Nutrition supplementation plus standard of care versus standard of care alone or standard of care plus unconditional cash transfer in the prevention of chronic malnutrition in Southern Angola: study protocol for the MuCCUA study, a cluster randomized controlled trial.

BACKGROUND: Chronic malnutrition is a condition associated with negative impacts on physical and cognitive development. It is multi-causal and can start very early in life, already in utero, thus it is especially challenging to find appropriate interventions to tackle it. The government of Angola is implementing a standard of care program with potential to prevent it, and the provision of cash transfers and the supplementation with small quantity lipid-based nutrients (SQ-LNS) are also promising interventions. We aimed to evaluate the impact of the standard of care program alone and of the standard of care plus a cash transfer intervention in the lineal growth of children less than 2 years old and compare it to the effectiveness of a nutrition supplementation plus standard of care program in Southern Angola. METHODS/DESIGN: The three-arm parallel cluster randomised controlled trial is set in four communes of Huila and Cunene provinces. Clusters are villages or neighbourhoods with a population around 1075 people. A total of twelve clusters were selected per arm and forty pregnant women are expected to be recruited in each cluster. Pregnant women receive the standard of care alone, or the standard of care plus unconditional cash transfer or plus nutritional supplementation during the first 1000 days, from pregnancy to the child reaching 24 months. The primary outcome is the prevalence of stunting measured as height-for-age Z-score (HAZ) < -2 in children below 2 years. Impact will be assessed at 3, 6, 12, 18 and 24 months of children's age. Secondary outcomes include mortality, morbidity, caring, hygiene and nutrition behaviours and practices, and women and children's dietary diversity. Quantitative data are also collected on women's empowerment, household food security, expenditure and relevant clinical and social events at baseline, endline and intermediate time points. DISCUSSION: The results will provide valuable information on the impact of the standard of care intervention alone as well as combined with an unconditional cash transfer intervention compared to a nutrition supplementation plus standard of care intervention, carried out during the first 1000 days, in the children´s growth up to 2 years and related outcomes in Southern Angola. TRIAL REGISTRATION: Clinical Trials NCT05571280. Registered 7 October 2022.

Chagas disease deaths detected among garbage codes registered in mortality statistics in Brazil: a study from the buRden of ChAgas dISEase in the contemporary world (RAISE) project.

OBJECTIVES: The objective of this study was to identify Brazil's most critical garbage codes (GCs) reclassified to Chagas disease (ChD) in mortality data and their proportions. We also estimated the potential impact of misclassification on the number of deaths attributed to ChD. STUDY DESIGN: Population-based descriptive study. METHODS: We used the Mortality Information System (SIM; in Portuguese) data before and after routine GC investigation in 2015-2019 to evaluate ChD deaths detected among them. We identified priority GCs, which contributed more than 0.1 % to the percentage of total ChD deaths registered. Spearman's correlation was used to evaluate the association between the reclassification of priority GCs and ChD prevalence. Then, we applied the GC correction factors to estimate the number of deaths attributed to ChD. RESULTS: 22,154 deaths were reported as ChD in the study period. Among them, 1004 deaths originally listed as priority GCs were deaths reclassified to ChD after an investigation in the SIM final database. Unspecific cardiomyopathy (10.2 %), unspecific heart diseases (4.7 %), and heart failure (2.8 %) were GCs with the highest proportions of reclassification to ChD in Brazil. Higher ChD prevalence at the state level was associated with a higher proportion of GC deaths reclassified as ChD. When applying correction factors identified after investigation, we estimated an increase of 26.4 % in registered ChD deaths, mostly in states with higher endemicity. CONCLUSIONS: GCs might conceal deaths due to ChD, particularly in Brazil's states with higher endemicity. The approach suggested in this study may offer an alternative method for estimating ChD-related deaths in endemic countries.

Balloon-Expandable Pulmonary Valves for Patched or Native Right Ventricular Outflow Tracts.

The implantation of percutaneous balloon expandable valves in native or patched right ventricular outflow tracts (nRVOT) is a challenging technique due to the diversity of anatomies and shapes, the large sizes, and the distensibility of the nRVOT, for which specific techniques have been developed. We present a single center experience with balloon expandable percutaneous pulmonary valves in nRVOT, describing the techniques used, complications observed, and a short-mid term follow-up.. This is a single center descriptive study of patients who underwent a percutaneous pulmonary valve implantation in a nRVOT with a balloon expandable pulmonary valve in our center between September 2012 and June 2022.. We implanted successfully 45 valves in 46 patients (20 Sapien and 25 Melody). Tetralogy of Fallot or pulmonary atresia with VSD were the main congenital heart disease (n = 32). All were pre-stented, 18 in a one step procedure. We used a Dryseal sheath in 13/21 Sapien. In 6 patients we used the anchoring technique, 5 with a very large nRVOT and one pyramidal nRVOT. In the 3.5 year follow-up 7 patients developed endocarditis and 3 required a valve redilation, no fractures were observed. PPVI of native RVOT with balloon expandable valves is feasible in a number of selected anatomies, including large or pyramidal nRVOT, using specific techniques, (presenting, LPA anchoring).

Acute respiratory distress syndrome due to COVID-19. Clinical and prognostic features from a medical Critical Care Unit in Valencia, Spain.

Objective: Information from critically ill coronavirus disease 2019 (COVID-19) patients is limited and in many cases coming from health systems approaches different from the national public systems existing in most countries in Europe. Besides, patient follow-up remains incomplete in many publications. Our aim is to characterize acute respiratory distress syndrome (ARDS) patients admitted to a medical critical care unit (MCCU) in a referral hospital in Spain. Design: Retrospective case series of consecutive ARDS COVID-19 patients admitted and treated in our MCCU. Setting: 36-bed MCCU in referral tertiary hospital. Patients and participants: SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal/pharyngeal swabs. Interventions: None. Main variables of interest: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Results: Forty-four ARDS COVID-19 patients were included in the study. Median age was 61.50 (53.25 - 67) years and most of the patients were male (72.7%). Hypertension and dyslipidemia were the most frequent co-morbidities (52.3 and 36.4% respectively). Steroids (1mg/Kg/day) and tocilizumab were administered in almost all patients (95.5%). 77.3% of the patients needed invasive mechanical ventilation for a median of 16 days [11-28]. Prone position ventilation was performed in 33 patients (97%) for a median of 3 sessions [2-5] per patient. Nosocomial infection was diagnosed in 13 patients (29.5%). Tracheostomy was performed in ten patients (29.4%). At study closing all patients had been discharged from the CCU and only two (4.5%) remained in hospital ward. MCCU length of stay was 18 days [10-27]. Mortality at study closing was 20.5% (n 9); 26.5% among ventilated patients. Conclusions: The seven-week period in which our MCCU was exclusively dedicated to COVID-19 patients has been challenging. Despite the severity of the patients and the high need for invasive mechanical ventilation, mortality was 20.5%.

Objetivo: La información de pacientes críticos con enfermedad por coronavirus 2019 (COVID-19) es limitada y, en muchos casos, proviene de sistemas de salud diferentes a la organización pública de la mayoría de los países de Europa. Además, el seguimiento del paciente sigue siendo incompleto en muchas publicaciones. Nuestro objetivo es caracterizar a los pacientes con síndrome de distres respiratorio agudo (SDRA) ingresados en una unidad de cuidados críticos médicos (MCCU) en un hospital de referencia en España. Diseño: Serie retrospectiva de casos de pacientes consecutivos con SDRA por COVID-19 ingresados y tratados en nuestra MCCU. Lugar: UCC de 36 camas en un hospital terciario de referencia. Pacientes y participantes: Infección por SARS-CoV-2 confirmada por ensayo en tiempo real de la transcriptasa inversa-reacción en cadena de la polimerasa (RT-PCR) de hisopos nasales/faríngeos. Intervenciones: Ninguna. Principales variables de interés: Se recopilaron datos demográficos y clínicos, incluidos datos sobre manejo clínico, insuficiencia respiratoria y mortalidad del paciente. Resultados: Cuarenta y cuatro pacientes con SDRA por COVID-19 fueron incluidos en el estudio. La mediana de edad fue de 61.50 (53.25 - 67) años y la mayoría de los pacientes eran hombres (72.7%). La hipertensión y la dislipidemia fueron las comorbilidades más frecuentes (52,3 y 36,4%, respectivamente). Se administraron esteroides (1mg/kg/día) y tocilizumab en casi todos los pacientes (95,5%). El 77,3% de los pacientes necesitaron ventilación mecánica invasiva durante una mediana de 16 días [11-28]. La ventilación en posición prono se realizó en 33 pacientes (97%) con una mediana de 3 sesiones [2-5] por paciente. Se diagnosticó una infección nosocomial en 13 pacientes (29,5%). La traqueotomía se realizó en diez pacientes (29,4%). Al cierre del estudio, todos los pacientes habían sido dados de alta de la MCCU y solo dos permanecían hospitalizados. La estancia en MCCU fue de 18 días [10-27]. La mortalidad al cierre del estudio fue del 20,5% (n 9); 26.5% para pacientes ventilados. Conclusiones: El período de siete semanas en el que nuestra MCCU se dedicó exclusivamente a pacientes con COVID-19 ha sido un gran desafío. A pesar de la gravedad de los pacientes y la elevada necesidad de ventilación mecánica invasiva, la mortalidad fue del 20,5%.

Pharmacokinetics of Benznidazole in Healthy Volunteers and Implications in Future Clinical Trials.

Despite its toxicity and low efficacy in the chronic phase, benznidazole is the drug of choice in Chagas disease. Scarce information about pharmacokinetics and pharmacodynamics of benznidazole has been published. We performed a phase I, open-label, nonrandomized pharmacokinetic study of benznidazole (Abarax) conducted with 8 healthy adult volunteers at the Infectious Diseases Department of the Vall d'Hebron University Hospital (Barcelona, Spain). The separation and detection of benznidazole were performed on a Waters Acquity ultraperformance liquid chromatography system (UPLC) coupled with a Waters Xevo TQ MS triple quadrupole mass spectrometer. The pharmacokinetic parameters were calculated based on a noncompartmental body model using Phoenix WinNonlin version 6.3 software. Furthermore, computational simulations were calculated for the multiple-dose administration at two dose regimens: 100 mg of benznidazole administered every 8 h and 150 mg of benznidazole administered every 12 h. After benznidazole administration, the median area under the concentration-time curve from time zero to time t (AUC0-t ) and extrapolated to infinity (AUC0-∞) were about 46.4 µg · h/ml and 48.4 µg · h/ml, respectively. Plasma benznidazole concentrations peaked at 3.5 h, with maximal concentrations of 2.2 µg/ml, and benznidazole exhibited a terminal half-life of 12.1 h. The median maximum concentration (Cmax) of benznidazole was lower in men than in women (1.6 versus 2.9 µg/ml), and median volume of distribution (V) as a function of bioavailability (F) was higher in men than in women (125.9 versus 88.6 liters). In conclusion, dose regimens (150 mg/12 h or 100 mg/8 h) reached a steady-state range concentration above of the minimum experimental therapeutic dose. Sex differences in the benznidazole pharmacokinetics were observed; mainly, men had lower Cmax and higher V/F than women.

Toxic Profile of Benznidazole in Patients with Chronic Chagas Disease: Risk Factors and Comparison of the Product from Two Different Manufacturers.

Benznidazole is considered the first-line treatment option against Chagas disease. The major drawback of benznidazole is its toxicity profile. The main objectives of this study were to describe the adverse events (AEs) in patients with chronic Chagas disease treated with benznidazole, determine the risk factors involved and compare the toxic profiles of two different preparations of the drug from ELEA and Roche. A total of 746 patients were diagnosed with Chagas disease in a 5-year period, and of these 472 were treated with benznidazole. A high proportion of patients (n = 360 [76%]) suffered AEs, the most frequent being those related to hypersensitivity (52.9% of patients), headache (12.5%), and epigastric pain (10.4%). In 72 (12.7%) cases, treatment was discontinued. Overall, women had a higher incidence of AEs compared to men (81.3% versus 66%, P = 0.001) and were subject to higher levels of hypersensitivity-related events. Dermatological events, digestive tract manifestations, and general symptoms had a greater likelihood to appear around day 10 and neurological AEs around day 40 after starting treatment. With respect to liver function and hematological tests, the majority of patients did not suffer significant perturbation of liver enzymes or altered blood cell counts. However, 14 patients suffered from neutropenia, and 14 patients had aminotransferase levels that were more than four times the upper limit of the normal range. Patients treated with the ELEA benznidazole product experienced more arthromyalgia, neutropenia, and neurological disorders (mainly paresthesias) than those treated with the Roche product. Both drug products resulted in approximately the same percentage of permanent withdrawals.

[Video-assisted sigmoidectomy as an option for Sigmoid volvulus management in the pediatric population]. / Sigmoidectomía videoasistida como opción de manejo del vólvulo del sigmoides en la población pediátrica.

INTRODUCTION: The aim of the present study was to evaluate clinical presentation and management of sigmoid volvulus in children. Sigmoid volvulus is one of the three leading causes of acute obstruction of the colon and is between 50 and 90% of all large bowel volvulus. In the pediatric population only 3 to 5% of bowel obstructions are caused by volvulus and there are less than 100 cases reported in the literature. The presence of a redundant sigmoid with a narrow mesentery (dolicosigmoide) is a prerequisite for the volvulus formation. The etiology in the pediatric population is considered secondary to the presence of a broad meso with a narrow base associated with abnormal fixation colon. Other factors include history of anorectal malformation, Prune Belly syndrome, intestinal malrotation and Hirschsprung disease. Initial management followed by endoscopic minimally invasive sigmoidectomy has proven safe and effective. MATERIALS AND METHODS: This paper presents the experience of 4 patients between 9 and 14 managed in our department in 2013, with a diagnosis of volvulus of the sigmoid, which were initially taken to a first surgical endoscopic decompression of volvulus and a second half were carried sigmoid which took place in a video-assisted. In this series, no intraoperative complications were documented and monitoring more than six months only one patient has required new interventions, in a special case because the patient has associated myopathy; inflammatory leiomioscitis, which predisposes to episodes of intestinal obstruction. CONCLUSION: We believe that endoscopic detorsion followed by an early video-assisted sigmoid is the ideal technique for the management of these patients.

INTRODUCCION: El objetivo del estudio es evaluar la presentación y el manejo del vólvulo del Colon Sigmoides (VS) en pacientes pediátricos. El (VS) es una de las tres principales causas de obstrucción aguda del colon y constituye entre el 50 y 90% de todos los vólvulos del intestino grueso. En la población pediátrica, solo del 3 al 5% de las obstrucciones intestinales son causadas por vólvulo, y son menos de 100 los casos publicados en la literatura médica. La etiología en la población pediátrica se considera secundaria a la presencia de un meso amplio con una base estrecha asociado a una fijación anormal del colon. Otros factores incluyen historia de malformación anorectal, síndrome de Prune Belly, malrotacion intestinal y enfermedad de Hirschsprung. El manejo inicial por vía endoscópica, seguido de la sigmoidectomía mínimamente invasiva, han demostrado ser seguros y efectivos. MATERIAL Y METODOS: El presente trabajo recoge la experiencia de 4 pacientes entre los 9 y 14 años manejados en nuestro servicio, en el año 2013, con diagnóstico de vólvulo del sigmoides, los cuales inicialmente fueron llevados a un primer tiempo quirúrgico para descompresión endoscópica del vólvulo y en un segundo tiempo fueron llevados a sigmoidectomía, la cual se llevó a cabo de forma videoasistida. En esta serie no se documentaron complicaciones intraoperatorias y, en el seguimiento a más de 6 meses, solo uno de los pacientes ha requerido nuevas intervenciones, en un caso especial, dado que el paciente presenta asociada una miopatía (leiomioscitis inflamatoria), la cual lo predispone a episodios de obstrucción intestinal. CONCLUSION: Consideramos que la devolvulación endoscópica seguida de una pronta sigmoidectomía videoasistida es la técnica ideal para el manejo de estos pacientes.

Paper-based microfluidic electro-analytical device (PMED) for magneto-assay automation: Towards generic point-of-care diagnostic devices.

Rapid diagnostic tests (RDTs) for point-of-care (POC) testing of infectious diseases are popular because they are easy to use. However, RDTs have limitations such as low sensitivity and qualitative responses that rely on subjective visual interpretation. Additionally, RDTs are made using paper-bound reagents, which leads to batch-to-batch variability, limited storage stability and detection of only the analytes they were designed for. This work presents the development of a versatile technology, based on short magneto-assays and inexpensive paper-based microfluidic electro-analytical devices (PMEDs). PMEDs were produced locally using low-cost equipment, they were stable at room temperature, easy to use, and provided quantitative and objective results. The devices served to detect alternatively a variety of magneto-assays, granting quantitation of streptavidin-HRP, biotinylated HRP and Pasmodium falciparum lactate dehydrogenase (Pf-LDH) in less than 25 min, using either commercial or customized screen-printed electrodes and measurement equipment. Furthermore, Pf-LDH detection in diluted lysed whole blood displayed a linear response between 3 and 25 ng mL-1, detection and quantification limits ranging between 1 and 3 ng mL-1 and 6-12 ng mL-1, respectively, and provided results that correlated with those of the reference ELISA. In short, this technology is versatile, simple, and highly cost-effective, making it perfect for POC testing.

X-linked thrombocytopenia in a female with a complex familial pattern of X-chromosome inactivation.

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, eczema and various degrees of immune deficiency caused by mutations in the WAS gene, which encodes the WASP protein, the expression of which is restricted to haematopoietic cells. Mild allelic variants are associated with X-linked thrombocytopenia (XLT). Female carriers tend in general to be asymptomatic as a consequence of a positive selection of cells with an active normal X chromosome, which results in a non-random inactivation of the mutated gene in affected cell lineages. We report on six female members of the same family carrying the mutated WAS allele p.V332A, which is known to be associated with XLT. One of them had presented severe thrombocytopenia from birth. Western blotting showed the WASP protein in peripheral blood cells to be normal in size and expression, and scanning electron microscopy revealed a normal distribution of microvilli on T cells. X-chromosome inactivation-pattern analysis showed total inactivation of the non-mutated paternal X chromosome in the patient's peripheral blood cells. All the other female family members were healthy and presented varying X-chromosome inactivation patterns, ranging from random X chromosome inactivation to total X-chromosome inactivation of the mutated chromosome. Our results in these female carriers of p.V332A show that manifestation of the disease requires a total inactivation of the non-mutated X chromosome and allow us to confirm that clinical manifestations in female carriers are highly dependent not only on the mutation characteristics but also on the X-chromosome inactivation pattern of affected line.

[Magnet intestinal lesions. Case series]. / Lesiones intestinales por imanes. Serie de casos.

The ingestion of foreign bodies is a common trouble in the pediatric population, and most of cases occur between 6 months and 3 years. In general the vast majority of foreign bodies are not associated with morbidity or mortality. Ingestion of two or more magnets can lead to obstruction, fistulas, ulceration, perforation and bowel volvulus. In this series we present 4 cases of patients ingesting multiple magnets and who due to the ingested foreign body characteristics and clinical profile required surgical treatment.

A tissue-specific, activation-inducible, lentiviral vector regulated by human CD40L proximal promoter sequences.

The application of new protocols for gene therapy against monogenic diseases requires the development of safer therapeutic vectors, particularly in the case of diseases in which expression of the mutated gene is subject to fine regulation, as it is with CD40L (CD154). CD40L, the gene mutated in the X-linked hyper-immunoglobulin M syndrome (HIGM1), is tightly regulated to allow surface expression of its product only on T cells stimulated by antigen encounter. Previous studies in an HIGM1 animal model showed that transduction of progenitor cells corrected the syndrome but caused a thymic lymphoproliferative disease because of the unregulated expression of the transgene by constitutive vectors. To develop a tissue-specific, activation-inducible, lentiviral vector (LV) for gene therapy to counter HIGM1, we have constructed two self-inactivating LVs, pCD40L-eGFP and pCD40L-CD40L, regulated by a 1.3 kb fragment of the human CD40L proximal promoter. The expression of pCD40L-eGFP LV is restricted to cells in which mRNA transcripts of the endogenous CD40L gene can be detected. Moreover, the expression of the reporter gene in primary T lymphocytes depends on the activation state of the cells. Remarkably, primary HIGM1 lymphocytes transduced with pCD40L-CD40L LV expressed CD40L only after T-cell stimulation. Therefore, the CD40L-promoter-driven vectors are able to achieve a near-physiological expression pattern that follows very closely that of the endogenous CD40L gene.

[Does decompressive craniectomy improve other parameters besides ICP? Effects of the decompressive craniectomy on tissular pressure?]. / ¿Mejora la craniectomía descompresiva otros parámetros además de la PIC? Efectos de la craniectomía descompresiva en la presión tisular.

Second level therapeutic maneuvres for controlling intracranial hypertension (ICH) proposed by the European Brain Injury Consortium and the American Association of Neurological Surgeons include barbiturates, moderate hypothermia and more recently the decompressive craniectomy (DC).In most patients, ICP can be maintained below 25 mmHg after a DC. However, the exact effect of DC on brain oxygenation (PtiO2) still unclear. From our point of view the ptIo2 monitoring with the probe located in the healthy area of the most severely damaged cerebral hemisphere is not only a important tool for timing craniectomy in the future but also for evaluating the therapeutic effectivity of DC.

[Initial experience in single site laparoscopic surgery in a pediatric hospital of Bogotá]. / Experiencia inicial en cirugía laparoscópica por puerto único en un hospital pediátrico de Bogotá.

BACKGROUND: Minimally invasive surgery is the current accepted approach for abdominal surgery. However, less invasive techniques such as single incision laparoscopic surgery (SILS) are being used more frequently and we believe it will become the standard choice for abdominal surgery. This report describes our initial experience with Single Port Incision Surgery (SILS). METHODS: We reviewed all the patients who underwent SILS in our hospital between November 2009 and July 2011. We used a surgical glove attached to a wound retractor to yield a multi-port hybrid. RESULTS: We present 80 patients with a mean age of 8.6 years and mean weight of 32,1 kg. The youngest patient was 8 days old and the smallest patient weighed 2.5 kg. The average duration of surgery was 48.2 minutes. The average length of stay was 48.7 hours. Different procedures were performed: appendectomies for early appendicitis (55%), hepatic biopsies (15%), appendectomies for perforated appendicitis (7.5%), and the following isolated cases: cholecystectomy, Meckel's diverticulum resection, oophorectomy, salpingo-oophorectomy, ovarian cystectomy, bowel biopsy, and a resection of an accessory spleen torsion. SILS was successfully completed in 78 cases, and 2 cases were converted to standard laparoscopy and none to open surgery. There were no intraoperative surgical complications. Postoperative complications presented in 5 cases: a superficial incisional site infection, two residual abdominal abscesses, one bowel obstruction and one evisceration. The last two cases subsequently resulted in reoperation and occurred early in our learning curve. CONCLUSIONS: SILS is a reproducible and viable technique that may be used successfully in pediatric surgery. It may be used safely in different procedures and age groups, even in neonates. Time of surgery decreased with our learning curve. Additionally, excellent cosmetic results were obtained as evidenced by imperceptible umbilical scarring.

Acute respiratory distress syndrome due to COVID-19. Clinical and prognostic features from a medical Critical Care Unit in Valencia, Spain.

OBJECTIVE: Information from critically ill coronavirus disease 2019 (COVID-19) patients is limited and in many cases coming from health systems approaches different from the national public systems existing in most countries in Europe. Besides, patient follow-up remains incomplete in many publications. Our aim is to characterize acute respiratory distress syndrome (ARDS) patients admitted to a medical critical care unit (MCCU) in a referral hospital in Spain. DESIGN: Retrospective case series of consecutive ARDS COVID-19 patients admitted and treated in our MCCU. SETTING: 36-bed MCCU in referral tertiary hospital. PATIENTS AND PARTICIPANTS: SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal/pharyngeal swabs. INTERVENTIONS: None MAIN VARIABLES OF INTEREST: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. RESULTS: Forty-four ARDS COVID-19 patients were included in the study. Median age was 61.50 (53.25 - 67) years and most of the patients were male (72.7%). Hypertension and dyslipidemia were the most frequent co-morbidities (52.3 and 36.4% respectively). Steroids (1mg/Kg/day) and tocilizumab were administered in almost all patients (95.5%). 77.3% of the patients needed invasive mechanical ventilation for a median of 16 days [11-28]. Prone position ventilation was performed in 33 patients (97%) for a median of 3 sessions [2-5] per patient. Nosocomial infection was diagnosed in 13 patients (29.5%). Tracheostomy was performed in ten patients (29.4%). At study closing all patients had been discharged from the CCU and only two (4.5%) remained in hospital ward. MCCU length of stay was 18 days [10-27]. Mortality at study closing was 20.5% (n 9); 26.5% among ventilated patients. CONCLUSIONS: The seven-week period in which our MCCU was exclusively dedicated to COVID-19 patients has been challenging. Despite the severity of the patients and the high need for invasive mechanical ventilation, mortality was 20.5%.

Impact of the COVID-19 pandemic on tuberculosis management in Spain.

BACKGROUND: The impact of COVID-19 on the diagnosis and management of tuberculosis (TB) patients is unknown. METHODS: Participating centres completed a structured web-based survey regarding changes to TB patient management during the COVID-19 pandemic. The study also included data from participating centres on patients aged ≥18 diagnosed with TB in 2 periods: March 15 to June 30, 2020 and March 15 to June 30, 2019. Clinical variables and information about patient household contacts were retrospectively collected. RESULTS: A total of 7 (70%) TB units reported changes in their usual TB team operations. Across both periods of study, 169 patients were diagnosed with active TB (90 in 2019, 79 in 2020). Patients diagnosed in 2020 showed more frequent bilateral lesions in chest X-ray than patients diagnosed in 2019 (P = 0.004). There was a higher percentage of latent TB infection and active TB among children in households of patients diagnosed in 2020, compared with 2019 (P = 0.001). CONCLUSIONS: The COVID-19 pandemic has caused substantial changes in TB care. TB patients diagnosed during the COVID-19 pandemic showed more extended pulmonary forms. The increase in latent TB infection and active TB in children of patient households could reflect increased household transmission due to anti-COVID-19 measures.

Epidemiologic changes in bloodstream infections in Andalucía (Spain) during the last decade.

OBJECTIVES: During the last decade, some changes in the epidemiology of invasive infections have been reported; however, specific studies with patient-level data are scarce. The aim of this study was to describe and evaluate the epidemiologic changes in bloodstream infections (BSI) during the last decade in Andalucía, Spain. METHODS: Data from two prospective cohorts of BSI in adults with the same methodology performed 10 years apart in 11 hospitals (eight tertiary and three community) in Andalucía, Spain, were compared; the 2006-7 cohort study was performed between October 2006 and March 2007, and the 2016-17 cohort study was performed between October 2016 and March 2017. Population-based incidence rates were calculated and extrapolated for 1 year. Relative risk ratios were calculated between the 2 periods. Multivariate analyses were performed by logistic regression. RESULTS: Overall, 1262 episodes of BSI were included, 563 (44.6%) in 2006-7 and 699 (55.3%) in 2016-17. Multivariate models selected the following changes in patients' features in 2016-17, after controlling for type of acquisition: higher age (odds ratio (OR) = 1.02; 95% confidence interval [CI] 1.01-1.03), lower urinary catheter (OR = 0.37; 95% CI, 0.26-0.48) and lower Pitt score (OR = 0.76; 95% CI, 0.71-0.82). Adjusted estimations considering patients' features and exposure to procedures showed a reduction in coagulase-negative staphylococci (OR = 0.47; 95% CI, 0.32-0.69), and an increase in Proteus spp. (OR = 3.12; 95% CI, 1.18-8.23) and Candida spp. (OR = 3.01; 95% CI, 1.03-8.86). CONCLUSIONS: We found relevant epidemiologic changes in BSI in our area, including rates, frequency of acquisition types, changes in patient's profiles and aetiologic agents.

T cell lines characterize events in the pathogenesis of the Wiskott-Aldrich syndrome.

The Wiskott-Aldrich syndrome (WAS) is a severe immunodeficiency and platelet deficiency disease arising from an X-linked defect. The disease is correctable by transplantation of hematopoietic stem cells, but the product of the defective gene is unidentified and the number of defects in patient blood cells is large. The current hurdle is the need to identify the early pathogenic event(s) that are the cause of other defects. As a step toward this goal, we have generated and examined a panel of interleukin 2-dependent allospecific T cell lines from peripheral lymphocytes of seven WAS patients and five normal individuals. WAS cell lines, like normal lines, undergo vigorous proliferation when challenged with specific allostimulant or with phorbol myristate acetate and ionomycin. Both normal and WAS T cell lines express cell surface molecules CD2, CD3, T cell receptor-alpha/beta, human histocompatibility leukocyte antigen class I, CD45 and CD11a, and varying ratios of CD4 and CD8, and are negative for natural killer cell and monocyte surface molecules. WAS T cell lines express CD43 (sialophorin/leukosialin) with molecular weight and in an amount comparable with normal T cell lines. WAS T cell lines thus do not express defects in CD43 (decreased amount, abnormal molecular weight), previously documented in WAS circulating lymphocytes. On the other hand, as detected by scanning electron microscopy, WAS cell lines exhibit severe morphological abnormalities, including decreased size and density of the microvillus surface projections. The morphological abnormalities of WAS T cell lines are similar to, or more extensive than, those previously reported for WAS peripheral lymphocytes, indicating that the generation of morphological (cytoarchitectural) defects is an early pathogenic event in this disease. The findings suggest that the gene that is defective in the WAS encodes a protein that normally functions to maintain or regulate the cytoskeletal structure of blood cells.