Sustained IL-6 and sTNF-αR1 levels after hip fracture predict 5-year mortality: A prospective cohort study from the Baltimore Hip Studies.

BACKGROUND: Persistent inflammation is associated with adverse health outcomes, but its impact on mortality has not been investigated previously among hip fracture patients. This article aims to investigate the influence of changes in levels of cytokines in the 2 months after a hip fracture repair on 5-year mortality. METHODS: This is a prospective cohort study from the Baltimore Hip Studies (BHS) with 191 community-dwelling older men and women (≥65 years) who had recently undergone surgical repair of an acute hip fracture, with recruitment from May 2006 to June 2011. Plasma interleukin-6 (IL-6), soluble tumor necrosis factor alpha receptor1 (sTNFα-R1), and interleukin-1 receptor agonist (IL-1RA) were obtained within 22 days of admission and at 2 months. All-cause mortality over 5 years was determined. Logistic regression analysis tested the associations between the cytokines' trajectories and mortality over 5 years, adjusted for covariates (age, sex, education, body mass index, lower extremity physical activities of daily living, and Charlson comorbidity index). RESULTS: High levels of IL-6 and sTNFα-R1 at baseline with small or no decline at 2 months were associated with higher odds of 5-year mortality compared with those with lower levels at baseline and greater decline at 2 months after adjustment for age, and other potential confounders (OR = 4.71, p = 0.01 for IL-6; OR = 15.03, p = 0.002 for sTNFα-R1). Similar results that failed to reach significance were found for IL-1RA (OR = 2.40, p = 0.18). Those with higher levels of cytokines at baseline with greater decline did not have significantly greater mortality than the reference group, those with lower levels at baseline and greater decline. CONCLUSION: Persistent elevation of plasma IL-6 and sTNFα-R1 levels within the first 2 months after hospital admission in patients with hip fracture is associated with higher 5-year mortality. These patients may benefit from enhanced care and earlier intensive interventions to reduce the risk of death.

A multi-center validation of the electronic health record admission source and discharge location fields against the clinical notes for identifying inpatients with long-term care facility exposure.

Identifying long-term care facility (LTCF)-exposed inpatients is important for infection control research and practice, but ascertaining LTCF exposure is challenging. Across a large validation study, electronic health record data fields identified 76% of LTCF-exposed patients compared to manual chart review. OBJECTIVE: Residence or recent stay in a long-term care facility (LTCF) is an important risk factor for antibiotic-resistant bacterial colonization. However, absent dedicated intake questionnaires or resource-intensive chart review, ascertaining LTCF exposure in inpatients is challenging. We aimed to validate the electronic health record (EHR) admission and discharge location fields against the clinical notes for identifying LTCF-exposed inpatients. METHODS: We conducted a retrospective study of 1020 randomly sampled adult admissions between 2016 and 2021 across 12 University of Maryland Medical System hospitals. Using study-developed guidelines, we categorized the following data for LTCF exposure: each admission's history & physical (H&P) note, each admission's EHR-extracted "Admission Source," and (3) the EHR-extracted admission and discharge locations for previous admissions (≤90 days). We estimated sensitivities, with 95% CIs, of H&P notes and of EHR admission/discharge location fields for detecting "current" and "any recent" (≤90 days, including current) LTCF exposure. RESULTS: For detecting current LTCF exposure, the sensitivity of the index admission's EHR-extracted "Admission Source" was 46% (95% CI: 35%­58%) and of the H&P note was 92% (83%­97%). For detecting any recent LTCF exposure, the sensitivity of "Admission Source" across the index and previous admissions was 32% (24%­41%), "Discharge Location" across previous admission(s) was 57% (47%­66%), and of the H&P note was 68% (59%­76%). The combined sensitivity of admission source and discharge location for detecting any recent LTCF exposure was 76% (67%­83%). CONCLUSIONS: The EHR-obtained admission source and discharge location fields identified 76% of LTCF-exposed patients compared to chart review but disproportionately missed currently exposed patients.

Substantial Improvement in Self-Reported Mental Health Following Total Hip Arthroplasty Occurs Independent of Anesthetic Technique.

BACKGROUND: The influence of anesthetic type on mental health after total hip arthroplasty (THA) is poorly understood. Adverse effects of general anesthesia (GA) on cognition following major non-cardiac surgery are well known, but mental health following THA is less well-studied. We hypothesized that neuraxial anesthesia (NA) would provide favorable mental health profiles compared with GA after THA. METHODS: Prospectively collected Patient-Reported Outcomes Measurement Information System-10 (PROMIS) Global Mental Health (GMH) scores at preoperative baseline, and 1, 3, and 6 months after THA were accessed on 4,353 patients in the Pulmonary Embolism Prevention After HiP and KneE Replacement (PEPPER) Trial (ClinicalTrials.gov: NCT02810704). Anesthesia was categorized as: general (GA), neuraxial (NA), and neuraxial with peripheral block (NAP). The GMH was assessed longitudinally and compared between groups. RESULTS: Postoperative GMH improved (P < .05) over preoperative in every anesthetic group. Groups receiving NA had higher baseline GMH scores. Improvement in GMH was diminished after GA alone and plateaued after 1 month. Adding NA or peripheral nerve block to GA conferred additional benefit to GMH improvement. CONCLUSIONS: Patient-perceived mental health improves significantly after THA regardless of anesthetic type. Patients who have higher baseline GMH scores more commonly received NA, likely due to nonsurgical care determinants; these differences in mental wellness persisted at follow-up. Adjunctive NA or peripheral nerve block favored GMH improvement, whereas solitary GA diminished GMH improvement, which plateaued after 1 month. Substantial mental health benefits of THA may overshadow subtle differences in GMH attributable to anesthetic type.

Does the use of corticosteroids and immunosuppressants increase the risk of COVID-19 infection among people with systemic lupus erythematosus?

OBJECTIVE: An important clinical question is whether the use of immunosuppressants or corticosteroids increases the risk of incident COVID-19 disease among patients with SLE. To address this question, we examined the incidence of COVID-19 infection in a large SLE cohort. METHODS: This study was based on a single-centre cohort of patients with SLE seen quarterly from March 2020 to August 2022. Clinical information from these visits was augmented with information on COVID-19 infections and vaccinations obtained from the electronic medical records and by patient self-report. We compared treated and untreated patients with respect to the incidence of COVID-19 infection per person month. Statistical significance was assessed based on logistic regression models. RESULTS: We observed 339 incident cases of COVID-19 experienced over 24 614 person-months of follow-up from 1052 different patients. The risk of infection per person-month of follow-up was similar among those not on prednisone (1.37%), on moderate doses of prednisone (<7 mg/day) (1.44%) and those on higher doses (1.52%) (p=0.87 for difference). We observed an elevated risk among those taking belimumab, however, after adjustment for potential confounding variables, the increased risk was not statistically significant (rate ratio 1.4, 95% CI 0.88 to 2.24, p=0.16) There was no evidence of an increased risk among those taking mycophenolate, methotrexate or azathioprine. CONCLUSION: It is reassuring that there was not strong evidence of an increased risk of infection among those taking prednisone or other immunosuppressants. However, given the range of our CIs, moderate effects of these medications on COVID-19 risk cannot be completely ruled out.

Efficacy of a continuously active disinfectant wipe on the environmental bioburden in the intensive care unit: A randomized controlled study.

OBJECTIVE: To evaluate the efficacy of a new continuously active disinfectant (CAD) to decrease bioburden on high-touch environmental surfaces compared to a standard disinfectant in the intensive care unit. DESIGN: A single-blind randomized controlled trial with 1:1 allocation. SETTING: Medical intensive care unit (MICU) at an urban tertiary-care hospital. PARTICIPANTS: Adult patients admitted to the MICU and on contact precautions. INTERVENTION: A new CAD wipe used for daily cleaning. METHODS: Samples were collected from 5 high-touch environmental surfaces before cleaning and at 1, 4, and 24 hours after cleaning. The primary outcome was the mean bioburden 24 hours after cleaning. The secondary outcome was the detection of any epidemiologically important pathogen (EIP) 24 hours after cleaning. RESULTS: In total, 843 environmental samples were collected from 43 unique patient rooms. At 24 hours, the mean bioburden recovered from the patient rooms cleaned with the new CAD wipe (intervention) was 52 CFU/mL, and the mean bioburden was 92 CFU/mL in the rooms cleaned the standard disinfectant (control). After log transformation for multivariable analysis, the mean difference in bioburden between the intervention and control arm was -0.59 (95% CI, -1.45 to 0.27). The odds of EIP detection were 14% lower in the rooms cleaned with the CAD wipe (OR, 0.86; 95% CI, 0.31-2.32). CONCLUSIONS: The bacterial bioburden and odds of detection of EIPs were not statistically different in rooms cleaned with the CAD compared to the standard disinfectant after 24 hours. Although CAD technology appears promising in vitro, larger studies may be warranted to evaluate efficacy in clinical settings.

Clinical, contextual and hospital-level factors associated with escalation and de-escalation of empiric Gram-negative antibiotics among US inpatients.

Background: Empiric Gram-negative antibiotics are frequently changed in response to new information. To inform antibiotic stewardship, we sought to identify predictors of antibiotic changes using information knowable before microbiological test results. Methods: We performed a retrospective cohort study. Survival-time models were used to evaluate clinical factors associated with antibiotic escalation and de-escalation (defined as an increase or decrease, respectively, in the spectrum or number of Gram-negative antibiotics within 5 days of initiation). Spectrum was categorized as narrow, broad, extended or protected. Tjur's D statistic was used to estimate the discriminatory power of groups of variables. Results: In 2019, 2 751 969 patients received empiric Gram-negative antibiotics at 920 study hospitals. Antibiotic escalation occurred in 6.5%, and 49.2% underwent de-escalation; 8.8% were changed to an equivalent regimen. Escalation was more likely when empiric antibiotics were narrow-spectrum (HR 19.0 relative to protected; 95% CI: 17.9-20.1), broad-spectrum (HR 10.3; 95% CI: 9.78-10.9) or extended-spectrum (HR 3.49; 95% CI: 3.30-3.69). Patients with sepsis present on admission (HR 1.94; 95% CI: 1.91-1.96) and urinary tract infection present on admission (HR 1.36; 95% CI: 1.35-1.38) were more likely to undergo antibiotic escalation than patients without these syndromes. De-escalation was more likely with combination therapy (HR 2.62 per additional agent; 95% CI: 2.61-2.63) or narrow-spectrum empiric antibiotics (HR 1.67 relative to protected; 95% CI: 1.65-1.69). Choice of empiric regimen accounted for 51% and 74% of the explained variation in antibiotic escalation and de-escalation, respectively. Conclusions: Empiric Gram-negative antibiotics are frequently de-escalated early in hospitalization, whereas escalation is infrequent. Changes are primarily driven by choice of empiric therapy and presence of infectious syndromes.

Association of parity with body mass index and cardiometabolic risk in high-parous women.

OBJECTIVE: Postpregnancy weight retention contributes to obesity, but the long-term effect of parity on body mass index (BMI) and other cardiometabolic risk factors is unclear. We aimed to evaluate the relationship between parity and BMI among highly parous Amish women, both before and after menopause, and to evaluate the associations of parity with glucose, blood pressure, and lipids. METHODS: We conducted a cross-sectional study among 3,141 Amish women 18 years or older from Lancaster County, PA, who participated in our community-based Amish Research Program between 2003 and 2020. We evaluated the association between parity and BMI across different age groups, both before and after the menopausal transition. We further assessed associations between parity and cardiometabolic risk factors among the 1,128 postmenopausal women. Finally, we evaluated the association of change in parity with change in BMI in 561 women followed longitudinally. RESULTS: Approximately 62% of women in this sample (mean age, 45.2 y) reported having four or more children, and 36% reported having seven or more. A one-child increase in parity was associated with increased BMI in both premenopausal women (estimate [95% confidence interval], 0.4 kg/m 2 [0.2-0.5]) and to a lesser degree in postmenopausal women (0.2 kg/m 2 [0.02-0.3], Pint = 0.02), suggesting that the impact of parity on BMI decreases over time. Parity was not associated with glucose, blood pressure, total cholesterol, low-density lipoprotein, or triglycerides ( Padj > 0.05). CONCLUSIONS: Higher parity was associated with increased BMI in both premenopausal and postmenopausal women, but more so in younger/premenopausal women. Parity was not associated with other indices of cardiometabolic risk.

Secretory-IgA binding to intestinal microbiota attenuates inflammatory reactions as the intestinal barrier of preterm infants matures.

Previous work has shown that Secretory-IgA (SIgA) binding to the intestinal microbiota is variable and may regulate host inflammatory bowel responses. Nevertheless, the impact of the SIgA functional binding to the microbiota remains largely unknown in preterm infants whose immature epithelial barriers make them particularly susceptible to inflammation. Here, we investigated SIgA binding to intestinal microbiota isolated from stools of preterm infants <33 weeks gestation with various levels of intestinal permeability. We found that SIgA binding to intestinal microbiota attenuates inflammatory reactions in preterm infants. We also observed a significant correlation between SIgA affinity to the microbiota and the infant's intestinal barrier maturation. Still, SIgA affinity was not associated with developing host defenses, such as the production of mucus and inflammatory calprotectin protein, but it depended on the microbiota shifts as the intestinal barrier matures. In conclusion, we reported an association between the SIgA functional binding to the microbiota and the maturity of the preterm infant's intestinal barrier, indicating that the pattern of SIgA coating is altered as the intestinal barrier matures.

Adherence to Antimicrobial Prophylaxis Guidelines for Elective Surgeries Across 825 US Hospitals, 2019-2020.

BACKGROUND: There are limited US data assessing adherence to surgical antimicrobial prophylaxis guidelines, particularly across a large, nationwide sample. Moreover, commonly prescribed inappropriate antimicrobial prophylaxis regimens remain unknown, hindering improvement initiatives. METHODS: We conducted a retrospective cohort study of adults who underwent elective craniotomy, hip replacement, knee replacement, spinal procedure, or hernia repair in 2019-2020 at hospitals in the PINC AI (Premier) Healthcare Database. We evaluated adherence of prophylaxis regimens, with respect to antimicrobial agents endorsed in the American Society of Health-System Pharmacist guidelines, accounting for patient antibiotic allergy and methicillin-resistant Staphylococcus aureus colonization status. We used multivariable logistic regression with random effects by hospital to evaluate associations between patient, procedural, and hospital characteristics and guideline adherence. RESULTS: Across 825 hospitals and 521 091 inpatient elective surgeries, 308 760 (59%) were adherent to prophylaxis guidelines. In adjusted analysis, adherence varied significantly by US Census division (adjusted OR [aOR] range: .61-1.61) and was significantly lower in 2020 compared with 2019 (aOR: .92; 95% CI: .91-.94; P < .001). The most common reason for nonadherence was unnecessary vancomycin use. In a post hoc analysis, controlling for patient age, comorbidities, other nephrotoxic agent use, and patient and procedure characteristics, patients receiving cefazolin plus vancomycin had 19% higher odds of acute kidney injury (AKI) compared with patients receiving cefazolin alone (aOR: 1.19; 95% CI: 1.11-1.27; P < .001). CONCLUSIONS: Adherence to antimicrobial prophylaxis guidelines remains suboptimal, largely driven by unnecessary vancomycin use, which may increase the risk of AKI. Adherence decreased in the first year of the COVID-19 pandemic.

Effect of Systemic Lupus Erythematosus and Immunosuppressive Agents on COVID-19 Vaccination Antibody Response.

OBJECTIVE: The risk of COVID-19 infection is increased in patients with systemic lupus erythematosus (SLE) versus those without SLE. Some immunosuppressive medications increase COVID-19 infection and decrease the efficacy of vaccination. Consensus documents have suggested management strategies for handling immunosuppressive medications to increase vaccine efficacy, but the benefit of such strategies has not been proven. The current study was undertaken to determine the effect of immunosuppressive drugs on vaccine response in SLE. METHODS: We collected information on COVID-19 infection, vaccination history, and COVID-19 antibodies in the Hopkins Lupus Cohort. A cohort of health care workers was used for comparison. Outcome measures included SARS-CoV-2 antibody IgG levels after vaccination over time in both cohorts and effect of immunosuppressive medications on postvaccination IgG levels in SLE patients. RESULTS: The analysis was based on 365 observations from 334 different patients in the SLE cohort, and 2,235 observations from 1,887 different health care workers. SLE patients taking immunosuppressive medications had lower vaccine IgG levels than SLE patients who were not; but both groups had lower levels than health care workers. Holding mycophenolate for 1 week after vaccination increased postvaccine IgG levels significantly without leading to clinical flares. In multiple variable models, mycophenolate mofetil, tacrolimus, and belimumab all significantly reduced antibody response to vaccination. CONCLUSION: SLE patients, regardless of background immunosuppressive therapy, had lower vaccine IgG levels than health care workers. Mycophenolate, tacrolimus, and belimumab significantly reduced IgG response to vaccination. Holding mycophenolate for 1 week improved vaccine efficacy, providing clinical benefit on vaccine response without leading to clinical flares.

A comparison of associations of body mass index and dual-energy x-ray absorptiometry measured percentage fat and total fat with global serum metabolites in young women.

OBJECTIVE: Body mass index (BMI) does not directly measure adiposity, whereas dual-energy x-ray absorptiometry (DXA) provides valid direct estimates of adiposity. Therefore, this study evaluated usefulness of BMI as a measure of adiposity in serum metabolomics studies. METHODS: A cross-sectional analysis was conducted of 202 women aged 25 to 29 years in the Dietary Intervention Study in Children Follow-Up Study. Heights and weights were measured, and body composition was quantified using clinical DXA protocols. Serum metabolomic profiling was performed by liquid chromatography-tandem mass spectrometry. Partial correlations of BMI, percentage fat (%FAT), and total fat (TOTFAT) with log transformed serum metabolites were calculated. RESULTS: There was significant overlap in the 93 metabolites that correlated with BMI, %FAT, and/or TOTFAT; 9 differently correlated with BMI and %FAT, whereas 15 differently correlated with BMI and TOTFAT. Even for these metabolites, absolute differences were modest. Metabolite set enrichment analysis identified diacylglycerol and sphingolipid metabolism as overrepresented among metabolites significantly correlated with all three measures of adiposity. CONCLUSIONS: BMI can be a good proxy for DXA measured %FAT and TOTFAT in descriptive metabolomic studies of healthy, young White women. Larger studies in more diverse populations are needed to endorse more generalized conclusions.

Patterns, Predictors, and Intercenter Variability in Empiric Gram-Negative Antibiotic Use Across 928 United States Hospitals.

BACKGROUND: Empiric antibiotic use among hospitalized adults in the United States (US) is largely undescribed. Identifying factors associated with broad-spectrum empiric therapy may inform antibiotic stewardship interventions and facilitate benchmarking. METHODS: We performed a retrospective cohort study of adults discharged in 2019 from 928 hospitals in the Premier Healthcare Database. "Empiric" gram-negative antibiotics were defined by administration before day 3 of hospitalization. Multivariable logistic regression models with random effects by hospital were used to evaluate associations between patient and hospital characteristics and empiric receipt of broad-spectrum, compared to narrow-spectrum, gram-negative antibiotics. RESULTS: Of 8 017 740 hospitalized adults, 2 928 657 (37%) received empiric gram-negative antibiotics. Among 1 781 306 who received broad-spectrum therapy, 30% did not have a common infectious syndrome present on admission (pneumonia, urinary tract infection, sepsis, or bacteremia), surgery, or an intensive care unit stay in the empiric window. Holding other factors constant, males were 22% more likely (adjusted odds ratio [aOR], 1.22 [95% confidence interval, 1.22-1.23]), and all non-White racial groups 6%-13% less likely (aOR range, 0.87-0.94), to receive broad-spectrum therapy. There were significant prescribing differences by region, with the highest adjusted odds of broad-spectrum therapy in the US West South Central division. Even after model adjustment, there remained substantial interhospital variability: Among patients receiving empiric therapy, the probability of receiving broad-spectrum antibiotics varied as much as 34+ percentage points due solely to the admitting hospital (95% interval of probabilities: 43%-77%). CONCLUSIONS: Empiric gram-negative antibiotic use is highly variable across US regions, and there is high, unexplained interhospital variability. Sex and racial disparities in the receipt of broad-spectrum therapy warrant further investigation.

Predicting the likelihood of lower respiratory tract Ureaplasma infection in preterms.

OBJECTIVE: To develop predictive models of Ureaplasma spp lower airway tract infection in preterm infants. METHODS: A dataset was assembled from five cohorts of infants born <33 weeks gestational age (GA) enrolled over 17 years (1999-2016) with culture and/or PCR-confirmed tracheal aspirate Ureaplasma status in the first week of life (n=415). Seventeen demographic, obstetric and neonatal factors were analysed including admission white blood cell (WBC) counts. Best subset regression was used to develop three risk scores for lower airway Ureaplasma infection: (1) including admission laboratory values, (2) excluding admission laboratory values and (3) using only data known prenatally. RESULTS: GA and rupture of membranes >72 hours were significant predictors in all 3 models. When all variables including admission laboratory values were included in the regression, WBC count was also predictive in the resulting model. When laboratory values were excluded, delivery route was found to be an additional predictive factor. The area under the curve for the receiver operating characteristic indicated high predictive ability of each model to identify infants with lower airway Ureaplasma infection (range 0.73-0.77). CONCLUSION: We developed predictive models based on clinical and limited laboratory information available in the perinatal period that can distinguish between low risk (<10%) and high risk (>40%) of lower airway Ureaplasma infection. These may be useful in the design of phase III trials of therapeutic interventions to prevent Ureaplasma-mediated lung disease in preterm infants and in clinical management of at-risk infants.

Comorbidities associated with 30-day readmission following index coronavirus disease 2019 (COVID-19) hospitalization: A retrospective cohort study of 331,136 patients in the United States.

OBJECTIVE: Hospital readmission is unsettling to patients and caregivers, costly to the healthcare system, and may leave patients at additional risk for hospital-acquired infections and other complications. We evaluated the association between comorbidities present during index coronavirus disease 2019 (COVID-19) hospitalization and the risk of 30-day readmission. DESIGN, SETTING, AND PARTICIPANTS: We used the Premier Healthcare database to perform a retrospective cohort study of COVID-19 hospitalized patients discharged between April 2020 and March 2021 who were followed for 30 days after discharge to capture readmission to the same hospital. RESULTS: Among the 331,136 unique patients in the index cohort, 36,827 (11.1%) had at least 1 all-cause readmission within 30 days. Of the readmitted patients, 11,382 (3.4%) were readmitted with COVID-19 as the primary diagnosis. In the multivariable model adjusted for demographics, hospital characteristics, coexisting comorbidities, and COVID-19 severity, each additional comorbidity category was associated with an 18% increase in the odds of all-cause readmission (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.17-1.19) and a 10% increase in the odds of readmission with COVID-19 as the primary readmission diagnosis (aOR, 1.10; 95% CI, 1.09-1.11). Lymphoma (aOR, 1.86; 95% CI, 1.58-2.19), renal failure (aOR, 1.32; 95% CI, 1.25-1.40), and chronic lung disease (aOR, 1.29; 95% CI, 1.24-1.34) were most associated with readmission for COVID-19. CONCLUSIONS: Readmission within 30 days was common among COVID-19 survivors. A better understanding of comorbidities associated with readmission will aid hospital care teams in improving postdischarge care. Additionally, it will assist hospital epidemiologists and quality administrators in planning resources, allocating staff, and managing bed-flow issues to improve patient care and safety.

Childhood adiposity, serum metabolites and breast density in young women.

BACKGROUND: Childhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its protective effect for breast cancer later in life. The objective of this study was to identify metabolites in childhood serum that may mediate the inverse association between childhood adiposity and young adult breast density. METHODS: Longitudinal data from 182 female participants in the Dietary Intervention Study in Children (DISC) and the DISC 2006 (DISC06) Follow-Up Study were analyzed. Childhood adiposity was assessed by anthropometry at the DISC visit with serum available that occurred closest to menarche and expressed as a body mass index (BMI) z-score. Serum metabolites were measured by untargeted metabolomics using ultra-high-performance liquid chromatography-tandem mass spectrometry. %DBV and ADBV were measured by magnetic resonance imaging at the DISC06 visit when participants were 25-29 years old. Robust mixed effects linear regression was used to identify serum metabolites associated with childhood BMI z-scores and breast density, and the R package mediation was used to quantify mediation. RESULTS: Of the 115 metabolites associated with BMI z-scores (FDR < 0.20), 4 were significantly associated with %DBV and 6 with ADBV before, though not after, adjustment for multiple comparisons. Mediation analysis identified 2 unnamed metabolites, X-16576 and X-24588, as potential mediators of the inverse association between childhood adiposity and dense breast volume. X-16576 mediated 14% (95% confidence interval (CI) = 0.002, 0.46; P = 0.04) of the association of childhood adiposity with %DBV and 11% (95% CI = 0.01, 0.26; P = 0.02) of its association with ADBV. X-24588 also mediated 7% (95% CI = 0.001, 0.18; P = 0.05) of the association of childhood adiposity with ADBV. None of the other metabolites examined contributed to mediation of the childhood adiposity-%DBV association, though there was some support for contributions of lysine, valine and 7-methylguanine to mediation of the inverse association of childhood adiposity with ADBV. CONCLUSIONS: Additional large longitudinal studies are needed to identify metabolites and other biomarkers that mediate the inverse association of childhood adiposity with breast density and possibly breast cancer risk.

Mucosal and Systemic Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination Determined by Severity of Primary Infection.

With much of the world infected with or vaccinated against severe acute respiratory syndrome coronavirus 2 (commonly abbreviated SARS-CoV-2; abbreviated here SARS2), understanding the immune responses to the SARS2 spike (S) protein in different situations is crucial to controlling the pandemic. We studied the clinical, systemic, mucosal, and cellular responses to two doses of SARS2 mRNA vaccines in 62 individuals with and without prior SARS2 infection that were divided into three groups based on antibody serostatus prior to vaccination and/or degree of disease symptoms among those with prior SARS2 infection: antibody negative (naive), low symptomatic, and symptomatic. Antibody negative were subjects who were antibody negative (i.e., those with no prior infection). Low symptomatic subjects were those who were antibody negative and had minimal or no symptoms at time of SARS2 infection. Symptomatic subjects were those who were antibody positive and symptomatic at time of SARS2 infection. All three groups were then studied when they received their SARS2 mRNA vaccines. In the previously SARS2-infected (based on antibody test) low symptomatic and symptomatic groups, reactogenic symptoms related to a recall response were elicited after the first vaccination. Anti-S trimer IgA and IgG titers, and neutralizing antibody titers, peaked after the 1st vaccination in the previously SARS2-infected groups and were significantly higher than for the SARS2 antibody-negative group in the plasma and nasal samples at most time points. Nasal and plasma IgA antibody responses were significantly higher in the low symptomatic group than in the symptomatic group at most time points. After the first vaccination, differences in cellular immunity were not evident between groups, but the activation-induced cell marker (AIM+) CD4+ cell response correlated with durability of IgG humoral immunity against the SARS2 S protein. In those SARS2-infected subjects, severity of infection dictated plasma and nasal IgA responses in primary infection as well as response to vaccination (peak responses and durability), which could have implications for continued protection against reinfection. Lingering differences between the SARS2-infected and SARS2-naive up to 10 months postvaccination could explain the decreased reinfection rates in the SARS2-infected vaccinees recently reported and suggests that additional strategies (such as boosting of the SARS2-naive vaccinees) are needed to narrow the differences observed between these groups. IMPORTANCE This study on SARS2 vaccination in those with and without previous exposure to the virus demonstrates that severity of infection dictates IgA responses in primary infection as well as response to vaccination (peak responses and durability), which could have implications for continued protection against reinfection.

Trajectory of Damage Accrual in Systemic Lupus Erythematosus Based on Ethnicity and Socioeconomic Factors.

OBJECTIVE: The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) is associated with increased healthcare costs and mortality. We compared the trajectory of total and individual damage items of the SDI in African American vs White ethnicities in a large prospective systemic lupus erythematosus (SLE) cohort. We also estimated the association between ethnicity and individual damage items after adjusting for several socioeconomic factors. METHODS: Poisson regression was used to calculate the rate of damage per year for each organ. Cox regression modeling was used to determine the association between time to the individual damage item and ethnicity. RESULTS: We included 2436 patients: 42.9% African American, 57.1% White, and 92% female. There was a linear relationship between time since diagnosis and mean SDI score, with no plateau. Compared to White patients, African American patients had a faster total, renal, pulmonary, and skin damage accrual rate even after adjustment for differences in socioeconomic variables. CONCLUSION: The linear increase in damage in both ethnicities over time is of particular concern. African American patients accrued more damage at a faster rate compared to White patients. For a few organs, higher rates of damage in African American patients was partially explained by socioeconomic differences, whereas for most organs, the difference persisted after adjustment for these factors.

Pregnancy and the Risk of In-Hospital Coronavirus Disease 2019 (COVID-19) Mortality.

OBJECTIVE: To evaluate whether pregnancy is an independent risk factor for in-hospital mortality among patients of reproductive age hospitalized with coronavirus disease 2019 (COVID-19) viral pneumonia. METHODS: We conducted a retrospective cohort study (April 2020-May 2021) of 23,574 female inpatients aged 15-45 years with an International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code for COVID-19 discharged from 749 U.S. hospitals in the Premier Healthcare Database. We used a viral pneumonia diagnosis to select for patients with symptomatic COVID-19. The associations between pregnancy and in-hospital mortality, intensive care unit (ICU) admission, and mechanical ventilation were analyzed using propensity score-matched conditional logistic regression. Models were matched for age, marital status, race and ethnicity, Elixhauser comorbidity score, payer, hospital number of beds, season of discharge, hospital region, obesity, hypertension, diabetes mellitus, chronic pulmonary disease, deficiency anemias, depression, hypothyroidism, and liver disease. RESULTS: In-hospital mortality occurred in 1.1% of pregnant patients and 3.5% of nonpregnant patients hospitalized with COVID-19 and viral pneumonia (propensity score-matched odds ratio [OR] 0.39, 95% CI 0.25-0.63). The frequency of ICU admission for pregnant and nonpregnant patients was 22.0% and 17.7%, respectively (OR 1.34, 95% CI 1.15-1.55). Mechanical ventilation was used in 8.7% of both pregnant and nonpregnant patients (OR 1.05, 95% CI 0.86-1.29). Among patients who were admitted to an ICU, mortality was lower for pregnant compared with nonpregnant patients (OR 0.33, 95% CI 0.20-0.57), though mechanical ventilation rates were similar (35.7% vs 38.3%, OR 0.90, 95% CI 0.70-1.16). Among patients with mechanical ventilation, pregnant patients had a reduced risk of in-hospital mortality compared with nonpregnant patients (0.26, 95% CI 0.15-0.46). CONCLUSION: Despite a higher frequency of ICU admission, in-hospital mortality was lower among pregnant patients compared with nonpregnant patients with COVID-19 viral pneumonia, and these findings persisted after propensity score matching.

Renal versus cerebral saturation trajectories: the perinatal transition in preterm neonates.

BACKGROUND: The aim of this study was to develop reference renal saturation (rSrO2) curves in premature infants, depict how they differ from cerebral saturation (rScO2) curves, and evaluate the effect of blood pressure on these values using near-infrared spectroscopy (NIRS). METHODS: This is a prospective cohort study of 57 inborn infants <12 h and <30 weeks gestation. rScO2, rSrO2, fractional tissue oxygen extraction (FTOE), and mean arterial blood pressure (MAP) were continuously monitored every 30 s for 96 h. Quantile regression was used to establish nomograms, and mean saturation values were evaluated for different MAP ranges. RESULTS: Median rSrO2 at the start of monitoring was ~10% higher than rScO2. rSrO2 showed a significant decline over time while rScO2 peaked at 26 h. FTOE demonstrated a similar but inverse trend to their saturation counterparts. rScO2 declined as MAP increased, while rSrO2 showed a peak and decline as MAP increased. CONCLUSIONS: We provide rSrO2 reference curves for the first 4 days of life, which differ in their trajectory from rScO2 and from what has previously been reported for rSrO2 in the full-term population. In addition, we observed a peak and decline in renal saturation with increasing MAP, suggesting a renovascular response to blood pressure changes. IMPACT: This article depicts reference renal saturation curves during the perinatal transition in preterm infants. We show how renal saturation compares to cerebral saturation trends over time. We describe a peak and decline in renal saturation with increasing MAP, suggesting a renovascular response to blood pressure changes.