Long-term antibody titers variation in unvaccinated patients receiving convalescent plasma or placebo for severe SARS-CoV-2 pulmonary infection.

BACKGROUND: Convalescent plasma (CP) became a prominent treatment in the early stages of the SARS-CoV-2 pandemic. In Argentina, a randomized clinical trial was executed to compare the use of CP in inpatients with severe COVID-19 pneumonia versus placebo. No differences in clinical outcomes or overall mortality between groups were observed. We conducted a cohort study in outpatients enrolled in the trial to describe long-term antibody titer variations between CP and placebo recipients. METHODS: Patients' total SARS-CoV-2 IgG antibodies against spike protein were collected 3, 6 and 12 months after hospital discharge from August 2020 to December 2021. In addition, reinfections, deaths and vaccination status were retrieved. Statistical analysis was performed using antibody geometric mean titers (GMT). All estimations were made considering the date of the trial infusion (placebo or CP) as time 0. RESULTS: From the 93 patients included in the follow-up, 64 had received CP and 29 placebo. We excluded all 12-month measurements because they were collected after the patients' vaccination date. At 90 days post-infusion, patients had an antibody GMT of 8.1 (IQR 7.4-8.1) in the CP group and 8.8 (IQR 8.1-9.1) in the placebo group. At 180 days, both groups had a GMT of 8.1 (IQR 7.4-8.1). No statistical differences in GMT were found between CP and placebo groups at 90 days (p = 0.12) and 180 days (p = 0.25). No patients registered a new COVID-19 infection; one died in the CP group from an ischemic stroke. CONCLUSIONS: No differences were observed in long-term antibody titers in unvaccinated patients that received CP or placebo after severe COVID-19 pneumonia.

Development and Validation of a Treatment Benefit Index to Identify Hospitalized Patients With COVID-19 Who May Benefit From Convalescent Plasma.

Importance: Identifying which patients with COVID-19 are likely to benefit from COVID-19 convalescent plasma (CCP) treatment may have a large public health impact. Objective: To develop an index for predicting the expected relative treatment benefit from CCP compared with treatment without CCP for patients hospitalized for COVID-19 using patients' baseline characteristics. Design, Setting, and Participants: This prognostic study used data from the COMPILE study, ie, a meta-analysis of pooled individual patient data from 8 randomized clinical trials (RCTs) evaluating CCP vs control in adults hospitalized for COVID-19 who were not receiving mechanical ventilation at randomization. A combination of baseline characteristics, termed the treatment benefit index (TBI), was developed based on 2287 patients in COMPILE using a proportional odds model, with baseline characteristics selected via cross-validation. The TBI was externally validated on 4 external data sets: the Expanded Access Program (1896 participants), a study conducted under Emergency Use Authorization (210 participants), and 2 RCTs (with 80 and 309 participants). Exposure: Receipt of CCP. Main Outcomes and Measures: World Health Organization (WHO) 11-point ordinal COVID-19 clinical status scale and 2 derivatives of it (ie, WHO score of 7-10, indicating mechanical ventilation to death, and WHO score of 10, indicating death) at day 14 and day 28 after randomization. Day 14 WHO 11-point ordinal scale was used as the primary outcome to develop the TBI. Results: A total of 2287 patients were included in the derivation cohort, with a mean (SD) age of 60.3 (15.2) years and 815 (35.6%) women. The TBI provided a continuous gradation of benefit, and, for clinical utility, it was operationalized into groups of expected large clinical benefit (B1; 629 participants in the derivation cohort [27.5%]), moderate benefit (B2; 953 [41.7%]), and potential harm or no benefit (B3; 705 [30.8%]). Patients with preexisting conditions (diabetes, cardiovascular and pulmonary diseases), with blood type A or AB, and at an early COVID-19 stage (low baseline WHO scores) were expected to benefit most, while those without preexisting conditions and at more advanced stages of COVID-19 could potentially be harmed. In the derivation cohort, odds ratios for worse outcome, where smaller odds ratios indicate larger benefit from CCP, were 0.69 (95% credible interval [CrI], 0.48-1.06) for B1, 0.82 (95% CrI, 0.61-1.11) for B2, and 1.58 (95% CrI, 1.14-2.17) for B3. Testing on 4 external datasets supported the validation of the derived TBIs. Conclusions and Relevance: The findings of this study suggest that the CCP TBI is a simple tool that can quantify the relative benefit from CCP treatment for an individual patient hospitalized with COVID-19 that can be used to guide treatment recommendations. The TBI precision medicine approach could be especially helpful in a pandemic.

Acquired factor XIII deficiency in patients under therapeutic plasma exchange: A poorly explored etiology.

INTRODUCTION: Factor XIII (FXIII) deficiency may cause bleeding under certain clinical circumstances. Therapeutic plasma exchange (TPE) may lead to a transient deficiency. OBJECTIVES: To describe the clinical evolution of patients with acquired FXIII deficiency secondary to TPE. METHODS: We respectively studied a cohort of consecutive patients from 2014 to 2019 who were treated with TPE with FXIII levels <50%. The FXIII was measured after the start of the TPE course, on days between the TPE sessions, due to suspected acquired deficiency. All TPE were performed using continuous flow cell separator. In all cases, the initial replacement fluid applied was albumin. Apheresis procedures were held at 24to 48 hours intervals. RESULTS: Eighteen patients were included, 13 of them were recipients of kidney transplants. The main TPE prescription was humoral rejection. Median FXIII at diagnosis (measured on days between sessions of the TPE course) was 19%(IQR17-25). The median of apheresis procedures before measurement of FXIII was 3(IQR2-4). Among the total cohort, 10 patients suffered hemorrhages. None of the patients without history of kidney transplants had bleeding (n = 5), however, 10/13 with kidney transplants did. Five kidney transplant patients received therapy with FXIII concentrate because of life-threatening bleeding. In all cases, the bleeding stopped within the first 24 hours. All patients had their FXIII levels measured again after finishing the TPE course, with normal results. CONCLUSIONS: TPE is an under-diagnosed cause of acquired FXIII deficiency since routine coagulation tests remain unaltered. It might cause major bleeding, particularly in patients with a recent history of surgery like kidney transplants.

A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia.

BACKGROUND: Convalescent plasma is frequently administered to patients with Covid-19 and has been reported, largely on the basis of observational data, to improve clinical outcomes. Minimal data are available from adequately powered randomized, controlled trials. METHODS: We randomly assigned hospitalized adult patients with severe Covid-19 pneumonia in a 2:1 ratio to receive convalescent plasma or placebo. The primary outcome was the patient's clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. RESULTS: A total of 228 patients were assigned to receive convalescent plasma and 105 to receive placebo. The median time from the onset of symptoms to enrollment in the trial was 8 days (interquartile range, 5 to 10), and hypoxemia was the most frequent severity criterion for enrollment. The infused convalescent plasma had a median titer of 1:3200 of total SARS-CoV-2 antibodies (interquartile range, 1:800 to 1:3200). No patients were lost to follow-up. At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83; 95% confidence interval [CI], 0.52 to 1.35; P = 0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of -0.46 percentage points (95% CI, -7.8 to 6.8). Total SARS-CoV-2 antibody titers tended to be higher in the convalescent plasma group at day 2 after the intervention. Adverse events and serious adverse events were similar in the two groups. CONCLUSIONS: No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. (PlasmAr ClinicalTrials.gov number, NCT04383535.).

Impacto del volumen de sangre extraído por flebotomía sobre el requerimiento transfusional en prematuros menores de 1500 g. Estudio cuasiexperimental / Impact of the volume of blood collected by phlebotomy on transfusion requirements in preterm infants with birth weight of less than 1500 g. A quasi-experimental study

Introducción. La anemia es una complicación para los recién nacidos de muy bajo peso al nacer, y los exámenes de laboratorio son un factor de riesgo preponderante. Más del 50 % recibe, al menos, una transfusión de glóbulos rojos. Estas se han asociado a mayor riesgo de infecciones, hemorragia intracraneal, enterocolitis necrotizante y displasia broncopulmonar. En 2012, se implementó, en el Hospital Italiano de Buenos Aires, una estrategia de menor volumen de extracción de sangre por flebotomía. El objetivo del presente estudio fue evaluar su asociación con el número detransfusiones.Métodos. Estudio cuasiexperimental del tipo antes/después. Se comparó el número de transfusiones entre dos grupos de prematuros de muy bajo peso con diferente volumen de extracción. Se evaluó la correlación entre el volumen extraído y el número de transfusiones estimando el coeficiente de Spearman. Para ajustar por confundidores, se realizó un modelo de regresión logística.Resultados. Se incluyeron en el estudio 178 pacientes con edad gestacional media de 29,4 semanas (desvío estándar: 2,7) y peso al nacer de 1145 gramos (875-1345). El perfil de la serie roja inicial fue similar entre ambos grupos. El número de transfusiones (p = 0,017) y el volumen transfundido (p = 0,048) disminuyeron significativamente. El coeficiente de correlación resultó de 0,83. En el análisis multivariado, volumen de extracción y peso al nacer se asociaron a un requerimiento mayor de 3 transfusiones.Conclusión. Un menor volumen de extracción de sangre en prematuros de muy bajo peso está asociado de manera independiente a menor requerimiento transfusional.

Introduction. Anemia is a complication in very low birth weight (VLBW) infants, and lab tests are a predominant risk factor. At least one red blood cell transfusion is given in more than 50 % of cases. Transfusions are associated with a higher risk for infections, intracranial hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia. In 2012, Hospital Italiano de Buenos Aires implemented a strategy to collect a lower blood volume by phlebotomy. The objective of this study was to assess its association with the number of transfusions.Methods. Before-and-after, quasi-experimental study. The number of transfusions was compared between two groups of VLBW preterm infants with different blood collection volumes. The correlation between the collection volume and the number of transfusions was assessed estimating Spearman's coefficient. A logistic regression model was used to adjust for confounders.Results. The study included 178 patients with a mean gestational age of 29.4 weeks (standard deviation: 2.7) and a birth weight of 1145 g (875-1345). The baseline red series profile was similar between both groups. The number of transfusions (p = 0.017) and the transfusion volume (p = 0.048) decreased significantly. The correlation coefficient was 0.83. In the multivariate analysis, collection volume and birth weight were associated with a requirement of more than three transfusions.Conclusion. A lower blood collection volume in VLBW preterm infants is independently associated with fewer transfusion requirements.

Impact of the volume of blood collected by phlebotomy on transfusion requirements in preterm infants with birth weight of less than 1500 g. A quasi-experimental study. / Impacto del volumen de sangre extraído por flebotomía sobre el requerimiento transfusional en prematuros menores de 1500 g. Estudio cuasiexperimental.

INTRODUCTION: Anemia is a complication in very low birth weight (VLBW) infants, and lab tests are a predominant risk factor. At least one red blood cell transfusion is given in more than 50 % of cases. Transfusions are associated with a higher risk for infections, intracranial hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia. In 2012, Hospital Italiano de Buenos Aires implemented a strategy to collect a lower blood volume by phlebotomy. The objective of this study was to assess its association with the number of transfusions. METHODS: Before-and-after, quasi-experimental study. The number of transfusions was compared between two groups of VLBW preterm infants with different blood collection volumes. The correlation between the collection volume and the number of transfusions was assessed estimating Spearman's coefficient. A logistic regression model was used to adjust for confounders. RESULTS: The study included 178 patients with a mean gestational age of 29.4 weeks (standard deviation: 2.7) and a birth weight of 1145 g (875-1345). The baseline red series profile was similar between both groups. The number of transfusions (p = 0.017) and the transfusion volume (p = 0.048) decreased significantly. The correlation coefficient was 0.83. In the multivariate analysis, collection volume and birth weight were associated with a requirement of more than three transfusions. CONCLUSION: A lower blood collection volume in VLBW preterm infants is independently associated with fewer transfusion requirements.

Introducción. La anemia es una complicación para los recién nacidos de muy bajo peso al nacer, y los exámenes de laboratorio son un factor de riesgo preponderante. Más del 50 % recibe, al menos, una transfusión de glóbulos rojos. Estas se han asociado a mayor riesgo de infecciones, hemorragia intracraneal, enterocolitis necrotizante y displasia broncopulmonar. En 2012, se implementó, en el Hospital Italiano de Buenos Aires, una estrategia de menor volumen de extracción de sangre por flebotomía. El objetivo del presente estudio fue evaluar su asociación con el número de transfusiones. Métodos. Estudio cuasiexperimental del tipo antes/después. Se comparó el número de transfusiones entre dos grupos de prematuros de muy bajo peso con diferente volumen de extracción. Se evaluó la correlación entre el volumen extraído y el número de transfusiones estimando el coeficiente de Spearman. Para ajustar por confundidores, se realizó un modelo de regresión logística. Resultados. Se incluyeron en el estudio 178 pacientes con edad gestacional media de 29,4 semanas (desvío estándar: 2,7) y peso al nacer de 1145 gramos (875-1345). El perfil de la serie roja inicial fue similar entre ambos grupos. El número de transfusiones (p = 0,017) y el volumen transfundido (p = 0,048) disminuyeron significativamente. El coeficiente de correlación resultó de 0,83. En el análisis multivariado, volumen de extracción y peso al nacer se asociaron a un requerimiento mayor de 3 transfusiones. Conclusión. Un menor volumen de extracción de sangre en prematuros de muy bajo peso está asociado de manera independiente a menor requerimiento transfusional.

Role of HLA-DP and HLA-DQ on the clearance of hepatitis B virus and the risk of chronic infection in a multiethnic population.

BACKGROUND & AIMS: HBV infection exhibits geographical variation in its distribution in South America. While HBV rates are low in central Argentina, the north-western region exhibits intermediate HBV rates. Unfortunately, the reasons that could explain this difference are still unknown. METHODS: A total of 1440 Argentines were recruited and grouped into HBV patients, HBV-resolved individuals and healthy controls. Genetic ancestry was assessed by analysis of biparental lineages and ancestry autosomal typing. SNPs of HLA-DPA1 (rs3077), HLA-DPB1 (rs9277542), HLA-DQB1 (rs2856718) and HLA-DQB2 (rs7453920) were determined, and HBV genotyping was performed by phylogenetic analysis in HBV patients. RESULTS: Native American ancestry prevailed in the north-western region when compared with central Argentina (P<.0001). However, no differences were observed among the three groups of each region. The distribution of HBV genotypes revealed significant differences (P<.0001). Three SNPs (rs3077, rs9277542 and rs7453920) showed a significant association with protection against chronic HBV and viral clearance in both regions. The remaining SNP showed a significant association with susceptibility to chronic HBV. The frequency rates of rs3077-T, related to protection against chronic HBV and viral clearance, were lower in north-western Argentina when compared with central Argentina. The same uneven frequency rates were observed for SNP rs9277542. CONCLUSIONS: This is the first study addressing the associations between the HLA-DP and HLA-DQ loci and the protection against chronic HBV and viral clearance in a multiethnic South American population. The uneven distribution of HLA-DP and HLA-DQ supports the HBV epidemiological differences observed in these two regions of Argentina with dissimilar ancestry genetic background.

Increased prevalence of human herpesvirus type 8 (HHV-8) genome among blood donors from North-Western Argentina.

The prevalence of HHV-8 infection varies widely in South American populations, displaying geographical variations in its distribution. The heterogeneous genetic contributions provided by the transatlantic parental populations that modified the Native American genomes may explain this epidemiological observation. Aiming to determine the prevalence of HHV-8 genome among healthy South American blood donors and its potential association with genetic ancestry, 772 individuals were screened by a highly sensitive PCR protocol and ancestry was assessed in 414 samples. HHV-8 DNA was significantly more prevalent among North-western Argentines than among those from the metropolitan region (P = 0.001) and Bolivians (P = 0.0008), but no differences were found when compared with Peruvians and Paraguayans. Although significant differences were observed in the ancestry components of the studied populations, no association was found in the genetic admixture between HHV-8 [+] and HHV-8 [-] samples from the same place. These results support the hypothesis of the existence of geographical factors related to HHV-8 prevalence which could be explained by the presence of specific risk factors, cultural characteristics or behaviors, probably related to contaminated saliva and/or sexual transmission. The presence of HHV-8 in South American blood units available for transfusion and an increased risk of infection in some provinces of North-western Argentina represent a hazard for immunosuppressed recipients. J. Med. Virol. 89:518-527, 2017. © 2016 Wiley Periodicals, Inc.

Medicina transfusional basada en la evidencia / Evidence-based transfusional medicine

La idea de publicar este trabajo, es estimular la utilización de preguntas surgidas de la práctica médica, para obtener respuestas con base en la mejor evidencia publicada. La medicina basada en la evidencia, es una herramienta fundamental para la toma de decisiones, no sólo en lo que respecta a un paciente o caso puntual, sino también para la salud y la sociedad en general. El caso que motiva esta publicación es una de las entidades que, como equipo dedicado a la medicina transfusional más nos convoca, ya que no sólo es una patología que requiere de nuestra participación activa como integrantes de un equipo médico, sino que además depende en gran medida del desarrollo de los bancos de sangre como servicios activos y pensados para dar respuesta a este tipo de problemática.

Publishing this paper aims to encourage doctors to take questions that arise from their medical practice to be answered basing their research on the best evidence published. Evidence-based medicine is an essential tool when making decisions not only when it comes to a patient or a particular case but also when these decisions have an impact on health and societies in general. The case that inspires this publication is one that concerns us the most because it consists in a pathology that requires our whole active participation as members of a transfusion medicine team. Furthermore, it heavily depends on the development of blood banks as an active service that is conceived to salve this type of problem.

Glomérulo esclerosis focal y segmentaria. Trasplante renal y plasmaféresis / Focal segmental glomerulo sclerosis renal transplant and plasmapheresis

La Glomérulo Esclerosis Focal y Segmentaria (GEFS) primaria es una entidad que se define histológicamente por el depósito de material hialino en los glomérulos renales. Su origen permanece aún desconocido y es una de las causas más importantes del Síndrome Nefrótico (SN) Corticorresistente. La GEFS es la causa diagnostica de base del 8,3 por ciento de los casos de Insuficiencia Renal Crónica (lRC), del 14 por ciento de pacientes en plan de diálisis y del 13,5 por ciento de los receptores de Trasplante Renal. Además, luego del trasplante renal, esta enfermedad tiene una tasa elevada de recaída sobre el injerto. Sobre la fisiopatología de esta enfermedad, las últimas líneas teóricas hacen hincapié en la función de los podocitos, estos datos surgieron del conocimiento de alteraciones genéticas que implican a estas células. La hipótesis de que un "factor plasmático circulante" aumenta la permeabilidad de los glomérulos a la albumina está apoyada en numerosos estudios clínicos y experimentales. Esta es la base fisiopatológica del tratamiento donde se encuentra ubicada como uno de los pilares la Plasmaféresis, acompañando a las nuevas modalidades de Inmunosupresión. Esta revisión está focalizada en los mecanismos fisiopatológicos involucrados en esta enfermedad y a describir las terapéuticas utilizadas en su tratamiento.

Primary focal segmental glomerulosclerosis (FSGS) is an entity defined in histological terms by the hyaline material depot that is found in renal glomerulus. Its origin still remains unknown and it's one of the most important causes of corticosteroid-resistant nephrotic syndrome. FSGS is the main diagnostic cause of: 8.3 per cent of chronic renal failure (CRF) cases, 14 per cent of dialysis patients and 13.5 per cent of people receiving a kidney transplant. Besides, after the renal transplantation, this disease has a high rate relapse over the graft. Concerning the pathophysiology of FSGS, the latest theoretical research emphasizes on the podocytes function. These data came out from the knowledge of the genetic disorder that these cells implicate. The hypothesis that a "plasmatic circulating factor" increases the permeability of the glomerulus for albumin is supported by both several clinical and experimental research. The plasmatic circulating factor is the pathophysiological base for the treatment whit plasmapheresis along whit immunosuppression procedures. This present revision is focused on the pathophysiological mechanisms involved in, and des­cribes the therapies used on its treatment.