Mortality and failure-to-rescue after esophagectomy in the procedure-targeted National Surgical Quality Improvement Program registry.

BACKGROUND: The association between procedural volume and esophagectomy outcomes has been established, but the relationship between higher levels of care and esophagectomy outcomes has not been explored. This study aims to investigate whether hospital participation in the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) esophagectomy-targeted registry is associated with superior outcomes. METHODS: The 2016-2020 ACS NSQIP standard and esophagectomy-targeted registries were queried. Esophagectomy outcomes were analyzed overall and stratified by esophagectomy type (Ivor Lewis vs. transhiatal vs. 3-field McKeown). RESULTS: A total of 2181 and 5449 esophagectomy cases were identified in the standard and targeted databases (68% Ivor Lewis esophagectomy). The median age was 65 years and 80% were male. Preoperative characteristics were largely comparable. On univariate analysis, targeted hospitals were associated with lower mortality (2% vs. 4%, p < 0.01) and failure-to-rescue rates (11% vs. 17%, p < 0.01), higher likelihood of an optimal outcome (62% vs. 58%, p = 0.01), and shorter hospital stay (median 9 vs. 10 days, p < 0.01). On multivariable analysis, Ivor Lewis esophagectomy at targeted centers was associated with reduced odds of mortality [odds ratio (OR) 0.57 and 95% confidence intervals 0.35-0.90] and failure-to-rescue [OR 0.54 (0.33-0.90)] with no difference in serious morbidity or optimal outcome. There was no statistically significant difference in odds of mortality or failure to rescue in targeted versus standard centers when performing transhiatal or McKeown esophagectomy. CONCLUSIONS: Esophagectomy performed at hospitals participating in the targeted ACS NSQIP is associated with roughly half the risk of mortality compared to the standard registry. The factors underlying this relationship may be valuable in quality improvement.

Using implementation science to decrease variation and high opioid administration in a surgical ICU.

BACKGROUND: High doses and prolonged duration of opioids are associated with tolerance, dependence, and increased mortality. Unfortunately, despite recent efforts to curb outpatient opioid prescribing because of the ongoing epidemic, utilization remains high in the intensive care setting, with intubated patients commonly receiving infusions with a potency much higher than doses required to achieve pain control. We attempted to use implementation science techniques to monitor and reduce excessive opioid prescribing in ventilated patients in our Surgical ICU. METHODS: We conducted a prospective study investigating opioid administration in a closed SICU at an academic medical center over 18 months. Commonly accepted conversions were used to aggregate daily patient opioid use. Patients with a history of chronic opioid use and those being treated with an ICP monitor/drain, neuromuscular blocker, or ECMO were excluded. If the patient spent a portion of a day on a ventilator, that day's total was included in the "vent group." MMEs per patient were collected for each patient and assigned to the on-call intensivist. Intensivists were blinded to the data for the first seven months. They were then provided with academic detailing followed by audit & feedback over the subsequent 11 months, demonstrating how opioid utilization during their time in the SICU compared to the unit average and a blinded list of the other attendings. Student's T-tests were performed to compare opioid utilization before and after initiation of academic detailing and audit & feedback. RESULTS: Opioid utilization in patients on a ventilator decreased by 20.1% during the feedback period, including less variation among all intensivists and a 30.9% reduction by the highest prescribers. CONCLUSION: Implementation science approaches can effectively reduce variation in opioid prescribing, especially for high outliers in a SICU. These interventions may reduce the risks associated with prolonged use of high-dose opioids. LEVEL OF EVIDENCE: Prospective pre-post-intervention, Level II.

Complications and failure-to-rescue after pancreatectomy and hospital participation in the targeted American College of Surgeons National Surgical Quality Improvement Program registry.

BACKGROUND: More than 700 hospitals participate in the American College of Surgeons National Surgical Quality Improvement Program, but most pancreatectomies are performed in 165 centers participating in the pancreas procedure-targeted registry. We hypothesized that these hospitals ("targeted hospitals") might provide more specialized care than those not participating ("standard hospitals"). METHODS: The 2014 to 2019 pancreas-targeted and standard American College of Surgeons National Surgical Quality Improvement Program registry were reviewed regarding patient demographics, comorbidities, and perioperative outcomes using standard univariate and multivariable logistic regression analyses. Primary outcomes included 30-day mortality and serious morbidity. RESULTS: The registry included 30,357 pancreatoduodenectomies (80% in targeted hospitals) and 14,800 distal pancreatectomies (76% in targeted hospitals). Preoperative and intraoperative characteristics of patients treated at targeted versus standard hospitals were comparable. On multivariable analysis, pancreatoduodenectomies performed at targeted hospitals were associated with a 39% decrease in 30-day mortality (odds ratio, 0.61; 95% confidence interval, 0.50-0.75), 17% decrease in serious morbidity (odds ratio, 0.83; 95% confidence interval, 0.77-0.89), and 41% decrease in failure-to-rescue (odds ratio, 0.59; 95% confidence interval, 0.47-0.74). These differences did not apply to distal pancreatectomies. Participation in the targeted registry was associated with higher rates of optimal surgery for both pancreatoduodenectomy (odds ratio, 1.33; 95% confidence interval, 1.25-1.41) and distal pancreatectomy (odds ratio, 1.17; 95% confidence interval, 1.06-1.30). CONCLUSION: Mortality and failure-to-rescue rates after pancreatoduodenectomy in targeted hospitals were nearly half of rates in standard American College of Surgeons National Surgical Quality Improvement Program hospitals. Further research should delineate factors underlying this effect and highlight opportunities for improvement.

Maternal effects, paternal effects, and their interactions in the freshwater snail Physa acuta.

Individuals exposed to predation risk can produce offspring with altered phenotypes. Most work on predation-induced parental effects has focused on maternal effects or on generalized parental effects where both parents are exposed to risk. We conducted an experiment to measure and compare maternal and paternal effects on offspring phenotypes and test for interactions in those effects. We exposed 82 snails from 22 lines to control or predator cues and created line dyads with the four possible mating pairings of control and predator cue exposed individuals. We measured the resulting body masses, shell masses, shell shapes, and anti-predator behaviors of the offspring. We found some evidence that offspring were larger and heavier when the mother was exposed to predation cues, but that this effect was negated when the father was also exposed. The mass of offspring shells relative to their total mass was unaffected by parental treatments. Shell shape was marginally affected by maternal treatment, but not paternal treatment. Behavioral responses to cues were not affected by maternal or paternal treatments. Our results suggest potential conflict between male and female parental effects and highlight the importance of examining the interactions of maternal and paternal effects.

COVID-19 Mortality in Vaccinated vs. Unvaccinated Liver & Kidney Transplant Recipients: A Single-Center United States Propensity Score Matching Study on Historical Data.

Introduction: Existing studies report variable impact of vaccination on Coronavirus Disease (COVID-19) morbidity and mortality in solid organ transplant (SOT) recipients. This study aimed to perform a propensity score matching (PSM) analysis on COVID-19 survival of vaccinated and unvaccinated SOT patients who contracted the disease at a single US academic transplant center. Methods: All consecutive COVID-19 positive cases on adult liver, kidney or combined liver-kidney recipients were identified and demographics, comorbidities, immunosuppression, COVID-19 treatment and hospitalization status, COVID-19 vaccination status, and early mortality recorded. PSM study was performed on age and sex for completed vaccination status at time of infection, followed by multivariable analysis and survival curve plotting. Results: 144 SOT patients were diagnosed with COVID-19, with 98 unvaccinated. PSM reduced study number to 101. Matched data multivariable analysis for 60-day mortality identified age and post-kidney transplant status to significantly increase 60-day mortality odds (OR 1.22, p < 0.001 and OR 40.93, p < 0.001, respectively). Kaplan−Meier analysis showed inferior post-infection survival in the unvaccinated group [(30 days; vaccinated vs. unvaccinated 97.8% vs. 89.1%, respectively; p = 0.089) (60 days; 97.8% vs. 83.6%, respectively; p = 0.019)]. Conclusions: Matched data survival analysis demonstrated inferior survival in the unvaccinated group, supporting COVID-19 vaccination in SOT recipients.

Impact of Prolonged Cold Ischemia Time on One Year Kidney Transplant Outcomes.

BACKGROUND: Prolonged cold ischemia times (CIT) of kidney allografts remains a significant reason for graft refusal in the new allocation system. We sought to investigate the effect of prolonged CIT on kidney transplant outcomes at a center without an international airport. METHODS: Retrospective study of kidney transplant patients treated at an academic medical center from January 1, 2018 to May 1, 2020. The 117 patients were divided into 2 categories. Fifty-four patients (46%) had CIT of 30-35.99 hours, and 63 (54%) had CIT of 36± hours. Kidney function was evaluated using creatinine and at 12 months, which was the primary endpoint. RESULTS: All of the transplanted allografts were carefully selected and had ≤ 20% glomerulosclerosis and an average kidney donor profile index of 54%. Among the 117 patients analyzed in this study, there was no significant difference in creatinine at 12 months between groups with CIT above 36 hours and < 35.99 hours (2.07 vs 1.78; P value .2339). There were a total of 18 rejection events (15%) and no cases of primary non-function in either group. Patients that were able to be maintained on calcineurin inhibitors had improved graft function at 12 months (1.69 vs 2.96; P value .0267). CONCLUSIONS: Our study indicated that prolonged CITs over 36 hours were not associated with poorer patient outcomes at 1 year when using creatinine as an endpoint. They also had similar rates of rejection, consistent with previously published rates for kidney transplantation.

Opioid Prescribing Behaviors Among Surgical Intensive Care Unit Attending Physicians.

BACKGROUND: More than 5 million Americans misuse opioids. Six percent of patients who receive opioids for acute pain progress to chronic use; this increases with higher doses and longer prescriptions. Prescribing variation exists within trauma centers and after emergency surgery but has not been demonstrated among intensivists. METHODS: Milligram morphine equivalents (MME) per patient-ICU-day provided by eleven surgical intensivists were analyzed. The patients were separated into 2 groups based on their percentage of time intubated in the surgical ICU. Both study groups were compared using demographics and comorbidity scores. The attendings were divided into high- and low-prescribing groups based on their MME/pt-ICU-day for intubated patients, and bivariate statistical analyses were performed. A similar analysis compared surgery vs anesthesia intensivists. RESULTS: The analysis included 257 patients in the "long-vent group" (LVG) and 668 patients in the "short-vent group" (SVG). The average MME/pt-ICU-day for the LVG was 222. Despite no significant differences in age, sex, or Elixhauser Comorbidity Index, there was a 45% difference between the high- and low-prescribing physicians in the LVG (253.7 vs 175.4 MME/pt-ICU-day; P = .008). This difference was not observed for patients in the SVG (74.3 vs 93.1 MME/pt-ICU-day; P = .141) nor based on intensivist specialty (LVG: 217.9 vs 209.5 MME/pt-ICU-day; P = .8) (SVG: 79.0 vs 93.3 MME/pt-ICU-day; P = .288).

Patient Outcomes in Disorders of Consciousness Following Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Individual Patient Data.

Background: There are few treatments with limited efficacy for patients with disorders of consciousness (DoC), such as minimally conscious and persistent vegetative state (MCS and PVS). Objective: In this meta-analysis of individual patient data (IPD), we examine studies utilizing transcranial magnetic stimulation (TMS) as a treatment in DoC to determine patient and protocol-specific factors associated with improved outcomes. Methods: We conducted a systematic review of PubMed, Ovid Medline, and Clinicaltrials.gov through April 2020 using the following terms: "minimally conscious state," or "persistent vegetative state," or "unresponsive wakefulness syndrome," or "disorders of consciousness" and "transcranial magnetic stimulation." Studies utilizing TMS as an intervention and reporting individual pre- and post-TMS Coma Recovery Scale-Revised (CRS-R) scores and subscores were included. Studies utilizing diagnostic TMS were excluded. We performed a meta-analysis at two time points to generate a pooled estimate for absolute change in CRS-R Index, and performed a second meta-analysis to determine the treatment effect of TMS using data from sham-controlled crossover studies. A linear regression model was also created using significant predictors of absolute CRS-R index change. Results: The search yielded 118 papers, of which 10 papers with 90 patients were included. Patients demonstrated a mean pooled absolute change in CRS-R Index of 2.74 (95% CI, 0.62-4.85) after one session of TMS and 5.88 (95% CI, 3.68-8.07) at last post-TMS CRS-R assessment. The standardized mean difference between real rTMS and sham was 2.82 (95% CI, -1.50 to 7.14), favoring rTMS. The linear regression model showed that patients had significantly greater CRS-R index changes if they were in MCS, had an etiology of stroke or intracranial hemorrhage, received 10 or more sessions of TMS, or if TMS was initiated within 3 months from injury. Conclusions: TMS may improve outcomes in MCS and PVS. Further evaluation with randomized, clinical trials is necessary to determine its efficacy in this patient population.

Distinct trajectories of antidepressant response to intravenous ketamine.

BACKGROUND: The N-methyl-D-aspartate receptor antagonist ketamine is potentially effective in treatment resistant depression. However, its antidepressant efficacy is highly variable, and there is little information about predictors of response. METHODS: We employed growth mixture modeling (GMM) analysis to examine specific response trajectories to intravenous (IV) ketamine (three infusions; mean dose 0.63 mg/kg, SD 0.28, range 0.30 - 2.98 mg/kg over 40 min) in 328 depressed adult outpatients referred to a community clinic. The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) assessed depression severity at baseline and before each infusion, up to three infusions for four total observations. RESULTS: GMM revealed three QIDS-SR response trajectories. There were two groups of severely depressed patients, with contrasting responses to ketamine. One group (n=135, baseline QIDS-SR=18.8) had a robust antidepressant response (final QIDS-SR=7.3); the other group (n=97, QIDS-SR=19.8) was less responsive (final QIDS-SR=15.6). A third group (n=96) was less severely depressed at baseline (QIDS-SR=11.7), with intermediate antidepressant response (final QIDS-SR=6.6). Comparisons of demographic and clinical characteristics between groups with severe baseline depression revealed higher childhood physical abuse in the group with robust ketamine response (p=0.01). LIMITATIONS: This was a retrospective analysis on a naturalistic sample. Patients were unblinded and more heterogenous than those included in most controlled clinical trial samples. Information pertaining to traumatic events occurring after childhood and pre-existing or concurrent medical conditions that may have affected outcomes was not available. CONCLUSIONS: Overall, ketamine's effect in patients with severe baseline depression and history of childhood maltreatment may be consistent with ketamine-induced blockade of behavioral sensitization.

Resting-state functional magnetic resonance imaging with independent component analysis for presurgical seizure onset zone localization: A systematic review and meta-analysis.

OBJECTIVE: One of the greatest challenges of achieving successful surgical outcomes in patients with epilepsy is the ability to properly localize the seizure onset zone (SOZ). Many techniques exist for localizing the SOZ, including intracranial electroencephalography, magnetoencephalography, and stereoelectroencephalography. Recently, resting-state functional magnetic resonance imaging (rs-fMRI) in conjunction with independent component analysis (ICA) has been utilized for presurgical planning of SOZ resection, with varying results. In this meta-analysis, we analyze the current role of rs-fMRI in identifying the SOZ for presurgical planning for patients with drug-resistant epilepsy. Specifically, we seek to demonstrate its current effectiveness compared to other methods of SOZ localization. METHODS: A literature review was conducted using the PubMed, MEDLINE, and Embase databases up to May of 2020. A total of 253 articles were screened, and seven studies were chosen for analysis. Each study was analyzed for SOZ localization by ground truth, SOZ localization by rs-fMRI with ICA, principal component analysis, or intrinsic connectivity contrast, and outcomes of surgery. A meta-analysis was performed to analyze how ground truth compares to rs-fMRI in SOZ localization. RESULTS: The odds ratio comparing ground truth to rs-fMRI was 2.63 (95% confidence interval = 0.66-10.56). Average concordance of rs-fMRI SOZ localization compared with ground truth localization across studies was 71.3%. SIGNIFICANCE: In the hunt for less invasive presurgical planning for epilepsy surgery, rs-fMRI with ICA provides a promising avenue for future standard practice. Our preliminary results show no significant difference in surgical outcomes between traditional standards of SOZ localization and rs-fMRI with ICA. We believe that rs-fMRI could be a step forward in this search. Further investigation comparing rs-fMRI to traditional methods of SOZ localization should be conducted, with the hope of moving toward relying solely on noninvasive screening methods.

The Impact of Childhood Maltreatment on Intravenous Ketamine Outcomes for Adult Patients with Treatment-Resistant Depression.

Childhood maltreatment is associated with a poor treatment response to conventional antidepressants and increased risk for treatment-resistant depression (TRD). The N-methyl-D-aspartate receptor (NDMAR) antagonist ketamine has been shown to rapidly improve symptoms of depression in patients with TRD. It is unknown if childhood maltreatment could influence ketamine's treatment response. We examined the relationship between childhood maltreatment using the Childhood Trauma Questionnaire (CTQ) and treatment response using the Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR) in TRD patients receiving intravenous ketamine at a community outpatient clinic. We evaluated treatment response after a single infusion (n = 115) and a course of repeated infusions (n = 63). Repeated measures general linear models and Bayes factor (BF) showed significant decreases in QIDS-SR after the first and second infusions, which plateaued after the third infusion. Clinically significant childhood sexual abuse, physical abuse, and cumulative clinically significant maltreatment on multiple domains (maltreatment load) were associated with better treatment response to a single and repeated infusions. After repeated infusions, higher load was also associated with a higher remission rate. In contrast to conventional antidepressants, ketamine could be more effective in TRD patients with more childhood trauma burden, perhaps due to ketamine's proposed ability to block trauma-associated behavioral sensitization.