Expanding access to pancreas transplantation for type 2 diabetes mellitus.

PURPOSE OF REVIEW: The vast majority of cases of diabetes mellitus (DM) in the United States are classified as type 2 DM (T2DM). Restrictive listing criteria and uncertainty regarding outcomes have historically limited access to pancreas transplantation for individuals with T2DM, although it has been used with success in patients with type 1 DM (T1DM). This review summarizes several recent studies that have sought to clarify the indications, appropriate patient selection, and outcomes of pancreas transplantation in the setting of T2DM. RECENT FINDINGS: Pancreas transplants have increased over the last few years, largely due to an increase in listings for simultaneous pancreas-kidney transplant (SPK) in patients with T2DM. Retrospective data demonstrate similar patient and allograft survival in patients with T1DM and T2DM undergoing SPK, and improved outcomes in patients with T2DM after SPK compared to those receiving a kidney transplant alone, although these studies are often confounded by selection biases. Patient selection for pancreas transplant has traditionally focused on body mass index, pretransplant insulin requirements, and fasting C-peptide, and the categorization of patients to T1DM or T2DM. Emerging data suggests this practice is inadvertently and unnecessarily restrictive. SUMMARY: There is a growing body of evidence to support increasing consideration of pancreas transplantation in patients with T2DM, with support for equivalent patient and graft survival and glycemic control. Future prospective studies are indicated to better evaluate the role of preoperative patient factors in selection for pancreas transplantation and to explore long-term outcomes in patients with T2DM.

Preoperative Tamsulosin to Prevent Postoperative Urinary Retention: A Randomized Controlled Trial.

BACKGROUND: The purpose of this study was to evaluate the efficacy of tamsulosin, administered preoperatively, for the prevention of postoperative urinary retention (POUR). POUR is a common complication of abdominal surgery, leading to the use of urinary catheters, which are a risk factor for urinary tract infection. Tamsulosin is a uroselective alpha-1a blocker used for the treatment of lower urinary tract symptoms. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was undertaken from August 2015 to May 2018. Adults undergoing elective inpatient abdominal surgery were randomized to receive either tamsulosin 0.4 mg or placebo daily for 7 d before surgery and continuing for up to 7 d postoperatively. The primary outcome was need for at least a single intermittent catheterization postoperatively. Secondary outcomes included first postvoid residual volume, number of catheterizations, need for replacement of an indwelling catheter, hospital length of stay, and urinary tract infection within 30 d of surgery. RESULTS: A total of 158 participants were enrolled, with a final analytic cohort of 141 participants. The two groups had similar baseline characteristics, operative characteristics, and timing of catheter removal. There was no difference in the incidence of POUR between the two groups (26% in tamsulosin versus 31% in placebo, P = 0.49). There was also no difference in any of the secondary outcomes between the two groups. Epidural usage, open surgery, and age <50 were identified as risk factors for POUR. CONCLUSIONS: Perioperative prophylaxis with tamsulosin is not effective in reducing the incidence of POUR in patients undergoing elective abdominal surgery.

Concordance Between Registry and Administrative Data in the Determination of Comorbidity: A Multi-institutional Study.

OBJECTIVE: To characterize agreement between administrative and registry data in the determination of patient-level comorbidities. BACKGROUND: Previous research finds poor agreement between these 2 types of data in the determination of outcomes. We hypothesized that concordance between administrative and registry data would also be poor. METHODS: A cohort of inpatient operations (length of stay 1 day or greater) was obtained from a consortium of 8 hospitals. Within each hospital, National Surgical Quality Improvement Program (NSQIP) data were merged with intra-institutional inpatient administrative data. Twelve different comorbidities (diabetes, hypertension, congestive heart failure, hemodialysis-dependence, cancer diagnosis, chronic obstructive pulmonary disease, ascites, sepsis, smoking, steroid, congestive heart failure, acute renal failure, and dyspnea) were analyzed in terms of agreement between administrative and NSQIP data. RESULTS: Forty-one thousand four hundred thirty-two inpatient surgical hospitalizations were analyzed in this study. Concordance (Cohen Kappa value) between the 2 data sources varied from 0.79 (diabetes) to 0.02 (dyspnea). Hospital variation in concordance (intersite variation) was quantified using a test of homogeneity. This test found significant intersite variation at a level of P < 0.001 for each of the comorbidities except for dialysis (P = 0.07) and acute renal failure (P = 0.19). These findings imply significant differences between hospitals in their generation of comorbidity data. CONCLUSION: This study finds significant differences in how administrative versus registry data assess patient-level comorbidity. These differences are of concern to patients, payers, and providers, each of which had a stake in the integrity of these data. Standardized definitions of comorbidity and periodic audits are necessary to ensure data accuracy and minimize bias.

Venous Thromboembolism after Inpatient Surgery in Administrative Data vs NSQIP: A Multi-Institutional Study.

BACKGROUND: Previous studies have documented significant differences between administrative data and registry data in the determination of postoperative venous thromboembolism (VTE). The goal of this study was to characterize the discordance between administrative and registry data in the determination of postoperative VTE. STUDY DESIGN: This study was performed using data from the American College of Surgeons NSQIP merged with administrative data from 8 different hospitals (5 different medical centers) between 2013 and 2015. Occurrences of postoperative vein thrombosis (VT) and pulmonary embolism (PE) as ascertained by administrative data and NSQIP data were compared. In each situation where the 2 sources disagreed (discordance), a 2-clinician chart review was performed to characterize the reasons for discordance. RESULTS: The cohort used for analysis included 43,336 patients, of which 53.3% were female and the mean age was 59.5 years. Concordance between administrative and NSQIP data was worse for VT (κ 0.57; 95% CI 0.51 to 0.62) than for PE (κ 0.83; 95% CI 0.78 to 0.89). A total of 136 cases of discordance were noted in the assessment of VT; of these, 50 (37%) were explained by differences in the criteria used by administrative vs NSQIP systems. In the assessment of postoperative PE, administrative data had a higher accuracy than NSQIP data (odds ratio for accuracy 2.86; 95% CI 1.11 to 7.14) when compared with the 2-clinician chart review. CONCLUSIONS: This study identifies significant problems in ability of both NSQIP and administrative data to assess postoperative VT/PE. Administrative data functioned more accurately than NSQIP data in the identification of postoperative PE. The mechanisms used to translate VTE measurement into quality improvement should be standardized and improved.

Postoperative Myocardial Infarction in Administrative Data vs Clinical Registry: A Multi-Institutional Study.

BACKGROUND: Previous studies have documented significant differences between administrative data and registry data in the determination of postoperative MI. The goal of this study was to characterize discordance between administrative and registry data in the determination of postoperative myocardial infarction (MI). STUDY DESIGN: This study was performed using data from the American College of Surgeons NSQIP merged with administrative data from 8 different hospitals, between 2013 and 2015. From each of these sources, the occurrence of a postoperative MI, as ascertained by administrative data and NSQIP data, were compared. In each situation in which the 2 sources disagreed (discordance), a 2-clinician chart review was performed to generate a "gold standard" determination as to the occurrence of postoperative MI. RESULTS: A total of 43,289 operations met our inclusion criteria for analysis. Within this cohort a total of 230 cases of MI were identified by administrative data and/or NSQIP data (administrative rate 0.41%, NSQIP rate 0.42%). A total of 89 discordant ascertainments were identified, of which 42 were admin+/NSQIP- and 47 were admin-/NSQIP+. Accuracy (99.9% for both) and concordance (kappa = 0.89 [95% CI 0.86 to 0.92] for administrative data, kappa = 0.87 [95% CI 0.84 to 0.91] for NSQIP data) of the 2 systems were similar when compared against our gold standard (chart review). The majority of errors were related to false negatives, with sensitivity rates of 81% in both data sources. CONCLUSIONS: In this multi-institutional study, administrative data and NSQIP demonstrated a similar ability to determine the occurrence of postoperative MI. These findings do not demonstrate an advantage of registry data over administrative data in the determination of postoperative MI.

Primary fascial closure during laparoscopic ventral hernia repair does not reduce 30-day wound complications.

BACKGROUND: Laparoscopic ventral hernia repair (LVHR) is associated with decreased wound morbidity compared to open repair. It remains unclear whether primary fascial closure (PFC) offers any benefit in reducing postoperative seroma compared to bridged repair. We hypothesized that PFC would have no effect on seroma formation following LVHR. METHODS: A retrospective cohort study was performed using data from the prospectively maintained Americas Hernia Society Quality Collaborative. All patients undergoing LVHR from 2013 to 2016 were included. The primary outcome was seroma formation, diagnosed either clinically or radiographically. Secondary outcomes included surgical site infections (SSI), surgical site occurrences (SSO), and SSO requiring intervention. Patient characteristics and outcomes were compared between groups with univariate analysis using Pearson's chi-squared or Wilcoxon tests. Multivariable logistic regression controlling for patient and hernia characteristics was then performed to investigate the independent effect of PFC on seroma formation. RESULTS: 1280 patients were included in the study. 69% (n = 887) underwent PFC. Patients undergoing bridged repairs had slightly larger defects and were more likely to have a recurrent hernia. The overall rate of seroma formation was 10.4% (n = 133). There was no association on univariate analysis between PFC and wound complications. Similarly, on multivariable analysis, PFC had no significant effect on the risk of seroma formation (OR 0.87, 95% CI 0.58-1.31). CONCLUSIONS: PFC does not decrease the risk of short-term wound complications. Given that prior studies have also suggested no difference in hernia recurrence, PFC does not appear to improve postoperative outcomes for patients undergoing LVHR.

The Impact of Operative Approach on Postoperative Complications Following Colectomy for Colon Caner.

BACKGROUND: Colectomy is one of the most common major abdominal procedures performed in the USA. A better understanding of risk factors and the effect of operative approach on adverse postoperative outcomes may significantly improve quality of care. METHODS: Adult patients with a primary diagnosis of colon cancer undergoing colectomy were selected from the National Surgical Quality Improvement Program 2013-2015 targeted colectomy database. Patients were stratified into five groups based on specific operative approach. Univariate and multivariate analyses were used to compare the five groups and identify risk factors for 30-day anastomotic leak, readmission, and mortality. RESULTS: In total, 25,097 patients were included in the study, with a 3.32% anastomotic leak rate, 1.20% mortality rate, and 9.57% readmission rate. After adjusting for other factors, open surgery and conversion to open significantly increased the odds for leak, mortality, and readmission compared to laparoscopy. Additionally, smoking and chemotherapy increased the risk for leak and readmission, while total resection was associated with increased mortality and leak. CONCLUSIONS: Operative approach and several other potentially modifiable perioperative factors have a significant impact on risk for adverse postoperative outcomes following colectomy. To improve quality of care for these patients, efforts should be made to identify and minimize the influence of such risk factors.

The effect of perioperative fluid management on postoperative ileus in rectal cancer patients.

BACKGROUND: Postoperative ileus is a common cause of increased morbidity and cost after operative intervention. The aim of this study was to assess how fluid type, volume, and timing may affect incidence of postoperative ileus. METHODS: A retrospective cohort study was performed on patients undergoing operative intervention for rectal cancer from 2008 to 2015 at a single institution. Univariate and multivariate analyses were used to assess the effect of type (crystalloid versus colloid), volume by quartile, and timing (perioperative versus postoperative) on rate of postoperative ileus. RESULTS: A total of 300 patients were included, and the overall incidence of ileus in our cohort was 30% (n = 90). Both univariate and multivariate analyses showed that increasing volume of crystalloid volume administered was associated with increased postoperative ileus incidence (first quartile: 16.3%; second quartile: 31.5%, third quartile: 34.2%; and fourth quartile: 39.2%; P = .012), and administration of colloid was not shown to correlate. Furthermore, timing was not shown to be associated with the rate of postoperative ileus. CONCLUSION: Increased volumes of crystalloid are associated with higher rates of ileus, while administration of colloid is not. Based on this retrospective data, limiting the volume of crystalloid perioperatively may help lower the rate of ileus postoperatively.

Preoperative blood transfusion is a predictor of worse short-term postoperative outcomes after colectomy.

BACKGROUND: Both anemia and blood transfusion are associated with poor outcomes. The aim of this study was to evaluate the effect of preoperative blood transfusion on postoperative outcomes after colectomy, stratified by severity of anemia. METHODS: Patients undergoing colectomy from 2012-2014 were selected from the National Surgical Quality Improvement Program targeted colectomy database. Patients were divided into 2 groups based on receipt of preoperative transfusion and then stratified by hematocrit. Univariate and multivariate analyses were used to compare 30-day outcomes between the 2 groups. RESULTS: A total of 60,785 patients were included in the study, with an overall preoperative transfusion rate of 3.4% (n = 2,073). On univariate analysis, transfusion was associated with significantly greater rates of postoperative morbidity. The risk-adjusted, multivariate model confirmed increased risk of complications with preoperative transfusion (odds ratio 1.32, 95% confidence interval, 1.18-1.48). Furthermore, transfusion did not improve outcomes even in the setting of moderate anemia (odds ratio 1.35, 95% confidence interval, 1.14-1.60) or severe anemia (odds ratio 0.97, 95% confidence interval, 0.66-1.41). CONCLUSIONS: Preoperative transfusion is an independent predictor of complications in patients with mild and moderate anemia. Furthermore, these retrospective data suggest that even severely anemic patients do not benefit from preoperative transfusion and empiric transfusion therefore should be avoided. Alternatives to preoperative optimization of this high-risk surgical population should be sought.

Preoperative urinary tract infection increases postoperative morbidity.

BACKGROUND: Preoperative urinary tract infection (UTI) may be associated with surgical site infections secondary to hematogenous spread of bacteria. The association between preoperative UTI and postoperative complications has not been evaluated in general surgery populations. MATERIALS AND METHODS: Patients undergoing elective general surgery procedures from 2011 to 2013 were selected from the American College of Surgeons National Surgical Quality Improvement Program database. Patients with UTI present at the time of surgery (PATOS) were identified as cases. Patients without UTI PATOS were selected and matched 2:1 on age, American Society of Anesthesiologists class, and Current Procedural Terminology code with identified cases. Univariate and multivariate analyses compared postoperative outcomes between the two groups. RESULTS: A total of 434,802 patients were identified for inclusion in the study, with an overall preoperative UTI rate of 0.1% (n = 363). On univariate analysis, the UTI group had a significantly higher incidence of overall complications, infectious complications, and noninfectious complications. Multivariate analysis confirmed that patients with UTI had a higher risk of postoperative complications compared with those without preoperative UTI (odds ratio [OR] 1.551, 95% confidence interval [CI] 1.071-2.247). This relationship persisted for both infectious (OR 1.515, 95% CI 1.000-2.296) and noninfectious (OR 1.683, 95% CI 1.012-2.799) complications. CONCLUSIONS: We demonstrated an increased rate of 30-d complications in elective general surgery patients with UTI PATOS. These findings suggest that diligent efforts to diagnose and treat UTI before surgery may result in improved outcomes. Furthermore, surgeons should consider postponing elective procedures to allow for the complete resolution of preoperative UTI.

Short-term outcomes of minimally invasive versus open colectomy for colon cancer.

BACKGROUND: Laparoscopic and open approaches to colon resection have equivalent long-term outcomes and oncologic integrity for the treatment of colon cancer. Differences in short-term outcomes should therefore help to guide surgeons in their choice of operation. We hypothesized that minimally invasive colectomy is associated with superior short-term outcomes compared to traditional open colectomy in the setting of colon cancer. MATERIALS AND METHODS: Patients undergoing nonemergent colectomy for colon cancer in 2012 and 2013 were selected from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) targeted colectomy participant use file. Patients were divided into two cohorts based on operative approach-open versus minimally invasive surgery (MIS). Univariate, multivariate, and propensity-adjusted multivariate analyses were performed to compare postoperative outcomes between the two groups. RESULTS: A total of 11,031 patients were identified for inclusion in the study, with an overall MIS rate of 65.3% (n = 7200). On both univariate and multivariate analysis, MIS approach was associated with fewer postoperative complications and lower mortality. In the risk-adjusted multivariate analysis, MIS approach was associated with an odds ratio of 0.598 for any postoperative morbidity compared to open (P < 0.001). CONCLUSIONS: This retrospective study of patients undergoing colectomy for colon cancer demonstrates significantly improved outcomes associated with a MIS approach, even when controlling for baseline differences in illness severity. When feasible, minimally invasive colectomy should be considered gold standard for the surgical treatment of colon cancer.

National Trends in Short-term Outcomes Following Non-emergent Surgery for Diverticular Disease.

INTRODUCTION: Elective surgery for diverticulitis has evolved over the last decade. We aimed to evaluate the impact of changing practice patterns on postoperative outcomes. We hypothesized that the increased use of laparoscopy, and other management changes, would correlate with a decrease in postoperative complications. METHODS: Patients undergoing non-emergent surgery for diverticulitis from 2005 to 2013 were selected from the National Surgical Quality Improvement Program (NSQIP) database. We compared patient demographics, comorbidities, and operative approach by year of operation using chi-square tests and investigated temporal trends in postoperative outcomes using univariate, trend, and multivariate analyses. RESULTS: The analytic cohort, which included 29,893 patients, had increasing rates of obesity, advanced age, and higher American Society of Anesthesiologists (ASA) class over the study period. The use of laparoscopy increased significantly from 48 % in 2005/2006 to 70 % in 2013 (p < 0.001), while the rate of stoma creation remained unchanged (10-12 %, p = 0.072). The absolute risk of any postoperative complication decreased by 5.8 % over the study period, driven primarily by a reduction in infectious complications. Year of operation was a significant independent predictor of fewer complications for 2011-2013. CONCLUSION: Despite a trend towards increasing patient complexity, there has been a decline in postoperative morbidity following non-emergent surgery for diverticulitis. This trend coincides with the steadily increasing use of laparoscopy in this population.

Mitochondrial gene therapy augments mitochondrial physiology in a Parkinson's disease cell model.

Neurodegeneration in Parkinson's disease (PD) affects mainly dopaminergic neurons in the substantia nigra, where age-related, increasing percentages of cells lose detectable respiratory activity associated with depletion of intact mitochondrial DNA (mtDNA). Replenishment of mtDNA might improve neuronal bioenergetic function and prevent further cell death. We developed a technology ("ProtoFection") that uses recombinant human mitochondrial transcription factor A (TFAM) engineered with an N-terminal protein transduction domain (PTD) followed by the SOD2 mitochondrial localization signal (MLS) to deliver mtDNA cargo to the mitochondria of living cells. MTD-TFAM (MTD = PTD + MLS = "mitochondrial transduction domain") binds mtDNA and rapidly transports it across plasma membranes to mitochondria. For therapeutic proof-of-principle we tested ProtoFection technology in Parkinson's disease cybrid cells, using mtDNA generated from commercially available human genomic DNA (gDNA; Roche). Nine to 11 weeks after single exposures to MTD-TFAM + mtDNA complex, PD cybrid cells with impaired respiration and reduced mtDNA genes increased their mtDNA gene copy numbers up to 24-fold, mtDNA-derived RNAs up to 35-fold, TFAM and ETC proteins, cell respiration, and mitochondrial movement velocities. Cybrid cells with no or minimal basal mitochondrial impairments showed reduced or no responses to treatment, suggesting the possibility of therapeutic selectivity. Exposure of PD but not control cybrid cells to MTD-TFAM protein alone or MTD-TFAM + mtDNA complex increased expression of PGC-1alpha, suggesting activation of mitochondrial biogenesis. ProtoFection technology for mitochondrial gene therapy holds promise for improving bioenergetic function in impaired PD neurons and needs additional development to define its pharmacodynamics and delineate its molecular mechanisms. It also is unclear whether single-donor gDNA for generating mtDNA would be a preferred therapeutic compared with the pooled gDNA used in this study.