Five-Year Outcomes among U.S. Bronchiectasis and NTM Research Registry Patients.

Rationale: Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives: To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods: Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results: In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions: Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM.

SCCM issued recommendations for corticosteroid use in acutely ill adults with sepsis, ARDS, or CAP.

SOURCE CITATION: Chaudhuri D, Nei AM, Rochwerg B, et al. 2024 focused update: guidelines on use of corticosteroids in sepsis, acute respiratory distress syndrome, and community-acquired pneumonia. Crit Care Med. 2024;52:e219-e233. 38240492.

EFFECTS OF BEEF SEMEN AND BEEF EMBRYO STRATEGIES ON PROFITABILITY: Economics of using beef semen and beef in vitro produced embryo transfer in Jersey herds.

Dairy herds have adopted sexed semen (SS) and beef semen (BS) to control heifer inventory and increase calf sales revenue. Beef in vitro-produced embryo transfer (beef IVP-ET) may be an alternative to increase calf sales revenue. Besides, raising those Jersey beef crossbred and/or pure beef animals in a dairy system may be a new source of revenue. We aimed to evaluate breed strategies combining dairy conventional semen (CS), SS, BS, and beef IVP-ET on herd dynamics and profitability by marketing those animals with one-day-old or raising them to 180 kg. A Markov chain model was developed to maximize the profitability of Jersey herds by changing the number of dairy heifers sold at birth and the culling rate of 3rd and greater parity cows. The model presents inputs on the reproductive and productive performance of heifers and cows over time. The last year's data (year 10 - steady state) was used to calculate accrual operational cost and revenue per cow per year. We varied the breeding strategy by breeding order and parities, the embryo transfer cost ($85 or $170), the pure beef calf market price ($200 or $300), and by marketing Jersey-beef and pure beef animals with one-day-old or raising them to 180 kg. A total of 8 scenarios + default scenario were simulated. Overall, the proportion of SS use was 47.3 ± 0.6%. For the scenarios replacing all CS breedings with BS breedings, the proportion of CS and BS used was 52.3 ± 0.6. When beef IVP-ET was used, the percentage of BS and beef IVP-ET used was 22.4 ± 0.1% and 31.0 ± 0.1%, respectively. We observed that when we compared SS:BS with the default scenario, the production of purebred Jersey male calves was reduced by 83.5%, and profit/cow per year was increased from $113.5 to $203.3 with SS:BS. When a beef IVP-ET of $85 per transfer was used (scenarios 2 and 3), profit/cow per year was $145.5 and $176.2 for a pure-beef calf price of $200 and $300, respectively. In scenario 4, with a beef IVP-ET cost of $170, the lowest profit ($52.9 per cow per year) was found when marketing one-day-old pure-beef calves at $200. The highest profit was achieved for scenario raising the Jersey-beef crossbred animals to 180 kg ($232.9, scenario 6), followed by scenario 7 ($222.9, SS:BS:IVP-ET) with an embryo transfer cost of $85. Under the current market conditions, combining SS and BS in the reproductive program was a feasible economic opportunity for Jersey herds, yielding the highest net return. The adoption of beef IVP-ET in a reproductive program can potentially increase profit/cow per year, but its profitability will depend on the beef IVP-ET pregnancy cost, the pure-beef market price, calf performance, and the herd reproductive performance. In conclusion, raising the Jersey-beef crossbred calves may be a profitable strategy, and dairy producers need to evaluate the best option to invest in since it will take an extra risk to produce high-quality animals to the market.

Association of morbidity, mortality, and average daily gain with transfer of passive immunity in dairy-beef crossbred calves up to 60 d of life.

Adequate transfer of passive immunity (TPI) is a cornerstone for a proper health status of calves. In the literature, there is limited information on the prevalence of failure of TPI in dairy-beef crossbred calves and its impact on morbidity, mortality, and average daily gain (ADG) during the preweaning period. Therefore, this study aimed to evaluate the association between TPI with morbidity, mortality, and ADG in pre-weaned dairy-beef crossbred calves. A total of 1,055 newborn dairy-beef crossbred calves were enrolled upon arrival at a calf-raising facility in California from January to August 2021. Farm of origin, genetic breed group, sex, and body weight were recorded upon arrival. Blood was collected at 24 ± 1 h post-arrival to evaluate serum IgG concentration, serum total protein (TP), and packed cell volume. Morbidity (diarrhea and respiratory treatment records) and mortality were recorded daily until 60 d of life. Calves were grouped into 2 genetic breed groups: Holstein x Beef (Ho x Be, 49.6%) and Jersey × Beef crossbred calves (Je × Be, 50.4%). Descriptive statistics and Cox proportional hazard models were created to evaluate the association of TPI categories for serum IgG (TPI-IgG: poor: < 10.0 g/L, fair: 10.0 - 17.9 g/L, good: 18.0 - 24.9 g/L, and excellent: ≥ 25.0 g/L) and TP (TPI-TP: poor: < 5.1 g/dL, fair: 5.1 - 5.7 g/dL, good: 5.8 - 6.1 g/dL, and excellent: ≥ 6.2 g/dL), sex, and genetic breed group with morbidity and mortality. Additionally, a mixed linear regression was performed to evaluate the association of sex, genetic breed group, and TPI categories with ADG. Overall morbidity and mortality were 84.8% (n = 895) and 2.5% (n = 26). Calves classified as TPI-IgG excellent were associated with the lowest (43.2% less) hazard of being treated compared with TPI-IgG poor calves. For mortality, dairy-beef crossbred calves with TPI-IgG excellent were associated with a reduction of 82.0% in the hazard of dying compared with TPI-IgG poor. The TPI-IgG poor and TPI-IgG fair calves were associated with a decreased ADG of 101.0 and 98.8 g/d, respectively, in comparison with TPI-IgG good calves. Average daily gain of TPI-IgG good and TPI-IgG excellent calves were not different. In our study, dairy-beef crossbred calves enrolled may have endured challenging conditions that increased morbidity. This reinforces the importance of high IgG levels to decrease morbidity and mortality and maximize ADG in dairy-beef crossbred calves raising systems. Further research should evaluate the long-term effects of TPI categories on the health and performance of dairy-beef crossbred calves.

Effectiveness of prolonged versus standard-course of oseltamivir in critically ill patients with severe influenza infection: A multicentre cohort study.

The aim of this study is to investigate the effectiveness of prolonged versus standard course oseltamivir treatment among critically ill patients with severe influenza. A retrospective study of a prospectively collected database including adults with influenza infection admitted to 184 intensive care units (ICUs) in Spain from 2009 to 2018. Prolonged oseltamivir was defined if patients received the treatment beyond 5 days, whereas the standard-course group received oseltamivir for 5 days. The primary outcome was all-cause ICU mortality. Propensity score matching (PSM) was constructed, and the outcome was investigated through Cox regression and RCSs. Two thousand three hundred and ninety-seven subjects were included, of whom 1943 (81.1%) received prolonged oseltamivir and 454 (18.9%) received standard treatment. An optimal full matching algorithm was performed by matching 2171 patients, 1750 treated in the prolonged oseltamivir group and 421 controls in the standard oseltamivir group. After PSM, 387 (22.1%) patients in the prolonged oseltamivir and 119 (28.3%) patients in the standard group died (p = 0.009). After adjusting confounding factors, prolonged oseltamivir significantly reduced ICU mortality (odds ratio [OR]: 0.53, 95% confidence interval [CI]: 0.40-0.69). Prolonged oseltamivir may have protective effects on survival at Day 10 compared with a standard treatment course. Sensitivity analysis confirmed these findings. Compared with standard treatment, prolonged oseltamivir was associated with reduced ICU mortality in critically ill patients with severe influenza. Clinicians should consider extending the oseltamivir treatment duration to 10 days, particularly in higher-risk groups of prolonged viral shedding. Further randomized controlled trials are warranted to confirm these findings.

The Current State of Antiracism Curricula in Undergraduate and Graduate Medical Education: A Qualitative Study of US Academic Health Centers.

PURPOSE: We undertook a study to evaluate the current state of pedagogy on antiracism, including barriers to implementation and strengths of existing curricula, in undergraduate medical education (UME) and graduate medical education (GME) programs in US academic health centers. METHODS: We conducted a cross-sectional study with an exploratory qualitative approach using semistructured interviews. Participants were leaders of UME and GME programs at 5 institutions participating in the Academic Units for Primary Care Training and Enhancement program and 6 affiliated sites from November 2021 to April 2022. RESULTS: A total of 29 program leaders from the 11 academic health centers participated in this study. Three participants from 2 institutions reported the implementation of robust, intentional, and longitudinal antiracism curricula. Nine participants from 7 institutions described race and antiracism-related topics integrated into health equity curricula. Only 9 participants reported having "adequately trained" faculty. Participants mentioned individual, systemic, and structural barriers to implementing antiracism-related training in medical education such as institutional inertia and insufficient resources. Fear related to introducing an antiracism curriculum and undervaluing of this curriculum relative to other content were identified. Through learners and faculty feedback, antiracism content was evaluated and included in UME and GME curricula. Most participants identified learners as a stronger voice for transformation than faculty; antiracism content was mainly included in health equity curricula. CONCLUSIONS: Inclusion of antiracism in medical education requires intentional training, focused institutional policies, enhanced foundational awareness of the impact of racism on patients and communities, and changes at the level of institutions and accreditation bodies.

Cardiovascular Complications in Coronavirus Disease 2019-Pathogenesis and Management.

The coronavirus disease 2019 (COVID-19) pandemic has caused a devastating impact on morbidity and mortality around the world. Severe acute respiratory syndrome-coronavirus-2 has a characteristic tropism for the cardiovascular system by entering the host cells and binding to angiotensin-converting enzyme 2 receptors, which are expressed in different cells, particularly endothelial cells. This endothelial injury is linked by a direct intracellular viral invasion leading to inflammation, microthrombosis, and angiogenesis. COVID-19 has been associated with acute myocarditis, cardiac arrhythmias, new onset or worsening heart failure, ischemic heart disease, stroke, and thromboembolic disease. This review summarizes key relevant literature regarding the epidemiology, diagnosis, treatment, and preventive measures related to cardiovascular complications in the setting of COVID-19.

Twelve tips for implementing and teaching anti-racism curriculum in medical education.

Racism has implicit and explicit manifestations that perpetuate disparities and negatively influence patient-centered health outcomes. Subsequently, a list of action items was provided to assist medical schools in becoming anti-racist institutions. A deep subject matter knowledge, beliefs, and reflections were a driving force for the management of medical schools or faculty members involved in undergraduate and postgraduate medical education to move forward toward inclusion of anti-racism in traditional medical curriculum or adapting existing training modules on diversity, equity, and inclusion. This paper proposes twelve practical and specific tips for implementing and teaching anti-racism in medical education. These twelve tips elaborate on the proposed actions for leaders in undergraduate and postgraduate medical education, valuable for designing future curricula and educational activities.

Community-acquired pneumonia.

Community-acquired pneumonia is not usually considered a high-priority problem by the public, although it is responsible for substantial mortality, with a third of patients dying within 1 year after being discharged from hospital for pneumoniae. Although up to 18% of patients with community-acquired pneumonia who were hospitalised (admitted to hospital and treated there) have at least one risk factor for immunosuppression worldwide, strong evidence on community-acquired pneumonia management in this population is scarce. Several features of clinical management for community-acquired pneumonia should be addressed to reduce mortality, morbidity, and complications related to community-acquired pneumonia in patients who are immunocompetent and patients who are immunocompromised. These features include rapid diagnosis, microbiological investigation, prevention and management of complications (eg, respiratory failure, sepsis, and multiorgan failure), empirical antibiotic therapy in accordance with patient's risk factors and local microbiological epidemiology, individualised antibiotic therapy according to microbiological data, appropriate outcomes for therapeutic switch from parenteral to oral antibiotics, discharge planning, and long-term follow-up. This Seminar offers an updated view on community-acquired pneumonia in adults, with suggestions for clinical and translational research.

Large-scale provocation studies identify maladaptive responses to ubiquitous aeroallergens as a correlate of severe allergic rhinoconjunctivitis and asthma.

BACKGROUND: Allergic asthma (AA) and allergic rhinoconjunctivitis (ARC) are common comorbid environmentally triggered diseases. We hypothesized that severe AA/ARC reflects a maladaptive or unrestrained response to ubiquitous aeroallergens. METHODS: We performed provocation studies wherein six separate cohorts of persons (total n = 217) with ARC, with or without AA, were challenged once or more with fixed concentrations of seasonal or perennial aeroallergens in an aeroallergen challenge chamber (ACC). RESULTS: Aeroallergen challenges elicited fully or partially restrained vs. unrestrained evoked symptom responsiveness, corresponding to the resilient and adaptive vs. maladaptive AA/ARC phenotypes, respectively. The maladaptive phenotype was evoked more commonly during challenge with a non-endemic versus endemic seasonal aeroallergen. In an AA cohort, symptom responses evoked after house dust mite (HDM) challenges vs. recorded in the natural environment were more accurate and precise predictors of asthma severity and control, lung function (FEV1), and mechanistic correlates of maladaptation. Correlates included elevated levels of peripheral blood CD4+ and CD8+ T-cells, eosinophils, and T-cell activation, as well as gene expression proxies for ineffectual epithelial injury/repair responses. Evoked symptom severity after HDM challenge appeared to be more closely related to levels of CD4+ and CD8+ T-cells than eosinophils, neutrophils, or HDM-specific IgE. CONCLUSIONS: Provocation studies support the concept that resilience, adaptation, and maladaptation to environmental disease triggers calibrate AA/ARC severity. Despite the ubiquity of aeroallergens, in response to these disease triggers in controlled settings (ie, ACC), most atopic persons manifest the resilient or adaptive phenotype. Thus, ARC/AA disease progression may reflect the failure to preserve the resilient or adaptive phenotype. The triangulation of CD8+ T-cell activation, airway epithelial injury/repair processes and maladaptation in mediating AA disease severity needs more investigation.

Nucleic Acid-based Testing for Noninfluenza Viral Pathogens in Adults with Suspected Community-acquired Pneumonia. An Official American Thoracic Society Clinical Practice Guideline.

Background: This document provides evidence-based clinical practice guidelines on the diagnostic utility of nucleic acid-based testing of respiratory samples for viral pathogens other than influenza in adults with suspected community-acquired pneumonia (CAP).Methods: A multidisciplinary panel developed a Population-Intervention-Comparison-Outcome question, conducted a pragmatic systematic review, and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel evaluated the literature to develop recommendations regarding whether routine diagnostics should include nucleic acid-based testing of respiratory samples for viral pathogens other than influenza in suspected CAP. The evidence addressing this topic was generally adjudicated to be of very low quality because of risk of bias and imprecision. Furthermore, there was little direct evidence supporting a role for routine nucleic acid-based testing of respiratory samples in improving critical outcomes such as overall survival or antibiotic use patterns. However, on the basis of direct and indirect evidence, recommendations were made for both outpatient and hospitalized patients with suspected CAP. Testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was not addressed in the literature at the time of the evidence review.Conclusions: The panel formulated and provided their rationale for recommendations on nucleic acid-based diagnostics for viral pathogens other than influenza for patients with suspected CAP.

Unveiling unstable non-acid incidence in Holstein cows fed with corn silage or sugarcane.

We aimed to evaluate the incidence of unstable non-acid milk (UNAM) in cows fed either sugarcane or corn silage. Second, we aimed to evaluate the effect of daily variation (d 1 to 4) and alcohol grades (72, 78, and 80%) on UNAM incidence. The experiment was conducted as a split-plot crossover design, with 2 periods and 2 roughage types (sugarcane or corn silage). Thirteen multiparous Holstein cows with an average of 281 ± 29 d in milk were randomly distributed into 2 diets. Individual blood (analysis of total proteins, albumin, urea, calcium, phosphorus, magnesium, iron, chloride, glucose, and lactate) and milk samples (analysis of protein, fat, lactose and total solids, somatic cell count, and characterization of the protein profile) were collected during the last 4 d of each period. For UNAM identification, the alcohol test was conducted in milk samples at 4°C; specifically, if the sample presented the formation of clots, this would be noted as positive for UNAM. In addition, the Dornic acidity analysis was performed in the same samples to evaluate the true milk acidity. The use of sugarcane and higher degrees of alcohol were associated with increased UNAM. We observed no daily variation in UNAM. Nevertheless, we found no roughage type effect on the variables most commonly associated with UNAM, such as changes in salts in the casein micelle and, consequently, the zeta potential and the κ-casein (CN) fraction. The Pearson correlation analysis showed that the zeta potential and the concentrations of αS2-CN, blood ionic calcium, lactate, and glucose increased as the incidence of UNAM increased, showing a positive correlation among these variables. In contrast, the concentrations of lactose, phosphorus, and potassium decreased as UNAM increased, presenting a negative correlation. This study brought important discoveries to unveil why cows manifest UNAM. For instance, higher alcohol grades and cows fed with sugarcane had increased the incidence of UNAM. Additionally, animals with a higher incidence of UNAM (sugarcane-fed cows) were related to increased ionic calcium and glucose and changes in milk protein profile, with lower levels of BSA, ß-CN, and α-lactalbumin and greater αS1-CN content, all of which were correlated with UNAM. Nonetheless, this trial also provides evidence for the need for further studies to better understand the physiological mechanisms that directly affect the stability of milk protein.

Repetitive aeroallergen challenges elucidate maladaptive epithelial and inflammatory traits that underpin allergic airway diseases.

BACKGROUND: Signifying the 2-compartments/1-disease paradigm, allergic rhinoconjunctivitis (ARC) and asthma (AA) are prevalent, comorbid conditions triggered by environmental factors (eg, house dust mites [HDMs]). However, despite the ubiquity of triggers, progression to severe ARC/AA is infrequent, suggesting either resilience or adaptation. OBJECTIVE: We sought to determine whether ARC/AA severity relates to maladaptive responses to disease triggers. METHODS: Adults with HDM-associated ARC were challenged repetitively with HDMs in an aeroallergen challenge chamber. Mechanistic traits associated with disease severity were identified. RESULTS: HDM challenges evoked maladaptive (persistently higher ARC symptoms), adaptive (progressive symptom reduction), and resilient (resistance to symptom induction) phenotypes. Symptom severity in the natural environment was an imprecise correlate of the phenotypes. Nasal airway traits, defined by low inflammation-effectual epithelial integrity, moderate inflammation-effectual epithelial integrity, and higher inflammation-ineffectual epithelial integrity, were hallmarks of the resilient, adaptive, and maladaptive evoked phenotypes, respectively. Highlighting a crosstalk mechanism, peripheral blood inflammatory tone calibrated these traits: ineffectual epithelial integrity associated with CD8+ T cells, whereas airway inflammation associated with both CD8+ T cells and eosinophils. Hallmark peripheral blood maladaptive traits were increased natural killer and CD8+ T cells, lower CD4+ mucosal-associated invariant T cells, and deficiencies along the TLR-IRF-IFN antiviral pathway. Maladaptive traits tracking HDM-associated ARC also contributed to AA risk and severity models. CONCLUSIONS: Repetitive challenges with HDMs revealed that maladaptation to disease triggers may underpin ARC/AA disease severity. A combinatorial therapeutic approach may involve reversal of loss-of-beneficial-function traits (ineffectual epithelial integrity, TLR-IRF-IFN deficiencies), mitigation of gain-of-adverse-function traits (inflammation), and blocking of a detrimental crosstalk between the peripheral blood and airway compartments.

Immunologic resilience and COVID-19 survival advantage.

BACKGROUND: The risk of severe coronavirus disease 2019 (COVID-19) varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR). OBJECTIVE: We sought to examine whether deficits in IR that antedate or are induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection independently predict COVID-19 mortality. METHODS: IR levels were quantified with 2 novel metrics: immune health grades (IHG-I [best] to IHG-IV) to gauge CD8+ and CD4+ T-cell count equilibrium, and blood gene expression signatures. IR metrics were examined in a prospective COVID-19 cohort (n = 522); primary outcome was 30-day mortality. Associations of IR metrics with outcomes in non-COVID-19 cohorts (n = 13,461) provided the framework for linking pre-COVID-19 IR status to IR during COVID-19, as well as to COVID-19 outcomes. RESULTS: IHG-I, tracking high-grade equilibrium between CD8+ and CD4+ T-cell counts, was the most common grade (73%) among healthy adults, particularly in females. SARS-CoV-2 infection was associated with underrepresentation of IHG-I (21%) versus overrepresentation (77%) of IHG-II or IHG-IV, especially in males versus females (P < .01). Presentation with IHG-I was associated with 88% lower mortality, after controlling for age and sex; reduced risk of hospitalization and respiratory failure; lower plasma IL-6 levels; rapid clearance of nasopharyngeal SARS-CoV-2 burden; and gene expression signatures correlating with survival that signify immunocompetence and controlled inflammation. In non-COVID-19 cohorts, IR-preserving metrics were associated with resistance to progressive influenza or HIV infection, as well as lower 9-year mortality in the Framingham Heart Study, especially in females. CONCLUSIONS: Preservation of immunocompetence with controlled inflammation during antigenic challenges is a hallmark of IR and associates with longevity and AIDS resistance. Independent of age, a male-biased proclivity to degrade IR before and/or during SARS-CoV-2 infection predisposes to severe COVID-19.

Performance and feeding behavior of Holstein and Holstein × Gyr crossbred heifers grazing temperate forages.

This study aimed to investigate the difference between Holstein and Holstein × Gyr breeds on feeding behavior and performance of heifers grazing temperate pasture. The experiment was carried out in 89 days, split into 14 days of adaptation, and 3 periods of 25 days. Two treatments were used: Holstein (HOL; n = 7) and Holstein × Gyr (HG; n = 7). Heifers grazed a consortium of ryegrass and bristle oats and were supplemented individually daily with cornmeal at 0.33% of body weight plus 5 kg/day of corn silage. For 3 consecutive days, feeding behavior was observed for individual animals from direct visual observation recording at 10-min intervals. The digestibility trial was performed on day (d) 16 to d24 of each period. Body measurements and weight were taken at d0 and at d23, 24, and 25 of each period. Grazing duration, grazing frequency, and bite rate were greater for HOL than those for HG. Rumination characteristics, intake, digestibility, and body measurements were not affected by breed. Breeds had differences in grazing characteristics, but they did not influence performance or intake parameters. Therefore, HOL and HG heifers managed under temperate pasture in tropical countries have similar performances.

Simulated Adoption of 2019 Community-Acquired Pneumonia Guidelines Across 114 Veterans Affairs Medical Centers: Estimated Impact on Culturing and Antibiotic Selection in Hospitalized Patients.

BACKGROUND: The 2019 American Thoracic Society/Infectious Diseases Society of America guidelines for community-acquired pneumonia (CAP) revised recommendations for culturing and empiric broad-spectrum antibiotics. We simulated guideline adoption in Veterans Affairs (VA) inpatients. METHODS: For all VA acute hospitalizations for CAP from 2006-2016 nationwide, we compared observed with guideline-expected proportions of hospitalizations with initial blood and respiratory cultures obtained, empiric antibiotic therapy with activity against methicillin-resistant Staphylococcus aureus (anti-MRSA) or Pseudomonas aeruginosa (antipseudomonal), empiric "overcoverage" (receipt of anti-MRSA/antipseudomonal therapy without eventual detection of MRSA/P. aeruginosa on culture), and empiric "undercoverage" (lack of anti-MRSA/antipseudomonal therapy with eventual detection on culture). RESULTS: Of 115 036 CAP hospitalizations over 11 years, 17 877 (16%) were admitted to an intensive care unit (ICU). Guideline adoption would slightly increase respiratory culture (30% to 36%) and decrease blood culture proportions (93% to 36%) in hospital wards and increase both respiratory (40% to 100%) and blood (95% to 100%) cultures in ICUs. Adoption would decrease empiric selection of anti-MRSA (ward: 27% to 1%; ICU: 61% to 8%) and antipseudomonal (ward: 25% to 1%; ICU: 54% to 9%) therapies. This would correspond to greatly decreased MRSA overcoverage (ward: 27% to 1%; ICU: 56% to 8%), slightly increased MRSA undercoverage (ward: 0.6% to 1.3%; ICU: 0.5% to 3.3%), with similar findings for P. aeruginosa. For all comparisons, P < .001. CONCLUSIONS: Adoption of the 2019 CAP guidelines in this population would substantially change culturing and empiric antibiotic selection practices, with a decrease in overcoverage and slight increase in undercoverage for MRSA and P. aeruginosa.

Small Airway Disease and Emphysema Are Associated with Future Exacerbations in Smokers with CT-derived Bronchiectasis and COPD: Results from the COPDGene Cohort.

Background Chronic obstructive pulmonary disease (COPD) and bronchiectasis can overlap and share pathologic features, such as small airway disease (SAD). Whether the presence of SAD and emphysema in smokers with CT-derived bronchiectasis is associated with exacerbations is unknown. Purpose To assess whether SAD and emphysema in smokers with CT-derived bronchiectasis are associated with future exacerbations. Materials and Methods SAD and emphysema were quantified using the parametric response map method in former and current heavy smokers with and without bronchiectasis at CT from the COPDGene Study (from July 2009 to July 2018). Exacerbations were prospectively assessed through biannual follow-up. An exacerbation was defined as an increase in or new onset of respiratory symptoms treated with antibiotics and/or corticosteroids. Severe exacerbations were defined as those that required hospitalization. The association of a high burden of SAD (≥15.6%) and high burden of emphysema (≥5%) at CT with exacerbations was assessed with generalized linear mixed models. Results Of 737 participants, 387 (median age, 64 years [interquartile range, 58-71 years]; 223 women) had CT-derived bronchiectasis. During a 9-year follow-up, after adjustment for age, sex, race, body mass index, current smoking status, pack-years, exacerbations before study entry, forced expiratory volume in 1 second, or FEV1, and bronchiectasis severity CT score, high burden of SAD and high burden of emphysema were associated with a higher number of exacerbations per year (relative risk [RR], 1.89 [95% CI: 1.54, 2.33] and 1.37 [95% CI: 1.13, 1.66], respectively; P ≤ .001 for both). Results were comparable among participants with bronchiectasis meeting criteria for COPD (n = 197) (RR, 1.67 [95% CI: 1.23, 2.27] for high burden of SAD and 1.51 [95% CI: 1.20, 1.91] for high burden of emphysema; P ≤ .001 for both). Conclusion In smokers with CT-derived bronchiectasis and chronic obstructive pulmonary disease, structural damage to lung parenchyma and small airways was associated with a higher number of exacerbations per year. Clinical trial registration no. NCT00608764 © RSNA, 2021.

Determination of energy and protein requirements of preweaned dairy calves: A multistudy approach.

The first studies concerning nutrient requirements for preweaned dairy calves were from the 1920s and 1930s; however, few studies were published in the following decades. We aimed to determine energy and protein requirements of preweaning Holstein and Holstein × Gyr dairy calves in a multistudy meta-regression. We used a database composed of individual measurements of 166 preweaned male calves (138 submitted to treatments and 28 used as the reference group) from 4 studies that used the methodology of comparative slaughter. Animals with less than 15/16 of Holstein genetic composition were considered crossbred Holstein × Gyr, whereas other animals were considered Holstein. Net energy requirements for maintenance (NEM) were determined by the regression between heat production and metabolizable energy intake (MEI). The metabolizable energy requirements for maintenance were calculated by the iterative method, and the efficiency of use of metabolizable energy for maintenance was obtained by NEM divided by the metabolizable energy requirements for maintenance. Net energy requirements for gain (NEG) were estimated using a regression of the retained energy (RE) as a function of empty body weight (EBW) and empty body gain (EBG). The efficiency of use of metabolizable energy for gain was estimated by the regression of RE as a function of MEI, but with partitioning the MEI into MEI from liquid feed and MEI from starter feed. Additionally, the effect of a liquid feed (milk or milk replacer) was tested on the slope of the regression. The metabolizable protein requirements for maintenance (MPM) were estimated using the intercept of the regression between the metabolizable protein intake (MPI) and average daily gain. The MPM was determined as the ratio between the intercept and the metabolic body weight. Net protein requirements for gain (NPG) were estimated by the regression between retained protein, EBG, and RE. The efficiency of use of metabolizable protein for gain was estimated by the regression of the retained protein as a function of MPI, but with partitioning the MPI into MPI from liquid feed and MPI from starter feed. Additionally, the effect of a liquid feed (milk or milk replacer) was tested on the regression slope. Breed did not influence any of the nutrient requirements' estimates. The NEM was estimated as 70.2 kcal/metabolic body weight per day. The efficiency of use of metabolizable energy for maintenance observed was 66%. The NEG was estimated by the equation NEG = 0.0901 × EBW0.75 × EBG0.9539. The efficiency of use of metabolizable energy for gain was estimated as 57.6, 49.3, and 41.2% for milk, milk replacer, and starter feed, respectively. The MPM was estimated as 4.22 g/EBW0.75 per day, and the NPG was determined by the equation: NPG = 30.06 × EBG + 70.98 × RE. The efficiency of use of metabolizable protein for gain was estimated as 71.9, 59.2, and 44.4% for milk, milk replacer, and starter feed, respectively. We concluded that no differences were observed in energy and protein requirements between Holstein and Holstein × Gyr crossbred cows. The efficiencies of use of metabolizable energy and protein are greater for milk when compared with milk replacer and starter feed. Therefore, we propose that the equations generated herein should be used to estimate energy and protein requirements of preweaned Holstein and Holstein × Gyr crossbred dairy calves raised under tropical conditions.

Fertility considerations in targeted biologic therapy with tyrosine kinase inhibitors: a review.

PURPOSE: To review the impact of tyrosine kinase inhibitors (TKIs) on fertility in men and women, embryo development, and early pregnancy, and discuss considerations for fertility preservation in patients taking TKIs. METHODS: A comprehensive literature search using the PubMed database was performed through February 2021 to evaluate the current literature on imatinib, nilotinib, dasatinib, and bosutinib as it relates to fertility and reproduction. Published case series were analyzed for pregnancy outcomes. RESULTS: TKIs adversely affect oocyte and sperm maturation, gonadal function, and overall fertility potential in a self-limited manner. There are insufficient studies regarding long-term consequences on fertility after discontinuation of TKIs. A total of 396 women and 236 men were on a first- or second-generation TKI at the time of conception. Of the women with detailed pregnancy and delivery outcomes (n = 361), 51% (186/361) resulted in a term birth of a normal infant, 4.3% (16/361) of pregnancies had a pregnancy complication, and 5% (20/361) of pregnancies resulted in the live birth of an infant with a congenital anomaly. About 22% of pregnant women (87/396) elected to undergo a termination of pregnancy, while 16% (63/396) of pregnancies ended in a spontaneous abortion. In contrast, of the 236 men, 87% conceived pregnancies which resulted in term deliveries of normal infants. Elective terminations, miscarriage rate, pregnancy complication rate, and incidence of a congenital malformation were all less than those seen in females (4%, 3%, 2%, and 2.5%, respectively). CONCLUSION: Women should be advised to avoid conception while taking a TKI. Women on TKIs who are considering pregnancy should be encouraged to plan the pregnancy to minimize inadvertent first trimester exposure. In women who conceive while taking TKIs, the serious risk of relapse due to discontinuation of TKI should be balanced against the potential risks to the fetus. The risk of teratogenicity to a fathered pregnancy with TKI use is considerably lower. Fertility preservation for a woman taking a TKI can be considered to plan a pregnancy with a minimal TKI-free period. With careful monitoring, providers may consider a TKI washout period followed by controlled ovarian stimulation to cryopreserve oocytes or embryos, with a plan to resume TKIs until ready to conceive or to transfer an embryo to achieve pregnancy quickly. Fertility preservation is also indicated if a patient on TKI is requiring a gonadotoxic therapy or reproductive surgery impacting fertility.

Metabolic Signatures Associated with Severity in Hospitalized COVID-19 Patients.

The clinical evolution of COVID-19 pneumonia is poorly understood. Identifying the metabolic pathways that are altered early with viral infection and their association with disease severity is crucial to understand COVID-19 pathophysiology, and guide clinical decisions. This study aimed at assessing the critical metabolic pathways altered with disease severity in hospitalized COVID-19 patients. Forty-nine hospitalized patients with COVID-19 pneumonia were enrolled in a prospective, observational, single-center study in Barcelona, Spain. Demographic, clinical, and analytical data at admission were registered. Plasma samples were collected within the first 48 h following hospitalization. Patients were stratified based on the severity of their evolution as moderate (N = 13), severe (N = 10), or critical (N = 26). A panel of 221 biomarkers was measured by targeted metabolomics in order to evaluate metabolic changes associated with subsequent disease severity. Our results show that obesity, respiratory rate, blood pressure, and oxygen saturation, as well as some analytical parameters and radiological findings, were all associated with disease severity. Additionally, ceramide metabolism, tryptophan degradation, and reductions in several metabolic reactions involving nicotinamide adenine nucleotide (NAD) at inclusion were significantly associated with respiratory severity and correlated with inflammation. In summary, assessment of the metabolomic profile of COVID-19 patients could assist in disease severity stratification and even in guiding clinical decisions.