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The Centers for Disease Control and Prevention (CDC) defines the social determinants of health (SDOH) as “the conditions in the environments where people are born, live, learn, work, play, worship, and age that affect a range of health, functioning, and quality-of-life outcomes and risks,” which includes economic stability, access to quality health care, and physical environment. There is increasing evidence that SDOH have an impact in shaping a patient's access and recovery from surgery. This review evaluates the role surgeons play in reducing these disparities.

Background Excessive postoperative opioid prescribing contributes to opioid misuse throughout the US. The Georgia Quality Improvement Program (GQIP) is a collaboration of ACS-NSQIP participating hospitals. GQIP aimed to develop a multi-institutional opioid data collection platform as well as understand our current opioid-sparing strategy (OSS) usage and postoperative opioid prescribing patterns. Methods This study was initiated 7/2019, when 4 custom NSQIP variables were developed to capture OSS usage and postoperative opioid oral morphine equivalents (OMEs). After pilot collection, our discharge opioid variable required optimization for adequate data capture and was expanded from a free text option to 4 drop-down selection variables. Data collection then continued from 2/2020-5/2021. Logistic regression was used to determine associations with OSS usage. Average OMEs were calculated for common general surgery procedures and compared to national guidelines. Results After variable optimization, the percentage where a total discharge prescription OME could be calculated increased from 26% to 70% ( P < .001). The study included 820 patients over 10 operations. There was a significant variation in OSS usage between GQIP centers. Laparoscopic cases had higher odds of OSS use (1.92 (1.38-2.66)) while OSS use had lower odds in black patients on univariate analysis (.69 (.51-.94)). On average 7 out of the 10 cases had higher OMEs prescribed compared to national guidelines recommendations. Conclusion Developing a multi-institutional opioid data collection platform through ACS-NSQIP is feasible. Preselected drop-down boxes outperform free text variables. GQIP future quality improvement targets include variation in OSS use and opioid overprescribing.

Enhanced recovery protocols (ERAS) aim to decrease physiological stress response to surgery and maintain postoperative physiological function. Proponents of ERAS state these protocols decrease lengths of stay (LOS) and complication rates. Our aim was to assess whether elderly patients receive the same benefit as younger patients using ERAS protocols.We queried patients from 2015 to 2017 at our institution with Enhanced Recovery in Surgery (ERIN) variables from the targeted colectomy NSQIP database. The patients were divided into sextiles and analyzed for readmission, LOS, return of bowel function, tolerating diet, mobilization, and multimodal pain management comparing the youngest sextile to the oldest sextile.Two hundred sixty-two patients (73% colectomies) were enrolled in ERAS. When compared with the youngest sextile (age 19-43.8), the oldest sextile (age 71.4-92.5) had similar readmission rates at 9.8% versus 9.5% (P-value = 0.87), quicker return of bowel function, average 1.9 d versus 3.7 d (P-value0.01), and tolerated diet quicker, average POD 2.4 d versus 5.1 d (P-value0.01). There was a slight decrease in the use of multimodal pain management 88% versus 100% (P-value = 0.07), but mobilization on POD1 was slightly better in the elderly at 80% versus 78% (P-value = 0.76). Elderly patients enrolled in ERAS had an average LOS of 4.9 days versus 7.8 in the younger patients (P-value = 0.08). Among elderly non-ERAS patients average LOS was 14.6 days.Overall, elderly patients fared better or the same on the ERIN variables analyzed than the younger cohort. ERAS protocols are beneficial and applicable to elderly patients undergoing colorectal surgery.

Mental Health Disorders (MHD) are a growing concern nationwide. The significant impact MHD have on surgical outcomes has only recently started to be understood. This literature review investigated how mental health impacts the outcomes of general surgery patients and what can be done to make improvements. Patients with schizophrenia had the poorest surgical outcomes. Mental health disorders increased post-surgical pain, hospital length of stay, complications, readmissions, and mortality. Mental health disorders decreased wound healing and quality of care. Optimizing outcomes will be best accomplished through integrating more effective perioperative screening tools and interventions. Screenings tools can incorporate artificial intelligence, MHD data, resilience and its biomarkers, and patient mental health questionnaires. Interventions include cognitive behavioral therapy, virtual reality, spirituality, pharmacology, and resilience training.

Introduction There is little consensus of quality measurements for restorative proctocolectomy with ileal pouch-anal anastomosis(RPC-IPAA) performed for ulcerative colitis(UC). The National Surgical Quality Improvement Program(NSQIP) cannot accurately classify RPC-IPAA staged approaches. We formed an IBD-surgery registry that added IBD-specific variables to NSQIP to study these staged approaches in greater detail. Methods We queried our validated database of IBD surgeries across 11 sites in the US from March 2017 to March 2019, containing general NSQIP and IBD-specific perioperative variables. We classified cases into delayed versus immediate pouch construction and looked for independent predictors of pouch delay and postoperative Clavien-Dindo complication severity. Results 430 patients received index surgery or completed pouches. Among completed pouches, 46(28%) and 118(72%) were immediate and delayed pouches, respectively. Significant predictors for delayed pouch surgery included higher UC surgery volume(p = 0.01) and absence of colonic dysplasia(p = 0.04). Delayed pouch formation did not significantly predict complication severity. Conclusions Our data allows improved classification of complex operations. Curating disease-specific variables allows for better analysis of predictors of delayed versus immediate pouch construction and postoperative complication severity. Short summary We applied our previously validated novel NSIP-IBD database for classifying complex, multi-stage surgical approaches for UC to a degree that was not possible prior to our collaborative effort. From this, we describe predictive factors for delayed pouch formation in UC RPC-IPAA with the largest multicenter effort to date.

Perianal Crohn’s disease (CD) is a complex manifestation of CD that affects approximately 10% of patients. The spectrum of disease is quite variable, ranging from relatively mild disease to severe, aggressive manifestations that result in frequent hospitalizations, multiple surgeries, and poor quality of life. Despite significant recent advances in surgical and medical management, treatment remains challenging and frequently requires a multidisciplinary medical-surgical approach. The goal of this article is to review the current literature regarding the work-up, treatment, and future directions of therapy. Crucial features of effective management include the precise identification of manifestations, control of sepsis, limiting rectal inflammation, frequently with use of antitumor necrosis factor agents, and avoidance of extensive surgery.

Early ambulation is a key component to postoperative recovery; however, measuring steps taken is often inconsistent and nonstandardized. This study aimed to determine whether an activity tracker with alarms would increase postoperative ambulation in patients after elective colorectal procedures. Forty-eight patients were randomly assigned to either trackers with 5 daily alarms or activity trackers alone. Over 223 total patient days, the trackers recorded a complete data set for 216 patient days (96.9%). Increasing the postoperative day significantly affected the number of steps taken, while age, sex, Risk Analysis Index score, and approach (laparoscopic versus open) did not show a significant effect. The mean steps per day in the intervention group were 1468 (median 495; interquartile range (IQR) 1345) and in the control group was 1645 (median 1014; IQR 2498). The use of trackers with alarms did not significantly affect the number of daily steps compared to trackers alone (ANOVA, P = .93). Although activity trackers with alarms did not increase postoperative ambulation compared with trackers with no alarms, we demonstrated a strategy to operationalize the use of trackers into postoperative care to provide a quantitative value for ambulation. This enables quantification of a key component in the Enhanced Recovery After Surgery protocol.

Objectives To review published clinical evidence on management of Clostridioides difficile infection in critically ill patients. Data sources We obtained relevant studies from a PubMed literature review and bibliographies of reviewed articles. Study selection We selected English-language studies addressing aspects of C. difficile infection relevant to critical care clinicians including epidemiology, risk factors, diagnosis, treatment, and prevention, with a focus on high-quality clinical evidence. Data extraction We reviewed potentially relevant studies and abstracted information on study design, methods, patient selection, and results of relevant studies. This is a synthetic (i.e., not systematic) review. Data synthesis C. difficile infection is the most common healthcare-associated infection in the United States. Antibiotics are the most significant C. difficile infection risk factor, and among antibiotics, cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam confer the highest risk. Age, diabetes mellitus, inflammatory bowel disease, and end-stage renal disease are risk factors for C. difficile infection development and mortality. C. difficile infection diagnosis is based on testing appropriately selected patients with diarrhea or on clinical suspicion for patients with ileus. Patients with fulminant disease (C. difficile infection with hypotension, shock, ileus, or megacolon) should be treated with oral vancomycin and IV metronidazole, as well as rectal vancomycin in case of ileus. Patients who do not respond to initial therapy should be considered for fecal microbiota transplant or surgery. Proper infection prevention practices decrease C. difficile infection risk. Conclusions Strong clinical evidence supports limiting antibiotics when possible to decrease C. difficile infection risk. For patients with fulminant C. difficile infection, oral vancomycin reduces mortality, and adjunctive therapies (including IV metronidazole) and interventions (including fecal microbiota transplant) may benefit select patients. Several important questions remain regarding fulminant C. difficile infection management, including which patients benefit from fecal microbiota transplant or surgery.

As one of the 12 clinical pathways of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program, the Colorectal Pathway intends to deliver didactic content organized along 3 levels of performance (competency, proficiency and mastery) each represented by an anchoring procedure (laparoscopic right colectomy, laparoscopic left/sigmoid colectomy, and intracorporeal anastomosis during minimally invasive (MIS) ileocecal or right colon resection). In this article, the SAGES Colorectal Task Force presents focused summaries of the top 10 seminal articles selected for laparoscopic right colectomy which surgeons should be familiar with.Using a systematic literature search of Web of Science, the most cited articles on laparoscopic right colectomy were identified, reviewed, and ranked by the SAGES Colorectal Task Force and invited subject experts. Additional articles not identified in the literature search were included if deemed impactful by expert consensus. The top 10 ranked articles were then summarized, with emphasis on relevance and impact in the field, findings, strengths and limitations, and conclusions.The top 10 seminal articles selected for the laparoscopic right colectomy anchoring procedure include articles on surgical techniques for benign and malignant disease, with anatomical and video illustrations, comparative outcomes of laparoscopic vs open colectomy, variations in technique with impact on clinical outcomes, and assessment of the learning curve.The top 10 seminal articles selected for laparoscopic right colectomy illustrate the diversity both in content and format of the educational curriculum of the SAGES Masters Program to support practicing surgeon progression to mastery within the Colorectal Pathway.

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Introduction: Our statewide surgical quality improvement (QI) collaborative began collecting opioid data to better understand our patients’ pain management and discharge opioid prescriptions. During our pilot there was invalid data requiring variable revision. Collection resumed in 1/2020 and was encouraged during COVID-19, acknowledging that we faced reduced and highly selective operative case volumes with reduced resources. Methods: Institutions from a statewide surgical QI collaborative participated in the revised custom variable opioid data collection. Utilizing the National Surgical Quality Improvement Program (NSQIP) platform, seven custom variable data were collected for 13 general surgery procedures. Variables were abstracted by Surgical Clinical Reviewers from 1/2020-12/2020. Results: 722 cases were performed. 460 (64%) cases had all variable data submitted, 102 (14%) had at least one and 160 (22%) cases had no variables submitted. Postoperative/in-patient opioids and non-opioids administered were the most likely to be submitted (73% and 73%). 489 cases (68%) had submitted data on use of an opioid sparing strategy. 483 (67%) cases had some discharge opioid prescription data, but only 357 cases (49%) had adequate data to standardize for comparison. Conclusion: A significant decrease in collection of the three minimally revised variables was observed. However, from revising the discharge opioid prescription variable from free text to a pre-populated selection, the quality of data improved significantly. This will allow the collaborative to standardize discharge opioid prescribing. Custom variable opioid data collection is feasible and can be utilized to inform collaborative opioid prescribing practices.

Minimizing perioperative fluid administration is a key component of enhanced recovery after surgery protocols (ERAS). Acute kidney injury (AKI) is a major cause of morbidity and mortality in hospitalized patients. Our aim was to assess the association of ERAS with the incidence and severity of AKI in patients undergoing elective colorectal surgery. In this single-study retrospective review, patients undergoing colorectal surgery from 2013 to 2017 were included. Primary endpoint was postoperative AKI. Secondary outcomes were hospital length of stay (LOS) and 30-day readmission. Baseline demographics and procedure types were similar between both groups. AKI was higher in the ERAS versus non-ERAS group (23 vs 9%; P = 0.002). Factors associated with increased risk of AKI on univariate regression included presence of preoperative cardiovascular risk factors (hazard ratio (HR) 3.5; 95% CI 1.3–9.7; P < 0.01), more complex colorectal operations (HR 5.1; 95% CI 1.6–16.1; P < 0.01), and management with an ERAS pathway (HR 2.9; 95% CI 1.5–5.8; P < 0.01). On multi-variable analysis, ERAS remained a significant risk factor for developing AKI (HR 3.44; 95% CI 1.5–7.7; P < 0.01). ERAS patients had a shorter hospital LOS (3.9 vs 5.9 days, P < 00.1) compared with non-ERAS patients, with no difference in 30-day readmission rates (11.5 vs 10.7%; P = 0.98). Although the incidence of AKI is higher in patients treated with ERAS protocols, the majority represent minor elevations in baseline serum creatinine and did not affect the reduction in hospital LOS associated with ERAS. Given the potential association of AKI, however, with increased long-term morbidity and mortality, ERAS protocols should be optimized to prevent postoperative AKI.

Introduction Enhanced recovery after surgery protocols are commonly used, but their utility in patients with inflammatory bowel disease and steroid use is poorly studied. We sought to examine influence of inflammatory bowel disease (IBD) and steroid use on hospital length of stay (LOS) and operative duration in patients undergoing colectomies in the era of ERAS. Methods We performed retrospective review of our institutional National Surgical Quality Improvement Program (NSQIP) registry (2016-2018) for colectomies. We performed 2 distinct analyses to examine influence of steroids and IBD on LOS and operative duration. Multivariable linear regression was used to predict outcomes after adjusting for relevant perioperative features. Results There were 366 patients in the cohort; 17.8% were on steroids and 16.4% had IBD. Patients using steroids had longer LOS (6 vs 4 days, P < .0001). IBD patients had a longer LOS (7 vs 5 days, P < .0001) and longer operative duration (383 min vs 335.5 minute, P = .01) compared to non-IBD patients. On multivariable analysis, steroid use was not associated with increased LOS or operative duration. Inflammatory bowel disease was associated with an increased hospital LOS and operative duration. Discussion Patients on steroids had longer LOS when compared to patients not on steroids. Inflammatory bowel disease regardless of steroid use was found to be a significant risk factor for both increased LOS and operative duration. A closer look at preoperative physiology may help to tailor ERAS protocols in patients with inflammatory conditions.

Background Nearly 30% of patients with newly formed ileostomies require hospital readmission from severe dehydration or associated complications. This contributes to significant morbidity and rising healthcare costs associated with this procedure. Our aim was to design and pilot a novel program to decrease readmissions in this patient population. Study Design An agreement was established with Visiting Nurse Health System (VNHS) in March 2015 that incorporated regular home visits with clinical triggers to institute surgeon-supervised corrective measures aimed at preventing patient decompensation associated with hospital readmissions. Thirty-day readmission data for patients managed with and without VNHS support for 10.5 months before and after implementation of this new program were collected. Results Of 833 patients with small bowel procedures, 162 were ileostomies with 47 in the VNHS and 115 in the non-VNHS group. Before program implementation, VNHS (n = 24) and non-VNHS patients (n = 54) had similar readmission rates (20.8% vs 16.7%). After implementation, VNHS patients (n = 23) had a 58% reduction in hospital readmission (8.7%) and non-VNHS patient hospital readmissions (n = 61) increased slightly (24.5%). Total cost of readmissions per patient in the cohort decreased by >80% in the pilot VNHS group. Conclusions Implementation of a novel program reduced the 30-day readmission rate by 58% and cost of readmissions per patient by >80% in a high risk for readmission patient population with newly created ileostomies. Future efforts will expand this program to a greater number of patients, both institutionally and systemically, to reduce the readmission-rate and healthcare costs for this high-risk patient population.

Anastomotic leak rates in colorectal surgery remain persistently high despite increased awareness of contributing factors, low threshold for proximal fecal diversion, and modern technologies to better assess bowel perfusion. Leak rates for low colorectal anastomoses range 3–30% with risk factors including malnutrition, smoking, immunosuppression, prior radiation therapy, obesity, and male gender. Technical factors such as tension on the anastomosis and adequacy of the blood supply also play a critical role in the occurrence of leaks. This chapter will review intraoperative strategies to assess the integrity of colorectal anastomoses, reduce the risk of anastomotic leaks, and salvage a failed anastomosis and ischemic colonic conduit. Reconstructive techniques to salvage intraoperative and postoperative anastomotic leaks will also be reviewed.

There are variations in the use of adjuvant chemotherapy (AC) in stage II colon cancer (CRC). We sought to determine which patients received chemotherapy, what factors were associated with receipt of AC, and how this impacted overall survival.Using the National Cancer Database, patients with stage II CRC who underwent surgical resection were selected; patients who received radiation or neoadjuvant chemotherapy were excluded. High-risk features (HRFs) were defined as pathological tumor stage IV, positive surgical margins, and perineural or lymphovascular invasion. Multivariable and subgroup analysis with eight subgroups stratified in the presence of HRFs, age, and the Charlson-Deyo score was performed.Of 77,739 patients identified with stage II CRC, 18.3% received AC. Younger, healthier patients with HRFs had the highest chemotherapy receipt rate (46.7%), whereas patients without HRFs, ≥ 75 y, and with the Charlson-Deyo score of 2+ had the lowest rate (2.1%). Community cancer centers were more likely to initiate AC (odds ratio = 1.24 P 0.01) especially among healthy HRF-negative patients and younger patients. No significant racial differences in AC use were observed. AC was associated with improved overall survival in subgroups with HRFs (hazard ratio [HR]: 0.81 P 0.001; HR: 0.75 P 0.001; HR: 0.65 P = 0.03; HR: 0.55, P 0.001) but not in patients without HRFs.AC receipt rates differed depending on patient age and type of institution delivering care. AC was associated with survival benefits only in patients with HRFs regardless of age. These findings are clinically relevant to inform appropriate use of AC in stage II CRC.

Minimizing perioperative fluid administration is a key component of enhanced recovery after surgery protocols (ERAS). Acute kidney injury (AKI) is a major cause of morbidity and mortality in hospitalized patients. Our aim was to assess the association of ERAS with the incidence and severity of AKI in patients undergoing elective colorectal surgery. In this single-study retrospective review, patients undergoing colorectal surgery from 2013 to 2017 were included. Primary endpoint was postoperative AKI. Secondary outcomes were hospital length of stay (LOS) and 30-day readmission. Baseline demographics and procedure types were similar between both groups. AKI was higher in the ERAS

Postoperative acute renal failure is a major cause of morbidity and mortality in colon and rectal surgery. Our objective was to identify preoperative risk factors that predispose patients to postoperative renal failure and renal insufficiency, and subsequently develop a risk calculator. Using the National Surgical Quality Improvement Program Participant Use Files database, all patients who underwent colorectal surgery in 2009 were selected (n = 21,720). We identified renal complications during the 30-day period after surgery. Using multivariate logistic regression analysis, a predictive model was developed. The overall incidence of renal complications among colorectal surgery patients was 1.6 per cent. Significant predictors include male gender (adjusted odds ratio [OR]: 1.8), dependent functional status (OR: 1.5), preoperative dyspnea (OR: 1.5), hypertension (OR: 1.6), preoperative acute renal failure (OR: 2.0), American Society of Anesthesiologists class ≥3 (OR: 2.2), preoperative creatinine >1.2 mg/dL (OR: 2.8), albumin

Surgical site infections (SSIs) result in patient morbidity and increased costs. The purpose of this study was to determine reasons underlying SSI to enable interventions addressing identified factors. Combining data from the American College of Surgeons National Surgical Quality Improvement Project with medical record extraction, we evaluated 365 patients who underwent colon resection from January 2009 to December 2012 at a single institution. Of the 365 patients, 84 (23%) developed SSI. On univariate analysis, significant risk factors included disseminated cancer, ileostomy, patient temperature less than 36°C for greater than 60 minutes, and higher glucose level. The median number of cases per surgeon was 36, and a case volume below the median was associated with a higher risk of SSI. On multivariate analysis, significant risks associated with SSI included disseminated cancer (odds ratio [OR], 4.31; P < .001); surgery performed by a surgeon with less than 36 cases (OR, 2.19; P = .008); higher glucose level (OR, 1.06; P 5.017); and transfusion of five units or more of blood (OR, 3.26; P 5.029). In this study we found both modifiable and unmodifiable factors associated with increased SSI. Identifying modifiable risk factors enables targeting specific areas to improve the quality of care and patient outcomes.

Postoperative acute renal failure is a major cause of morbidity and mortality in colon and rectal surgery. Our objective was to identify preoperative risk factors that predispose patients to postoperative renal failure and renal insufficiency, and subsequently develop a risk calculator. Using the National Surgical Quality Improvement Program Participant Use Files database, all patients who underwent colorectal surgery in 2009 were selected (n = 21,720). We identified renal complications during the 30-day period after surgery. Using multivariate logistic regression analysis, a predictive model was developed. The overall incidence of renal complications among colorectal surgery patients was 1.6 per cent. Significant predictors include male gender (adjusted odds ratio [OR]: 1.8), dependent functional status (OR: 1.5), preoperative dyspnea (OR: 1.5), hypertension (OR: 1.6), preoperative acute renal failure (OR: 2.0), American Society of Anesthesiologists class ≥3 (OR: 2.2), preoperative creatinine1.2 mg/dL (OR: 2.8), albumin3.5 g/dL (OR: 1.8), and emergency operation (OR: 1.5). This final model has an area under the curve (AUC) of 0.79 and was validated with similar excellent discrimination (area under the curve: 0.76). Using this model, a risk calculator was developed with excellent predictive ability for postoperative renal complications in colorectal patients and can be used to aid clinical decision-making, patient counseling, and further research on measures to improve patient care.

Memory CD8 T cells are a critical component of protective immunity, and inducing effective memory T-cell responses is a major goal of vaccines against chronic infections and tumours. Considerable effort has gone into designing vaccine regimens that will increase the magnitude of the memory response, but there has been minimal emphasis on developing strategies to improve the functional qualities of memory T cells. Here we show that mTOR (mammalian target of rapamycin, also known as FRAP1) is a major regulator of memory CD8 T-cell differentiation, and in contrast to what we expected, the immunosuppressive drug rapamycin has immunostimulatory effects on the generation of memory CD8 T cells. Treatment of mice with rapamycin following acute lymphocytic choriomeningitis virus infection enhanced not only the quantity but also the quality of virus-specific CD8 T cells. Similar effects were seen after immunization of mice with a vaccine based on non-replicating virus-like particles. In addition, rapamycin treatment also enhanced memory T-cell responses in non-human primates following vaccination with modified vaccinia virus Ankara. Rapamycin was effective during both the expansion and contraction phases of the T-cell response; during the expansion phase it increased the number of memory precursors, and during the contraction phase (effector to memory transition) it accelerated the memory T-cell differentiation program. Experiments using RNA interference to inhibit expression of mTOR, raptor (also known as 4932417H02Rik) or FKBP12 (also known as FKBP1A) in antigen-specific CD8 T cells showed that mTOR acts intrinsically through the mTORC1 (mTOR complex 1) pathway to regulate memory T-cell differentiation. Thus these studies identify a molecular pathway regulating memory formation and provide an effective strategy for improving the functional qualities of vaccine- or infection-induced memory T cells.

Crohn's disease is an inflammatory bowel disease that can affect the entire gastrointestinal tract. It is chronic and incurable, and the mainstay of therapy is medical management with surgical intervention as complications arise. Surgery is required in approximately 70% of patients with Crohn's disease. Because repeat interventions are often needed, these patients may benefit from bowel-sparing techniques and minimally invasive approaches. Various bowel-sparing techniques, including strictureplasty, can be applied to reduce the risk of short-bowel syndrome.A review of the available literature using the PubMed search engine was undertaken to compile data on the surgical treatment of Crohn's disease.Data support the use of laparoscopy in treating Crohn's disease, although the potential technical challenges in these settings mandate appropriate prerequisite surgical expertise.

The widespread clinical implementation of alloislet transplantation as therapy for type 1 diabetes has been hindered by the lack of suitable islet donors. Pig-to-human islet xenotransplantation is one strategy with potential to alleviate this shortage. Long-term survival of porcine islets has been achieved using CD154-specific antibodies to interrupt the CD40/CD154 costimulation pathway; however, CD154-specific antibodies seem unlikely candidates for clinical translation. An alternative strategy for CD40/CD154 pathway interruption is use of CD40-specific antibodies. Herein, we evaluate the ability of a chimeric CD40-specific monoclonal antibody (Chi220) to protect islet xenografts. Neonatal porcine islets (∼50 000 IEQ/kg) were transplanted intraportally into pancreatectomized diabetic macaques. Immunosuppression consisted of induction therapy with Chi220 and the IL-2 receptor-specific antibody basiliximab, and maintenance therapy with sirolimus and the B7-specific fusion protein belatacept. Chi220 effectively promoted xenoislet engraftment and survival, with five of six treated recipients achieving insulin-independent normoglycemia (median rejection-free survival 59 days; mean 90.8 days, maximum 203 days). No thromboembolic phenomena were observed. CD40 represents a promising alternative to CD154 as a therapeutic target, and the efficacy of CD40-specific antibodies in islet xenotransplantation warrants further investigation.

Previous data from the National Cancer Database (NCBD) showed increasing rates of transanal local excision for early rectal cancer despite a lack of evidence supporting its oncologic adequacy. The aim of this study is to update national trends, compare overall survival, and determine factors associated with survival in patients with stage I rectal cancer. Survival of 15, 149 patients with stage I rectal adenocarcinoma were examined retrospectively from 2004-2012. The rate of local excision over this time period was sustained at 22% (20.88 - 24.9%; p = 0.077). Five-year overall survival (OS) after transanal local excision was less than transabdominal standard resection (76.6% vs. 80.7%; p 4 cm, low volume centers, uninsured patients and increasing comorbidities. This is the first study of national data showing sustained use of transanal local excision over the past decade. Local excision has a lower 5-year OS compared to transabdominal standard resection. Transanal excision of early rectal cancer should be offered to select patients only after careful consideration of risk factors balanced against the decrease in overall survival.

The recent introduction of transanal minimally invasive surgery (TAMIS) offers a safe and cost-effective method for the local resection of rectal neoplasms. The ability to standardize a technique for TAMIS will lead to the most reproducible outcomes and enable teaching. A retrospective, IRB-approved chart review was conducted of 32 patients who underwent the TAMIS procedure at one institution over a 3-year period. TAMIS was performed for 11 benign and 21 malignant lesions. The majority of resections were full thickness (29/32) and all were R0. Average distance from the anal verge was 7.5 ± 3 cm, defect circumference was 43.7 ± 10 %, operative time was 131 ± 80 min, and length of stay was 1.1 ± 1 days. Two patients had morbidities requiring readmission and further treatment for (1) an aspiration pneumonia with CHF exacerbation and (2) a rectal abscess. This report outlines an operative technique for TAMIS that is reproducible for the excision of rectal lesions, associated with low morbidity.

To determine the relationship between complications after 3 common general surgery procedures and per-episode hospital finances.With impending changes in health care reimbursement, maximizing the value of care delivered is paramount. Data on the relative clinical and financial impact of postoperative complications are necessary for directing surgical quality improvement efforts.We reviewed the medical records of patients enrolled in the American College of Surgeons' National Surgical Quality Improvement Program who underwent pancreaticoduodenectomy, hepatectomy, and colectomy at a single academic institution between September 2009 and August 2012. Clinical outcomes data were subsequently linked with hospital billing data to determine hospital finances associated with each episode. We describe the association between postoperative complications, hospital length of stay, and different financial metrics. Multivariable linear regression modeling tested linear association between postoperative outcomes and cost data.There was a positive association between the number of surgical complications, payments, length of stay, total charges, total costs, and contribution margin for the three procedures. Multivariable models indicated that complications were independently associated with total cost among the selected procedures. Payments increased with complications, offsetting increased costs.In the current fee-for-service environment, the financial incentives are misaligned with quality improvement efforts. As we move to a value-driven method of reimbursement, administrators and health care providers alike will need to focus on improving the quality of patient care while remaining conscious of the cost of care delivered. Reducing complications effectively improves value.

Islet transplantation to treat type 1 diabetes has been limited in part by toxicities of current immunosuppression and recipient humoral sensitization. Blockade of the CD28/CD80/86 and CD40/CD154 pathways has shown promise to remedy both these limitations, but translation has been hampered by difficulties in translating CD154-directed therapies. Prior CD40-directed regimens have led to prolonged islet survival, but fail to prevent humoral allosensitization. We therefore evaluated the addition of CTLA4Ig to a CD40 blockade-based regimen in nonhuman primate (NHP) alloislet transplantation. Diabetic rhesus macaques were transplanted allogeneic islets using the CD40-specific antibody 3A8, basiliximab induction, and sirolimus with or without CTLA4Ig maintenance therapy. Allograft survival was determined by fasting blood glucose levels and flow cytometric techniques were used to test for donor-specific antibody (DSA) formation. CTLA4Ig plus 3A8, basiliximab and sirolimus was well tolerated and induced long-term islet allograft survival. The addition of CTLA4Ig prevented DSA formation, but did not facilitate withdrawal of the 3A8-based regimen. Thus, CTLA4Ig combines with a CD40-specific regimen to prevent DSA formation in NHPs, and offers a potentially translatable calcineurin inhibitor-free protocol inclusive of a single investigational agent for use in clinical islet transplantation without relying upon CD154 blockade.

Sirolimus is a potent anti-proliferative agent used clinically to prevent renal allograft rejection. However, little is known about the effects of maintenance immunosuppressive agents on the immune response to potentially protective vaccines. Here we show that sirolimus paradoxically increases the magnitude and quality of the CD8+ T cell response to vaccinia vaccination in non-human primates, fostering more robust recall responses compared to untreated and tacrolimus-treated controls. Enhancement of both the central and effector memory compartments of the vaccinia-specific CD8+ T cell response was observed. These data elucidate new mechanistic characteristics of sirolimus and suggest immune applications extending beyond its role as an immunosuppressant.