Modulation of the gut microbiome and Firmicutes phylum reduction by a nutraceutical blend in the obesity mouse model and overweight humans: A double-blind clinical trial.

Overweight and obesity are closely linked to gut dysbiosis/dysmetabolism and disrupted De-Ritis ratio [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio], which may contribute to chronic noncommunicable diseases onset. Concurrently, extensive research explores nutraceuticals, and health-enhancing supplements, for disease prevention or treatment. Thus, sedentary overweight volunteers were double-blind randomized into two groups: Novel Nutraceutical_(S) (without silymarin) and Novel Nutraceutical (with silymarin). Experimental formulations were orally administered twice daily over 180 consecutive days. We evaluated fecal gut microbiota, based on partial 16S rRNA sequences, biochemistry and endocrine markers, steatosis biomarker (AST/ALT ratio), and anthropometric parameters. Post-supplementation, only the Novel Nutraceutical group reduced Clostridium clostridioforme (Firmicutes), Firmicutes/Bacteroidetes ratio (F/B ratio), and De-Ritis ratio, while elevating Bacteroides caccae and Bacteroides uniformis (Bacteroidetes) in Brazilian sedentary overweight volunteers after 180 days. In summary, the results presented here allow us to suggest the gut microbiota as the action mechanism of the Novel Nutraceutical promoting metabolic hepatic recovery in obesity/overweight non-drug interventions.

COVID-19 in hematopoietic stem cell transplant recipients during three years of the pandemic: a multicenter study in Brazil.

Hematopoietic stem cell transplant (HSCT) recipients are at -increased risk for severe COVID-19. The aim of this study was to evaluate the burden of COVID-19 in a cohort of HSCT recipients. This retrospective study evaluated a cohort of adult hospitalized HSCT recipients diagnosed with COVID-19 in two large hospitals in São Paulo, Brazil post-HSCT, from January 2020 to June 2022. The primary outcome was all-cause mortality. Of 49 cases, 63.2% were male with a median age of 47 years. Allogeneic-HSCT (51.2%) and autologous-HSCT (48.9%) patients were included. The median time from HSCT to COVID-19 diagnosis was 398 days (IQR: 1211-134), with 22 (44.8%) cases occurring within 12 months of transplantation. Most cases occurred during the first year of the pandemic, in non-vaccinated patients (n=35; 71.4%). Most patients developed severe (24.4%) or critical (40.8%) disease; 67.3% received some medication for COVID-19, primarily corticosteroids (53.0%). The probable invasive aspergillosis prevalence was 10.2%. All-cause mortality was 40.8%, 51.4% in non-vaccinated patients and 14.2% in patients who received at least one dose of the vaccine. In the multiple regression analyses, the variables mechanical ventilation (OR: 101.01; 95% CI: 8.205 - 1,242.93; p = 0.003) and chest CT involvement at diagnosis ≥50% (OR: 26.61; 95% CI: 1.06 - 664.26; p = 0.04) remained associated with all-cause mortality. Thus, HSCT recipients with COVID-19 experienced high mortality, highlighting the need for full vaccination and infection prevention measures.

Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency. Methods: At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output. Results: Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19. Discussion: Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.

Multiple myeloma and Chagas disease: qPCR as a marker for preemptive antiparasitic therapy: a case reports series and review.

Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.

Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation.

Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

Prevalence and clinical consequences of Hepatitis C virus infection in patients undergoing hematopoietic stem cell transplantation

ABSTRACT Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality among hematopoietic stem cell transplant (HCT) recipients. In Brazil, its occurrence in HCT recipients remains undetermined. We now report on HCV prevalence in HCT recipients and its clinical consequences. The medical records of all HCT recipients seen at Hospital das Clinicas, Sao Paulo University Medical School, from January 2010 to January 2020 were reviewed to determine HCV serostatus. A retrospective analysis of medical charts was undertaken on all seropositive cases to determine HCV genotype, presence of liver fibrosis, co-infections with other viruses, previous treatments, and clinical evolution of liver pathology after HCT. Of the 1,293 HCT recipients included in the study, seven (0.54%) were HCV antibody-positive and five (0.39%) were also viremic for HCV-RNA. Four of these individuals had moderate to severe liver fibrosis (METAVIR F2/F3) and one was cirrhotic. Two of the viremic patients developed acute liver dysfunction following transplantation. All patients had their acute episode of liver dysfunction resolved with no further complications. Four of the viremic patients were treated for HCV infection with direct acting agents (DAA). Information regarding HCV treatment was lacking for one of the viremic HCV patients due to loss of follow up. Sustained anti-virologic responses were observed in three cases after the use of DAA. The detection of HCV in hematological adults undergoing HCT and its successful treatment with DAA highlight the necessity of testing for HCV both prior to and following transplantation.

Multiple myeloma and Chagas disease: qPCR as a marker for preemptive antiparasitic therapy: a case reports series and review

ABSTRACT Multiple myeloma (MM) associated with Chagas disease is rarely described. This disease and its therapy suppress T cell and macrophage functions and increase regulatory T cell function, allowing the increase of parasitemia and the risk of Chagas Disease Reactivation (CDR). We aimed to analyze the role of conventional (cPCR) and quantitative Polymerase Chain Reaction (qPCR) for prospective monitoring of T. cruzi parasitemia, searching for markers of preemptive antiparasitic therapy in MM patients with Chagas disease. Moreover, we investigated the incidence and management of hematological diseases and CDR both inside and outside the transplant setting in the MEDLINE database. We found 293 studies and included 31 of them. Around 1.9-2.0% of patients with Chagas disease were reported in patients undergoing Stem Cell Transplantation. One case of CDR was described in eight cases of MM and Chagas disease. We monitored nine MM and Chagas disease patients, seven under Autologous Stem Cell Transplantation (ASCT), during 44.56±32.10 months (mean±SD) using parasitological methods, cPCR, and qPCR. From these patients, three had parasitemia. In the first, up to 256 par Eq/mL were detected, starting from 28 months after ASCT. The second patient dropped out and died soon after the detection of 161.0 par Eq/mL. The third patient had a positive blood culture. Benznidazole induced fast negativity in two cases; followed by notably lower levels in one of them. Increased T. cruzi parasitemia was related to the severity of the underlying disease. We recommend parasitemia monitoring by qPCR for early introduction of preemptive antiparasitic therapy to avoid CDR.

COVID-19 in hematopoietic stem cell transplant recipients during three years of the pandemic: a multicenter study in Brazil

ABSTRACT Hematopoietic stem cell transplant (HSCT) recipients are at -increased risk for severe COVID-19. The aim of this study was to evaluate the burden of COVID-19 in a cohort of HSCT recipients. This retrospective study evaluated a cohort of adult hospitalized HSCT recipients diagnosed with COVID-19 in two large hospitals in São Paulo, Brazil post-HSCT, from January 2020 to June 2022. The primary outcome was all-cause mortality. Of 49 cases, 63.2% were male with a median age of 47 years. Allogeneic-HSCT (51.2%) and autologous-HSCT (48.9%) patients were included. The median time from HSCT to COVID-19 diagnosis was 398 days (IQR: 1211-134), with 22 (44.8%) cases occurring within 12 months of transplantation. Most cases occurred during the first year of the pandemic, in non-vaccinated patients (n=35; 71.4%). Most patients developed severe (24.4%) or critical (40.8%) disease; 67.3% received some medication for COVID-19, primarily corticosteroids (53.0%). The probable invasive aspergillosis prevalence was 10.2%. All-cause mortality was 40.8%, 51.4% in non-vaccinated patients and 14.2% in patients who received at least one dose of the vaccine. In the multiple regression analyses, the variables mechanical ventilation (OR: 101.01; 95% CI: 8.205 - 1,242.93; p = 0.003) and chest CT involvement at diagnosis ≥50% (OR: 26.61; 95% CI: 1.06 - 664.26; p = 0.04) remained associated with all-cause mortality. Thus, HSCT recipients with COVID-19 experienced high mortality, highlighting the need for full vaccination and infection prevention measures.

COVID-19 in hematopoietic stem-cell transplant recipients: A systematic review and meta-analysis of clinical characteristics and outcomes.

Patients who undergo hematopoietic stem-cell transplantation (HSCT) are more susceptible to developing severe forms of COVID-19 with an increased risk of mortality. The aim of this study was to analyze, by performing a systematic review and meta-analysis, all studies that evaluated COVID-19 in HSCT adult recipients and present clinical characteristics and outcomes. Studies were eligible for inclusion if they: (I) described the clinical characteristics of COVID-19 in adult (aged 18 years old or above) HSCT recipients; (II) described outcomes of COVID-19 in this population, mainly lethality; (III) were full-text articles. We searched MedLine, Embase, SCOPUS, LILACS and Web of Science for full-text studies that evaluated COVID-19 in adult HSCT patients until 26 Apr 2023. Two independent reviewers screened the articles and extracted the data. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Studies Reporting Prevalence Data was used to assess quality of the included studies. Meta-analysis was performed and the pooled prevalence of severe/critical disease and of death with a 95% CI was calculated with the random-effects model. Sixteen studies were included; seven (43.7%) were multicenter. Most of the studies were from Europe (37.5%). All of them had a low risk of bias using the JBI Checklist. A total of 1186 patients were included. Allogeneic HSCT patients were the majority in most studies, with a total of 861 patients (72.5%). The symptomatic rate was 79.4%. The pooled prevalence of severe/critical COVID-19 was 24.0% (95% CI 0.13-0.36; I2  = 94%; n = 334/990). The pooled prevalence of death for the entire population was 17% (95% CI 0.13-0.22; I2  = 76%; n = 221/1117), 17% (95% CI 0.12-0.23; I2  = 67%; n = 152/822) for allogeneic-HSCT and 14% (95% CI 0.08-0.22; I4  = 65%; n = 48/293) for autologous-HSCT. In conclusion, frequently the infection of SARS-CoV-2 in HSCT was symptomatic and lethality is higher than in general population. Thus, it is essential to focus on the implementation of measures to mitigate the risk of SARS-CoV-2 infection in this population, as well as to carefully assess HSCT recipients who develop COVID-19.

Strongyloides infection screening in transplant candidates: What is the best strategy?

BACKGROUND: The potential that Strongyloides stercoralis infection has to cause major morbidity and high mortality when the disseminated form occurs in transplant patients is of particular concern. METHODS: In this study, the objective was to observe S. stercoralis infection in patients who are candidates for transplantation by using parasitological, serological, and molecular techniques and to propose an algorithm for the detection of that infection in transplant candidates. RESULTS: By parasitological techniques, 10% of fecal samples were positive. Anti-Strongyloides antibodies immunoglobulin G were detected in 19.3% and 20.7% of patients by immunofluorescence assay and enzyme-linked immunosorbent assay, respectively. S. stercoralis DNA was observed in 17.3% of samples by conventional polymerase chain reaction and 32.7% of samples by quantitative polymerase chain reaction (qPCR). CONCLUSION: The set of results allows us to reinforce that a positive result by parasitological techniques and/or qPCR indicates that the specific treatment should be applied. However, the improvement of diagnostic techniques may suggest changes in the screening for strongyloidiasis in these patients.

Evaluation of Dengue, Zika virus, and Chikungunya virus transmission by blood components in recipients of haematopoietic stem cell transplantation.

BACKGROUND: Brazil has a high prevalence of arboviruses, especially Dengue (DENV), Zika (ZKV), and Chikungunya (CHKV). OBJECTIVES: To study the risk of DENV, ZKV, and CHKV transmission by blood components in the haematopoietic stem cell transplantation (HSCT) population. METHODS: Prospective cohort of HSCT recipients and donors performed at the Hospital das Clinicas da FMUSP, São Paulo-Brazil. Patients were evaluated by serology and RT-PCR for DENV, ZKV, and CHKV pre-transplantation and once a week until neutrophil grafting. In positive cases (positive RT-PCR and/or serology conversion), an investigation was carried out on the blood components that the patient received to evaluate the possibility of it being transfusion transmitted. RESULTS: A total of 93 patients were included during the study period. The mean age was 52 years with a predominance of males (56.9%). We considered five (5.3%) DENV cases positive by seroconversion in our study. One patient had IgM seroconversion and the other four presented IgG seroconversion to DENV. In the investigation of the blood components, 145 individual samples were analysed. None of the investigated blood components showed a positive RT-PCR. CONCLUSION: We observed a low prevalence of DENV, ZKV, and CHKV in HSCT donors and recipients by serology and RT-PCR, and no case of blood transfusion transmission by RT-PCR.

Association between development of severe COVID-19 and a polymorphism in the CIAS1 gene that codes for an inflammasome component.

An elevated pro-inflammatory cytokine response is associated with severe life-threatening symptoms in individuals with Coronavirus Disease-2019 (COVID). The inflammasome is an intracellular structure responsible for generation of interleukin (IL)-1ß and IL-18. NALP3, a product of the CIAS1 gene, is the rate-limiting component for inflammasome activity. We evaluated if a CIAS1 42 base pair length polymorphism (rs74163773) was associated with severe COVID. DNA from 93 individuals with severe COVID, 38 with mild COVID, and 98 controls were analyzed for this polymorphism. The 12 unit repeat allele is associated with the highest inflammasome activity. Five alleles, corresponding to 6, 7, 9, 12 or 13 repeat units, divided into 12 genotypes were identified. The frequency of the 12 unit repeat allele was 45.3% in those with severe disease as opposed to 30.0% in those with mild disease and 26.0% in controls (p < 0.0001, severe vs. controls). In contrast, the 7 unit repeat allele frequency was 30.1% in controls as opposed to 14.0% and 12.5% in those with severe or mild disease, respectively (p ≤ 0.0017). We conclude that individuals positive for the CIAS1 12 allele may be at elevated risk for development of severe COVID due to an increased level of induced pro-inflammatory cytokine production.

Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation.

The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.

Case Report: Successful Treatment of Recurrent Urinary Tract Infection Due to Extensively Drug-Resistant Klebsiella Pneumoniae in a Kidney Transplant Recipient Using Chloramphenicol.

Effective therapies for multidrug-resistant (MDR) microorganisms, especially Gram-negative bacteria, are becoming rare. Also, solid-organ transplant recipients are at high risk of MDR Gram-negative bacilli infection. Urinary tract infections are the most frequent bacterial infections in kidney transplant recipients and are an important cause of mortality after renal transplantation. We describe a case of complicated urinary tract infection in a kidney transplant patient due to extensively drug-resistant (XDR) K. pneumoniae treated successfully with a regimen comprising a combination of chloramphenicol and ertapenem. We do not recommend chloramphenicol as a first-line choice for treating complicated urinary tract infections. Still, we believe it is an alternative for infections caused by MDR and/or XDR pathogens in renal transplant patients, as other options are nephrotoxic.

Streptococcus constellatus causing concomitant extra and intracranial abscesses complicated with sagittal sinus thrombosis.

Streptococcus constellatus is a gram-positive coccus member of the Streptococcus anginosus group (SAG). It can be found in the oral flora, and may cause abscess more commonly in the gastrointestinal tract, lungs, and heart. Brain abscesses are severe neurological infections with high mortality rates. Streptococcus species other than S. pneumoniae are rare causes of brain abscesses. This case report highlights a severe case of extra and intracranial abscesses due to S. constellatus in an immunocompetent host.

Reinfection rate in a cohort of healthcare workers over 2 years of the COVID-19 pandemic.

In this large cohort of healthcare workers, we aimed to estimate the rate of reinfections by SARS-CoV-2 over 2 years of the COVID-19 pandemic. We investigated the proportion of reinfections among all the cases of SARS-CoV-2 infection from March 10, 2020 until March 10, 2022. Reinfection was defined as the appearance of new symptoms that on medical evaluation were suggestive of COVID-19 and confirmed by a positive RT-PCR. Symptoms had to occur more than 90 days after the previous infection. These 2 years were divided into time periods based on the different variants of concern (VOC) in the city of São Paulo. There were 37,729 medical consultations due to COVID-19 at the hospital's Health Workers Services; and 25,750 RT-PCR assays were performed, of which 23% (n = 5865) were positive. Reinfection by SARS-CoV-2 was identified in 5% (n = 284) of symptomatic cases. Most cases of reinfection occurred during the Omicron period (n = 251; 88%), representing a significant increase on the SARS-CoV-2 reinfection rate before and during the Omicron variant period (0.8% vs. 4.3%; p < 0.001). The mean interval between SARS-CoV-2 infections was 429 days (ranged from 122 to 674). The Omicron variant spread faster than Gamma and Delta variant. All SARS-CoV-2 reinfections were mild cases.

Risk factors for reduction in adherence to protective measures following coronavirus disease 2019 (COVID-19) vaccination and vaccine perceptions among healthcare workers, in São Paulo, Brazil.

A survey evaluated 2,300 healthcare workers following the first dose of a coronavirus disease 2019 (COVID-19) vaccine in a tertiary-quaternary hospital in São Paulo, Brazil. Adherence to protective measures following vaccination was compared to previous non-work-related behaviors. Younger age, previous COVID-19, and burnout symptoms were associated with reduced adherence to mitigation measures.