Association of autoantibody concentrations and trajectories with lupus nephritis histological features and treatment response.

OBJECTIVE: Autoantibodies are a hallmark of lupus nephritis (LN), but their association with LN classes and treatment response are not adequately known. In this study, we quantified circulating autoantibodies in the Accelerating Medicines Partnership (AMP) LN longitudinal cohort to identify serological biomarkers of LN histological classification and treatment response, and how these biomarkers change over time based on treatment response. METHODS: Peripheral blood samples were collected from 279 SLE patients undergoing diagnostic kidney biopsy based on proteinuria. Of these, 268 were diagnosed with LN. Thirteen autoantibody specificities were measured by bead-based assays (Bio-Rad Bioplex 2200) and anti-C1q by ELISA at the time of biopsy (baseline) and at 3-, 6-, and 12-months post-biopsy. Clinical response was determined at 12 months. RESULTS: Proliferative LN (ISN/RPS class III/IV+V, n=160) was associated with higher concentrations of anti-C1q, -chromatin, -dsDNA, and -ribosomal P autoantibodies compared to non-proliferative LN (classes I/II/V/VI, n=108). Anti-C1q and-dsDNA were independently associated with proliferative LN. In proliferative LN, higher baseline anti-C1q levels predicted complete response (AUC, 0.72; p, 0.002) better than baseline proteinuria (0.59; 0.21). Furthermore, all autoantibody levels, except for anti-La/SSB, decreased over 12 months in proliferative, but not membranous, LN patients with a complete response. CONCLUSIONS: Baseline levels of anti-C1q and -dsDNA may serve as noninvasive biomarkers of proliferative LN, and anti-C1q may predict complete response at the time of kidney biopsy. In addition, tracking autoantibodies over time may provide further insights into treatment response and pathogenic mechanisms in proliferative LN patients.

Comparing Two Training Modalities Supporting the Adoption of the SEEK Approach in Pediatric Primary Care 6/30/24.

OBJECTIVE: To compare the impact of two common continuing medical education training modalities - independent online training (IND) and a Maintenance of Certification-4 activity (MOC) - on primary care professionals' (PCPs') thinking and practice behavior regarding the Safe Environment for Every Kid (SEEK) approach. This was part of an implementation science study scaling up the evidence-based practice, SEEK. METHODS: This is a longitudinal, multi-site, mixed methods, cluster randomized controlled trial comparing 21 pediatric primary care practices across the U.S. randomized to one of two training modalities. Two hundred and ten PCPs completed surveys up to 4 times over a two-year period to assess their thinking and practice regarding SEEK; a subset was interviewed up to 3 times. RESULTS: Training led to significant and sustained improvements in PCPs' thinking and behavior related to SEEK, with no significant differences between the IND and MOC groups. PCPs mostly viewed their training positively, but several described shortcomings. PCP characteristics, such as age and sex, did not moderate the impact of the training, nor did the presence of a behavioral health professional. CONCLUSIONS: The lack of significant differences between the training modalities favors the simpler IND modality. This was despite the MOC training employing key principles of adult education. Of note, MOC-4 credits are required for pediatric board certification. More research is needed to optimize continuing medical education and to tailor approaches for different learners.

Netarsudil 0.02% Alters Episcleral Venous Flowrates: A Clinical Trial Using Erythrocyte-Mediated Angiography.

Objective: To characterize the effect of netarsudil 0.02% on episcleral blood flow in treatment-naive glaucoma suspect or ocular hypertension subjects. Design: Prospective, unmasked, single-arm cohort study. Participants: Ten treatment-naive patients with a diagnosis of glaucoma suspect or ocular hypertension. Methods: Erythrocyte-mediated angiography (EMA) was used to measure episcleral erythrocyte velocity, vessel diameter, and blood flow at baseline before treatment, 1 hour after drop instillation (T1), 1 to 2 weeks after daily netarsudil 0.02% drop use (T2), and 1 hour after drop instillation at the 1-to-2-week time point (T3). Intraocular pressure (IOP) and blood pressure were measured at each visit. Main Outcome Measures: Change in episcleral venous erythrocyte velocity, diameter, and blood flow between time points analyzed using generalized estimating equation models. Results: Of the 18 eligible study eyes of 10 enrolled treatment-naive subjects, baseline IOP was 16.8 ± 3.6 mmHg (mean ± standard deviation), which significantly decreased to 13.9 ± 4.2 mmHg at T1, 12.6 ± 4.1 mmHg at T2, and 11.8 ± 4.7 mmHg at T3 (P < 0.05 at each time point compared with baseline). Episcleral vessels averaged 61.3 ± 5.3 µm in diameter at baseline which increased significantly at all posttreatment time points (78.0 ± 6.6, 74.0 ± 5.2, 76.9 ± 6.9 µm, respectively; mean ± standard deviation, P < 0.05 for each time point). Episcleral venous flowrates were 0.40 ± 0.22 uL/minute (mean ± standard deviation) at baseline, which increased significantly to 0.69 ± 0.45 uL/min at T1 (P = 0.01), did not significantly differ at T2 (0.38 ± 0.30 uL/minute), and increased significantly to 0.54 ± 0.32 uL/minute at T3 (P < 0.05 compared with baseline and T2). Conclusions: Netarsudil causes episcleral venous dilation at all time points and resulting increases in episcleral venous flowrates 1 hour after drop instillation. Increased episcleral venous flow, associated with decreased episcleral venous pressure, may result in lowered IOP. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Retinal blood flow association with age and weight in infants at risk for retinopathy of prematurity.

This prospective study evaluated the relationship between laser speckle contrast imaging (LSCI) ocular blood flow velocity (BFV) and five birth parameters: gestational age (GA), postmenstrual age (PMA) and chronological age (CA) at the time of measurement, birth weight (BW), and current weight (CW) in preterm neonates at risk for retinopathy of prematurity (ROP). 38 Neonates with BW < 2 kg, GA < 32 weeks, and PMA between 27 and 47 weeks underwent 91 LSCI sessions. Correlation tests and regression analysis were performed to quantify relationships between birth parameters and ocular BFV. Mean ocular BFV index in this cohort was 8.8 +/- 4.0 IU. BFV positively correlated with PMA (r = 0.3, p = 0.01), CA (r = 0.3, p = 0.005), and CW (r = 0.3, p = 0.02). BFV did not correlate with GA nor BW (r = - 0.2 and r = - 0.05, p > 0.05). Regression analysis with mixed models demonstrated that BFV increased by 1.2 for every kilogram of CW, by 0.34 for every week of CA, and by 0.36 for every week of PMA (p = 0.03, 0.004, 0.007, respectively). Our findings indicate that increased age and weight are associated with increased ocular BFV measured using LSCI in premature infants. Future studies investigating the associations between ocular BFV and ROP clinical severity must control for age and/or weight of the infant.

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.

Hydroxychloroquine Improves Low Complement Levels.

OBJECTIVE: Having a low complement level is associated with clinical systemic lupus erythematosus (SLE) disease activity and future organ damage. We studied the association of hydroxychloroquine (HCQ) whole blood levels with changes in complement level. METHODS: We performed two analyses on data prospectively collected from an SLE cohort. In the first (a "new starts on HCQ" analysis), we compared changes in complement level between those starting HCQ and those not starting it. The second analysis evaluated the association between HCQ whole blood levels and low complement level in all cohort visits using conditional logistic regression. RESULTS: In the "new starts on HCQ" analysis, a higher percentage of patients starting HCQ (as reflected in HCQ blood levels >50) experienced a normalization of C4 level compared to those not starting HCQ (23 of 57 [40%] vs. 9 of 56 [13%]; P = 0.011), as well as a significantly greater increase in both C3 and C4 level (P = 0.048 and P = 0.017, respectively). In the "all cohort visits" analysis, there was a statistically significant higher probability of having normal C4 levels in visits with higher HCQ whole blood levels (odds ratio 1.8-2.6 depending on the levels). This relationship was most pronounced for whole blood HCQ levels of 200 ng/mL or more. CONCLUSION: We observed significant improvement in complement levels when HCQ was started and among those with higher whole blood levels of HCQ, particularly with respect to C4. Modulating the pathogenic mechanisms that lead to complement consumption may be one mode by which HCQ prevents poor outcomes in SLE.

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.

Retinal blood flow association with age and weight in infants at risk for retinopathy of prematurity.

This prospective study evaluated the relationship between laser speckle contrast imaging (LSCI) ocular blood flow velocity (BFV) and five birth parameters: gestational age (GA), postmenstrual age (PMA), and chronological age (CA) at the time of measurement, birth weight (BW), and current weight (CW) in preterm neonates at risk for retinopathy of prematurity (ROP).38 Neonates with BW < 2 kg, GA < 32 weeks, and PMA between 27-47 weeks underwent 91 LSCI sessions. Correlation tests and regression analysis were performed to quantify relationships between birth parameters and ocular BFV. Mean ocular BFV index in this cohort was 8.8 +/- 4.0 IU. BFV positively correlated with PMA (r = 0.3, p = 0.01), CA (r = 0.3, p = 0.005), and CW (r = 0.3, p = 0.02). BFV did not correlate with GA nor BW (r=-0.2 and r=-0.05, p > 0.05). Regression analysis with mixed models demonstrated that BFV increased by 1.2 for every kilogram of CW, by 0.34 for every week of CA, and by 0.36 for every week of PMA (p = 0.03, 0.004, 0.007, respectively). Our findings indicate that increased age and weight are associated with increased ocular BFV measured using LSCI in premature infants. Future studies investigating the associations between ocular BFV and ROP clinical severity must control for age and/or weight of the infant.

Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis.

Lupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30%-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 patients with LN (573 samples) in the longitudinal Accelerating Medicines Partnership in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PR3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.91, EGFR 0.9, CD163 0.89, proteinuria 0.8). Candidate biomarkers were validated and provide potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN and guide treatment and as surrogate endpoints for clinical trials. These findings provide insights into the processes involved in LN activity. This data set is a public resource to generate and test hypotheses and validate biomarkers.

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.

Multicomponent Home-based Physical Therapy Versus Usual Care for Recovery After Hip Fracture.

OBJECTIVE: To quantify the effect of 2 home-based 16-week multi-component physical therapy interventions on functional recovery compared to usual care after hip fracture. DESIGN: Cross-study comparison using participants from the Community Ambulation Project (CAP; a randomized controlled trial) were compared to the Baltimore Hip Studies-seventh cohort (BHS-7; an observational cohort study) at 3 different time points (CAP: 15, 31, 55 weeks; BHS-7: 8, 26, and 52 weeks). SETTING: General community PARTICIPANTS: Combined convenience sample of hip-fracture patients 8-26 weeks post admission from a prospective cohort study and randomized controlled trial. (N=549) INTERVENTIONS: CAP participants were randomized to one of 2 interventions (PUSH: specific multi-component intervention; PULSE: non-specific multi-component intervention) after standard rehabilitation; BHS-7 participants received usual care. MAIN OUTCOME MEASURES: Mean function (as measured by Short Physical Performance Battery (SPPB) and gait speed) was estimated in each cohort as quadratic functions of time using data from 3 post-fracture assessments in both studies (CAP: 15, 31, 55 weeks; BHS-7: 8, 26, and 52 weeks). RESULTS: The harmonized samples included 101 PUSH, 100 PULSE, and 128 BHS-7 participants that had different demographic and clinical characteristics. Mean baseline SPPB scores (meters per second) were PUSH: 5.5 (SD=2.2), PULSE: 5.5 (SD=2.4), and BHS-7: 4.6 (SD=2.5); and mean gait speeds were 0.60 m/s (SD=0.20) for PUSH, 0.59 m/s (SD=0.17) for PULSE, and 0.46 m/s SD=(0.21) for BHS-7, respectively. Estimated between-group differences for SPPB improvement from 75 days to 1-year post admission were 0.7 (P=.04) in PUSH vs BHS-7; and 0.9 (P=.01) in PULSE vs BHS-7. Mean differences in change in gait speed were 0.08 (P=.002) for PUSH vs BHS-7; and 0.06 (P=.02) PULSE vs BHS-7 (P=.02). CONCLUSIONS: Findings from this cross-study comparison that combined participants from 2 separate studies, with different designs and samples, suggest that home-based multi-component physical therapy programs were associated with greater functional improvement after hip fracture compared to usual care.

Repeatability and Comparability of Retinal Blood Vessel Caliber Measurements by OCTA.

BACKGROUND: To investigate the repeatability in vessel caliber measurements by optical coherence tomography angiography (OCTA). METHODS: In this prospective study, 28 patients (47 eyes) underwent sequential OCTA imaging of the optic nerve head and macula. Two independent masked graders measured vessel caliber for sequential images of the optic nerve head and macula. The average vessel width was determined and variability between graders and images. RESULTS: A total of 8400 measurements of 420 vessels from 84 OCTA images were included in the analysis. Overall, inter-grader agreement was excellent (ICC 0.90). The coefficient of variation (CoV) for all repeated OCTA images was 0.10. Greater glaucoma severity, older age, macular location, and diagnosis of diabetes were associated with thinner vessels (p < 0.05). CoV was higher in the peripapillary region (0.07) as compared to the macula (0.15). ICC was high for all subgroups except for the macula (ICC = 0.72). CONCLUSIONS: Overall, the repeatability of vessel caliber measurements by OCTA was high and variability low. There was greater variability in the measurement of macular vessels, possibly due to technical limitations in acquiring accurate vessel widths for smaller macular vessels.

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.