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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.

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.

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. Level of Evidence: 4

Background The aim was to evaluate the necessity of coronavirus disease 2019 (COVID-19) vaccination in persons with prior COVID-19. Methods Employees of the Cleveland Clinic working in Ohio on 16 December 2020, the day COVID-19 vaccination was started, were included. Anyone who tested positive for COVID-19 at least once before the study start date was considered previously infected. One was considered vaccinated 14 days after receiving the second dose of COVID-19 mRNA vaccine. Cumulative incidences of COVID-19, symptomatic COVID-19, and hospitalizations for COVID-19 were examined over the next year. Results Among 52 238 employees, 4718 (9%) were previously infected and 36 922 (71%) were vaccinated by the study’s end. Cumulative incidence of COVID-19 was substantially higher throughout for those previously uninfected who remained unvaccinated than for all other groups, lower for the vaccinated than unvaccinated, and lower for those previously infected than those not. Incidence of COVID-19 increased dramatically in all groups after the Omicron variant emerged. In multivariable Cox proportional hazards regression, both prior COVID-19 and vaccination were independently associated with significantly lower risk of COVID-19. Among previously infected subjects, a lower risk of COVID-19 overall was not demonstrated, but vaccination was associated with a significantly lower risk of symptomatic COVID-19 in both pre-Omicron (HR, .60; 95% CI, .40–.90) and Omicron (HR, .36; 95% CI, .23–.57) phases. Conclusions Both previous infection and vaccination provide substantial protection against COVID-19. Vaccination of previously infected individuals does not provide additional protection against COVID-19 for several months, but after that provides significant protection at least against symptomatic COVID-19.

Additional details regarding the methods for cells, reagents, animal studies, immunofluorescence, transcytosis, and ELISA assays.

Figure S3 shows co-localization of different fractions of bevacizumab or human IgG (hIgG) with Rab4 or LAMP1 in CD133+ GBM cells in vitro, and of rat anti-mouse VEGF-A IgG in an established tumor in the immune competent mouse model of GBM in vivo, show similar trafficking patterns.

Figure S1 shows that bevacizumab gains access to the perivascular tumor space and is internalized by tumor cells when administered to an orthotopic xenograft model of GBM and confirmation of cancer stem-like cell markers in vivo.

Purpose: Bevacizumab, a humanized monoclonal antibody to VEGF, is used routinely in the treatment of patients with recurrent glioblastoma (GBM). However, very little is known regarding the effects of bevacizumab on the cells in the perivascular space in tumors.Experimental Design: Established orthotopic xenograft and syngeneic models of GBM were used to determine entry of monoclonal anti-VEGF-A into, and uptake by cells in, the perivascular space. Based on the results, we examined CD133+ cells derived from GBM tumors in vitro. Bevacizumab internalization, trafficking, and effects on cell survival were analyzed using multilabel confocal microscopy, immunoblotting, and cytotoxicity assays in the presence/absence of inhibitors.Results: In the GBM mouse models, administered anti-mouse-VEGF-A entered the perivascular tumor niche and was internalized by Sox2+/CD44+ tumor cells. In the perivascular tumor cells, bevacizumab was detected in the recycling compartment or the lysosomes, and increased autophagy was found. Bevacizumab was internalized rapidly by CD133+/Sox2+-GBM cells in vitro through macropinocytosis with a fraction being trafficked to a recycling compartment, independent of FcRn, and a fraction to lysosomes. Bevacizumab treatment of CD133+ GBM cells depleted VEGF-A and induced autophagy thereby improving cell survival. An inhibitor of lysosomal acidification decreased bevacizumab-induced autophagy and increased cell death. Inhibition of macropinocytosis increased cell death, suggesting macropinocytosis of bevacizumab promotes CD133+ cell survival.Conclusions: We demonstrate that bevacizumab is internalized by Sox2+/CD44+-GBM tumor cells residing in the perivascular tumor niche. Macropinocytosis of bevacizumab and trafficking to the lysosomes promotes CD133+ cell survival, as does the autophagy induced by bevacizumab depletion of VEGF-A. Clin Cancer Res; 23(22); 7059–71. ©2017 AACR.

Figure S7 shows bevacizumab is transcytosed across normal brain ECs and TECs.

Figure S5 shows co-localization of a fraction of the bevacizumab-VEGF complex with Rab4 and a fraction with LAMP1 in CD133+ GBM tumor cells.

Figure S6 shows bevacizumab treatment causes a reduction in phospho-VEGFR2 and downregulation of VEGF-A induces autophagy in CD133+ GBM cells.

Figure S4 shows FcRn staining largely colocalizes with the endothelial cell marker vWf in xenograft GBM tumors.

Figure S2 shows the internalization of bevacizumab by CD133-negative non-stem GBM tumor cells was not inhibited by EIPA.

PDF file - 695K, Significantly increased mRNA Expression of TNF-R1 and TNF-R2 in GBM as compared to normal brain

PDF file - 658K, Characterization of the integrin receptors mediating the attachment of primary brain ECs to collagen, fibronectin and laminin.

PDF file - 481K, Dose-dependent TNF�\�{induced apoptosis of primary brain ECs.

PDF file - 1MB, Absence of cFLIP expression in human GBM cells and human GBM stem cells plated on laminin

PDF file - 72K, Increased Expression of TNFalpha, TNF-R1 and TNF-R2 in the ECs in Recurrent GBM

PDF file - 972K, Percent of ECs expressing integrin alpha 6 beta 1 versus integrin alpha 6 beta 4.

PDF file - 71K, Increased Expression of TNFalpha, TNF-R1 and TNF-R2 in the ECs in Untreated GBM

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

Blood transfusion can have detrimental effects on the pulmonary system, leading to lung injury and respiratory decompensation with subsequent increased morbidity and mortality in surgical and critically ill patients. How much of this effect is carried from a lung donor to transplant recipient is not fully understood, raising questions regarding transplant suitability of lungs from transfused donors.United Network for Organ Sharing data were reviewed. Lung transplants from adult donors and known donor transfusion status were included; multiorgan transplants and retransplants were excluded. Recipient mortality was evaluated based on donor and recipient characteristics using a Kaplan-Meier survival estimate, Cox proportional hazards, and logistic regression models. We further assessed whether recipient mortality risk modified the donor transfusion effect.From March 1996 to June 2017, 20,294 transplants were identified. Outcome analysis based on transfusion status showed nonsignificant difference in 1-year mortality (P = .214). Ninety-day recipient mortality was significantly higher with transfusion of10 units (U) vs 1-10 U or no transfusion (8.5%, 6.1%, and 6.0%, respectively, P = .005). Multivariable analysis showed increased 90-day mortality with transfusion of10 U compared to no transfusion (odds ratio 1.62, P.001), whereas 1-10 U showed no difference (odds ratio 1.07, P = .390). When stratified by recipient transplant risk, transfusion of10 U was associated with increased mortality even with the lowest-risk recipients, while transfusion of 1-10 U showed no mortality increase even in the highest-risk recipients.Donor transfusion of10 U of blood was associated with increased 90-day recipient mortality even in low-risk transplants. This risk should be considered when evaluating donor lungs.

BackgroundThe purpose of this study was to evaluate whether a bivalent COVID-19 vaccine protects against COVID-19.MethodsEmployees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available, were included. 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.ResultsAmong 51017 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 (HR, .71; 95% C.I., .63-.79) and the BQ dominant (HR, .80; 95% C.I., .69-.94) phases, but decreased risk was not found during the XBB dominant phase (HR, .96; 95% C.I., .82-.1.12). Estimated vaccine effectiveness (VE) was 29% (95% C.I., 21%-37%), 20% (95% C.I., 6%-31%), and 4% (95% C.I., -12%-18%), during the BA.4/5, BQ, and XBB dominant phases, respectively. Risk of COVID-19 also increased with time since most recent prior COVID-19 episode and with the number of vaccine doses previously received.ConclusionsThe 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.SummaryAmong 51017 working-aged Cleveland Clinic employees, the bivalent COVID-19 vaccine was 29% effective in preventing infection while the BA.4/5 lineages were dominant, and 20% effective while the BQ lineages were. Effectiveness was not demonstrated when the XBB lineages were dominant.

Purpose The intravitreal injection (IVI) of pharmacologic agents is the most commonly performed ocular procedure and is associated with a host of complications. Most IVI-related complications data are derived from randomized controlled clinical trials, which report a high adverse event rate. The nature of these protocol-driven trials limit their applicability to the diverse circumstances seen in routine clinical practice. The goal of this study was to determine the prevalence of patient-reported IVI-related complications, their risk factors, and the manner in which patients sought treatment at a tertiary eye care center. Design Retrospective, institutional review board–approved study. Participants Forty-four thousand seven hundred thirty-four injections in 5318 unique patients at the Cleveland Clinic Cole Eye Institute from 2012 through 2016. Methods Intravitreal injection. Main Outcome Measures Complication occurrence within 15 days of injection. Results From 2012 through 2016, a total of 44734 injections were performed in 5318 unique patients. Overall, complication rates were low, representing 1.9% of all injections, with 1031 unique complications in 685 patients (12.9%). The most common minor complications, or those not requiring intervention, were irritation (n = 312) and subconjunctival hemorrhage (n = 284). The most common serious complications, or those requiring intervention, were corneal abrasion (n = 46) and iritis (n = 31). Most complications (66%) were managed adequately by a telephone or Epic (Epic Systems Corp., Verona, WI) electronic message encounter only. Importantly, no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication. However, a patient’s gender, age, number of previous injections, and provider strongly influenced the risk of patient-reported complications. Conclusions Overall, complication rates seen in routine clinical practice were low compared with clinical trial reporting. Providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. When performing an IVI, factors such as a patient’s gender, age, number of previous injections, and provider must be taken into account to ensure the best possible outcomes.

Objectives Determine whether D-dimer concentration in the absence of imaging can differentiate patients that require anti-coagulation from patients who do not require anti-coagulation. Methods Data was obtained retrospectively from 366 hemodynamically stable adult ED patients with suspected pulmonary embolism (PE). Patients were categorized by largest occluded artery and aggregated into: ‘Require anti-coagulation’ (main, lobar, and segmental PE), ‘Does not require anti-coagulation’ (sub-segmental and No PE), ‘High risk of deterioration’ (main and lobar PE), and ‘Not high risk of deterioration’ (segmental, sub-segmental, and No PE) groups. Wilcoxon rank-sum test was used for 2 sample comparisons of median D-dimer concentrations. Receiver operating characteristic (ROC) curve analysis was utilized to determine a D-dimer cut-off that could differentiate ‘Require anti-coagulation’ from ‘Does not require anti-coagulation’ and ‘High risk of deterioration’ from ‘Low risk of deterioration’ groups. Results The ‘Require anti-coagulation’ group had a maximum area under the curve (AUC) of 0.92 at an age-adjusted D-dimer cut-off of 1540 with a specificity of 86% (95% CI, 81–91%), and sensitivity of 84% (79–90%). The ‘High risk of deterioration’ group had a maximum AUC of 0.93 at an age-adjusted D-dimer cut-off of 2500 with a specificity of 90% (85–93%) and sensitivity of 83% (77–90%). Conclusions An age-adjusted D-dimer cut-off of 1540 ng/mL differentiates suspected PE patients requiring anti-coagulation from those not requiring anti-coagulation. A cut-off of 2500 differentiates those with high risk of clinical deterioration from those not at high risk of deterioration. When correlated with clinical outcomes, these cut-offs can provide an objective method for clinical decision making when imaging is unavailable., Highlights • ED providers are faced with risks and benefits when empirically administering anti-coagulation for suspected PE patients. • We show that D-dimer concentration can be used as a clinical decision making tool to minimize these risks. • A D-dimer cut-off of 1540 ng/mL can be used to minimize unnecessary anti-coagulation exposure in patients who do not need it. • A D-dimer cut-off of 2500 ng/mL can be used to minimize risk of withholding treatment for patients at risk of clinical deterioration. • Together these cut-offs provide an objective measure that can be combined with clinical gestalt to weight the risks and benefits of empiric anti-coagulation.

Background In medical education, self-administered questionnaires are used to gather information for needs assessments, innovation projects, program evaluations, and research studies. Despite the importance of survey methodology, response rates have declined for years, especially for physicians. Objective This study explored residents' experiences with survey participation and perceptions of survey design and implementation. Methods In 2019, residents at a large Midwestern academic medical center were recruited via email to participate in mixed specialty focus groups (FGs). Narrative comments were recorded, transcribed, and then analyzed via conventional content analysis, utilizing cognitive sociology as a conceptual framework. Themes and subthemes were generated iteratively. Results Postgraduate year 1–4 residents (n = 33) from internal medicine, surgery, and neurology participated in 7 FGs (3–7 participants/group) from April–May 2019. Eight themes were generated during content analysis: Negative emotions, professionalism, accuracy, impact, survey design/implementation, biases, survey fatigue, and anonymity. Residents questioned the accuracy of survey data, given the tendency for self-selection to drive survey participation. Residents wanted survey participation to be meaningful and reported non-participation for a variety of reasons, including doubts over impact. Satisficing and breakoffs were commonly reported. Conclusions Though residency program cultures differ across institutions, the findings from this study, including potential barriers to survey participation, should be relevant to anyone in graduate medical education using survey methodology for programmatic data collection, accreditation, and research purposes.

Steroids are often utilized to manage patients with non-small cell lung cancer brain metastases (NSCLCBM). Steroids and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with decreased overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI). We retrospectively investigated patients treated with ICI after the diagnosis of NSCLCBM at a single tertiary care institution examing the impact of steroids and NLR. Overall survival (OS) and intracranial progression-free survival (PFS) were analyzed. 171 patients treated with ICI for NSCLCBM were included. Thirty-six received steroids within 30 days of the start of ICI, and 53 patients had an NLR ≥ 5 before the start of ICI. Upfront steroids was associated with decreased OS on multivariable analysis (median OS 10.5 vs. 17.9 months, p = .03) and intracranial PFS (5.0 vs. 8.7 months, p = .045). NLR ≥ 5 was indicative of worse OS (10.5 vs. 18.4 months, p = .04) but not intracranial PFS (7.2 vs. 7.7 months, p = .61). When NLR and upfront steroids are modeled together, there is a strong interaction (p = .0008) indicating that the impact of steroids depended on the patient’s NLR. In a subgroup analysis, only in patients with NLR p = .032). The impact of steroids on the efficacy of ICI in patients with NSCLCBM is dependent on the patient's NLR underscoring its importance in these patients. Patients with a low NLR, steroid use decreases the efficacy of ICI. These results can inform clinicians about the impact of steroids in patients treated with ICI.

OBJECTIVE Patient demographics, comorbidities, and baseline quality of life (QOL) are major contributors to postoperative outcomes. The frequency and cost of lumbar spine surgery has been increasing, with controversy revolving around optimal management strategies and outcome predictors. The goal of this study was to generate predictive nomograms and a clinical calculator for postoperative clinical and QOL outcomes following lumbar spine surgery for degenerative disease. METHODS Patients undergoing lumbar spine surgery for degenerative disease at a single tertiary care institution between June 2009 and December 2012 were retrospectively reviewed. Nomograms and an online calculator were modeled based on patient demographics, comorbidities, presenting symptoms and duration of symptoms, indication for surgery, type and levels of surgery, and baseline preoperative QOL scores. Outcomes included postoperative emergency department (ED) visit or readmission within 30 days, reoperation within 90 days, and 1-year changes in the EuroQOL-5D (EQ-5D) score. Bootstrapping was used for internal validation. RESULTS A total of 2996 lumbar surgeries were identified. Thirty-day ED visits were seen in 7%, 30-day readmission in 12%, 90-day reoperation in 3%, and improvement in EQ-5D at 1 year that exceeded the minimum clinically important difference in 56%. Concordance indices for the models predicting ED visits, readmission, reoperation, and dichotomous 1-year improvement in EQ-5D were 0.63, 0.66, 0.73, and 0.84, respectively. Important predictors of clinical outcomes included age, body mass index, Charlson Comorbidity Index, indication for surgery, preoperative duration of symptoms, and the type (and number of levels) of surgery. A web-based calculator was created, which can be accessed here: https://riskcalc.org/PatientsEligibleForLumbarSpineSurgery/. CONCLUSIONS The prediction tools derived from this study constitute important adjuncts to clinical decision-making that can offer patients undergoing lumbar spine surgery realistic and personalized expectations of postoperative outcome. They may also aid physicians in surgical planning, referrals, and counseling to ultimately lead to improved patient experience and outcomes.

Therapeutic targeting of angiogenesis in glioblastoma has yielded mixed outcomes. Investigation of tumor-associated angiogenesis has focused on the factors that stimulate the sprouting, migration, and hyperproliferation of the endothelial cells. However, little is known regarding the processes underlying the formation of the tumor-associated vessels. To address this issue, we investigated vessel formation in CD31+ cells isolated from human glioblastoma tumors. The results indicate that overexpression of integrin α3β1 plays a central role in the promotion of tube formation in the tumor-associated endothelial cells in glioblastoma. Blocking α3β1 function reduced sprout and tube formation in the tumor-associated endothelial cells and vessel density in organotypic cultures of glioblastoma. The data further suggest a mechanistic model in which integrin α3β1-promoted calcium influx stimulates macropinocytosis and directed maturation of the macropinosomes in a manner that promotes lysosomal exocytosis during nascent lumen formation. Altogether, our data indicate that integrin α3β1 may be a therapeutic target on the glioblastoma vasculature.

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, pOne Sentence SummarySARS-CoV-2-induced immune dysregulation contributes to pressure-induced sacral skin ulceration in hospitalized patients with severe COVID-19.

Objective To develop a model to predict the probability of mood decline in adults following temporal lobe resection for the treatment of pharmacoresistant epilepsy. Methods Variable selection was performed on 492 patients from the Cleveland Clinic using best subsets regression. After completing variable selection, a subset of variables was requested from four epilepsy surgery centers across North America (n = 100). All data were combined to develop a final model to predict postoperative mood decline (N = 592). Internal validation with bootstrap resampling was performed. A clinically significant increase in depressive symptoms was defined as a 15% increase in Beck Depression Inventory-Second Edition score and a postoperative raw score > 11. Results Fourteen percent of patients in the Cleveland Clinic cohort and 22% of patients in the external cohort experienced clinically significant increases in depressive symptoms following surgery. The final prediction model included six predictor variables: psychiatric history, resection side, relationship status, verbal fluency score, age at preoperative testing, and presence/absence of malformation of cortical development on magnetic resonance imaging. The model had an optimism-adjusted c-statistic of .70 and good calibration, with slight probability overestimation in higher risk patients. Significance Clinicians can utilize our nomogram via a paper tool or online calculator to estimate the risk of postoperative mood decline for individual patients prior to temporal lobe epilepsy surgery.

Study design This was a retrospective consecutive cohort analysis. Objective This study aimed to examine the association between commonly prescribed medications and outcomes following posterior lumbar spine surgery. Summary of background data Postoperative complications and prolonged length of stay significantly increase costs following posterior lumbar spine surgery and worsen patient outcomes. To control costs and complications, providers should focus on modifiable risk factors, such as preoperative medications. Antihypertensive and anticholinergic drugs are among the most commonly prescribed medications but can carry significant risks in the perioperative period. Materials and methods This study was a retrospective cohort analysis of patients undergoing posterior lumbar spine surgery from January 2014 through December 2015 at a large tertiary care center. The variable selection followed by multivariable logistic and negative binomial regressions were performed. An α threshold of 0.0056 was used for significance after correction for multiple comparisons. A secondary analysis was performed to evaluate confounding or effect modifying variables. Results This study included 1577 patients. Postoperative urinary retention risk was increased in patients taking loop diuretics. Acute kidney injury risk was increased for patients on nondihydropyridine calcium-channel blockers. Surgical site infection risk was increased for patients on aldosterone receptor blockers. Urinary tract infection risk was increased for patients on anticholinergics for urinary incontinence. Length of stay was decreased for patients on angiotensin II antagonists and angiotensin-converting enzyme inhibitors. Conclusion A care path should be established in the perioperative period for patients who are deemed to be at higher risk due to medication status to either modify medications or improve postoperative monitoring. Level of evidence Level III.

BACKGROUND CONTEXT Anterior lumbar interbody fusion (ALIF) exposes the anterior aspect of the spine through a retroperitoneal approach. Access to the anterior spine requires mobilization of intra-abdominal viscera/vasculature, which can become complicated as scarring and/or adhesions develop from prior abdominal surgical interventions, increasing risk of intraoperative complications. The literature suggests that “significant prior abdominal surgery” is a relative contraindication of ALIF surgery; however, there is no consensus within the literature as to what defines “major/significant” abdominal surgeries. Additionally, the association between the number of prior abdominal surgeries and perioperative complications in ALIF surgery has not been explored within the literature. PURPOSE This study seeks to explore the association between perioperative complications of ALIF surgery and the type (major and/or minor) and number of prior abdominal surgeries. DESIGN A retrospective cohort study was performed to examine perioperative complications in ALIF patients with or without prior history of abdominal surgery. PATIENT SAMPLE All consecutive patients undergoing ALIF with or without a history of prior abdominal surgery from 2008 to 2018 at a single tertiary center were evaluated. Patients under the age of 18, patients with spinal malignancy, or patients who had ALIF above L3 were excluded. OUTCOME MEASURES Perioperative complications included intraoperative complications during ALIF surgery and postoperative complications within 90 days of ALIF surgery. Intraoperative complications include vascular injury, ureter injury, retroperitoneal hematoma, etc. Postoperative complications include urinary tract infection, revision of abdominal scar, ileus, deep vein thrombosis, pulmonary embolism, etc. Other outcome measures include readmission within 90 days, length of ALIF surgery, and length of hospital stay. METHODS Electronic medical records of 660 patients who underwent ALIF between 2008 and 2018 were retrospectively reviewed. Patient demographics, Charleston Comorbidity Index (CCI), level of fusion, past abdominal surgical history, use of access surgeon during exposure, intraoperative, and postoperative complications were collected. Predictors of intraoperative and postoperative complications were analyzed using simple and multivariable logistic regression. Statistical analysis was performed using JMP 14.0 (SAS, Cary, NC, USA) software. RESULTS After controlling for age, length of ALIF, gender, multilevel ALIF, and the use of an access surgeon, there was no significant association between the type of prior abdominal surgery (major and/or minor) and intraoperative complications on multivariable logistic regression analysis (Minor: odds ratio [OR]=1.68; 95% confidence interval [CI]: 0.58–4.86 & Major: OR=1.99; 95% CI: 0.80–4.91). On multivariable logistic regression, the odds of developing an intraoperative complication increases by 52% for each additional prior abdominal surgery after adjusting for age, length of ALIF, gender, multilevel ALIF, and the use of an access surgeon (OR=1.52, 95% CI: 1.10–2.11). Iliac vein laceration was the most common intraoperative complication (n=27, 4%). Neither the type (major and/or minor) nor the number of prior abdominal surgeries were significant predictors of postoperative complications (Minor: OR=1.29; 95% CI: .72–2.31, Major: OR=1.24; 95% CI: 0.77–2.00, & Number: OR=1.03; 95% CI: .84–1.26). CONCLUSION With each additional prior abdominal surgery, accumulation of scarring and adhesions can likely obscure anatomical landmarks and increase the risk of developing an intraoperative complication. Therefore, the number of prior abdominal surgeries should be taken into consideration during planning and operative exposure of the anterior spine via a retroperitoneal approach.

To compare pathologic and survival outcomes between primary muscle invasive (pMIBC) and secondary muscle invasive (sMIBC) bladder cancer patients who were treated with or without cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC).We reviewed cT2-T4/N0 MIBC patients at our institution between 2010-2019. pMIBC was defined as presenting withcT2 disease on initial or restaging TURBT with no prior history of bladder cancer. sMIBC was defined as prior history of NMIBC that was treated with at least one induction course of BCG that progressed to MIBC. Outcomes analyzed included pathologic downstaging rates defined aspT2/N0, pathologic complete response rates (pT0/N0), and survival outcomes (RFS, CSS, OS). Survival outcomes were analyzed using the Kaplan-Meier Method or Gray's test with log rank. Cox Proportional Hazards and semiparametric hazards models proposed by Fine and Gray were constructed to identify predictors of oncologic outcomes.333 patients were included in the analysis (sMIBC: 48 vs pMIBC: 285). There were no differences in pathologic downstaging (sMIBC: 54% vs pMIBC: 51%, P = .67) or pathologic complete response (sMIBC: 33% vs pMIBC: 28, P = .46). Survival analysis showed no differences when patients were treated with NAC+RC in oncologic outcomes. On regression analysis, onlypT2 and N+ disease were predictors of poorer CSS and OS. Separate analysis of sMIBC patients whom underwent RC only (N = 61), demonstrated inferior oncologic outcomes to other cohorts (P.01).There were no differences in pathologic response or survival between pMIBC and sMIBC patients when managed with NAC and RC.

BackgroundThe purpose of this study was to evaluate whether boosting healthcare personnel, already reasonably protected by prior infection or vaccination, with a vaccine developed for an earlier variant of COVID-19 protects against the Omicron variant.MethodsEmployees of Cleveland Clinic who were previously infected with or vaccinated against COVID-19, and were working in Ohio the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over two months during an Omicron variant surge. Protection provided by boosting (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate overt immunologic challenge (POIC) as a time-dependent covariate.ResultsAmong 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since POIC. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those with vaccine-induced immunity (HR, .43; 95% CI, .41-.46) as well as those with natural immunity (HR, .66; 95% CI, .58-.76). Among those with natural immunity, receiving 2 compared to 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21-1.97).ConclusionsAdministering a COVID-19 vaccine not designed for the Omicron variant, 6 months or more after prior infection or vaccination, protects against Omicron variant infection in both previously infected and previously vaccinated individuals. There is no evidence of an advantage to administering more than 1 dose of vaccine to previously infected persons.SummaryAmong 39 766 Cleveland Clinic employees already protected by prior infection or vaccination, vaccine boosting after 6 months was associated with significantly lower risk of COVID-19. After COVID-19 infection, there was no advantage to more than one dose of vaccine.

Background The purpose of this study was to determine whether boosting previously infected or vaccinated individuals with a vaccine developed for an earlier variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protects against the Omicron variant. Methods Employees of Cleveland Clinic, previously infected with or vaccinated against coronavirus disease 2019 (COVID-19) and working the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over 2 months during an Omicron variant surge. Protection provided by boosting was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate SARS-CoV-2 exposure. Results Among 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since proximate SARS-CoV-2 exposure, and boosting protected those >6 months since prior infection or vaccination. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those vaccinated but not previously infected (hazard ratio [HR], .43; 95% confidence interval [CI], .41–.46) as well as those previously infected (HR, .66; 95% CI, .58–.76). Among those previously infected, receipt of 2 compared with 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21–1.97). Conclusions Administering a COVID-19 vaccine not designed for the Omicron variant >6 months after prior infection or vaccination protects against Omicron variant infection. There is no advantage to administering more than 1 dose of vaccine to previously infected persons.

Background The purpose of this study was to evaluate the necessity of COVID-19 vaccination in persons previously infected with SARS-CoV-2. Methods Employees of the Cleveland Clinic Health System working in Ohio on Dec 16, 2020, the day COVID-19 vaccination was started, were included. Any subject who tested positive for SARS-CoV-2 at least 42 days earlier was considered previously infected. One was considered vaccinated 14 days after receipt of the second dose of a SARS-CoV-2 mRNA vaccine. The cumulative incidence of SARS-CoV-2 infection over the next five months, among previously infected subjects who received the vaccine, was compared with those of previously infected subjects who remained unvaccinated, previously uninfected subjects who received the vaccine, and previously uninfected subjects who remained unvaccinated. Results Among the 52238 included employees, 1359 (53%) of 2579 previously infected subjects remained unvaccinated, compared with 22777 (41%) of 49659 not previously infected. The cumulative incidence of SARS-CoV-2 infection remained almost zero among previously infected unvaccinated subjects, previously infected subjects who were vaccinated, and previously uninfected subjects who were vaccinated, compared with a steady increase in cumulative incidence among previously uninfected subjects who remained unvaccinated. Not one of the 1359 previously infected subjects who remained unvaccinated had a SARS-CoV-2 infection over the duration of the study. In a Cox proportional hazards regression model, after adjusting for the phase of the epidemic, vaccination was associated with a significantly lower risk of SARS-CoV-2 infection among those not previously infected (HR 0.031, 95% CI 0.015 to 0.061) but not among those previously infected (HR 0.313, 95% CI 0 to Infinity). Conclusions Individuals who have had SARS-CoV-2 infection are unlikely to benefit from COVID-19 vaccination, and vaccines can be safely prioritized to those who have not been infected before. Summary Cumulative incidence of COVID-19 was examined among 52238 employees in an American healthcare system. COVID-19 did not occur in anyone over the five months of the study among 2579 individuals previously infected with COVID-19, including 1359 who did not take the vaccine.

Beginning early in childhood, patients with sickle cell disease [SCD; a group of genetic haemoglobin disorders characterized by the sickle or HbS mutation (HBB E7V)] are at risk of life-threatening and debilitating health events. Despite the high morbidity and mortality of this disease, haematopoietic cell transplantation (HCT), a curative therapy for SCD, remains underutilized. A variety of factors, including the limited availability of suitable donors, play a role in this trend, but do not fully explain the low frequency with which this therapy is employed. The objective of this study was to identify paediatric haematologists' attitudes about HCT as a treatment option for SCD, and to describe the impact of these attitudes on their practices of discussing HCT with families of children affected by this disease. A nationwide survey of paediatric haematologists in the United States was conducted between February and May 2016. Two hundred and eighty-seven surveys were included in the final analysis (response rate 20%). On average, respondents reported informing 42% of families about HCT as a treatment option (N = 248, 95% confidence interval: 38-46). Clinician attitudes about the cost and safety of HCT were associated with practices of discussing this therapy with families. These findings suggest that clinician attitudes and referral practices may play a role in the underutilization of this therapy in the SCD population.

Introduction This study examines the association of the domains of knowledge for HIV and sexually transmitted infections (STIs) among emergency medicine providers (EP). Methods From February 2018 to March 2018, 75 EP (physicians, residents, and advanced practice providers) completed an anonymous, self-administered survey. The primary outcome of strength of correlation between HIV and STI sections of the survey was analyzed using Spearman’s rank-order coefficient. Results Respondents were physicians (54.6%), male (56%), Caucasian (83.7%), with eight years in practice (IQR: 2,16). Spearman’s correlation of HIV and STIs showed a weak positive correlation ( r = 0.35, p = 0.002). There was no association between HIV scores and provider type ( p = 0.67) or provider gender ( p = 0.89) as well as no association between STI scores and provider type ( p = 0.10) or provider gender ( p = 0.79). Conclusion The results of our study reveal that when presented with a patient at high risk for undiagnosed HIV or with undiagnosed symptomatic HIV infection, most providers either do not test or do not have HIV in the differential diagnosis. Similarly, knowledge of STIs is only weakly correlated with knowledge of HIV risk factors and symptomatic HIV infection. Further research and screening efforts may benefit by focusing on HIV education among emergency medicine providers.