Effectiveness of the 2023-2024 Formulation of the Coronavirus Disease 2019 mRNA Vaccine.

BACKGROUND: The purpose of this study was to evaluate whether the 2023-2024 formulation of the COVID-19 mRNA vaccine protects against COVID-19. METHODS: Employees of Cleveland Clinic in employment when the 2023-2024 formulation of the COVID-19 mRNA vaccine became available to employees, were included. Cumulative incidence of COVID-19 over the following 17 weeks was examined prospectively. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with time-dependent coefficients used to separate effects before and after the JN.1 lineage became dominant. The analysis was adjusted for the propensity to get tested, age, sex, pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses. RESULTS: Among 48210 employees, COVID-19 occurred in 2462 (5.1%) during the 17 weeks of observation. In multivariable analysis, the 2023-2024 formula vaccinated state was associated with a significantly lower risk of COVID-19 before the JN.1 lineage became dominant (HR, .58; 95% C.I., .49-.68, p-value < .001), and lower risk but one that did not reach statistical significance after (HR, .81; 95% C.I., .65-1.01, p-value 0.06). Estimated vaccine effectiveness (VE) was 42% (95% C.I., 32%-51%) before the JN.1 lineage became dominant, and 19% (C.I., -1%-35%) after. Risk of COVID-19 was lower among those previously infected with an XBB or more recent lineage, and increased with the number of vaccine doses previously received. CONCLUSIONS: The 2023-2024 formula COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 before the JN.1 lineage became dominant, and less protection after.

Clinical and immunological outcomes of HIV-exposed uninfected and HIV-unexposed uninfected children in the first 24 months of life in Western Kenya.

BACKGROUND: Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life. METHODS: Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months. All mothers living with HIV received combination antiretroviral therapy. Children who were HEU received standard-of-care cotrimoxazole prophylaxis through 18 months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. RESULTS: Children who were HEU and children who were HUU had similar growth curves. Children who were HEU had lower rates of malaria (rate ratio 0.54, 95% CI 0.38, 0.77) and respiratory illness (rate ratio 0.80, 95% CI 0.68, 0.93). Trajectories of plasma cytokines and vaccine-specific antibodies were similar in children who were HEU and HUU. There were subtle differences in antimalarial antibody dynamics, in which children who were HEU had overall lower antibody levels against five of the 14 malaria antigens tested. CONCLUSIONS: Children who were HEU and born to optimally treated mothers living with HIV had similar growth characteristics and immune profiles compared to children who were HUU. Children who were HEU had reduced risk for malaria and respiratory illness, which may be secondary to cotrimoxazole prophylaxis.

Propensity-Matched Analysis of the Risk of Age-Related Macular Degeneration with Systemic Immune-Mediated Inflammatory Disease.

PURPOSE: The pathogenesis of age-related macular degeneration (AMD) involves aberrant complement activation and is a leading cause of vision loss worldwide. Complement aberrations are also implicated in many systemic immune-mediated inflammatory diseases (IMIDs), but the relationship between AMD and these conditions remains undescribed. The aim of this study is to first assess the association between AMD and IMIDs, and then assess the risk of AMD in patients with specific IMIDs associated with AMD. DESIGN: Cross-sectional study and cohort study. SUBJECTS AND CONTROLS: Patients with AMD were compared with control patients with cataracts and no AMD to ensure evaluation by an ophthalmologist. Patients with IMIDs were compared with patients without IMIDs but with cataracts. METHODS: This study used deidentified data from a national database (2006-2023), using International Classification of Diseases 10 codes to select for IMIDs. Propensity score matching was based on patients on age, sex, race, ethnicity, and smoking. Odds ratios were generated for IMIDs and compared between AMD and control patients. For IMIDs associated with AMD, the risk of AMD in patients with the IMID versus patients without IMIDs was determined utilizing a cohort study design. MAIN OUTCOME MEASURES: Odds ratio of IMID, risk ratios (RRs), and 95% confidence intervals (CIs) of AMD diagnosis, given an IMID. RESULTS: After propensity score matching, AMD and control cohorts (n = 217 197 each) had a mean ± standard deviation age of 74.7 ± 10.4 years, were 56% female, and 9% of patients smoked. Age-related macular degeneration showed associations with systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis, rheumatoid arthritis (RA), psoriasis, sarcoidosis, scleroderma, giant cell arteritis, and vasculitis. Cohorts for each positively associated IMID were created and matched to control cohorts with no IMID history. Patients with RA (RR, 1.40; 95% CI, 1.30-1.49), SLE (RR, 1.73; 95% CI, 1.37-2.18), Crohn's disease (RR, 1.42; 95% CI, 1.20-1.71), ulcerative colitis (RR, 1.45; 95% CI, 1.29-1.63), psoriasis (RR, 1.48; 95% CI, 1.37-1.60), vasculitis (RR, 1.48; 95% CI, 1.33-1.64), scleroderma (RR, 1.65; 95% CI, 1.35-2.02), and sarcoidosis (RR, 1.42; 95% CI, 1.24-1.62) showed a higher risk of developing AMD compared with controls. CONCLUSIONS: The results suggest that there is an increased risk of developing AMD in patients with RA, SLE, Crohn's disease, ulcerative colitis, psoriasis, vasculitis, scleroderma, and sarcoidosis compared with patients with no IMIDs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ergonomics, musculoskeletal disorders, and surgeon gender in spine surgery: a survey of practicing spine surgeons.

OBJECTIVE: The objective of this study was to gain a greater understanding of the burden of musculoskeletal disorders (MSDs) in spine surgeons, their impact on practice, and risk factors contributing to MSDs, including surgical instrument design and surgical ergonomics. METHODS: An anonymous REDCap survey was distributed via email to the departments of several academic and private centers across the United States, as well as to the AANS/CNS Women in Neurosurgery Section email list. Chi-square tests and Wilcoxon rank-sum tests were used to compare responses by gender. Multivariable linear regression analysis was performed to identify predictors of discomfort in instrument utilization. RESULTS: Survey responses were received from 120 spine surgeons (29.1% response rate), of which 73 were included in the analysis. A very high number of respondents had experienced an MSD (70.4%), 38.2% had undergone treatment for at least one MSD, and 13.4% had lost time at work for at least one MSD. Women were more likely than men to have lost time at work due to an MSD (22.6% vs 5.6%, p = 0.04). Women were more likely than men to report difficulty in instrument grip, comfort, and use on a 20-point Likert scale (mean 10.7 vs 15.2 points, p < 0.0001). This effect persisted when adjusting for glove size and days per week spent operating (p = 0.002). Specifically, women were less likely to agree that the handles of surgical instruments were an appropriate grip (p < 0.0001), that they rarely experienced difficulty when using them (p < 0.0001), and that they rarely needed to use two hands with instruments meant to be used with one hand (p = 0.0002). CONCLUSIONS: The MSD burden in spine surgeons is substantial. While there was no evidence of gender differences in MSD rates and severity, female surgeons report significantly more discomfort with the use of surgical instruments. There is a need for more investigation of MSD risk factors in spine surgeons and mitigation strategies. Gender differences in comfort in instrument use should be further explored and addressed by spine surgeons and device manufacturers.

Comorbid anxiety is associated with more changes in the Management of Postural Orthostatic Tachycardia Syndrome.

OBJECTIVE: Postural Orthostatic Tachycardia Syndrome (POTS) is not an anxiety disorder, but it shares similar symptomatology. The impact of this comorbidity on management is unknown. This information may lead to better strategies to improve the care of this subgroup. METHOD: The electronic medical records of 322 patients seen at our institution between 2018 and 2022 with confirmed POTS diagnoses were analyzed. Demographics, anxiety comorbidities, questionnaire responses, and treatment course changes were collected. Negative binomial regression models examined if the presence of an anxiety disorder was associated with the number of POTS treatment course changes offset by observation time. RESULTS: When adjusted for sex, age, baseline GAD-7 score, and baseline PROMIS global mental health score, those with a diagnosis of an anxiety disorder had2.6 times the incident rate of treatment changes for POTS management (IRR = 2.66 (95% CI: 1.43-4.95)). CONCLUSION: Individuals carrying the diagnosis of an anxiety disorder had an increase in the incident rate of treatment changes for POTS therapy. This finding may be due to the underlying pathophysiology and treatment of anxiety disorders, the effect of bias, and difficulty with symptom differentiation. More work needs to be done to determine how to best care for POTS patients with comorbid anxiety.

Painless photodynamic therapy for facial actinic keratoses: A retrospective cohort study of the post-treatment inflammatory response.

INTRODUCTION: Photodynamic therapy (PDT) is a safe, non-mutagenic, and non-scarring treatment for actinic keratoses (AK). BACKGROUND: 'Painless' photodynamic therapy (p-PDT) is a regimen for AK that employs simultaneous aminolevulinate incubation and blue light illumination. The efficacy of p-PDT resembles that of traditional PDT, but detailed mechanisms of action for p-PDT are not well understood. METHODS: To characterize the inflammatory effects of the p-PDT procedure 48 h following treatment and determine the association of inflammation with precancer burden, we performed a retrospective cohort study of 104 patients with AK of face or scalp treated with p-PDT between 2017 and 2019. Patients self-reported their side effects 48 h following p-PDT and took photographs of their face and scalp. Photographs were edited to define seven anatomic regions, and erythema was scored by four investigators. RESULTS: Ninety-eight patients provided photographs suitable for erythema evaluation. Most patients experienced 2 or more side effects and some pain 48 h post-procedure. Females experienced more pain (p = 0.01) and side effects (p = 0.002) compared to males. AK burden was positively associated with post p-PDT erythema response (p < 0.0001) at all sites, but particularly in the temples (p = 0.002) and supralabial area (p = 0.009). DISCUSSION: This study confirms a strong clinical inflammatory response after p-PDT. Severity of inflammation is positively associated with AK tumor burden, suggesting that post-treatment inflammation may be a pre-requisite for p-PDT efficacy. Interestingly, the results also identify certain gender-related differences in the severity of side effects experienced by patients post-PDT.

Clinical Utility of Spectral-Domain Optical Coherence Tomography Marker Disorganization of Retinal Inner Layers in Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: Disorganization of retinal inner layers (DRIL) is a potential spectral-domain optical coherence tomography (SD-OCT) imaging biomarker with clinical utility in diabetic retinopathy (DR). PATIENTS AND METHODS: A cross-sectional study was conducted at a large academic center. The cohort was composed of 1,175 patients with type 2 diabetes with and without retinopathy on initial examination between September 2009 and January 2019 (n = 2,083 eyes). DR risk and progression factors were obtained from the medical record. Trained graders masked to patients' clinical histories evaluated SD-OCT scans for DRIL. RESULTS: Of 2,083 eyes, 28.1% (n = 585) demonstrated presence of DRIL with high interrater reliability (K = 0.88, 95% CI 0.86-0.90). DRIL was associated with worse visual acuity (VA) (P < 0.001) and DR severity (P < 0.0001). Insulin users had more severe DR (P < 0.0001). DR-related factors, race (Black, White) and sex (male) were significantly associated with DRIL (P < 0.05). CONCLUSIONS: DRIL was strongly associated with DR severity and worse VA, supporting its utility as an unfavorable prognostic indicator. [Ophthalmic Surg Lasers Imaging Retina 2023;54:692-700.].

Outcomes of a Multicenter 10-Year Review of Postinjection Endophthalmitis and Associated Systemic Medical Comorbidities.

Purpose: To investigate whether any systemic medical conditions may be associated with a higher risk for developing postinjection endophthalmitis. Methods: This case-control study is a retrospective review within the Emory Eye Center from 2009 to 2019 and The Cleveland Clinic Foundation from 2012 to 2019. Each case was matched in a 1:4 case-to-control ratio. The associations between medical comorbidities and endophthalmitis were explored using multivariable logistic regression models on the combined sample. Results: Sixty-six individuals were diagnosed with injection-associated endophthalmitis. Systemic immunocompromised status was found to be a risk factor associated with developing endophthalmitis with an adjusted odds ratio (aOR) of 3.17 (P = .009). Other conditions with increased risk approaching statistical significance included a history of pulmonary disease (aOR, 1.74; P = .08) and a history of smoking (aOR, 1.72; P = .06). Conclusions: This is the first report to our knowledge demonstrating that immunocompromised status is associated with an increased risk for developing postinjection endophthalmitis. While this study may be limited due to its retrospective nature, the result may nevertheless serve as a guidance for risk counseling. Future analysis using a large-scale database will be needed.

Derivation and external validation of a prediction model for pneumococcal urinary antigen test positivity in patients with community-acquired pneumonia.

Objective: Derive and externally validate a prediction model for pneumococcal urinary antigen test (pUAT) positivity. Methods: Retrospective cohort study of adults admitted with community-acquired pneumonia (CAP) to 177 U.S. hospitals in the Premier Database (derivation and internal validation samples) or 12 Cleveland Clinic hospitals (external validation sample). We utilized multivariable logistic regression to predict pUAT positivity in the derivation dataset, followed by model performance evaluation in both validation datasets. Potential predictors included demographics, comorbidities, clinical findings, and markers of disease severity. Results: Of 198,130 Premier patients admitted with CAP, 27,970 (14.1%) underwent pUAT; 1962 (7.0%) tested positive. The strongest predictors of pUAT positivity were history of pneumococcal infection in the previous year (OR 6.99, 95% CI 4.27-11.46), severe CAP on admission (OR 1.76, 95% CI 1.56-1.98), substance abuse (OR 1.57, 95% CI 1.27-1.93), smoking (OR 1.23, 95% CI 1.09-1.39), and hyponatremia (OR 1.35, 95% CI 1.17-1.55). Negative predictors included IV antibiotic use in past year (OR 0.65, 95% CI 0.52-0.82), congestive heart failure (OR 0.72, 95% CI 0.63-0.83), obesity (OR 0.71, 95% CI 0.60-0.85), and admission from skilled nursing facility (OR 0.60, 95% CI 0.45-0.78). Model c-statistics were 0.60 and 0.67 in the internal and external validation cohorts, respectively. Compared to guideline-recommended testing of severe CAP patients, our model would have detected 23% more cases with 5% fewer tests. Conclusion: Readily available data can identify patients most likely to have a positive pUAT. Our model could be incorporated into automated clinical decision support to improve test efficiency and antimicrobial stewardship.

Risk of Coronavirus Disease 2019 (COVID-19) among those up-to-date and not up-to-date on COVID-19 vaccination by US CDC criteria.

BACKGROUND: The CDC recently defined being "up-to-date" on COVID-19 vaccination as having received at least one dose of a COVID-19 bivalent vaccine. The purpose of this study was to compare the risk of COVID-19 among those "up-to-date" and "not up-to-date". METHODS: Employees of Cleveland Clinic in Ohio, USA, in employment when the COVID-19 bivalent vaccine first became available, and still employed when the XBB lineages became dominant, were included. Cumulative incidence of COVID-19 since the XBB lineages became dominant was compared across the"up-to-date" and "not up-to-date" states, by treating COVID-19 bivalent vaccination as a time-dependent covariate whose value changed on receipt of the vaccine. Risk of COVID-19 by vaccination status was also evaluated using multivariable Cox proportional hazards regression adjusting for propensity to get tested for COVID-19, age, sex, most recent prior SARS-CoV-2 infection, and number of prior vaccine doses. RESULTS: COVID-19 occurred in 1475 (3%) of 48 344 employees during the 100-day study period. The cumulative incidence of COVID-19 was lower in the "not up-to-date" than the "up-to-date" state. On multivariable analysis, being "up-to-date" was not associated with lower risk of COVID-19 (HR, 1.05; 95% C.I., 0.88-1.25; P-value, 0.58). Results were very similar when those 65 years and older were only considered "up-to-date" after 2 doses of the bivalent vaccine. CONCLUSIONS: Since the XBB lineages became dominant, adults "up-to-date" on COVID-19 vaccination by the CDC definition do not have a lower risk of COVID-19 than those "not up-to-date", bringing into question the value of this risk classification definition.

Essential team science skills for biostatisticians on collaborative research teams.

Introduction: Despite the critical role that quantitative scientists play in biomedical research, graduate programs in quantitative fields often focus on technical and methodological skills, not on collaborative and leadership skills. In this study, we evaluate the importance of team science skills among collaborative biostatisticians for the purpose of identifying training opportunities to build a skilled workforce of quantitative team scientists. Methods: Our workgroup described 16 essential skills for collaborative biostatisticians. Collaborative biostatisticians were surveyed to assess the relative importance of these skills in their current work. The importance of each skill is summarized overall and compared across career stages, highest degrees earned, and job sectors. Results: Survey respondents were 343 collaborative biostatisticians spanning career stages (early: 24.2%, mid: 33.8%, late: 42.0%) and job sectors (academia: 69.4%, industry: 22.2%, government: 4.4%, self-employed: 4.1%). All 16 skills were rated as at least somewhat important by > 89.0% of respondents. Significant heterogeneity in importance by career stage and by highest degree earned was identified for several skills. Two skills ("regulatory requirements" and "databases, data sources, and data collection tools") were more likely to be rated as absolutely essential by those working in industry (36.5%, 65.8%, respectively) than by those in academia (19.6%, 51.3%, respectively). Three additional skills were identified as important by survey respondents, for a total of 19 collaborative skills. Conclusions: We identified 19 team science skills that are important to the work of collaborative biostatisticians, laying the groundwork for enhancing graduate programs and establishing effective on-the-job training initiatives to meet workforce needs.

Testosterone and luteinizing hormone predict semen parameter improvement in infertile men treated with anastrozole.

OBJECTIVE: To identify patient factors associated with a clinically significant improvement in semen parameters among infertile men treated with the aromatase inhibitor anastrozole. DESIGN: Multi-institutional retrospective cohort study. SETTING: Two Tertiary Academic Medical Centers. PATIENTS: A total of 90 infertile men treated at 2 tertiary academic medical centers who met inclusion criteria and obtained pretreatment and posttreatment semen analyses. INTERVENTION: Prescription of anastrozole (median 3 mg/wk). MAIN OUTCOME MEASURES: Upgrade in the World Health Organization sperm concentration category (WHO-SCC). Univariate logistic regression, multivariable logistic regression, and partitioning analyses were performed to identify statistically significant patient factors capable of predicting treatment response. RESULTS: With anastrozole treatment, 46% (n = 41/90) of men responded favorably with a WHO-SCC upgrade, and 12% (n = 11/90) experienced a downgrade. Responders exhibited lower pretreatment levels of luteinizing hormone (LH, 4.7 vs. 8.3 IU/L) and follicle-stimulating hormone (4.7 vs. 6.7 IU/mL), higher pretreatment levels of testosterone (T, 356 vs. 265 ng/dL), and similar baseline level of estradiol (E2, 73% vs. 70% with detectible level). Baseline semen parameters differed, with anastrozole responders demonstrating higher baseline semen concentration (3.6 vs. 0.3 M/mL) and higher total motile sperm counts (3.7 vs. 0.1 M). Anastrozole therapy converted 29% (n = 26/90) of the cohort to normozoospermia and enabled intrauterine insemination access in 31% (n = 20/64) of previously ineligible patients. Interestingly, neither body mass index nor the baseline E2 level or E2-T ratio was associated with WHO-SCC upgrade. Multivariable logistic regression revealed the T-LH ratio (odds ratio: 1.02, 95% confidence interval: 1.00-1.03) and baseline nonazoospermia (odds ratio: 9.4, 95% confidence interval: 1.1-78.9) to be statistically significant predictors of WHO-SCC upgrade (area under receiver operating characteristic curve: 0.77). The final user-friendly partitioning model consisting of the T-LH ratio ≥100 and baseline non-azoospermia was 98% sensitive and 33% specific for WHO-SCC upgrades (area under the curve: 0.77). CONCLUSION: Anastrozole therapy decreases serum E2 levels, increases serum gonadotropins, and clinically improves semen parameters in half of men with idiopathic infertility. Nonazoospermic infertile men with T-LH ratios ≥100 are likely to benefit from anastrozole treatment irrespective of baseline E2 level or E2-T ratio. Men with azoospermia rarely respond to anastrozole and should be counseled on alternative treatments.

Clinical and Immunological Outcomes of HIV-Exposed Uninfected and HIV-Unexposed Uninfected Children in the First 24 Months of Life in Western Kenya.

Background: Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life. Methods: Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months. All mothers with HIV received combination antiretroviral therapy. HEU children received standard-of-care cotrimoxazole prophylaxis through 18 months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. Results: HEU and HUU children had similar growth curves. HEU children had lower rates of malaria and respiratory illness. Trajectories of plasma cytokines and vaccine-specific antibodies were similar in HEU and HUU children. There were subtle differences in antimalarial antibody dynamics, in which HEU children had overall lower antibody levels against five of the 14 malaria antigens tested. Conclusions: HEU children born to optimally treated mothers living with HIV had similar growth characteristics and immune profiles compared to HUU children. HEU children had reduced risk for malaria and respiratory illness, which may be secondary to cotrimoxazole prophylaxis.

Effectiveness of the Coronavirus Disease 2019 Bivalent Vaccine.

Background: The purpose of this study was to evaluate whether a bivalent coronavirus disease 2019 (COVID-19) vaccine protects against COVID-19. Methods: The study included employees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available. Cumulative incidence of COVID-19 over the following 26 weeks was examined. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with change in dominant circulating lineages over time accounted for by time-dependent coefficients. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred and the number of prior vaccine doses. Results: Among 51 017 employees, COVID-19 occurred in 4424 (8.7%) during the study. In multivariable analysis, the bivalent-vaccinated state was associated with lower risk of COVID-19 during the BA.4/5-dominant (hazard ratio, 0.71 [95% confidence interval, .63-79]) and the BQ-dominant (0.80 [.69-.94]) phases, but decreased risk was not found during the XBB-dominant phase (0.96 [.82-.1.12]). The estimated vaccine effectiveness was 29% (95% confidence interval, 21%-37%), 20% (6%-31%), and 4% (-12% to 18%), during the BA.4/5-, BQ-, and XBB-dominant phases, respectively. The risk of COVID-19 also increased with time since the most recent prior COVID-19 episode and with the number of vaccine doses previously received. Conclusions: The bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 while the BA.4/5 lineages were the dominant circulating strains, afforded less protection when the BQ lineages were dominant, and effectiveness was not demonstrated when the XBB lineages were dominant.

Risk of Complications in Combined Plastic Surgery Procedures Using the Tracking Operations and Outcomes for Plastic Surgeons Database.

BACKGROUND: Combining multiple surgical procedures into a single operative session is widespread in the field of plastic surgery; however, the implications of this practice are not fully understood. OBJECTIVES: This study compared 30-day complication rates associated with combined plastic surgery procedures with the rates for index procedures. METHODS: This retrospective cohort analysis utilized the Tracking Operations and Outcomes for Plastic Surgeons database from 2016 to 2020 to identify the 3 most frequent combinations of augmentation mammaplasty, reduction mammaplasty, trunk liposuction, mastopexy, and abdominoplasty. RESULTS: The 30-day overall complication rate was 5.0% (1400 of 26,771 patients), with a higher complication rate for combined procedures compared with index (7.6% vs 4.2%, adjusted odd ratio [aOR], 1.91 [95% CI, 1.61-2.27], P < .001). There were no significant differences in complication rates for abdominoplasty or mastopexy combinations compared with index. Complication rates for reduction mammaplasty combinations compared with index were not statistically different after controlling for demographics (aOR, 1.02 [95% CI, 0.61-1.64], P = .93). Higher rates of minor and major complications were observed for combinations of trunk liposuction (aOR, 4.84 [95% CI, 3.31-7.21), P < .001) and augmentation mammaplasty (aOR, 1.60 [95% CI 1.13-2.22], P = .007) compared with index. CONCLUSIONS: Combinations with trunk liposuction or augmentation mammaplasty present with increased risk of complications compared with index, controlling for demographics. Abdominoplasty and mastopexy may be combined with other plastic surgery procedures without increased risk to patients. The complication risk of reduction mammaplasty combinations is mediated by other variables, suggesting the need for shared surgical decision-making when recommending these combinations to patients.

Abnormal thrombosis and neutrophil activation increase hospital-acquired sacral pressure injuries and morbidity in COVID-19 patients.

Hospitalized patients have an increased risk of developing hospital-acquired sacral pressure injury (HASPI). However, it is unknown whether SARS-CoV-2 infection affects HASPI development. To explore the role of SARS-CoV-2 infection in HASPI development, we conducted a single institution, multi-hospital, retrospective study of all patients hospitalized for ≥5 days from March 1, 2020 to December 31, 2020. Patient demographics, hospitalization information, ulcer characteristics, and 30-day-related morbidity were collected for all patients with HASPIs, and intact skin was collected from HASPI borders in a patient subset. We determined the incidence, disease course, and short-term morbidity of HASPIs in COVID-19(+) patients, and characterized the skin histopathology and tissue gene signatures associated with HASPIs in COVID-19 disease. COVID-19(+) patients had a 63% increased HASPI incidence rate, HASPIs of more severe ulcer stage (OR 2.0, p<0.001), and HASPIs more likely to require debridement (OR 3.1, p=0.04) compared to COVID-19(-) patients. Furthermore, COVID-19(+) patients with HASPIs had 2.2x increased odds of a more severe hospitalization course compared to COVID-19(+) patients without HASPIs. HASPI skin histology from COVID-19(+) patients predominantly showed thrombotic vasculopathy, with the number of thrombosed vessels being significantly greater than HASPIs from COVID-19(-) patients. Transcriptional signatures of a COVID-19(+) sample subset were enriched for innate immune responses, thrombosis, and neutrophil activation genes. Overall, our results suggest that immunologic dysregulation secondary to SARS-CoV-2 infection, including neutrophil dysfunction and abnormal thrombosis, may play a pathogenic role in development of HASPIs in patients with severe COVID-19.

Characterization and Prediction of Short-term Outcomes in Memory After Temporal Lobe Resection in Children With Epilepsy.

BACKGROUND AND OBJECTIVES: The aim of this study was to characterize short-term outcomes in episodic memory, as assessed by the Children's Memory Scale (CMS), after temporal lobe resection in children with epilepsy using empirical methods for assessing cognitive change (i.e., reliable change indices [RCI] and standardized regression-based change scores [SRB]) and develop and internally validate clinically applicable models to predict postoperative memory decline. METHODS: This retrospective cohort study included children aged 6-16 years who underwent resective epilepsy surgery that included the temporal lobe (temporal only: "temporal" and multilobar: "temporal plus") and who completed preoperative and postoperative neuropsychological assessments including the CMS. Change scores on the CMS delayed memory subtests (Faces, Stories, and Word Pairs) were classified as decline, no change, or improvement using epilepsy-specific RCI and SRB. Logistic regression models for predicting postoperative memory decline were developed and internally validated with bootstrapping. RESULTS: Of the 126 children included, most of them demonstrated either no significant change (54%-69%) or improvement (8%-14%) in memory performance using RCI on individual measures at a median of 7 months after surgery. A subset of children (23%-33%) showed postoperative declines. Change distributions obtained using RCI and SRB were not statistically significantly different from each other. Preoperative memory test score, surgery side, surgery extent, and preoperative full-scale IQ were predictors of memory decline. Prediction models for memory decline included subsets of these variables with bias-corrected concordance statistics ranging from 0.70 to 0.75. The models were well calibrated although slightly overestimated the probability of verbal memory decline in high-risk patients. DISCUSSION: This study used empiric methodology to characterize memory outcome in children after temporal lobe resection. Provided online calculator and nomograms may be used by clinicians to estimate the risk of postoperative memory decline for individual patients before surgery.

Leveraging published randomized controlled trials to inform clinical trial design: a simulation-based study of laminectomy versus laminectomy and fusion.

OBJECTIVE: The US-based Spinal Laminectomy versus Instrumented Pedicle Screw (SLIP) trial reported improvement in disability following laminectomy with fusion versus laminectomy alone for patients with lumbar spondylolisthesis. Despite using similar methods, a concurrent Swedish trial investigating the same question did not reach the same conclusion. The authors performed a simulation-based analysis to elucidate potential causes of these divergent results. METHODS: The mean and standard deviation of the preoperative and 2-year postoperative Oswestry Disability Index (ODI) scores for each study group (laminectomy with fusion and laminectomy alone) were collected from the spondylolisthesis stratum of the Swedish trial and used to create a MATLAB simulator using linear transformations to predict postoperative ODI distributions. Applying this simulator to both varied and published preoperative ODI distributions from the SLIP trial, the authors simulated the results of the US-based trial using treatment effects from the Swedish study and compared simulated US results to those published in the SLIP trial. RESULTS: Simulated US results showed that as preoperative disability increased, the difference in postoperative ODI scores grew between treatment groups and increasingly favored laminectomy alone (p < 0.0001). In 100 simulations of a similarly sized US trial, the average mean change in ODI scores postoperatively was significantly higher than was published for laminectomy alone in the SLIP trial (-21.3 vs -17.9), whereas it was significantly lower than published for fusion (-16.9 vs -26.3). CONCLUSIONS: The expected benefit of surgical treatments for spondylolisthesis varied according to preoperative disability. Adapting Swedish-estimated treatment effects to the US context mildly overapproximated the improvement in postoperative disability scores for laminectomy, but more severely underapproximated the improvement reported for laminectomy and fusion in the SLIP trial. The observed heterogeneity between these studies is influenced more by patient response to fusion than response to laminectomy. This analysis paves the way for future studies on the impact of preoperative treatment group heterogeneity, differences in surgical methods, and empirical design on reported clinical benefits. Although bayesian reanalysis of published randomized controlled trial data is susceptible to biases that typically limit post hoc analyses, the authors' method offers a simple and cost-effective approach to improve the understanding of published clinical trial results and their implications for future studies.

Crohn's Disease Is Associated with Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Chronic inflammation in IBD is postulated to drive NAFLD progression from steatosis to fibrosis. AIMS: To study the histopathological spectrum of NAFLD in Crohn disease (CD) and Ulcerative colitis (UC). METHODS: Patients with biopsy proven NAFLD at a quaternary center from 2008 to 2018 were included in this retrospective analysis. Inflammatory bowel disease (IBD) diagnosed either clinically and/or endoscopically at the time of liver biopsy. Multivariable regression and propensity score (PS) weighted analysis were conducted. Statistical analysis were performed using SAS statistical software. RESULTS: Among 1009 patients with NAFLD a diagnosis of IBD was identified in 50 cases (34 CD and 16 UC). On multivariable analysis; CD was independently associated with significantly higher odds of advanced fibrosis (AF) on liver biopsy (adjusted OR = 4.09, 95% CI = 1.40-11.94) compared to NAFLD patients without IBD. Similar results were obtained with both the overlap PS weighted model (OR = 3.17, 95% CI = 1.55-6.49) and the PS matched model (OR = 3.49, 95% CI = 1.50-8.13). CONCLUSION: In a large cohort of patients with histologically well characterized NAFLD, AF was more common in CD patients than NAFLD patients without IBD. These findings must be confirmed in a larger cohort, but suggest CD patients with NAFLD could be at greater risk for liver fibrosis.