Detection of naturally acquired, strain-transcending antibodies against rosetting Plasmodium falciparum strains in humans.

Strain-transcending antibodies against virulence-associated subsets of P. falciparum-infected erythrocyte surface antigens could protect children from severe malaria. However, the evidence supporting the existence of such antibodies is incomplete and inconsistent. One subset of surface antigens associated with severe malaria, rosette-mediating Plasmodium falciparum Erythrocyte Membrane Protein one (PfEMP1) variants, cause infected erythrocytes to bind to uninfected erythrocytes to form clusters of cells (rosettes) that contribute to microvascular obstruction and pathology. Here, we tested plasma from 80 individuals living in malaria-endemic regions for IgG recognition of the surface of four P. falciparum rosetting strains using flow cytometry. Broadly reactive plasma samples were then used in antibody elution experiments in which intact IgG was eluted from the surface of infected erythrocytes and transferred to heterologous rosetting strains to look for strain-transcending antibodies. We found that seroprevalence (percentage of positive plasma samples) against allopatric rosetting strains was high in adults (63%-93%) but lower in children (13%-48%). Strain-transcending antibodies were present in nine out of eleven eluted antibody experiments, with six of these recognizing multiple heterologous rosetting parasite strains. One eluate had rosette-disrupting activity against heterologous strains, suggesting PfEMP1 as the likely target of the strain-transcending antibodies. Naturally acquired strain-transcending antibodies to rosetting P. falciparum strains in humans have not been directly demonstrated previously. Their existence suggests that such antibodies could play a role in clinical protection and raises the possibility that conserved epitopes recognized by strain-transcending antibodies could be targeted therapeutically by monoclonal antibodies or vaccines.

Quality of Life in Patients With Definite Chronic Pancreatitis: A Nationwide Longitudinal Cohort Study.

INTRODUCTION: Chronic pancreatitis (CP) has a negative impact on quality of life (QoL). Because CP is a chronic condition, multiple assessments of QoL are required to obtain a thorough understanding of its impact on patients. Such studies are currently lacking. This study aims to gain insight into the course and predictors of QoL in patients with CP using prospective longitudinal data from a large cohort of patients. METHODS: Post hoc analysis of consecutive patients with definite CP registered in a prospective database between 2011 and 2019 in the Netherlands. Patient and disease characteristics, nutritional status, pain severity, medication usage, pancreatic function, and pancreatic interventions were assessed from medical records and through standard follow-up questionnaires. The physical and mental component summary scales of the Short-Form 36 were used to assess physical and mental QoL at baseline and during follow-up. The course of both physical and mental QoL and their associated factors were longitudinally assessed by using generalized linear mixed models. RESULTS: Overall, 1,165 patients with definite CP were included for this analysis. During 10-year follow-up, generalized linear mixed model analyses revealed improvements in both physical (41.6-45.2, P < 0.001) and mental (45.9-46.6, P = 0.047) QoL. Younger age, current alcohol consumption, employment, no need for dietetic consultation, no steatorrhea, lower Izbicki pain score, and pain coping mechanism were positively associated with physical QoL ( P < 0.05). For mental QoL, a positive correlation was found between employment, nonalcoholic CP, no need for dietetic consultation, no steatorrhea, lower Izbicki pain score, pain coping mechanism, and surgical treatment. No association was observed between disease duration and longitudinal QoL per patient. DISCUSSION: This nationwide study provides insight into the dynamics of physical and mental QoL in patients with CP over time. Important and potentially influenceable factors to improve QoL are nutritional status, exocrine pancreatic function, employment status, and patients' coping strategy.

Impact of Medicaid Expansion on Abdominal Surgery Morbidity, Mortality, and Hospital Readmission.

INTRODUCTION: Medicaid expansion's (ME) impact on postoperative outcomes after abdominal surgery remains poorly defined. We aimed to evaluate ME's effect on surgical morbidity, mortality, and readmissions in a state that expanded Medicaid (Virginia) compared to a state that did not (Tennessee) over the same time period. METHODS: Virginia Surgical Quality Collaborative (VSQC) American College of Surgeons National Surgical Quality Improvement Program data for Medicaid, uninsured, and private insurance patients undergoing abdominal procedures before Virginia's ME (3/22/18-12/31/18) were compared with post-ME (1/1/19-12/31/19), as were corresponding non-ME state Tennessee Surgical Quality Collaborative (TSQC) data for the same 2018 and 2019 time periods. Postexpansion odds ratios for 30-d morbidity, 30-d mortality, and 30-d unplanned readmission were estimated using propensity score-adjusted logistic regression models. RESULTS: In Virginia, 4753 abdominal procedures, 2097 pre-ME were compared to 2656 post-ME. In Tennessee, 5956 procedures, 2484 in 2018 were compared to 3472 in 2019. VSQC's proportion of Medicaid population increased following ME (8.9% versus 18.8%, P < 0.001) while uninsured patients decreased (20.4% versus 6.4%, P < 0.001). Post-ME VSQC had fewer 30-d readmissions (12.2% versus 6.0%, P = 0.013). Post-ME VSQC Medicaid patients had significantly lower probability of morbidity (-8.18, 95% confidence interval: -15.52 ∼ -0.84, P = 0.029) and readmission (-6.92, 95% confidence interval: -12.56 ∼ -1.27, P = 0.016) compared to pre-ME. There were no differences in probability of morbidity or readmission in the TSQC Medicaid population between study periods (both P > 0.05); there were no differences in mortality between study periods in VSQC and TSQC patient populations (both P > 0.05). CONCLUSIONS: ME was associated with decreased 30-d morbidity and unplanned readmissions in the VSQC. Data-driven policies accounting for ME benefits should be considered.

Long-term surveillance of branch-duct intraductal papillary mucinous neoplasms without worrisome or high-risk features.

INTRODUCTION: Long-term data evaluating clinical outcomes in patients with branch-duct Intraductal papillary mucinous neoplasms (BD-IPMN) without high-risk stigmata (HRS) or worrisome features (WF) remain limited. METHODS: This observational cohort study included all patients diagnosed with BD-IPMN without HRS or WF between 2003 and 2019 who were enrolled in a prospective surveillance program. Time-to-progression analysis was performed using a cumulative incidence function plot and survival analysis was conducted using Kaplan-Meier. RESULTS: The median follow-up time for the 267 patient cohort was 44.5 months (interquartile range [IQR]: 24.1-72.2). Radiographic cyst growth was observed in 123 (46.1%) patients; 65 (24.3%) patients progressed to WF/HRS. Twenty-six (9.7%) patients were selected for resection during surveillance: 21 (80.8%) WF, 4 (15.4%) HRS; 1 (3.9%) transformed to mixed-duct. Of all the patients who underwent resection, 5 (19.2%) had adenocarcinoma, and 1 (3.8%) had carcinoma-in-situ. The probability of any radiographic progression was 21.3% (5-year) and 51.3% (10-year). For the entire cohort, there was 1.1% mortality secondary to pancreatic adenocarcinoma and 8.2% all-cause mortality. The 5-year overall survival rate was 91.5%, and at 10 years, 81.5%. CONCLUSION: Approximately one in four patients with nonworrisome BD-IPMN have progression to WF/HRS stigmata during surveillance. However, the risk of malignant transformation remains low. Surveillance strategy remains prudent in this patient population.

Astrocyte-targeting RNA interference against mutated superoxide dismutase 1 induces motoneuron plasticity and protects fast-fatigable motor units in a mouse model of amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS) caused by SOD1 gene mutations, both cell-autonomous and noncell-autonomous mechanisms lead to the selective degeneration of motoneurons (MN). Here, we evaluate the therapeutic potential of gene therapy targeting mutated SOD1 in mature astrocytes using mice expressing the mutated SOD1G93A protein. An AAV-gfaABC1 D vector encoding an artificial microRNA is used to deliver RNA interference against mutated SOD1 selectively in astrocytes. The treatment leads to the progressive rescue of neuromuscular junction occupancy, to the recovery of the compound muscle action potential in the gastrocnemius muscle, and significantly improves neuromuscular function. In the spinal cord, gene therapy targeting astrocytes protects a small pool of the most vulnerable fast-fatigable MN until disease end stage. In the gastrocnemius muscle of the treated SOD1G93A mice, the fast-twitch type IIB muscle fibers are preserved from atrophy. Axon collateral sprouting is observed together with muscle fiber type grouping indicative of denervation/reinnervation events. The transcriptome profiling of spinal cord MN shows changes in the expression levels of factors regulating the dynamics of microtubules. Gene therapy delivering RNA interference against mutated SOD1 in astrocytes protects fast-fatigable motor units and thereby improves neuromuscular function in ALS mice.

N-terminal mutant huntingtin deposition correlates with CAG repeat length and symptom onset, but not neuronal loss in Huntington's disease.

Huntington's disease (HD) is caused by a CAG repeat expansion mutation in the gene encoding the huntingtin (Htt) protein, with mutant Htt protein subsequently forming aggregates within the brain. Mutant Htt is a current target for novel therapeutic strategies for HD, however, the lack of translation from preclinical research to disease-modifying treatments highlights the need to improve our understanding of the role of Htt protein in the human brain. This study aims to undertake an immunohistochemical screen of 12 candidate antibodies against various sequences along the Htt protein to characterize Htt distribution and expression in post-mortem human brain tissue microarrays (TMAs). Immunohistochemistry was performed on middle temporal gyrus TMAs comprising of up to 28 HD and 27 age-matched control cases, using 12 antibodies specific to various sequences along the Htt protein. From this study, six antibodies directed to the Htt N-terminus successfully immunolabeled human brain tissue. Htt aggregates and Htt protein expression levels for the six successful antibodies were subsequently quantified with a customized automated image analysis pipeline on the TMAs. A 2.5-12 fold increase in the number of Htt aggregates were detected in HD cases using antibodies MAB5374, MW1, and EPR5526, despite no change in overall Htt protein expression compared to control cases, suggesting a redistribution of Htt into aggregates in HD. MAB5374, MW1, and EPR5526 Htt aggregate numbers were positively correlated with CAG repeat length, and negatively correlated with the age of symptom onset in HD. However, the number of Htt aggregates did not correlate with the degree of striatal degeneration or the degree of cortical neuron loss. Together, these results suggest that longer CAG repeat lengths correlate with Htt aggregation in the HD human brain, and greater Htt cortical aggregate deposition is associated with an earlier age of symptom onset in HD. This study also reinforces that antibodies MAB5492, MW8, and 2B7 which have been utilized to characterize Htt in animal models of HD do not specifically immunolabel Htt aggregates in HD human brain tissue exclusively, thereby highlighting the need for validated means of Htt detection to support drug development for HD.

Early Patient Discharge in Selected Patients is Not Associated With Higher Readmission After Major Abdominal Operations.

OBJECTIVE: Our objective was to examine the associations between early discharge and readmission after major abdominal operations. BACKGROUND: Advances in patient care resulted in earlier patient discharge after complex abdominal operations. Whether early discharge is associated with patient readmissions remains controversial. METHODS: Patients who had colorectal, liver, and pancreas operations abstracted in 2011-2017 American College of Surgeons National Surgical Quality Improvement Program Participant Use Data Files were included. Patient readmission was stratified by 6 operative groups. Patients who were discharged before median discharge date within each operative group were categorized as an early discharge. Analyses tested associations between early discharge and likelihood of 30-day postoperative unplanned readmission. RESULTS: A total of 364,609 patients with major abdominal operations were included. Individual patient groups and corresponding median day of discharge were: laparoscopic colectomy (n = 152,575; median = 4), open colectomy (n =137,462; median = 7), laparoscopic proctectomy (n = 12,238; median = 5), open proctectomy (n = 24,925; median = 6), major hepatectomy (n = 9,805; median = 6), pancreatoduodenectomy (n = 27,604; median = 8). Early discharge was not associated with an increase in proportion of readmissions in any operative group. Early discharge was associated with a decrease in average proportion of patient readmissions compared to patients discharged on median date in each of the operative groups: laparoscopic colectomy 6% versus 8%, open colectomy 11% versus 14%, laparoscopic proctectomy 13% versus 16%, open proctectomy 13% vs 17%, major hepatectomy 8% versus 12%, pancreatoduodenectomy 16% versus 20% (all P ≤ 0.02). Serious morbidity composite was significantly lower in patients who were discharged early than those who were not in each operative group (all P < 0.001). CONCLUSIONS: Early discharge in selected patients after major abdominal operations is associated with lower, and not higher, rate of 30-day unplanned readmission.

Defining and Studying Errors in Surgical Care: A Systematic Review.

OBJECTIVE: Our objective was to determine the extent surgical disciplines categorize, define, and study errors, then use this information to provide recommendations for both current practice and future study. SUMMARY OF BACKGROUND DATA: The report "To Err is Human" brought the ubiquity of medical errors to public attention. Variability in subsequent literature suggests the true prevalence of error remains unknown. METHODS: In January 2020, PubMed, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched. Only studies with Oxford Level of Evidence Level 3 or higher were included. RESULTS: Of 3064 studies, 92 met inclusion criteria: 6 randomized controlled trials, 4 systematic reviews, 24 cohort, 10 before-after, 35 outcome/audit, 5 cross sectional and 8 case-control studies. Over 15,933,430 patients and 162,113 errors were represented. There were 6 broad error categories, 13 different definitions of error, and 14 study methods. CONCLUSIONS: Reported prevalence of error varied widely due to a lack of standardized categorization, definitions, and study methods. Future research should focus on immediately recognizing errors to minimize harm.

Errors in Surgery: A Case Control Study.

OBJECTIVE: While errors can harm patients they remain poorly studied. This study characterized errors in the care of surgical patients and examined the association of errors with morbidity and mortality. BACKGROUND: Errors have been reported to cause <10% or >60% of adverse events. Such discordant results underscore the need for further exploration of the relationship between error and adverse events. METHODS: Patients with operations performed at a single institution and abstracted into the American College of Surgeons National Surgical Quality Improvement Program from January 1, 2018, to December 31, 2018 were examined. This matched case control study comprised cases who experienced a postoperative morbidity or mortality. Controls included patients without morbidity or mortality, matched 2:1 using age (±10 years), sex, and Current Procedural Terminology (CPT) group. Two faculty surgeons independently reviewed records for each case and control patient to identify diagnostic, technical, judgment, medication, system, or omission errors. A conditional multivariable logistic regression model examined the association between error and morbidity. RESULTS: Of 1899 patients, 170 were defined as cases who experienced a morbidity or mortality. The majority of cases (n=93; 55%) had at least 1 error; of the 329 matched control patients, 112 had at least 1 error (34%). Technical errors occurred most often among both cases (40%) and controls (23%). Logistic regression demonstrated a strong independent relationship between error and morbidity (odds ratio=2.67, 95% confidence interval: 1.64-4.35, P <0.001). CONCLUSION: Errors in surgical care were associated with postoperative morbidity. Reducing errors requires measurement of errors.

Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study.

INTRODUCTION: Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. METHODS: An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. RESULTS: Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. CONCLUSION: This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.

Evaluating the Impact of Preoperative Geriatric-Specific Variables and Modified Frailty Index on Postoperative Outcomes After Elective Pancreatic Surgery.

BACKGROUND: Pursuing pancreatic resection in elderly patients is often complex and limited by concern for functional status and postoperative risk. This study examines the associations between two different preoperative functional status metrics with postoperative outcomes in the geriatric population. METHODS: Patients who participated in the ACS NSQIP Geriatric Surgery Research File pilot program (2014-2018) undergoing elective pancreatic operations were included. Two clinically meaningful functional status scores were calculated: the presence of one or more geriatric-specific variable (GSV) and a 5-factor modified frailty index (mFI-5). Multivariable logistic regression adjusting for ACS NSQIP-estimated risk was performed to evaluate associations between preoperative GSV, mFI-5 and 30-day outcome measures. RESULTS: A total of 1266 patients were included: 808 (64%) age 65-74, 302 (24%) age 75-80, and 156 (12%) age ≥ 81; 843 (67%) patients underwent pancreatoduodenectomy. Operations were performed for pancreatic adenocarcinoma in 712 (56%) patients. Older patients had greater likelihood of postoperative morbidity (35% vs 31% vs 47%, by age group, p = 0.004) and discharge to a facility (12% vs 23% vs 48%, by age group, p < 0.001). Adjusting for ACS NSQIP predicted risk, patients with a preoperative GSV were more likely to require reoperation and discharge to a facility (OR 1.81 [95% CI 1.03-3.16] and 3.95 [95% CI 2.91-5.38], respectively). The mFI-5 was not associated with postoperative outcomes (all p ≥ 0.18). CONCLUSION: The presence of a preoperative GSV is associated with reoperation and discharge to a skilled facility following elective pancreatic resection. Geriatric-specific variables should be considered in joint preoperative decision making to optimize care.

Clinical indications referrals - what is the risk of premalignant and malignant female genital tract disease in women referred to a dedicated nurse-led colposcopy service? A retrospective cohort study.

Post-coital bleeding (PCB) is a poor predictive factor for cancer and should not be managed as urgent referral. Urgent referral to colposcopy is justified however, in the presence of a visible suspicion of cervical cancer. This retrospective cohort study of women attending a clinical indications referral service aims to identify the risk of pre-malignant and malignant disease in women with clinical indication referrals to colposcopy. Thirty-seven of 3521 women (1%) were diagnosed with pre-malignant cervical or endometrial disease; 14 women (0.4%) were diagnosed with cancer (11 cervix, three endometrial). To detect one cancer in women referred with an abnormal cervix, one would need to see 70 women; to detect one cancer in women referred with PCB one would need to see 790 women. Improved education in primary care and obstetrics and gynaecology training is key to improving clinical indications referral services, which is otherwise an effective and efficient service.Impact StatementWhat is already known on this subject? Post-coital bleeding is a poor predictive factor for cancer and should not be considered an urgent referral.What do the results of this study add? The presence of a visible suspicion of cervical cancer however does warrant urgent referral as approximately one in 70 women will have a malignancy detected.What are the implications of these findings for clinical practice and/or further research? Improved education in primary care and obstetrics and gynaecology training is the key to improving clinical indications referral services.

Efficacy of opioid spinal analgesia for postoperative pain management after pancreatoduodenectomy.

BACKGROUND: Efficacy of single-shot opioid spinal analgesia after pancreatoduodenectomy remains understudied and lacks comparison to standard continuous thoracic epidural analgesia (TEA). METHODS: Pancreatoduodenectomy patients who underwent TEA or opioid spinal for postoperative pain management from 2015 to 2020 were included in this observational cohort study. Primary outcome was patient-reported mean daily pain scores. Secondary outcomes included postoperative morphine milligram equivalents (MMEs) and length of stay (LOS). Multivariable linear regression models were constructed to compare risk-adjusted outcomes. RESULTS: 180 patients were included: 56 TEA and 124 opioid spinal. Compared to epidural patients, opioid spinal patients were more likely to be older (67.0 vs. 64.6, p=0.045), have greater BMI (26.5 vs. 24.4, p=0.02), and less likely to be smokers (19.4% vs. 41.1%, p=0.002). Opioid spinal, compared to TEA, was associated with lower intraoperative MMEs (0.25 vs. 22.7, p<0.001) and postoperative daily MMEs (7.9 vs. 10.3, p=0.03) on univariate analysis. However, after multivariable adjustment, there was no difference in average pain scores across the postoperative period (spinal vs. epidural: 4.18 vs. 4.14, p=0.93), daily MMEs (p=0.50), or LOS (p=0.23). DISCUSSION: There was no significant difference in postoperative pain scores, opioid use, or LOS between patients managed with TEA or opioid spinal after pancreatoduodenectomy.

Determining the Association Between Unplanned Reoperation and Readmission in Selected General Surgery Operations.

BACKGROUND: Unplanned reoperations and unplanned readmissions can increase morbidity and mortality. Few studies however, have explored the association of reoperation and readmission among general surgery patients. Our aim was to examine this relationship in selected abdominal operations. METHODS: Data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data Files from 2014 to 2018 were utilized. Six groups of operations, defined by ACS NSQIP procedure codes for ventral hernia repair, colectomy, appendectomy, proctectomy, small bowel resection, and gastrectomy, were assessed. Patients discharged ≤ 14 days after operation were included in the study. This time period was selected to reduce ACS NSQIP 30 day post-surgery follow-up bias. Unplanned reoperations were defined as those occurring during the index hospitalization. The primary outcome was unplanned readmission that occurred ≤ 14 days from the date of discharge. Logistic regression models were used to examine variables associated with unplanned readmission for each procedure group. RESULTS: A total of 787,118 patients were included: ventral hernia repair 35.2%, colectomy 30.6%, appendectomy 26.5%, proctectomy 3.7%, small bowel resection 3.2%, and gastrectomy 0.8%. Unplanned reoperation was independently associated with unplanned readmission for ventral hernia repair (OR 2.84, 95% CI 2.28-3.54, P < 0.001), colectomy (OR 1.58, CI 1.42- 1.76, P < 0.001), appendectomy (OR 2.91, CI 2.21-3.84, P < 0.001), and proctectomy (OR 1.41, CI 1.10-1.81, P = 0.006). Other clinically relevant covariates associated with readmission were partially dependent functional status before colectomy (OR 1.34, CI 1.23-1.46, P < 0.001), ventral hernia repair (OR 1.79, CI 1.54-2.09, P < 0.001), and small bowel resection (OR 1.44, CI 1.18-1.77, P < 0.001; and ASA 4/5 classification for colectomy (OR 2.71, CI 2.36-3.11, P < 0.001), proctectomy (OR 2.10, CI 1.48-2.97, P < 0.001), ventral hernia repair (OR 8.19, CI 6.78-9.88, P < 0.001), appendectomy (OR 2.80, CI 2.35-3.34, P < 0.001), and small bowel resection (OR 3.42, CI 2.20-5.32, P < 0.001). ASA 2, ASA 3 classification, age, and sex were also associated with unplanned readmission for most procedures. CONCLUSIONS: Unplanned reoperations are associated with an increase in unplanned readmission after selected abdominal operations included in this study. This factor should be considered in discharge and follow-up planning to help reduce unplanned readmissions.

Preoperative opioid use is associated with increased risk of postoperative complications within a colorectal-enhanced recovery protocol.

BACKGROUND: As the opioid epidemic escalates, preoperative opioid use has become increasingly common. Recent studies associated preoperative opioid use with postoperative morbidity. However, limited study of its impact on patients within enhanced recovery protocols (ERP) exists. We assessed the impact of preoperative opioid use on postoperative complications among colorectal surgery patients within an ERP, hypothesizing that opioid-exposed patients would be at increased risk of complications. METHODS: Elective colorectal cases from August 2013 to June 2017 were reviewed in a retrospective cohort study comparing preoperative opioid-exposed patients to opioid-naïve patients. Postoperative complications were defined as a composite of complications captured by the American College of Surgeons National Surgical Quality Improvement Program. Logistic regression identified risk factors for postoperative complications. RESULTS: 707 patients were identified, including 232 (32.8%) opioid-exposed patients. Opioid-exposed patients were younger (57.9 vs 61.9 years; p < 0.01) and more likely to smoke (27.6 vs 17.1%; p < 0.01). Laparoscopic procedures were less common among opioid-exposed patients (44.8 vs 58.1%; p < 0.01). Median morphine equivalents received were higher in opioid-exposed patients (65.0 vs 20.1 mg; p < 0.01), but compliance to ERP elements was otherwise equivalent. Postoperative complications were higher among opioid-exposed patients (28.5 vs 15.0%; p < 0.01), as was median length of stay (4.0 vs 3.0 days; p < 0.01). Logistic regression identified multiple patient- and procedure-related factors independently associated with postoperative complications, including preoperative opioid use (p = 0.001). CONCLUSION: Preoperative opioid use is associated with increased risk of postoperative complications in elective colorectal surgery patients within an ERP. These results highlight the negative impact of opioid use, suggesting an opportunity to further reduce the risk of surgical complications through ERP expansion to include preoperative mitigation strategies for opioid-exposed patients.

Socioeconomic "Distressed Communities Index" Improves Surgical Risk-adjustment.

OBJECTIVE: We hypothesize the Distressed Communities Index (DCI), a composite socioeconomic ranking by ZIP code, will predict risk-adjusted outcomes after surgery. SUMMARY OF BACKGROUND DATA: Socioeconomic status affects surgical outcomes; however, the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) database does not account for these factors. METHODS: All ACS NSQIP patients (17,228) undergoing surgery (2005 to 2015) at a large academic institution were paired with the DCI, which accounts for unemployment, education level, poverty rate, median income, business growth, and housing vacancies. Developed by the Economic Innovation Group, DCI scores range from 0 (no distress) to 100 (severe distress). Multivariable regressions were used to evaluate ACS NSQIP predicted risk-adjusted effect of DCI on outcomes and inflation-adjusted hospital cost. RESULTS: A total of 4522 (26.2%) patients came from severely distressed communities (top quartile). These patients had higher rates of medical comorbidities, transfer from outside hospital, emergency status, and higher ACS NSQIP predicted risk scores (all P < 0.05). In addition, these patients had greater resource utilization, increased postoperative complications, and higher short- and long-term mortality (all P < 0.05). Risk-adjustment with multivariate regression demonstrated that DCI independently predicts postoperative complications (odds ratio 1.1, P = 0.01) even after accounting for ACS NSQIP predicted risk score. Furthermore, DCI independently predicted inflation-adjusted cost (+$978/quartile, P < 0.0001) after risk adjustment. CONCLUSIONS: The DCI, an established metric for socioeconomic distress, improves ACS NSQIP risk-adjustment to predict outcomes and hospital cost. These findings highlight the impact of socioeconomic status on surgical outcomes and should be integrated into ACS NSQIP risk models.

Incidence rate, predictors and outcomes of interruption of HIV care: nationwide results from the Belgian HIV cohort.

OBJECTIVES: We aimed to study the incidence rate, predictors and outcomes of HIV care interruption (HCI) in Belgium. METHODS: We analysed data for adult patients with at least two HIV care records in the Belgian HIV cohort between 1 January 2007 and 31 December 2016. An HCI episode was defined as 1 year without an HIV care record. The HCI incidence rate was analysed using Poisson regression, return to HIV care using a cumulative incidence function with death as a competing risk, and viral load (VL) status upon return to HIV care using logistic regression. RESULTS: We included 16 066 patients accounting for 78 625 person-years of follow-up. The incidence rate of HCI was 5.3/100 person-years [95% confidence interval (CI) 5.1-5.4/100 person-years]. The incidence of return to HIV care after HCI was estimated at 77.5% (95% CI 75.7-79.2%). Of those who returned to care, 43.7% had a VL ≤ 200 HIV-1 RNA copies/mL, suggesting care abroad or suboptimal care (without an HIV-related care record) in Belgium during the HCI, and 56.3% returned without controlled VL and were therefore considered as having experienced a real gap in HIV care; they represented 2.3/100 person-years of follow-up. Factors individually associated with HCI were no antiretroviral therapy (ART) uptake, lower age, injecting drug use, non-Belgian nationality, male gender, not being a man who has sex with men, a shorter time since HIV diagnosis, no high blood pressure and CD4 count < 350 cells/µL. CONCLUSIONS: This study highlights the need to investigate return to care and viral status at return, to better understand HCI. Identified predictors can help health care workers to target patients at higher risk of HCI for awareness and support.

Enhancing Medical Students' Interprofessional Teamwork Through Simulated Room of Errors Experience.

BACKGROUND: Fostering medical students' appreciation for team members particularly those from other disciplines with varying levels of experience promotes a promising beginning to a health care career. METHODS: During surgical clerkship orientation, third-year medical students completed 30-item TeamSTEPPS Teamwork Attitudes Questionnaire preintervention and postintervention, spent 7 min identifying errors in a simulated operating room, followed by recorded physician-led 30-min discussions. RESULTS: Postintervention (67) compared with preintervention (141) mean TeamSTEPPS Teamwork Attitudes Questionnaire domain scores were statistically significantly higher for team structure (4.59, 4.70; P = 0.03) and higher but not significant for leadership (4.74, 4.75; P = 0.86), situation monitoring (4.62, 4.68; P = 0.32), communication (4.40, 4.50; P = 0.14), and decreased for mutual support (4.43, 4.36; P = 0.43). Medical students identified 2%-93% of 33 staged errors and 291 additional errors, which were placed into 14 categories. Soiled gloves in the operative field and urinary bag on the floor were the most frequently identified staged errors. Experienced nurses compared with medical students identified significantly more errors (mean, 17.7 versus 11.7, respectively; P < 0.001). Recognizing errors when lacking familiarity with the operative environment and appreciating teammates' perspectives were themes that emerged from discussions. CONCLUSIONS: This well-received teamwork exercise enabled medical students to appreciate team members' contributions and other disciplines' perspectives, in addition to the synergy that occurs with multidisciplinary teams.

Safety of Major Abdominal Operations in the Elderly: A Study of Geriatric-Specific Determinants of Health.

BACKGROUND: Preoperative assessment of geriatric-specific determinants of health may enhance perioperative risk stratification among elderly patients. This study examines effects of geriatric-specific variables on postoperative outcomes in patients undergoing elective major abdominal operations. METHODS: Patients included in the ACS NSQIP pilot Geriatric Surgery Research File program who underwent elective pancreatic, liver, and colorectal operations between 2014 and 2016 were examined. Multivariable analyses were performed to evaluate associations between patient-specific geriatric variables and risk of death, morbidity, readmission, and discharge destination. RESULTS: A total of 4165 patients were included. Patients ≥85 years were more likely to die, experience postoperative morbidity, and be discharged to a facility (all p ≤ 0.039) than younger patients. Preoperatively, patients ≥85 years were more likely to use a mobility aid, have a prior fall, have consent signed by a surrogate, and to live alone at home prior to operation (all p < 0.001). After adjustment for ACS NSQIP-estimated probabilities of morbidity or mortality, no geriatric-specific preoperative risk factors were significantly associated with increased risk of death or complications in any age group (all p > 0.055). Patients 75-84 and ≥85 years were more likely to be discharged to facility (OR 2.33 and 4.75, respectively, both p < 0.001) compared to patients 65-74 years. All geriatric-specific variables: use of mobility aid, living alone, consent signed by a surrogate, and fall history, were significantly associated with discharge to a facility (all p ≤ 0.001). CONCLUSIONS: After adjusting for comorbid conditions, geriatric-specific variables are not associated with postoperative mortality and morbidity among elderly patients; however, geriatric-specific variables are significantly associated with discharge to a facility.

Strain-Level Metagenomic Data Analysis of Enriched In Vitro and In Silico Spiked Food Samples: Paving the Way towards a Culture-Free Foodborne Outbreak Investigation Using STEC as a Case Study.

Culture-independent diagnostics, such as metagenomic shotgun sequencing of food samples, could not only reduce the turnaround time of samples in an outbreak investigation, but also allow the detection of multi-species and multi-strain outbreaks. For successful foodborne outbreak investigation using a metagenomic approach, it is, however, necessary to bioinformatically separate the genomes of individual strains, including strains belonging to the same species, present in a microbial community, which has up until now not been demonstrated for this application. The current work shows the feasibility of strain-level metagenomics of enriched food matrix samples making use of data analysis tools that classify reads against a sequence database. It includes a brief comparison of two database-based read classification tools, Sigma and Sparse, using a mock community obtained by in vitro spiking minced meat with a Shiga toxin-producing Escherichia coli (STEC) isolate originating from a described outbreak. The more optimal tool Sigma was further evaluated using in silico simulated metagenomic data to explore the possibilities and limitations of this data analysis approach. The performed analysis allowed us to link the pathogenic strains from food samples to human isolates previously collected during the same outbreak, demonstrating that the metagenomic approach could be applied for the rapid source tracking of foodborne outbreaks. To our knowledge, this is the first study demonstrating a data analysis approach for detailed characterization and phylogenetic placement of multiple bacterial strains of one species from shotgun metagenomic WGS data of an enriched food sample.