The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear.
To evaluate whether recovery and mortality improved as SOC evolved, using ...data from ACTT (Adaptive COVID-19 Treatment Trial).
ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 ACTT-1, NCT04401579 ACTT-2, NCT04492475 ACTT-3, and NCT04640168 ACTT-4).
94 hospitals in 10 countries (86% U.S. participants).
Adults hospitalized with COVID-19.
SOC.
28-day mortality and recovery.
Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 95% CI, 0.92 to 1.17; HR for mortality, 0.90 CI, 0.56 to 1.40). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 CI, 0.53 to 0.97), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 CI, 1.24 to 1.64; HR for mortality, 0.45 CI, 0.21 to 0.97). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages.
Unmeasured confounding.
Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas.
National Institute of Allergy and Infectious Diseases.
Abstract
Background
Abnormal liver function is a common manifestation of human disease and may also occur in approved and investigational medications as drug-induced liver injury (DILI). Capillary ...blood collection devices may allow for more frequent and convenient measurement outside of the clinic. Validation of such approaches is lacking.
Methods
This prospective, biospecimens collection study evaluated the Tasso+ in patients with abnormal liver tests (NCT05259618). The primary objective was to define the concordance of alanine aminotransferase (ALT) obtained via Tasso+ compared to standard venipuncture. Secondary objectives included measurement of 14 other analytes and patient surveys. At the time of venipuncture, 2 Tasso+ samples were collected: one was centrifuged and shipped, and the other was refrigerated and shipped as whole blood.
Results
Thirty-six patients with elevated ALT values were enrolled. In total, 100 venipuncture, 50 Tasso+ centrifuged, and 48 Tasso+ whole blood samples were obtained. Tasso+ centrifuged samples demonstrated concordance correlation coefficients (CCC) of >0.99 for ALT, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and total bilirubin and CCC >0.95 for albumin, chloride, enzymatic creatinine, serum glucose, magnesium, and phosphorus. Tasso+ whole blood showed CCC of >0.99 for AST, bilirubin total, and enzymatic creatinine and CCC >0.95 for ALT, ALP, albumin, magnesium, and phosphorus. Hemolysis was comparable across the 3 sample types, but its impact was reflected in the Tasso+ potassium data. Patient feedback indicated a very favorable patient experience.
Conclusions
The capillary blood collection device, Tasso+, showed substantial to almost perfect concordance to standard venipuncture for measurement of abnormal liver function. Studies are ongoing to validate longitudinal sampling outside of the clinic.
Clinicaltrials.gov Registration Number: NCT05259618
Local immune activation at mucosal surfaces, mediated by mucosal lymphoid tissues, is vital for effective immune responses against pathogens. While pathogens like severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) can spread to multiple organs, patients with coronavirus disease 2019 (COVID-19) primarily experience inflammation and damage in their lungs. To investigate this apparent organ-specific immune response, we develop an analytical framework that recognizes the significance of mucosal lymphoid tissues. This framework combines histology, immunofluorescence, spatial transcript profiling, and mathematical modeling to identify cellular and gene expression differences between the lymphoid tissues of the lung and the gut and predict the determinants of those differences. Our findings indicate that mucosal lymphoid tissues are pivotal in organ-specific immune response to SARS-CoV-2, mediating local inflammation and tissue damage and contributing to immune dysfunction. The framework developed here has potential utility in the study of long COVID and may streamline biomarker discovery and treatment design for diseases with differential pathologies at the organ level.
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•Mucosal lymphoid tissues drive organ-specific response during SARS-CoV-2 infection•Injury signature is enriched in the lymphoid tissues of the lung relative to the gut•Lung lymphoid tissues harbor increased inflammatory macrophages during infection•Absence of activated dendritic cells in those tissues suggests immune dysfunction
Ng et al. investigate the role of mucosal lymphoid tissues in SARS-CoV-2 infection, uncovering distinct immune responses in the lung versus the gut. Lung lymphoid tissues exhibit elevated inflammatory macrophages, diminished activated dendritic cells, and amplified injury signatures, underscoring their pivotal role in organ-specific infection response.
Short-course directly observed isoniazid plus rifapentine (INH/RPT) combination could have potential advantages over a standard 9-month INH regimen for the treatment of latent tuberculosis infection ...in solid-organ transplant (SOT) candidates.
We prospectively assessed the safety and tolerability of 12 weeks of INH/RPT given directly observed therapy in 17 consecutive SOT candidates with latent tuberculosis infection.
The median age was 57 years and 82% were men. Of the 17 patients, 13 (76%) successfully completed therapy and 4 (24%) eventually underwent SOT. Treatment was prematurely discontinued in four patients. One of these patients underwent a kidney transplant. The overall dose compliance was 83% (169/204 scheduled doses), and 12 (71%) of 17 patients received 100% of scheduled doses. No patient developed transaminase elevations greater than twice baseline or greater than four times the upper limit of normal or clinical hepatotoxicity. No cases of TB developed during 20.4 months after transplant among INH/RPT-treated recipients.
For carefully selected SOT candidates, combination INH/RPT weekly given as directly observed therapy seems to be reasonably well tolerated and is associated with a relatively high completion rate. Future larger prospective studies to confirm the safety and high completion rates reported here and to identify the most appropriate SOT candidates for this regimen are warranted.
We characterized regulatory T cells from antiretroviral-naive HIV patients by flow cytometry. The proportion of CD4 cells positive for CD25 and Foxp3 was increased, mainly in those with CD4 cell ...counts less than 200 cells/microl. The total number of Foxp3-positive cells correlated with the CD4 cell count. Further studies are needed on whether Foxp3-positive cell numbers or function explain the susceptibility to autoimmune and inflammatory diseases seen in some patients with advanced HIV.
Summary Objectives Our aim was to investigate CD4+ cell recovery and adverse outcome after highly active antiretroviral therapy (HAART) under the Peruvian National Program for HIV. Methods A ...prospective, observational study was conducted between May 2004 and September 2005. Data were collected from records of patients receiving HAART at a public hospital under the Peruvian National Program for HIV. Predictors of CD4+ cell count recovery and adverse outcome were analyzed by multiple regression. Results Three hundred and twenty-six patients were included in the study. The mean increase in CD4+ cell count at six months was 114 cells/μl (95% confidence interval: 103–126). Patients with a lower CD4+ cell count at baseline and those starting HAART with a didanosine-based regimen had a higher increase in CD4+ cell count at six months. Patients starting HAART with a stavudine-based regimen had a lower increase in CD4+ cell count at six months. World Health Organization clinical stage IV at diagnosis of HIV infection, a low body weight at baseline, and starting HAART with a stavudine-based regimen were independently associated with an adverse outcome. Conclusions The CD4+ cell response to HAART under the Peruvian National Program for HIV was comparable with reports from other countries. However, the fact that advanced clinical disease predicted adverse outcome emphasizes the need for earlier access to HAART.
Alam Sehat Lestari (ASRI), an Indonesian-American, non-profit organization located on the border of Gunung Palung National Park in west Kalimantan on the island of Borneo, is linking the delivery of ...health care to the conservation of natural resources. The clinic's experience shows that an unconventional 'forests-for-health care' incentive programme can provide a powerful way to break the cycle that links poverty, poor health and environmental destruction around the park. However, the challenges of preventing, diagnosing and treating tuberculosis in this setting remain considerable and success will still depend upon a multilateral collaborative approach.
The search for unequivocal signs of life on other planetary bodies is one of the major challenges for astrobiology. The failure to detect organic molecules on the surface of Mars by measuring ...volatile compounds after sample heating, together with the new knowledge of martian soil chemistry, has prompted the astrobiological community to develop new methods and technologies. Based on protein microarray technology, we have designed and built a series of instruments called SOLID (for "Signs Of LIfe Detector") for automatic in situ detection and identification of substances or analytes from liquid and solid samples (soil, sediments, or powder). Here, we present the SOLID3 instrument, which is able to perform both sandwich and competitive immunoassays and consists of two separate functional units: a Sample Preparation Unit (SPU) for 10 different extractions by ultrasonication and a Sample Analysis Unit (SAU) for fluorescent immunoassays. The SAU consists of five different flow cells, with an antibody microarray in each one (2000 spots). It is also equipped with an exclusive optical package and a charge-coupled device (CCD) for fluorescent detection. We demonstrated the performance of SOLID3 in the detection of a broad range of molecular-sized compounds, which range from peptides and proteins to whole cells and spores, with sensitivities at 1-2 ppb (ng mL⁻¹) for biomolecules and 10⁴ to 10³ spores per milliliter. We report its application in the detection of acidophilic microorganisms in the Río Tinto Mars analogue and report the absence of substantial negative effects on the immunoassay in the presence of 50 mM perchlorate (20 times higher than that found at the Phoenix landing site). Our SOLID instrument concept is an excellent option with which to detect biomolecules because it avoids the high-temperature treatments that may destroy organic matter in the presence of martian oxidants.
INTRODUCCIÓN: La diarrea es una complicación común y una de las principales causas de malabsorción y desnutrición entre los paciente con SIDA. Nuestro objetivo es determinar las causas parasitarias ...de diarrea en pacientes con VIH-SIDA del Hospital Nacional Cayetano Heredia (Lima, Perú). MÉTODOS: Fueron incluidos 217 pacientes con VIH-SIDA que reportaron diarrea entre Mayo-2002 y Septiembre-2005. Fueron analizadas 1-3 muestras de heces mediante seis métodos para la detección de ooquistes, quistes, huevos y larvas de parásitos. RESULTADOS: La edad promedio fue 34.5 años (rango 15-68 años), 75.12% eran hombres. De ellos, 149/217 (68.66%) presentaron diarrea durante dos o más semanas. Se detectaron 123 parásitos en 103/217 pacientes (47.5%), presentando 18 de ellos (8.3%) infecciones parasitarias mixtas. Cryptosporidium spp. fue detectado con más frecuencia, sin embargo fue más prevalente en el grupo que presentaba dos o más semanas de diarrea, siendo esta diferencia estadísticamente significativa (22.82% vs. 10.29%, p=0.029). Otras parasitosis frecuentes fueron isosporidiasis (10.6%), giardiasis (8.3%) y strongyloidiasis (6.9%). CONCLUSIÓN: La enteroparasitosis es una condición frecuente entre los paciente con VIH SIDA que acuden al Hospital Nacional Cayetano Heredia, siendo frecuente la presencia de agentes oportunistas (Cryptosporidium spp. e Isospora belli) y no oportunistas ( Giardia lamblia y Strongyloides stercoralis).
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