of regional blocks as opioid-sparing techniques, highlighting their role in rapid functional recovery with no motor impairment.

Achievements and challenges in the health of Mexican women, 1990 and 2019: ecological analysis based on the global burden of disease data.

OBJECTIVES: To describe the burden and causes of disease in Mexican women in 1990 and 2019, based on the data disaggregation by age groups and states. Also, to evaluate the relationship of years of healthy life lost with the Socio-demographic Index (SDI) and with the Healthcare Access and Quality (HAQ) Index. STUDY DESIGN: This was an ecological descriptive study. METHODS: Based on the Global Burden of Disease, Injuries, and Risk Factors Study study, the age-standardized and age-specific rates for mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) were reported. RESULTS: At the national level, the all-cause age-standardized rates for Mexican women decreased in mortality -28.8%; YLLs -39.8%; YLDs -1.3%; and DALYs -26.2%. For 2019, the indicators analyzed had the worst performances in Chiapas and Chihuahua, while women in Sinaloa had the lowest age-standardized rates. In 1990, it is worth noting that there was a remarkable presence of CDs, mainly in YLLs. In all age groups, diabetes mellitus was the leading cause of DALYs in Mexico's 32 states, followed by CKD (in 24 states), and ischemic heart disease (in 18 states). In both 1990 and 2019, a negative and statistically significant correlation between DALYs and the HAQ Index was evident. The correlation between DALYs and the SDI was only significant in 1990. CONCLUSION: In the last 30 years, the burden of disease on Mexican women has undergone substantial changes that reflect progress in the improvement of their health conditions. However, the current scenario is complex because the convergence of communicable diseases, non-communicable diseases, and injuries is evident, which implies important challenges that must be addressed as soon as possible.

Generation of a bank of clinical-grade, HLA-homozygous iPSC lines with high coverage of the Spanish population.

BACKGROUND: Induced pluripotent stem cell (iPSC)-derived cell therapies are an interesting new area in the field of regenerative medicine. One of the approaches to decrease the costs of iPSC-derived therapies is the use of allogenic homozygous human leukocyte antigen (HLA)-matched donors to generate iPSC lines and to build a clinical-grade iPSC bank covering a high percentage of the Spanish population. METHODS: The Spanish Stem Cell Transplantation Registry was screened for cord blood units (CBUs) homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes. Seven donors were selected with haplotypes covering 21.37% of the haplotypes of the Spanish population. CD34-positive hematopoietic progenitors were isolated from the mononuclear cell fraction of frozen cord blood units from each donor by density gradient centrifugation and further by immune magnetic labeling and separation using purification columns. Purified CD34 + cells were reprogrammed to iPSCs by transduction with the CTS CytoTune-iPS 2.1 Sendai Reprogramming Kit. RESULTS: The iPSCs generated from the 7 donors were expanded, characterized, banked and registered. Master cell banks (MCBs) and working cell banks (WCBs) from the iPSCs of each donor were produced under GMP conditions in qualified clean rooms. CONCLUSIONS: Here, we present the first clinical-grade, iPSC haplobank in Spain made from CD34 + cells from seven cord blood units homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes within the Spanish population. We describe their generation by transduction with Sendai viral vectors and their GMP-compliant expansion and banking. These haplolines will constitute starting materials for advanced therapy medicinal product development (ATMP).

Usefulness of resuscitative endovascular balloon occlusion of the aorta (REBOA) in controlling puerperal bleeding in patients with abnormal placental implantation.

BACKGROUND AND AIMS: Abnormalities of placental implantation, which make up the spectrum of placenta accreta, are associated with high maternal morbidity and mortality due to massive bleeding during delivery. Placing aortic occlusion balloons helps control the bleeding, facilitating surgical intervention. A new device, resuscitative endovascular balloon occlusion of the aorta (REBOA), minimizes the risks and complications associated with the placement of traditional aortic balloons and is also efficacious in controlling bleeding. The aim of this study is to evaluate the usefulness, efficacy, and safety of REBOA in puerperal bleeding due to abnormalities of placental implantation. MATERIAL AND METHODS: Between November 2019 and November 2021, our interventional radiology team placed six REBOA devices in six women scheduled for cesarean section due to placenta accrete. RESULTS: Mean blood loss during cesarean section after REBOA (3507.5 mL) was similar to the amounts reported for other aortic balloons. The mean number of units of packed red blood cells required for transfusion was 3.5. Using REBOA provided the surgical team with adequate conditions to perform the surgery. There were no complications derived from REBOA, and the mean ICU stay was <2 days. CONCLUSION: The technical characteristics of the REBOA device make it a safe and useful alternative for controlling massive bleeding in patients with placenta accreta.

Nuclear Charge Radius of

Collinear laser spectroscopy was performed on the isomer of the aluminium isotope ^{26m}Al. The measured isotope shift to ^{27}Al in the 3s^{2}3p ^{2}P_{3/2}^{○}→3s^{2}4s ^{2}S_{1/2} atomic transition enabled the first experimental determination of the nuclear charge radius of ^{26m}Al, resulting in R_{c}=3.130(15) fm. This differs by 4.5 standard deviations from the extrapolated value used to calculate the isospin-symmetry breaking corrections in the superallowed ß decay of ^{26m}Al. Its corrected Ft value, important for the estimation of V_{ud} in the Cabibbo-Kobayashi-Maskawa matrix, is thus shifted by 1 standard deviation to 3071.4(1.0) s.

Cohort study to assess the prevalence of prolonged QT and arrhythmias in critically ill patients during the early phase of the COVID-19 pandemic.

INTRODUCTION: Patients with SARS-CoV-2 infection may present cardiovascular involvement including myocarditis, arrhythmias and QT interval prolongation. Our objective was to evaluate the impact of COVID-19 and its treatment on ventricular repolarization and development of arrhythmias in critically ill patients. METHODS: Retrospective cohort study of critically ill COVID-19 patients during a 3-month period in whom at least one ECG was available. Relevant clinical data and specific treatment administered for COVID-19 were recorded. Prolonged QTc was considered prolonged when it measured ≥ 460 ms in women and ≥450 ms in men. The incidence and type of arrhythmias during the same period were recorded. RESULTS: A total of 77 patients with a mean age of 62 ±â€¯13 years, 20 women and 57 men, were evaluated. Sixty percent of the patients were hypertensive, 52% had a BMI > 30, and 70% developed acute renal failure during admission. Some 56% of the patients presented QTc prolongation. Forty-four percent presented some type of arrhythmia during their stay in the ICU, 21% of which were atrial arrhythmias. Overall mortality was 53%, with no differences between patients with or without prolonged QTc. CONCLUSIONS: In our series, a high proportion of critical patients with COVID-19 presented prolonged QTc and arrhythmias. The factors involved have been related to the elevation of cardiac biomarkers, the myocardial involvement of the virus and concomitant medication received in the ICU.