Sleeve Gastrectomy Reduces the Need for Liver Transplantation in Patients with Obesity and Non-Alcoholic Steatohepatitis: a Predictive Model.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is one of the leading indications for liver transplantation (LT) in the United States. As with the current obesity epidemic, the incidence of NASH continues to rise. However, the impact of broad utilization of bariatric surgery (BS) for patients with NASH is unknown, particularly in regard to mitigating the need for LT. METHODS: Markov decision analysis was performed to simulate the lives of 20,000 patients with obesity and concomitant NASH who were deemed ineligible to be waitlisted for LT unless they achieved a body mass index (BMI) < 35 kg/m2. Life expectancy following medical weight management (MWM) and sleeve gastrectomy (SG) were estimated. Base case patients were defined as having NASH without fibrosis and a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: Simulated base case analysis patients who underwent SG gained 14.3 years of life compared to patients who underwent MWM. One year after weight loss intervention, 9% of simulated MWM patients required LT compared to only 5% of SG patients. Survival benefit for SG was observed above a BMI of 32.2 kg/m2. CONCLUSION: In this predictive model of 20,000 patients with obesity and concomitant NASH, surgical weight loss is associated with a reduction in the progression of NASH, thereby reducing the need for LT. A reduced BMI threshold of 32 kg/m2 for BS may offer survival benefit for patients with obesity and NASH.

Ventricular Remodeling Following Metabolic and Bariatric Surgery Decreases Need for Heart Transplantation: A Predictive Model.

PURPOSE: For patients with obesity and congestive heart failure (CHF) who require heart transplantation (HT), aggressive weight loss has been associated with ventricular remodeling, or subclinical alterations in left and right ventricular structure that affect systolic function. Many have suggested offering metabolic and bariatric surgery (MBS) for these patients. As such, we evaluated the role of MBS in HT for patients with obesity and CHF using predictive modelling techniques. MATERIALS AND METHODS: Markov decision analysis was performed to simulate the life expectancy of 30,000 patients with concomitant obesity, CHF, and 30% ejection fraction (EF) who were deemed ineligible to be waitlisted for HT unless they achieved a BMI < 35 kg/m2. Life expectancy following diet and exercise (DE), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) was estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. RESULTS: RYGB patients had lower rates of HT and received HT quicker when needed. Base case patients who underwent RYGB gained 2.2 additional mean years survival compared with patients who underwent SG and 10.3 additional mean years survival compared with DE. SG patients gained 6.2 mean years of life compared with DE. CONCLUSION: In this simulation of 30,000 patients with obesity, CHF, and reduced EF, MBS was associated with improved survival by not only decreasing the need for transplantation due to improvements in EF, but also increasing access to HT when needed due to lower average BMI.

The IgG4 hinge with CD28 transmembrane domain improves VHH-based CAR T cells targeting a membrane-distal epitope of GPC1 in pancreatic cancer.

Heterogeneous antigen expression is a key barrier influencing the activity of chimeric antigen receptor (CAR) T cells in solid tumors. Here, we develop CAR T cells targeting glypican-1 (GPC1), an oncofetal antigen expressed in pancreatic cancer. We report the generation of dromedary camel VHH nanobody (D4)-based CAR T cells targeting GPC1 and the optimization of the hinge (H) and transmembrane domain (TM) to improve activity. We find that a structurally rigid IgG4H and CD28TM domain brings the two D4 fragments in proximity, driving CAR dimerization and leading to enhanced T-cell signaling and tumor regression in pancreatic cancer models with low antigen density in female mice. Furthermore, single-cell-based proteomic and transcriptomic analysis of D4-IgG4H-CD28TM CAR T cells reveals specific genes (e.g., HMGB1) associated with high T-cell polyfunctionality. This study demonstrates the potential of VHH-based CAR T for pancreatic cancer therapy and provides an engineering strategy for developing potent CAR T cells targeting membrane-distal epitopes.

Remote Activity Monitoring and Electronic Patient-Reported Outcomes Collection During Radiotherapy for Head and Neck Cancer: A Pilot Study.

PURPOSE: Modern wearable devices provide objective and continuous activity data that could be leveraged to enhance cancer care. We prospectively studied the feasibility of monitoring physical activity using a commercial wearable device and collecting electronic patient-reported outcomes (ePROs) during radiotherapy (RT) for head and neck cancer (HNC). METHODS: Patients planned for a course of external beam RT with curative intent for HNC were instructed to use a commercial fitness tracker throughout the RT course. During weekly clinic visits, physician-scored adverse events were recorded during using Common Terminology Criteria for Adverse Events version 4.0, and patients completed ePRO surveys using a clinic tablet or computer. Feasibility of activity monitoring was defined as collection of step data for at least 80% of the RT course for at least 80% of patients. Exploratory analyses described associations between step counts, ePROs, and clinical events. RESULTS: Twenty-nine patients with HNC were enrolled and had analyzable data. Overall, step data were recorded on 70% of the days during patients' RT courses, and there were only 11 patients (38%) for whom step data were collected on at least 80% of days during RT. Mixed effects linear regression models demonstrated declines in daily step counts and worsening of most PROs during RT. Cox proportional hazards models revealed a potential association between high daily step counts and both reduced risk of feeding tube placement (hazard ratio [HR], 0.87 per 1,000 steps, P < .001) and reduced risk of hospitalization (HR, 0.60 per 1,000 steps, P < .001). CONCLUSION: We did not achieve our feasibility end point, suggesting that rigorous workflows are required to achieve continuous activity monitoring during RT. Although limited by a modest sample size, our findings are consistent with previous reports indicating that wearable device data can help identify patients who are at risk for unplanned hospitalization.

Uncontrolled donation after cardiac death kidney transplantation: Opportunity to expand the donor pool?

BACKGROUND: Compared to controlled donation after cardiac death (cDCD), uncontrolled DCD (uDCD) kidney transplantation remains an underutilized resource in the United States. However, it is unclear whether long-term allograft outcomes following uDCD are inferior to that of cDCD kidney transplantation. METHODS: From January 1995 to January 2018, the OPTN/UNOS database was queried to discover all reported cases of uDCD and cDCD kidney transplantation. Primary non-function, delayed graft function, ten-year graft and patient survival were compared among uDCD and cDCD patients. RESULTS: Rates of primary non-function (4.0% [uDCD] vs. 1.8% [cDCD], P < 0.001) and delayed graft function (51.1% [uDCD] vs. 41.7% [cDCD], P < 0.001) were higher following uDCD transplant. However, ten-year graft survival (47.5% [uDCD] vs. 48.4% [cDCD], P = 0.21) and patient survival were similar to cDCD transplantation (59.4% [uDCD] vs. 59.2% [cDCD], P = 0.32). CONCLUSION: Although initial allograft outcomes are inferior following uDCD, long-term durability of uDCD kidney allografts is on par to cDCD transplantation. Kidney allografts derived by uDCD may be a viable and durable option to increase the donor pool.

Online information for incisional hernia repair: What are patients reading?

PURPOSE: Patients increasingly access online materials for health-related information. Using validated assessment tools, we aim to assess the quality and readability of online information for patients considering incisional hernia (IH) repair. METHODS: The top three online search engines (Google, Bing, Yahoo) were searched in July 2022 for "Incisional hernia repair" and "Surgical hernia repair". Included websites were classified as academic, hospital-affiliated, commercial, and unspecified. The quality of information was assessed using the Journal of the American Medical Association (JAMA) benchmark criteria (0-4), DISCERN instrument (16-80), and the presence of Health On the Net code (HONcode) certification. Readability was assessed using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level (FKGL) tests. RESULTS: 25 unique websites were included. The average JAMA and DISCERN scores of all websites were 0.68 ± 1.02 and 36.50 ± 10.91, respectively. Commercial sites showed a significantly higher DISCERN mean score than academic sites (p = 0.034), while no significant difference was demonstrated between other website categories. 3 (12%) websites reported HONcode certification and had significantly higher JAMA (p = 0.016) and DISCERN (p = 0.045) mean scores than sites without certification. Average FRE and FKGL scores were 39.84 ± 13.11 and 10.62 ± 1.76, respectively, corresponding to college- and high school-level comprehensibility. CONCLUSIONS: Our findings suggest online patient resources on IH repair are of poor overall quality and may not be comprehensible to the public. Patients accessing internet resources for additional information on IH repair should be made aware of these inadequacies and directed to sites bearing HONcode certification.

Definitive radiotherapy for meningeal brainstem melanocytoma: a case report.

Meningeal melanocytomas are rare, benign tumours of the central nervous system arising from the melanocytes of the leptomeninges. First-line treatment consists of either gross or subtotal resection with or without radiotherapy. However, given the sensitive locations of these tumours, alternative treatment options such as definitive radiotherapy may be warranted in patients deemed high-risk or without accessible tumours. A 67-year-old male presenting with spastic gait, frequent falls, and vertical gaze palsy was diagnosed with a 2.4 cm primary meningeal melanocytoma arising from the interpeduncular fossa. Given the critical tumour position within the brainstem, definitive radiotherapy was recommended. He received fractionated stereotactic radiotherapy (FSRT) to a total dose of 54 Gy in 27 fractions, resulting in a gradual improvement in gait and ocular range of motion. Follow-up imaging over the next three years revealed largely stable disease and an increase in edema with mild upper extremity weakness that improved with steroids. He was followed for three years and expired four years after treatment due to pneumonia. For patients unable to receive surgical resection, definitive RT may provide local control with minimal morbidity.

Quality and readability assessment of online patient information on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: We aim to assess the quality and readability of online information available to patients considering cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: The top three search engines (Google, Bing, and Yahoo) were searched in March 2022. Websites were classified as academic, hospital-affiliated, foundation/advocacy, commercial, or unspecified. Quality of information was assessed using the JAMA benchmark criteria (0-4) and DISCERN tool (16-80), and the presence of a Health On the Net code (HONcode) seal. Readability was evaluated using the Flesch Reading Ease score. RESULTS: Fifty unique websites were included. The average JAMA and DISCERN scores of all websites were 0.72 ± 1.14 and 39.58 ± 13.71, respectively. Foundation/advocacy websites had significantly higher JAMA mean score than commercial (p = 0.044), academic (p < 0.001), and hospital-affiliated websites (p = 0.001). Foundation/advocacy sites had a significantly higher DISCERN mean score than hospital-affiliated (p = 0.035) and academic websites (p = 0.030). The HONcode seal was present in 4 (8%) websites analyzed. Readability was difficult and at the level of college students. CONCLUSIONS: The overall quality of patient-oriented online information on CRS-HIPEC is poor and available resources may not be comprehensible to the general public. Patients seeking information on CRS-HIPEC should be directed to sites affiliated with foundation/advocacy organizations.

How safe is adolescent bariatric surgery? An analysis of short-term outcomes.

BACKGROUND: The prevalence of childhood obesity in the U.S. has tripled over the last three decades. However, fewer than 1% of children with severe obesity undergo surgical weight loss interventions each year. MATERIALS AND METHODS: All patients age 10 to 19 years old who underwent laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) from 2015 through 2018 in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database were included in this retrospective cohort analysis. The primary outcomes were mortality and overall complications. Procedural trends, readmission and reoperation rates were also examined using a multivariate regression model. RESULTS: Patients had a mean BMI of 47.3 kg/m2 and 80.0% were either 18 or 19 years old (n = 4,051). There were two reported deaths. Reoperation within 30 days occurred in 1.1% of patients, readmission in 3.5%, and complications in 1.2%. Among all readmissions, primary reasons included nausea/vomiting or nutritional depletion (41.3%) and abdominal pain (16.3%). RYGB was associated with higher odds for readmission (p = 0.006) and complications (p = 0.005). Higher BMI and younger age were not associated with an increased likelihood to experience poorer outcomes. The proportion of patients undergoing SG increased yearly over RYGB from 73.9% in 2015 to 84.3% in 2018. CONCLUSIONS: Bariatric surgery appears to be low risk for adolescents and SG has become the operation of choice. More research on early consideration of surgical therapy in adolescents with severe obesity is needed given the safety profile. LEVEL OF EVIDENCE: III.

Comparison of nontechnical skills grading rubrics for OR in situ simulation for general surgery and Obstetrician/Gynecologist residents.

BACKGROUND: This study utilized the Team Strategies and Tools to Enhance Performance and Patient Safety and the Nontechnical Skills for Surgeons grading systems to evaluate the nontechnical skills of general surgery and obstetrician/gynecologist residents to see if these grading systems were concordant. These simulations were also intended to teach about crisis resources available at our institution. METHODS: Nineteen teams were created consisting of either one general surgery resident or 2 Obstetrician/Gynecologist residents plus 2 Anesthesia residents and 2 to 4 nurses. Each team was given a short briefing on Team Strategies and Tools to Enhance Performance and Patient Safety, then performed 2 simulated operating room crises. All exercises were graded by 2 independent observers with experience in the operating room and in using the Team Strategies and Tools to Enhance Performance and Patient Safety and Nontechnical Skills for Surgeons grading systems. RESULTS: Averaged general surgery Team Strategies and Tools To Enhance Performance and Patient Safety score increased between scenarios (14.3-17; P ≤ .01), as did obstetrician/gynecologist Team Strategies and Tools to Enhance Performance and Patient Safety score (14.9-19.2; P ≤ .01). Averaged general surgery Nontechnical Skills for Surgeons score increased between scenarios (10.3-12.2; P ≤ .02), as did obstetrician/gynecologist Nontechnical Skills for Surgeons score (10.2-14.3; P ≤ .01). Surgery Team Strategies and Tools to Enhance Performance and Patient Safety scores demonstrated a strong correlation of movement with Nontechnical Skills for Surgeons scores (r = 0.83), as did obstetrician/gynecologist (r = 0.91). On average both general surgery (11%-100%; P ≤ .01) and obstetrician/gynecologist (50%-90%; P ≤ .01) saw a statistically significant increase in their awareness of the crisis checklist. CONCLUSION: Team Strategies and Tools to Enhance and Patient Safety scores and Nontechnical Skills for Surgeons are effective and concordant tools for gauging general surgery and obstetrician/gynecologist resident nontechnical skills. In situ simulations are an effective way to teach general surgery and obstetrician/gynecologist residents about available crisis resources.

Reverse epidemiology and the obesity paradox for patients with chronic kidney disease: a Markov decision model.

BACKGROUND: Obesity has been associated with both increased progression of chronic kidney disease (CKD) as well as with a paradoxical improvement in survival among end-stage renal disease patients undergoing hemodialysis. As such, the optimal weight management strategy for obese CKD patients remains unclear. OBJECTIVE: To estimate the outcomes of obese, CKD stage 3b patients after 3 weight loss interventions, including medical weight management, sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB), were followed to determine which strategy optimizes long-term survival. SETTING: University hospital, Aurora, Colorado. METHODS: A decision analytic Markov state transition model was created to simulate the life of 30,000 obese patients with CKD stage 3b, as they progressed to end-stage renal disease, transplantation, and death. Life expectancy after conservative medical weight management, RYGB, and SG were estimated. Base case patients were defined as being 50 years old and having a preintervention BMI of 40 kg/m2. Sensitivity analysis of initial BMI was performed. All Markov parameters were extracted from literature review. RESULTS: RYGB and SG were associated with improved survival for patients with preintervention body mass index of >38 kg/m2. Compared with conservative weight management, base case patients who underwent RYGB gained 10.6 months of life, and gained 8.3 months of life after SG. CONCLUSIONS: Balancing progression of CKD with improved survival on end-stage renal disease for obese patients requires selective use of weight management strategies. RYGB and SG improved survival for CKD patients with Class II and III obesity, but not for patients with Class I obesity. As such, aggressive weight loss interventions should be reserved for patients with Class II and III obesity, while more conservative methods should be offered to those with Class I obesity.

STEP improves long-term survival for pediatric short bowel syndrome patients: A Markov decision analysis.

INTRODUCTION: Increasingly, for pediatric patients with short bowel syndrome (SBS), intestinal lengthening procedures such as serial transverse enteroplasty (STEP) are being offered with the hope of improving patients' chances for achieving enteral autonomy. However, it remains unclear to what extent STEP reduces the long-term need for intestinal transplant or improves survival. METHODS: Based on existing literature, a decision analytic Markov state transition model was created to simulate the life of 1,000 pediatric SBS patients. Two simulations were modeled: 1) No STEP: patients were listed for transplant once medical management failed and 2) STEP: patients underwent STEP therapy and subsequent transplant listing if enteral autonomy was not achieved. Sensitivity analysis of small bowel length and anatomy was completed. Base case patients were defined as neonates with a small bowel length of 30cm. RESULTS: For base case patients with an ostomy and a NEC SBS etiology, STEP was associated with increased rates of enteral autonomy after 10 years for patients with an ICV (53.9% [STEP] vs. 51.1% [No STEP]) and without an ICV (43.4% [STEP] vs. 36.3% [No STEP]). Transplantation rates were also reduced following STEP therapy for both ICV (17.5% [STEP] vs. 18.2% [No STEP]) and non-ICV patients (20.2% [STEP] vs. 22.1% [No STEP]). 10-year survival was the highest in the (+) STEP and (+) ICV group (85.4%) and lowest in the (-) STEP and (-) ICV group (83.3%). CONCLUSIONS: For SBS patients, according to our model, STEP increases rates of enteral autonomy, reduces need for intestinal transplantation, and improves long-term survival. TYPE OF STUDY: Economic/Decision Analysis or Modeling Studies LEVEL OF EVIDENCE: Level III.

Sleeve Gastrectomy Compared with Gastric Bypass for Morbidly Obese Patients with End Stage Renal Disease: a Decision Analysis.

INTRODUCTION: The use of bariatric surgery has increased for morbidly obese patients with end stage renal disease (ESRD) for whom listing on the waitlist is often restricted until a certain BMI threshold is achieved. Effective weight loss for this population improves access to life-saving renal transplantation. However, it is unclear whether sleeve gastrectomy (SG) vs Roux-en-Y gastric bypass (RYGB) is a more effective therapy for these patients. METHODS: A decision analytic Markov state transition model was created to simulate the life of morbidly obese patients with ESRD who were deemed ineligible to be waitlisted for renal transplantation unless they achieved a BMI less than 35 kg/m2. Life expectancy following weight management (MWM), RYGB, and SG were estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. Markov parameters were extracted from literature review. RESULTS: RYGB improved survival compared with SG and MWM. RYGB patients had higher rates of transplantation, leading to improved mean long-term survival. Base case patients who underwent RYGB gained 1.3 additional years of life compared with patient's who underwent SG and 2.6 additional years of life compared with MWM. CONCLUSIONS: RYGB improves access to renal transplantation and thereby increases long-term survival compared with SG and MWM. The use of SG may be incongruent with the goal of improving access to renal transplantation for morbidly obese patients.