Combined frequency domain near-infrared spectroscopy and diffuse correlation spectroscopy system for comprehensive metabolic monitoring of inspiratory muscles during loading.

Significance: Mechanical ventilation (MV) is a cornerstone technology in the intensive care unit as it assists with the delivery of oxygen in critically ill patients. The process of weaning patients from MV can be long and arduous and can lead to serious complications for many patients. Despite the known importance of inspiratory muscle function in the success of weaning, current clinical standards do not include direct monitoring of these muscles. Aim: The goal of this project was to develop and validate a combined frequency domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) system for the noninvasive characterization of inspiratory muscle response to a load. Approach: The system was fabricated by combining a custom digital FD-NIRS and DCS system. It was validated via liquid phantom titrations and a healthy volunteer study. The sternocleidomastoid (SCM), an accessory muscle of inspiration, was monitored during a short loading period in fourteen young, healthy volunteers. Volunteers performed two different respiratory exercises, a moderate load and a high load, which consisted of a one-minute baseline, a one-minute load, and a six-minute recovery period. Results: The system has low crosstalk between absorption, reduced scattering, and flow when tested in a set of liquid titrations. Faster dynamics were observed for changes in blood flow index (BFi), and metabolic rate of oxygen (MRO2) compared with hemoglobin + myoglobin (Hb+Mb) based parameters after the onset of loads in males. Additionally, larger percent changes in BFi, and MRO2 were observed compared with Hb+Mb parameters in both males and females. There were also sex differences in baseline values of oxygenated Hb+Mb, total Hb+Mb, and tissue saturation. Conclusions: The dynamic characteristics of Hb+Mb concentration and blood flow were distinct during loading of the SCM, suggesting that the combination of FD-NIRS and DCS may provide a more complete picture of inspiratory muscle dynamics.

In vitro activity of omadacycline against clinical isolates of Nocardia.

Nocardiosis typically requires a prolonged treatment duration of ≥6 months and initial combination therapy with 2-3 antibiotics. First-line regimens for nocardiosis are associated with considerable toxicity; therefore, alternative therapies are needed. Omadacycline is an aminomethylcycline with broad antimicrobial activity whose in vitro activity against Nocardia species has not been formally assessed. The in vitro potency of omadacycline was evaluated against 300 Nocardia clinical isolates by broth microdilution. The most common Nocardia species tested were N. cyriacigeorgica (21%), N. nova (20%), and N. farcinica (12%). The most common specimens were respiratory (178 isolates, 59%) and wound (57 isolates, 19%). Omadacycline minimum inhibitory concentrations (MICs) across all Nocardia species ranged from 0.06 µg/mL to 8 µg/mL, with an MIC50 of 2 µg/mL and MIC90 of 4 µg/mL. The lowest MICs were found among N. paucivorans (MIC50 = 0.25 µg/mL, MIC90 = 0.25 µg/mL), N. asiatica (MIC50 = 0.25 µg/mL, MIC90 = 1 µg/mL), N. abscessus complex (MIC50 = 0.5 µg/mL, MIC90 = 1 µg/mL), N. beijingensis (MIC50 = 0.5 µg/mL, MIC90 = 2 µg/mL), and N. otitidiscaviarum (MIC50 = 1 µg/mL, MIC90 = 2 µg/mL). The highest MICs were found among N. farcinica (MIC50 = 4 µg/mL, MIC90 = 8 µg/mL). In vitro potency differed by species among Nocardia clinical isolates. Further studies are warranted to evaluate the potential clinical utility of omadacycline for nocardiosis.

Experimental strategy for the preparation of adsorbent materials from torrefied palm kernel shell oriented to CO2 capture.

In this study, an experimental strategy to obtain biochar and activated carbon from torrefied palm kernel shell as an efficient material for CO2 removal was evaluated. Biochar was obtained by slow pyrolysis of palm kernel shell at different temperatures (350 °C, 550 °C, and 700 °C) and previously torrefied palm kernel shell at different temperatures (220 °C, 250 °C, and 280 °C). Subsequently, activated carbons were prepared by physical activation with CO2 from previously obtained biochar samples. The CO2 adsorption capacity was measured using TGA. The experimental results showed that there is a correlation between the change in the O/C and H/C ratios and the functional groups -OH and C=O observed via FTIR in the obtained char, indicating that both dehydration and deoxygenation reactions occur during torrefaction; this favors the deoxygenation reactions and makes them faster through CO2 liberation during the pyrolysis process. The microporous surface area shows a significant increase with higher pyrolysis temperatures, as a product of the continuous carbonization reactions, allowing more active sites for CO2 removal. Pyrolysis temperature is a key factor in CO2 adsorption capacity, leading to a CO2 adsorption capacity of up to 75 mg/gCO2 for biochar obtained at 700 °C from non-torrefied palm kernel shell (Char700). Activated carbon obtained from torrefied palm kernel shell at 280 °C (T280-CHAR700-AC) exhibited the highest CO2 adsorption capacity (101.9 mg/gCO2). Oxygen-containing functional groups have a direct impact on CO2 adsorption performance due to electron interactions between CO2 and these functional groups. These findings could provide a new experimental approach for obtaining optimal adsorbent materials exclusively derived from thermochemical conversion processes.

Effective Approaches to Diagnostic Stewardship of Syndromic Molecular Panels.

BACKGROUND: Syndromic molecular panels for the diagnosis of gastroenteritis, meningitis/encephalitis, and pneumonia are becoming routinely used for patient care throughout the world. CONTENT: These rapid, sample-to-answer assays have great potential to improve patient care, infection control, and antimicrobial stewardship. However, diagnostic stewardship is essential for their optimal use and accuracy, and interventions can be applied at all phases of the diagnostic process. SUMMARY: The aim of this review article is to describe effective approaches to diagnostic stewardship for syndromic molecular panels to ensure appropriate test utilization and quality assured results.

Infectious complications among patients receiving ibrutinib for the treatment of hematological malignancies.

PURPOSE: Ibrutinib is a Bruton's tyrosine kinase inhibitor used to treat multiple hematologic malignancies and graft-versus-host disease. Though less myelosuppressive than cytotoxic chemotherapy, increased infections, including invasive fungal infections (IFIs), have been reported with ibrutinib use. This study aimed to determine the characteristics and risk factors for infection associated with ibrutinib at our institution. METHODS: Patients who received ibrutinib between June 2014 and August 2019 were included. Primary endpoints were the incidence of any infection and the incidence of serious infection (defined as hospitalization, parenteral antimicrobial therapy, or pneumonia regardless of hospitalization). Infection risk factors were assessed using logistic regression. RESULTS: One hundred thirty-two patients were identified (78% male; median age, 71 years). The most common indications for ibrutinib were chronic lymphocytic leukemia (67%) and mantle cell lymphoma (12%). Infection and serious infection occurred in 94 (71%) and 47 (36%) patients, respectively; when pneumonia was excluded as a criterion for serious infection, the serious infection rate was 27%. The median time from ibrutinib initiation to first infection was 125 days. Prior allogeneic hematopoietic stem cell transplantation (allo-HSCT) (odds ratio [OR], 4.60; 95% CI, 1.22-17.4) and corticosteroid use (OR, 5.55; 95% CI, 1.52-20.3) were significant risk factors for serious infection. IFIs were diagnosed in 7 patients (5%): 5 had Pneumocystis jirovecii pneumonia and 2 were infected with invasive molds. CONCLUSION: Serious infection and IFI rates are high but similar to those previously described. Risk factors for serious infection included allo-HSCT and corticosteroid use. Targeted antimicrobial prophylaxis should be evaluated in prospective studies in patients on ibrutinib to reduce serious infections and IFI.

A combined frequency domain near infrared spectroscopy and diffuse correlation spectroscopy system for comprehensive metabolic monitoring of inspiratory muscles during loading.

Significance: Mechanical ventilation (MV) is a cornerstone technology in the intensive care unit as it assists with the delivery of oxygen in critical ill patients. The process of weaning patients from MV can be long, and arduous and can lead to serious complications for many patients. Despite the known importance of inspiratory muscle function in the success of weaning, current clinical standards do not include direct monitoring of these muscles. Aim: The goal of this project was to develop and validate a combined frequency domain near infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) system for the noninvasive characterization of inspiratory muscle response to a load. Approach: The system was fabricated by combining a custom digital FD-NIRS and DCS system. It was validated via liquid phantom titrations and a healthy volunteer study. The sternocleidomastoid (SCM), an accessory muscle of inspiration, was monitored during a short loading period in fourteen young healthy volunteer. Volunteers performed two different respiratory exercises, a moderate and high load, which consisted of a one-minute baseline, a one-minute load, and a six-minute recovery period. Results: The system has low crosstalk between absorption, reduced scattering, and flow when tested in a set of liquid titrations. Faster dynamics were observed for changes in blood flow index (BFi), and metabolic rate of oxygen (MRO2) compared to hemoglobin + myoglobin (Hb+Mb) based parameters after the onset of loads in males. Additionally, larger percent changes in BFi, and MRO2 were observed compared to Hb+Mb parameters in both males and females. There were also sex differences in baseline values of oxygenated Hb+Mb, total Hb+Mb, and tissue saturation. Conclusion: The dynamic characteristics of Hb+Mb concentration and blood flow were distinct during loading of the SCM, suggesting that the combination of FD-NIRS and DCS may provide a more complete picture of inspiratory muscle dynamics.

How I approach diarrhea in hematological transplant patients: A practical tool.

Diarrhea in hematopoietic stem-cell transplantation (HSCT) remains a multifactorial challenge that demands a nuanced diagnostic approach. The causes of infectious diarrhea in HSCT recipients are diverse and influenced by patient-specific risk factors, the post-transplant timeline, and local epidemiology. During the past decade, our understanding of diarrhea in HSCT has witnessed a transformative shift through the incorporation of gastrointestinal (GI) multiplex polymerase chain reaction (PCR) panels. However, the judicious application of these panels is imperative to avoid overtesting and prevent adverse outcomes. The challenge lies in distinguishing between the diverse causes of diarrhea, ascertaining the clinical significance of detected pathogens, and navigating the diagnostic uncertainty presented by several non-infectious conditions such as mucositis, intestinal dysbiosis, and acute graft-versus-host disease (aGvHD), all of which mimic infection. This review examines the landscape of infectious diarrhea in the HSCT population, encompassing both established (e.g., Cytomegalovirus, Clostridioides difficile, and norovirus) and emerging pathogens (e.g., sapoviruses, astroviruses). We propose a multifaceted diagnostic algorithm that combines clinical assessment, risk stratification, and tailored utilization of molecular platforms. While multiplex GI panels present invaluable opportunities for rapid and comprehensive pathogen detection, their judicious use is pivotal in preserving diagnostic stewardship. Customization of diagnostic algorithms tailored to local epidemiology ensures optimal patient care and resource utilization.

Evaluating Demographic Representation in Clinical Trials: Use of the Adaptive Coronavirus Disease 2019 Treatment Trial (ACTT) as a Test Case.

Background: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. Methods: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. Results: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

Infectious complications following CAR-t cell therapy for B cell non-Hodgkin lymphoma: a single-center experience and review of the literature.

Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL). Several risk factors including CAR-T cell-related toxicities and their treatments often lead to infectious complications (ICs); however, the pattern and timeline is not well established. We evaluated ICs in 48 patients with R/R B-cell NHL following CAR-T cell therapy at our institution. Overall, 15 patients experienced 22 infection events. Eight infections (4 bacterial, 3 viral and 1 fungal) occurred within the first 30 days and 14 infections (7 bacterial, 6 viral, 1 fungal) between days 31 to 180 following CAR-T infusion. Most infections were mild-to-moderate and fifteen infections involved the respiratory tract. Two patients developed mild-to-moderate COVID-19 infection and one patient a cytomegalovirus reactivation after CAR-T infusion. Two patients developed IFIs: one case each of fatal disseminated candidiasis and invasive pulmonary aspergillosis at day 16 and 77, respectively. Patients with more than 4 prior antitumor regimens and patient's ≥ 65 years had a higher infection rate. Infections in patients with relapsed/refractory B-cell NHL are common after CAR-T despite the use of infection prophylaxis. Age ≥ 65 years and having > 4 prior antitumor treatments were identified as risk factors for infection. Fungal infections carried significant impact in morbidity and mortality, suggesting a role for increase fungal surveillance and/or anti-mold prophylaxis following high-dose steroids and tocilizumab. Four of ten patients developed an antibody response following two doses of SARS-CoV-2 mRNA vaccine.

Variation in Seed Dormancy of Chaco Seasonally Dry Forest Species: Effects of Seed Traits and Population Environmental Conditions.

The persistence of subtropical seasonally dry forests urgently requires the implementation of ex situ conservation and restoration programs. We studied variation in seed traits and dormancy of six native species growing in seasonally dry Chaco forests of Argentina. We documented high intra- and interspecific variability in seed traits and dormancy. Fresh seeds of Geoffroea decorticans and Parasenegalia visco (Fabaceae) were water-permeable and nondormant (ND), while those of Parkinsonia praecox and Vachellia aroma (Fabaceae) were water-impermeable and had physical dormancy (PY). Seeds of Schnopsis lorentzii (Anacardiaceae) and Sarcomphalus mistol (Rhamnaceae) were water-permeable and had physiological dormancy (PD). Mechanical and chemical scarification were the most effective methods to break PY, and dry storage for 3 months was effective in breaking PD. Seeds of large-seeded species were ND or had PD, and those of small-seeded species had PY. Species inhabiting moist habitats had ND seeds, whereas those from seasonally dry habitats had seeds with PY or PD. These results suggest that seed traits and dormancy are species-specific and that intraspecific variation in seed traits is likely associated with high phenotypic plasticity of species in response to local environmental heterogeneity. These findings should be considered at the time of implementation of conservation techniques and for seed sourcing decisions for restoration.

Analysis of the Capacity of the Fenton Process for the Treatment of Polluted Wastewater from the Leather Dyeing Industry.

In this work, the capacity of the Fenton oxidation process for the degradation of color and organic matter contained in the wastewater generated in the leather dyeing stage (WWDS) of an industrial tannery was evaluated. The wastewater characteristics included, among others, high toxicity (lethal concentration for Artemia salina, 24 h test, 50% of population = 93.71 ppm), high dye concentration (36 mg/L, yellow color), high chromium concentration (3.34 mg/L), and low biodegradability index (BOD5/COD ratio = 0.083). From an experimental design, the response surface methodology, and the multiobjective optimization analysis, the following optimal operating conditions were established: initial pH = 3.15, [Fe2+] = 0.981 mM, and [H2O2] = 5.38 mM. After 10 min of oxidation (determined from kinetic studies), it reached approximately 97% decolorization, COD reduction of approximately 82%, and TOC mineralization of approximately 92%. A synergistic effect of Fenton's reagents for TOC removal (S TOC = 0.8) and decolorization (S CN = 0.28) of the WWDS under study was confirmed experimentally. An increase in the biodegradability index, to a value of approximately 0.3, was confirmed. The cost of the treatment was estimated at 0.0112 USD/m3. Thus, the Fenton oxidation process allowed compliance with current Colombian environmental regulations and considerably improved the biodegradability and toxicity characteristics of the studied industrial effluent. It can be considered as an efficient alternative, easy to carry out on an industrial batch scale, and economically viable for the treatment of wastewater from the leather dyeing stage of an industrial tannery.

Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial.

BACKGROUND: The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear. OBJECTIVE: To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial). DESIGN: 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]). SETTING: 94 hospitals in 10 countries (86% U.S. participants). PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: SOC. MEASUREMENTS: 28-day mortality and recovery. RESULTS: 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. LIMITATION: Unmeasured confounding. CONCLUSION: 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. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Hemofilia A adquirida: un diagnóstico de infarto / Acquired Hemophilia A: a heart attacking diagnosis

Resumen La hemofilia A adquirida es una entidad poco reportada y potencialmente fatal, que se asocia con la aparición de autoanticuerpos contra el factor VIII de la coagulación. Si bien puede estar subestimada, se calcula una incidencia aproximada de 1 a 1.5 casos por millón de habitantes con una mortalidad reportada entre el 9 y el 33%. Se manifiesta con equimosis extensas espontáneas y sangrado en mucosas, tracto gastrointestinal o en el periodo postparto. Se debe sospechar en adultos a partir de la cuarta década de la vida con sangrados espontáneos y un tiempo parcial de tromboplastina prolongado en ausencia de anticoagulante lúpico. Se reporta el caso de un adulto mayor con cardiopatía isquémica, en quien, en el contexto de un evento coronario agudo, se diagnosticó hemofilia A adquirida ante la presencia de sangrado subcutáneo extenso en cuello, con compresión de faringe y laringe que amenazó su vida representando un verdadero reto terapéutico.

Abstract Acquired hemophilia A is an underreported and potentially fatal entity that is associated with the formation of autoantibodies against coagulation factor VIII. Although it may be underestimated, the estimated incidence is between 1-1.5 cases per million people with a reported mortality between 9 and 33%2. It presents with extensive spontaneous ecchymosis, mucosal, gastrointestinal, or postpartum bleeding. It should be suspected in adults from the fourth decade of life with spontaneous bleeding and prolonged TPT in the absence of lupus anticoagulant. We report the case of an older adult with ischemic heart disease in the context of an acute coronary syndrome, who was diagnosed with acquired hemophilia A and presented with significant cervical subcutaneous bleeding with pharyngeal and laryngeal compression that threatened his life, constituting a real therapeutic challenge.

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant. Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results: Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusions: In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.

BACKGROUND: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING: National Institute of Allergy and Infectious Diseases.

Enteric methane emissions by lactating and dry cows in the high Andes of Peru.

The objective of the study was to determine enteric methane emissions using the sulfur hexafluoride (SF6) technique and comparing with The Intergovernmental Panel on Climate Change (IPCC) methodology in lactating cows (LC) and dry cows (DC) in the Peruvian highlands. Enteric methane (CH4) emissions were measured on 5 LC and 6 DC Brown Swiss in a grazing system without concentrate. Forages samples were collected and analyzed for dry matter, crude protein, and neutral detergent fiber. Milk samples were collected and analyzed for fat, crude protein, and lactose to estimate energy-corrected milk. Animal intakes were measured using the external marker titanium dioxide (production of feces) and crude protein in feces (organic digestibility of the feed) and estimated by using performance data. The enteric methane emissions of LC were higher than methane emissions of DC (325 and 266 g CH4/cow/day for LC and DC, respectively (P < 0.001)). Methane emissions were 358.5 g CH4/day by SF6 technique and 291.6 g CH4/day by IPCC methodology for LC and 337.4 g CH4/day by SF6 technique and 195.8 g CH4/day by IPCC methodology for DC. Methane yields measured by SF6 were higher than methane yields estimated by IPCC methodology (29 g CH4/kg DM and 22 g CH4/kg DM using SF6 technique and IPCC methodology, respectively (P < 0.001)). Methane yields were differently for all expressions by physiological stage and method. The methane conversion factor (Ym) was 9.7% for LC and 9.6% for DC. Methane intensities were similar by method (P > 0.05). It was concluded that IPCC's methodology underestimate the CH4 emissions of dairy systems in the Peruvian Andes; therefore, in order to obtain precise Ym, direct measurements of enteric CH4 in the different regions of Peruvian highlands are required.

Effect of two formulations of recombinant bovine somatotropin on milk production and body condition of cattle under intensive management in Peru.

The effect of recombinant somatotropin (rbST) application in cattle has been demonstrated in temperate climate but very limited studies are available in tropical regions. The objective of this study was to compare the effect of the application of two different formulations of rbST on the milk yield and body condition of dairy cattle in a commercial herd under intensive production in Peru. We evaluated the application of 500 mg of active rbST in a zinc sesame oil (ZSO-rbST; n = 44) or vitamin E lecithin (VEL-rbST; n = 45) vehicle while control cows (n = 42) did not receive any application. The application of rbST was performed by every 14 days for 12 cycles, for a total of 168 days. The application of rbST increased the milk production of primiparous and multiparous cows by 3 and 3.2 kg/day for the VEL-rbST formulation respectively when compared with control cows (p < 0.01) and no difference in milk production was observed between the ZSO-rbST formulation and the control group (p > 0.05). However, no significant difference on milk production was observed between the rbST formulations evaluated. The effect of rbST per injection cycle indicated differences in milk production and economic return for the 12 cycles between rbST and control in primiparous group, while in multiparous, no differences were found between ZSO-rbST and control (p > 0.05), but differences were observed between VEL-rbST and control in 41% of the cycles (p < 0.05). No differences in body condition were found between the two rbST formulations and the control group during the evaluation. In conclusion, the application of rbST promoted higher milk production of cattle which had a positive impact on the economic income of the farmer.