Dynamics of HLA and angiotensin II type 1 receptor antibodies during pregnancy.

BACKGROUND: Alloantibodies, especially anti-human leukocyte antigen antibodies (HLA antibodies), and autoantibodies, as angiotensin II type 1 receptor antibodies (AT1R antibodies), may complicate the access and the course of transplantation. Pregnancy is a known source of HLA antibodies, with most studies evaluating pregnancy-induced sensitization by complement-dependent cytotoxicity assays, mainly after childbirth. AT1R antibodies have been evaluated in the context of preeclampsia. We aimed to evaluate pregnancy as a natural source of HLA antibodies and AT1R antibodies, their dynamics along gestation and the potential factors involved in antibody appearance. METHODS: Serum samples from pregnant women were collected during the three trimesters of pregnancy (1T, 2T, 3T). Presence of HLA antibodies was assessed by screening beads on Luminex and AT1R antibodies by ELISA. RESULTS: A cohort of 138 pregnant women were included. Samples from all were tested in 1T, 127 in 2T and 102 in 3T. HLA antibodies increased from 29.7 % (1T) to 38.2 % (3T). AT1R antibodies were stable around 30 % along pregnancy. Up to 43.2 % multiparous women had HLA antibodies, with a similar proportion of class I and class II antibodies. In primiparous women HLA antibodies increased along pregnancy (from 17.6 % to 34.1 %), with predominance of class II HLA antibodies. AT1R antibodies were not different in primiparous and multiparous women. CONCLUSIONS: Pregnancy is a relevant source of HLA antibodies sensitization, but not of AT1R antibodies. HLA antibodies increased clearly in primiparous women with predominance of class II. The use of newer solid-phase techniques on Luminex evidence a higher degree of HLA sensitization during pregnancy.

Mielitis transversa aguda asociada a Covid-19. Reporte de caso

Desde el inicio de la pandemia por COVID-19 (coronavirus disease), en el 2019, se han descrito numerosas manifestaciones clínicas de la enfermedad causada por este virus, destacando el compromiso respiratorio, hematológico, cardiovascular y neurológico. Dentro de las manifestaciones y/o complicaciones neurológicas, se encuentra la mielitis aguda transversa por COVID-19(1), cuyo diagnóstico se ha realizado principalmente clínico-imagenológico y PCR (reacción de polimerasa en cadena), o serología (+) para COVID-19, con manejos y resultados no siempre afortunados. Presentamos el caso de un paciente con mielitis aguda transversa longitudinalmente extensa en relación a COVID-19, tratada con éxito clínico con rituximab.

Since the beginning of the COVID-19 pandemic in 2019, numerous clinical manifestations of the disease caused by this virus have been described, highlighting respiratory, hematological, cardiovascular, and neurological compromise. Among the neurological manifestations and/or complications, there is acute transverse myelitis due to COVID-19(1), whose diagnosis has been made mainly clinical-imaging and PCR or serology (+) for COVID-19, with management and results not always lucky. We present the case of a patient with longitudinally extensive acute transverse myelitis in relation to COVID-19, treated with clinical success with rituximab.

Spatiotemporal variability in socioeconomic inequalities in COVID-19 vaccination in Catalonia, Spain.

OBJECTIVES: Socioeconomic inequalities have played a significant role in the unequal coverage of the COVID-19 vaccine. The objectives of this study were to (1) assess the socioeconomic inequalities in COVID-19 vaccination coverage in Catalonia, Spain; (2) analyse the spatial variation over time of these inequalities; and (3) assess variations in time and space in the effect of vaccination on inequalities in COVID-19 outcomes. STUDY DESIGN: A mixed longitudinal ecological study design was used. METHODS: Catalonia is divided in to 373 Basic Health Areas. Weekly data from these Basic Health Areas were obtained from the last week of December 2020 until the first week of March of 2022. A joint spatio-temporal model was used with the dependent variables of vaccination and COVID-19 outcomes, which were estimated using a Bayesian approach. The study controlled for observed confounders, unobserved heterogeneity, and spatial and temporal dependencies. The study allowed the effect of the explanatory variables on the dependent variables to vary in space and in time. RESULTS: Areas with lower socioeconomic level were those with the lowest vaccination rates and the highest risk of COVID-19 outcomes. In general, individuals in areas that were located in the upper two quartiles of average net income per person and in the lower two quartiles of unemployment rate (i.e., the least economically disadvantaged) had a higher propensity to be vaccinated than those in the most economically disadvantaged areas. In the same sense, the greater the percentage of the population aged ≥65 years, the higher the propensity to be vaccinated, while areas located in the two upper quartiles of population density and areas with a high percentage of poor housing had a lower propensity to be vaccinated. Higher vaccination rates reduced the risk of COVID-19 outcomes, while COVID-19 outcomes did not influence the propensity to be vaccinated. The effects of the explanatory variables were not the same in all areas or between the different waves of the pandemic, and clusters of excess risk of low vaccination in the most disadvantaged areas were detected. CONCLUSIONS: COVID-19 vaccination inequalities in the most disadvantaged areas could be a result of structural barriers, such as the lack of access to information about the vaccination process, and/or logistical challenges, such as the lack of transportation, limited Internet access or difficulty in scheduling appointments. Public health strategies should be developed to mitigate these barriers and reduce vaccination inequalities.

Short-term effects of air pollution and noise on emergency hospital admissions in Madrid and economic assessment.

INTRODUCTION: The aim of this study was to study the effect of air pollution and noise has on the population in Madrid Community (MAR) in the period 2013-2018, and its economic impact. METHODS: Time series study analysing emergency hospital admissions in the MAR due to all causes (ICD-10: A00-R99), respiratory causes (ICD-10: J00-J99) and circulatory causes (ICD-10: I00-I99) across the period 2013-2018. The main independent variables were mean daily PM2.5, PM10, NO2, 8-h ozone concentrations, and noise. We controlled for meteorological variables, Public Holidays, seasonality, and the trend and autoregressive nature of the series, and fitted generalised linear models with a Poisson regression link to ascertain the relative risks and attributable risks. In addition, we made an economic assessment of these hospitalisations. RESULTS: The following associations were found: NO2 with admissions due to natural (RR: 1.007, 95% CI: 1.004-1.011) and respiratory causes (RR: 1.012, 95% CI: 1.005-1.019); 8-h ozone with admissions due to natural (RR: 1.049, 95% CI: 1.014-1.046) and circulatory causes (RR: 1.088, 95% CI: 1.039-1.140); and diurnal noise (LAeq7-23h) with admissions due to natural (RR: 1.001, 95% CI: 1.001-1.002), respiratory (RR: 1.002, 95% CI: 1.001-1.003) and circulatory causes (RR: 1.003, 95% CI: 1.002-1.005). Every year, a total of 8246 (95% CI: 4580-11,905) natural-cause admissions are attributable to NO2, with an estimated cost of close on €120 million and 5685 (95% CI: 2533-8835) attributed to LAeq7-23h with an estimated cost of close on €82 million. CONCLUSIONS: Nitrogen dioxide, ozone and noise are the main pollutants to which a large number of hospitalisations in the MAR are attributed, and are thus responsible for a marked deterioration in population health and high related economic impact.

Incidence and Severity of Community- and Hospital-Acquired Hyponatremia in Pediatrics.

Hyponatremia is the most common electrolyte disturbance in hospitalized children, with a reported incidence of 15-30%, but its overall incidence and severity are not well known. The objective of our study was to determine the incidence, severity, and associated risk factors of community- and hospital-acquired hyponatremia on a general pediatric ward. Data of 5550 children admitted from June 2012 to December 2019 on plasma sodium and discharge diagnosis were analyzed by logistic regression model. Clinically relevant diagnostic groups were created. Hyponatremia was classified as mild, moderate, and severe. The incidence of community- and hospital-acquired hyponatremia was 15.8% and 1.4%, respectively. Most of the cases were mild (90.8%) to moderate (8.6%), with only two cases of severe community-acquired hyponatremia. There were no clinical complications in any of the hyponatremic children. Age and diagnosis at discharge were principal factors significantly correlated with hyponatremia. Community-acquired hyponatremia is more common than hospital-acquired hyponatremia in clinical practice. Severe cases of both types are rare. Children from 2 to 11 years of age presenting with infections, cardiovascular disorders, and gastrointestinal disorders are at risk of developing hyponatremia.

Phosphorylation of S6RP in peritubular capillaries of kidney grafts and circulating HLA donor-specific antibodies.

Antibody-mediated rejection (ABMR) caused by donor-specific HLA-antibodies (DSA) is a mediator of allograft loss after kidney transplantation (KT). DSA can activate microvascular endothelium damage through the mTOR pathway. In this study we assessed the mTOR pathway activation by DSA in KT with ABMR (ABMR + DSA+) compared to controls (ABMR-DSA-), biopsies with ABMR changes without DSA (ABMR + DSA-) and DSA without ABMR changes (ABMR-DSA+), and the potential modulation by mTOR inhibitors (mTORi). We evaluated 97 biopsies: 31 ABMR + DSA+, 33 controls ABMR-DSA-, 16 ABMR + DSA-, and 17 ABMR-DSA+ cases. Regarding immunosuppression of full ABMR + DSA+ and controls, 21 biopsies were performed under mTORi treatment (11 of them ABMR + DSA+ cases) and 43 without mTORi (20 of them ABMR + DSA+) so as to explore its effect on the mTOR pathway. Biopsies were stained for C4d, Ki67, and phosphorylated (p) S6RP, ERK, and mTOR by immunohistochemistry. Labeling was graded according to peritubular capillary staining. ABMR biopsies showed significantly higher C4d, p-S6RP, and Ki67 staining in peritubular capillaries (PTC) compared to controls, and light differences in p-ERK or p-mTOR. mTORi treatment did not modify p-S6RP, p-mTOR, and p-ERK staining. Diffuse p-S6RP in PTC in the biopsies significantly associated with circulating HLA-DSA independently of graft rejection, and with worse death-censored graft survival. These findings suggest that activation of endothelium through the mTOR pathway evidence different mechanisms of damage in ABMR + DSA+ and ABMR + DSA- despite similar histological injury.

Implementation of an enhanced recovery after surgery program including a patient school: Impact on quality of life results.

INTRODUCTION: Enhanced Recovery After Surgery (ERAS) protocols and educational programmes have been shown to accelerate orthopaedic surgery recovery with fewer complications, and improve patient-reported outcomes (PROs) for different types of surgery. The objective was to evaluate the impact of an ERAS programme including a patient school on health outcomes and PROs for Total Knee Replacement (TKR) surgery. MATERIAL AND METHODS: A multidisciplinary group created the programme and the patient school (preoperative consultations where the patients' surgical processes are explained and are also given instructions for an appropriate perioperative care management). An observational, prospective study was conducted on all patients operated for TKR from March 2021 to March 2022. Main health outcomes were: hospital stay length, surgical complications and surgery cancellations due to a wrong preoperative medication management. PROs evaluated were: patient satisfaction with pain management, the school, and quality of life before and after surgery (EQ-5D). RESULTS: One hundred thirty-three patients were included. Median hospital stay length was 3 days (IQR 3-5). Rate of surgical complications was 25.6%. No surgery was cancelled. Patient satisfaction rates with pain management and with the school were 8.10/10 and 9.89/10, respectively. Concerning quality of life, mean improvement in mobility and knee pain after the surgery was 0.66 (p < 0.05) and 0.84 (p < 0.05), respectively. CONCLUSIONS: The ERAS programme including a patient school was highly successful with a fast recovery, a short hospital stay length, no surgery cancellations, and improved PROs.

Manejo avanzado del infarto cerebral en un hospital público chileno: trombectomía mecánica en el Hospital Barros Luco Trudeau / Mechanical thrombectomy in a Chilean public hospital. Experience in 149 patients

BACKGROUND: Mechanical thrombectomy is the accepted treatment for acute ischemic stroke in Large Vessel Occlusion. The Barros Luco Trudeau hospital developed endovenous thrombolysis in 2010, and since 2012, implemented endovascular management, becoming the neurovascular center in the southern area of the metropolitan region. AIM: To describe endovascular management of acute ischemic stroke in a Chilean public hospital. Material and Methods: Analysis of patients with acute ischemic stroke that were treated with mechanical throm-bectomy from 2012 to 2019 in the Barros Luco Hospital. RESULTS: In the study period, a mechanical thrombectomy was carried out in 149 patients aged 61 ± 15 years (46% females). The average National institute of Health Stroke Scale (NIHSS) at presentation was 19 ± 4-5. Anterior or posterior circulation involvement was present in 89.9 and 10.1 % of patients. Twenty-five percent of patients were referred from other public centers. The mean lapse between onset of symptoms and thrombectomy was 266 ± 178 in. Ninety days after the procedure, 58% of patients had minimal or absent disability (Modified Ranson score of 0-2), and 19,2% died. CONCLUSIONS: Mechanical thrombectomy, according to this experience, has favorable clinical outcomes in patients with high NIHSS scores at entry.

Evaluation of the Feasibility, Safety and Efficacy of the Use of Intravenous Infusions of Adenosine Triphosphate (ATP) in People Affected by Moderate to Severe Alzheimer's Disease: A Double-Blind Masked Clinical Trial for Dose Finding.

BACKGROUND: There are currently no drug therapies modifying the natural history of patients suffering Alzheimer's disease (AD). Most recent clinical trials in the field include only subjects in early stage of the disease, while patients with advanced AD are usually not represented. OBJECTIVES: To evaluate the feasibility, safety and efficacy of systemic infusions of adenosine triphosphate (ATP) in patients with moderate to severe AD, and to select the minimum effective dose of infusion. DESIGN: A phase IIb, randomized, double-blind, placebo-controlled clinical trial investigates. PARTICIPANTS: A total of 20 subjects with moderate or severe AD were included, 16 in the treatment group and 4 in the placebo group (4:1 randomization) at two dosage regimens, 6-hour or 24-hour infusions. RESULTS: The proof-of-concept study was successfully conducted, with no significant deviations from the study protocol and no serious adverse events reported. Regarding efficacy, only marginal differences were observed between ATP and placebo arms for H-MRS and MMSE variables. CONCLUSIONS: Our study demonstrates that the use of ATP infusion as therapy is feasible and safe. Larger studies are however needed to assess the efficacy of ATP in moderate to severe AD.

Dynamical landscapes of cell fate decisions.

The generation of cellular diversity during development involves differentiating cells transitioning between discrete cell states. In the 1940s, the developmental biologist Conrad Waddington introduced a landscape metaphor to describe this process. The developmental path of a cell was pictured as a ball rolling through a terrain of branching valleys with cell fate decisions represented by the branch points at which the ball decides between one of two available valleys. Here we discuss progress in constructing quantitative dynamical models inspired by this view of cellular differentiation. We describe a framework based on catastrophe theory and dynamical systems methods that provides the foundations for quantitative geometric models of cellular differentiation. These models can be fit to experimental data and used to make quantitative predictions about cellular differentiation. The theory indicates that cell fate decisions can be described by a small number of decision structures, such that there are only two distinct ways in which cells make a binary choice between one of two fates. We discuss the biological relevance of these mechanisms and suggest the approach is broadly applicable for the quantitative analysis of differentiation dynamics and for determining principles of developmental decisions.

[Mechanical thrombectomy in a Chilean public hospital. Experience in 149 patients]. / Manejo avanzado del infarto cerebral en un hospital público chileno: trombectomía mecánica en el Hospital Barros Luco Trudeau.

BACKGROUND: Mechanical thrombectomy is the accepted treatment for acute ischemic stroke in Large Vessel Occlusion. The Barros Luco Trudeau hospital developed endovenous thrombolysis in 2010, and since 2012, implemented endovascular management, becoming the neurovascular center in the southern area of the metropolitan region. AIM: To describe endovascular management of acute ischemic stroke in a Chilean public hospital. MATERIAL AND METHODS: Analysis of patients with acute ischemic stroke that were treated with mechanical throm-bectomy from 2012 to 2019 in the Barros Luco Hospital. RESULTS: In the study period, a mechanical thrombectomy was carried out in 149 patients aged 61 ± 15 years (46% females). The average National institute of Health Stroke Scale (NIHSS) at presentation was 19 ± 4-5. Anterior or posterior circulation involvement was present in 89.9 and 10.1 % of patients. Twenty-five percent of patients were referred from other public centers. The mean lapse between onset of symptoms and thrombectomy was 266 ± 178 in. Ninety days after the procedure, 58% of patients had minimal or absent disability (Modified Ranson score of 0-2), and 19,2% died. CONCLUSIONS: Mechanical thrombectomy, according to this experience, has favorable clinical outcomes in patients with high NIHSS scores at entry.

Características de la ventilación no invasiva prolongada en los servicios de urgencias hospitalarios y su impacto en la eficacia. Análisis del registro VNICat / Characteristics of prolonged noninvasive ventilation in emergency departments and impact upon effectiveness. Analysis of the VNICat registry

Objetivo: Analizar las características y variables asociadas con la ventilación no invasiva realizada completamente en los servicios de urgencias hospitalarios (VNI-SUH) de manera prolongada y su influencia en la eficacia de la técnica. Diseño Estudio multicéntrico observacional prospectivo de cohorte multipropósito. Ámbito Registro VNICat. Participantes Pacientes en los que se realiza VNI-SUH en 11 hospitales catalanes en los meses de febrero o marzo de 2015.IntervenciónNinguna.VariablesLa variable de estudio fue la VNI-SUH, que en función del tiempo se definió como prolongada o no prolongada. La variable de eficacia fue el éxito de la técnica por mejoría. Resultados Se incluyeron 125 pacientes con una mediana de tiempo de VNI-SUH de 12h, que fue el punto de corte para los 2 grupos comparados. En 60 (48%) la VNI-SUH fue no prolongada (<12h) y en 65 (52%) prolongada (≥12h). La VNI-SUH no prolongada se asoció con la indicación de insuficiencia cardiaca aguda y la prolongada con la presencia de diabetes. Entre la VNI-SUH no prolongada y la prolongada no hubo diferencias en la eficacia, éxito por mejoría del 68,3% y del 76,9%, respectivamente, con un odds ratio ajustado de 1,49 (intervalo de confianza del 95% de 0,61-3,60).Conclusiones La VNI-SUH prolongada es una situación frecuente, pero las variables estudiadas que se asocian a ella son escasas. Su presencia no influyo en el éxito de la VNI. (AU)

Objective: To analyze the characteristics and variables associated with prolonged noninvasive ventilation performed completely in Emergency Departments (NIV-ED) and its influence upon effectiveness. Design A prospective, multicenter, observational multipurpose cohort study was carried out. Setting VNICat Registry. Subjects Patients in which NIV-ED was performed in 11 Catalan hospitals in the months of February or March 2015. Intervention No. Variables The study variable was NIV-ED, which as a function of time was defined as prolonged or not prolonged. The efficacy variable was the success of the technique in terms of patient improvement. Results A total of 125 patients were included, with a median NIV-ED duration of 12hours, which was the cut-off point for the comparator groups. In 60 cases (48%) NIV-ED was not prolonged (<12hours), while in 65 cases (52%) ventilation was prolonged (≥12hours). Non-prolonged NIV-ED was associated to the indication of acute heart failure and prolonged ventilation to the presence of diabetes. There were no differences between non-prolonged and prolonged NIV-ED in terms of efficacy, and the success rate in terms of improvement was 68.3% and 76.9%, respectively, with an adjusted odds ratio of 1.49 (95%CI 0.61-3.60). Conclusions Prolonged NIV-ED is a frequent situation, but few variables associated to it have been studied. The presence of prolonged ventilation did not influence the success rate of NIV. (AU)

Characteristics of prolonged noninvasive ventilation in emergency departments and impact upon effectiveness. Analysis of the VNICat registry.

OBJECTIVE: To analyze the characteristics and variables associated with prolonged noninvasive ventilation performed completely in Emergency Departments (NIV-ED) and its influence upon effectiveness. DESIGN: A prospective, multicenter, observational multipurpose cohort study was carried out. SETTING: VNICAT Registry. SUBJECTS: Patients in which NIV-ED was performed in 11 Catalan hospitals in the months of February or March 2015. INTERVENTION: No. VARIABLES: The study variable was NIV-ED, which as a function of time was defined as prolonged or not prolonged. The efficacy variable was the success of the technique in terms of patient improvement. RESULTS: A total of 125 patients were included, with a median NIV-ED duration of 12 h, which was the cut-off point for the comparator groups. In 60 cases (48%) NIV-ED was not prolonged (<12 h), while in 65 cases (52%) ventilation was prolonged (≥12 h). Non-prolonged NIV-ED was associated to the indication of acute heart failure and prolonged ventilation to the presence of diabetes. There were no differences between non-prolonged and prolonged NIV-ED in terms of efficacy, and the success rate in terms of improvement was 68.3% and 76.9%, respectively, with an adjusted odds ratio of 1.49 (95%CI 0.61-3.60). CONCLUSIONS: Prolonged NIV-ED is a frequent situation, but few variables associated to it have been studied. The presence of prolonged ventilation did not influence the success rate of NIV.

TROPHY registry - status report.

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

Neuronavegación asociada a resonancia funcional motora, validación por estimulación cortical directa en cirugías de tumores de área motora / Neuronavigation associated with functional motor resonance, validation by direct cortical stimulation in motor area tumor surgeries

Objetivo: Determinar la confiabilidad de rm funcional motora (rmfm) en la localización de la corteza motora primaria en condiciones patológicas causadas por la proximidad de lesiones expansivas cerebrales con el uso intraoperatorio de electro estimulación cortical directa (ecd) Material y método: Se incluyeron 48 pacientes portadores de tumores intra axiales (nº 25) y extraaxiales (nº23) próximas al área motora, con capacidad de realizar la tarea funcional motora por rmf, y que fueron sometidos a cirugía con ecd. Durante la cirugía se realizaron 220 registros de ecd en total de la población de pacientes estudiados. La población estuvo constituida por una serie consecutiva de casos, el estudio se planificó de manera prospectiva entre los años 2007-2019, y tiene como objetivo la evaluación de la eficacia de pruebas diagnósticas (stard 2015).Se realizó una comparación sitio por sitio entre la imagen por rmfm y la ecm con la ayuda del neuronavegador. Discusión: Los resultados estadísticos de la prueba fueron: sensibilidad 82.2%, Especificidad: 76,5%, lr+:3.49, Lr-: 0,23; vpp: 74.8%, Vpn: 83.5%; Odds Postest+:2.96, Odds postest-: 0,19 y fueron publicados acordes con los standards stard 2015. Conclusiones: Las técnicas de rmfm basadas en tareas, no son suficientes para la toma de decisiones críticas intraoperatorias. No obstante, la integración de la rmfm por neuronavegación implica una planificación espacial muy confiable que permite asociar el área de activación bold a la topografía del tumor y a la tractografía, de esta forma orientar una validación por ecd rápida y segura en la resección de los tumores cerebrales