Attenuated Dengue virus PV001-DV induces oncolytic tumor cell death and potent immune responses.

BACKGROUND: Viral therapies developed for cancer treatment have classically prioritized direct oncolytic effects over their immune activating properties. However, recent clinical insights have challenged this longstanding prioritization and have shifted the focus to more immune-based mechanisms. Through the potential utilization of novel, inherently immune-stimulating, oncotropic viruses there is a therapeutic opportunity to improve anti-tumor outcomes through virus-mediated immune activation. PV001-DV is an attenuated strain of Dengue virus (DEN-1 #45AZ5) with a favorable clinical safety profile that also maintains the potent immune stimulatory properties characterstic of Dengue virus infection. METHODS: In this study, we utilized in vitro tumor killing and immune multiplex assays to examine the anti-tumor effects of PV001-DV as a potential novel cancer immunotherapy. RESULTS: In vitro assays demonstrated that PV001-DV possesses the ability to directly kill human melanoma cells lines as well as patient melanoma tissue ex vivo. Importantly, further work demonstrated that, when patient peripheral blood mononuclear cells (PBMCs) were exposed to PV001-DV, a substantial induction in the production of apoptotic factors and immunostimulatory cytokines was detected. When tumor cells were cultured with the resulting soluble mediators from these PBMCs, rapid cell death of melanoma and breast cancer cell lines was observed. These soluble mediators also increased dengue virus binding ligands and immune checkpoint receptor, PD-L1 expression. CONCLUSIONS: The direct in vitro tumor-killing and immune-mediated tumor cytotoxicity facilitated by PV001-DV contributes support of its upcoming clinical evaluation in patients with advanced melanoma who have failed prior therapy.

Pancreatic Exocrine Secretion and Weight Gain After Pancreas Transplantation.

INTRODUCTION: Weight gain after pancreas transplant is a poorly understood phenomenon thought to be related to increased posttransplant insulin production, immunosuppressive medications, and appetite changes. No study has investigated the effect of increased exocrine secretion posttransplant. AIMS AND HYPOTHESIS: We hypothesized that exocrine function, measured by fecal elastase-1 (FE-1), was normal posttransplant and not correlated with weight gain. Our primary aim was to investigate changes in FE-1 levels with pancreas transplantation and to correlate this with weight gain. Establishing weight trends and identifying additional correlating factors were secondary aims. DESIGN: Forty-two patients that underwent simultaneous pancreas and kidney or pancreas after kidney transplant at a single center between 2013 and 2021 were included. Fecal elastase was measured prospectively in each patient at a single time point, with >500 µg/g categorized as high. Weight and C-peptide values were obtained. All the patients were on steroid-free immunosuppression. RESULTS: Nineteen patients (45%) had fecal elastase levels >500 µg/g, with a maximum of 3910 µg/g; 43% had levels greater than twice the upper limit of normal. The biggest increase in weight occurred between years 1 and 2, which continued to a median weight gain of 14% at 3 years. There was no correlation between weight gain and FE-1, pretransplant C-peptide levels, or duration of diabetes. CONCLUSION: This study demonstrated supranormal fecal elastase levels and weight gain posttransplant; however, there was no correlation. Future study with serial FE-1 before and after transplant is needed to better assess its correlation with weight gain.

Ursodiol Prescriptions Following Bariatric Surgery: National Prescribing Trends and Outcomes.

BACKGROUND: Rapid weight loss after bariatric surgery is a risk factor for gallstone development. Numerous studies have shown that ursodiol after surgery decreases rates of gallstone formation and cholecystitis. Real-world prescribing practices are unknown. This study aimed to examine prescription patterns for ursodiol and reassess its impact on gallstone disease using a large administrative database. METHODS: The Mariner database (PearlDiver, Inc.) was queried using Current Procedural Terminology codes for Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between 2011 and 2020. Only patients with International Classification of Disease codes for obesity were included. Patients with pre-operative gallstone disease were excluded. The primary outcome was gallstone disease within 1 year, which was compared between patients who did and did not receive an ursodiol prescription. Prescription patterns were also analyzed. RESULTS: Three hundred sixty-five thousand five hundred patients fulfilled inclusion criteria. Twenty-eight thousand seventy-five (7.7%) patients were prescribed ursodiol. There was a statistically significant difference in development of gallstones (p < 0.001), development of cholecystitis (p = .049), and undergoing cholecystectomy (p < 0.001). There was a statistically significant decrease in the adjusted odds ratio (aOR) for the development of gallstones (aOR 0.81, 95% CI: 0.74, 0.89), development of cholecystitis (aOR 0.59, 95% CI: 0.36, 0.91), and undergoing cholecystectomy (aOR 0.75, 95% CI: 0.69, 0.81). CONCLUSION: Ursodiol significantly decreases the odds of development of gallstones, cholecystitis, or cholecystectomy within 1 year following bariatric surgery. These trends hold true when analyzing RYGB and SG separately. Despite the benefit of ursodiol, only 10% of patients received an ursodiol prescription postoperatively in 2020.

Refractory Immune Thrombocytopenic Purpura with Abdominal Splenosis: A Complex Case.

Immune thrombocytopenia (ITP) is an acquired thrombocytopenia resulting from immune-mediated platelet destruction via antiplatelet antibodies and T cells. Medical management of ITP includes corticosteroids and multiple other adjunct therapies, with splenectomy generally being reserved for severe, refractory cases. In this clinical case report, we describe the evaluation of a 35-year-old male with a history of prior traumatic splenic injury who presented to the emergency department endorsing easy bruising and a petechial rash, ultimately found to have severe thrombocytopenia. The patient was diagnosed with primary ITP that proved to be refractory to a number of first- and second-line medical therapies. His course was complicated by the presence of abdominal splenosis discovered at the time of planned splenectomy and intra-abdominal hemorrhage requiring splenic artery embolization thereafter. To our knowledge, this is one of few published cases of ITP complicated by abdominal splenosis, highlighting the need to consider splenosis and the presence of accessory splenic tissue in cases of refractory ITP.

Laser Ablation of Pilonidal Sinus Disease: A Pilot Study.

BACKGROUND: Pilonidal disease is classically treated with wide local excision, although a number of minimally invasive approaches are currently under investigation. We aimed to determine the safety and feasibility of laser ablation of pilonidal sinus disease. IMPACT OF INNOVATION: Laser ablation provides a minimally invasive means of obliterating pilonidal sinus tracts without a need for excessive tract dilation. Laser ablation can be performed more than once on the same patient if necessary. TECHNOLOGY MATERIALS AND METHODS: This technique uses the NeoV V1470 Diode Laser (neoLaser Ltd, Caesarea, Israel) with a 2-mm probe. We performed laser ablation in adults and pediatric patients. PRELIMINARY RESULTS: We performed 27 laser ablation procedures in 25 patients, with a median operative time of 30 minutes. Eighty percent of patients reported either no pain or mild pain at the 2-week postoperative visit. The median time to return to work or school was 3 days. Eighty-eight percent of patients reported being satisfied or very satisfied with the procedure at their most recent follow-up (median, 6 mo). Eighty-two percent of patients were healed at 6 months. CONCLUSIONS AND FUTURE DIRECTIONS: Laser ablation of pilonidal disease is safe and feasible. Patients experienced short recovery time and reported low levels of pain and high levels of satisfaction.

Prophylactic antireflux procedures are not necessary in neurologically impaired children undergoing gastrostomy placement.

PURPOSE: Fundoplication is frequently used in children with neurologic impairment even in the absence of reflux due to concerns for future gastric feeding intolerance, but supporting data are lacking. We aimed to determine the incidence of secondary antireflux procedures (fundoplication or gastrojejunostomy (GJ)) post gastrostomy tube (GT) placement in children with and without neurologic impairment. METHODS: Children under 18 undergoing a GT placement without fundoplication between 2010 and 2020 were identified utilizing the PearlDiver Mariner national patient claims database. Children with a diagnosis of cerebral palsy or a degenerative neurologic disease were identified and compared to children without these diagnoses. The incidence of delayed fundoplication or conversion to GJ were compared utilizing Kaplan-Meier and Cox proportional hazards regression analyses. RESULTS: A total of 14,965 children underwent GT placement, of which 3712 (24.8%) had a diagnosis of neurologic impairment. The rate of concomitant fundoplication was significantly higher among children with a diagnosis of neurologic impairment as compared to those without (9.3% vs 6.4%, p < 0.001). While children with neurologic impairment had a significantly higher rate of fundoplication or GJ conversion at 5 years compared to children without (12.6% [95% confidence interval (CI): 11.4%-13.8%] vs 8.6% [95% CI 8.0%-9.2%], p < 0.001), the overall incidence remained low. CONCLUSION: Although children with neurologic impairment have a higher rate of requiring an antireflux procedure or GJ conversion than other children, the overall rate remains less than 15%. Fundoplication should not be utilized in children without clinical reflux on the basis of neurologic impairment alone.

Accuracy of Surgeon and Patient Estimated Cost and Reimbursement for Common General Surgical Operations and Benefit of Centers for Medicare and Medicaid Services Price Transparency Rules.

BACKGROUND: On January 1, 2021, the Centers for Medicare and Medicaid Services implemented a hospital price transparency rule. Consumerism as a means of reducing healthcare expenditure is predicated on informed consumers making discrete choices. STUDY DESIGN: For 10 months, immediately after a preoperative clinic visit at an academic medical center, patients and their surgeons were surveyed regarding their estimation of hospital cost and hospital reimbursement for the upcoming operation. Responses were compared to average institutional cost (fiscal year 2019) for Medicare patients undergoing a laparoscopic approach for each operation. We calculated the difference between actual reimbursement and cost with patients' estimates and actual reimbursement and cost with surgeons' estimates. RESULTS: Sixty-six questionnaires were collected from patients who underwent laparoscopic operations, that included cholecystectomy (n = 20), inguinal hernia (n = 17), umbilical hernia repair (n = 6), ventral hernia repair (n = 6), incisional hernia (n = 6), hiatal hernia repair (n = 1), and lipoma or cyst excision (n = 10). Patients' estimates of hospital cost exceeded actual hospital cost by a median of $4,502 and were less than hospital reimbursement by a median of $1,834. Surgeon estimates for direct cost were $825 less than hospital direct cost and $1,659 less than hospital reimbursement. CONCLUSIONS: Patients as well as their surgeons do not estimate healthcare cost or remuneration accurately and therefore will be ineffective change agents in reducing surgical spending based on price transparency without further education of both parties. Patients consistently overestimated surgical cost while surgeons consistently underestimated surgical cost and reimbursement. It is likely that better-informed surgeons and patients are necessary prerequisites for Centers for Medicare and Medicaid Services price transparency rules to be effective in reducing Medicare expenditures in surgery.

Mediating Factors Between Race and Time to Treatment in Colorectal Cancer.

BACKGROUND: Previous disparities research has demonstrated that underrepresented racial minority patients have worse colorectal cancer outcomes and that they experience unnecessary delays in time to treatment. These delays may explain worse colorectal cancer outcomes for minority patients and serve as a marker of inequalities in our healthcare system. OBJECTIVE: This study aims to quantify the mechanisms that contribute to this disparity in treatment delay. DESIGN: This is a retrospective analysis of colorectal cancer patients who underwent elective resection from 2004 to 2017. A causal inference mediation analysis using the counterfactual framework was utilized to estimate the extent to which racial disparities among patient factors explain the racial disparities in time to treatment. Mediators included income, education, comorbidities, insurance, and hospital type. SETTINGS: This study was conducted at hospitals participating in the National Cancer Database. PATIENTS: Stage I-III colorectal cancer patients, ≥18 years old, who underwent elective resection from 2004 through 2017 were included. MAIN OUTCOMES MEASURES: The primary measures were indirect effects of mediators between race and delayed time to treatment. RESULTS: Of the 504,405 patients (370,051 colon and 134,354 rectal), 10%, 5%, and 4% were black, Hispanic, and other. In multivariable models, compared to white patients, these patients had 25%, 27%, and 17% greater odds of delayed treatment. Mediation analyses suggested that 43%, 20%, and 31% of the treatment delay among them could be removed if an intervention equalized income, education, comorbidities, insurance, and hospital type to that of white patients. Treatment at an academic hospital explained 15% to 32% of the racial disparity and was the most potent mediator. LIMITATIONS: This study was limited by its retrospective design and failure to capture all meaningful mediators. CONCLUSIONS: Black, Hispanic, and other colorectal cancer patients experience treatment delays when compared to white patients. Equalization of the mediators used in this study could reduce treatment delays by 20% to 43% depending on the racial/ethnic group. Future research should identify other causes of racial disparities in treatment delay and intervene accordingly. See Video Abstract at http://links.lww.com/DCR/B871 . FACTORES MEDIADORES ENTRE LA RAZA Y EL TIEMPO HASTA EL TRATAMIENTO EN EL CNCER COLORECTAL: ANTECEDENTES:Investigaciones anteriores sobre disparidades han demostrado que los pacientes de minorías raciales subrepresentados tienen peores resultados de cáncer colorrectal y que experimentan retrasos innecesarios en el tiempo de tratamiento. Estos retrasos pueden explicar los peores resultados del cáncer colorrectal para los pacientes de minorías y servir como un marcador de desigualdades en nuestro sistema de salud.OBJETIVO:Este estudio tiene como objetivo cuantificar los mecanismos que contribuyen a esta disparidad en el retraso del tratamiento.DISEÑO:Este es un análisis retrospectivo de pacientes con cáncer colorrectal que se sometieron a resección electiva entre 2004 y 2017. Se utilizó un análisis de mediación de inferencia causal utilizando el marco contra factual para estimar hasta qué punto las disparidades raciales entre los factores del paciente explican las disparidades raciales en el tiempo hasta el tratamiento. Los mediadores incluyeron ingresos económicos, educación, comorbilidades, seguro médico y tipo de hospital.AJUSTES:Este estudio se realizó en hospitales que participan en la Base de datos nacional del cáncer.PACIENTES:Se incluyeron pacientes con cáncer colorrectal en estadio I-III, ≥18 años, que se sometieron a resección electiva entre 2004 y 2017.PRINCIPALES RESULTADOS MEDIDAS:Las principales mediciones fueron el efecto indirecto de los mediadores entre la raza y el retraso en el tratamiento.RESULTADOS:De los 504,405 pacientes (370,051 de colon, 134,354 rectal), 10%, 5%, 4% eran negros, hispanos, y otros, respectivamente. En modelos multivariables, en comparación con los pacientes blancos, estos pacientes tenían un 25%, 27%, y 17% más de probabilidades de retrasar el tratamiento. Los análisis de medición sugirieron que el 43%, 20%, 31% del retraso del tratamiento entre, respectivamente, podría eliminarse si una intervención igualara los ingresos económicos, la educación, las comorbilidades, el seguro médico y el tipo de hospital a los de los pacientes blancos. El tratamiento en un hospital académico demostró entre el 15% y el 32% de la disparidad racial y fue el mediador más potente.LIMITACIONES:Este estudio estuvo limitado por su diseño retrospectivo; falla en capturar a todos los mediadores significativos.CONCLUSIONES:Los pacientes negros, hispanos y otros con cáncer colorrectal experimentan retrasos en el tratamiento en comparación con los pacientes blancos. La igualación de los mediadores utilizados en este estudio podría reducir los retrasos en el tratamiento en un 20-43%, según el grupo racial / étnico. Las investigaciones futuras deberían identificar otras causas de disparidades raciales en el retraso del tratamiento e intervenir sobre ellas. Consulte Video Resumen en http://links.lww.com/DCR/B871 . (Traducción-Dr. Yolanda Colorado ).

Associations of Race, Ethnicity, and Social Determinants of Health With Colorectal Cancer Screening.

BACKGROUND: Racial and ethnic disparities in receipt of recommended colorectal cancer screening exist; however, the impact of social determinants of health on such disparities has not been recently studied in a national cohort. OBJECTIVE: This study aimed to determine whether social determinants of health attenuate racial disparities in receipt of colorectal cancer screening. DESIGN: This was a cross-sectional telephone survey of self-reported race and ethnicity and up-to-date colorectal cancer screening. Associations between race/ethnicity and colorectal cancer screening were tested before and after adjustment for demographics, behavioral factors, and social determinants of health. SETTING: This was a nationally representative telephone survey of US residents in 2018. PATIENTS: The patients included were US residents aged 50 to 75 years. MAIN OUTCOME MEASURES: The primary outcome was up-to-date colorectal cancer screening status, according to 2008 US Preventive Services Task Force recommendations. RESULTS: This study included 226,106 respondents aged 50 to 75 years. Before adjustment, all minority racial and ethnic groups demonstrated a significantly lower odds of screening than those of non-Hispanic white respondents. After adjustment for demographics, behavioral factors, and social determinants of health, compared to non-Hispanic white respondents, odds of screening were found to be increased among non-Hispanic black respondents (OR, 1.10; p = 0.02); lower but attenuated among Hispanic respondents (OR, 0.73; p < 0.001), non-Hispanic American Indian/Alaskan Native respondents (OR, 0.85; p = 0.048), and non-Hispanic respondents of other races (OR, 0.82; p = 0.01); and lower but not attenuated among non-Hispanic Asian respondents (OR, 0.68; p < 0.001). LIMITATIONS: Recall bias, participant bias, and residual confounding. CONCLUSIONS: Adjustment for social determinants of health reduced racial and ethnic disparities in colorectal cancer screening among all minority racial and ethnic groups except non-Hispanic Asian individuals; however, other unmeasured confounders likely exist. See Video Abstract at http://links.lww.com/DCR/B977 . ASOCIACIN DE RAZA, ETNICIDAD Y DETERMINANTES SOCIALES DE LA SALUD CON LA DETECCIN DEL CNCER COLORRECTAL: ANTECEDENTES: Existen disparidades raciales y étnicas en la recepción de las pruebas recomendadas de detección de cáncer colorrectal; sin embargo, el impacto de los determinantes sociales de la salud en dichas disparidades no se ha estudiado recientemente en una cohorte nacional.OBJETIVO: El objetivo de este estudio fue determinar si los determinantes sociales de la salud atenúan las disparidades raciales en la recepción de pruebas de detección del cáncer colorrectal.DISEÑO: Encuesta telefónica transversal de raza y etnia autoinformada y detección actualizada de cáncer colorrectal. Las asociaciones entre la raza/etnicidad y la detección del cáncer colorrectal se probaron antes y después del ajuste por demografía, factores conductuales y determinantes sociales de la salud.ESCENARIO: Esta fue una encuesta telefónica representativa a nivel nacional de los residentes de EE. UU. en 2018.PACIENTES: Los pacientes eran residentes de EE. UU. de 50 a 75 años.PRINCIPALES MEDIDAS DE RESULTADO: Estado actualizado de detección de cáncer colorrectal, según las recomendaciones del Grupo de Trabajo de Servicios Preventivos de EE. UU. de 2008.RESULTADOS: Este estudio incluyó a 226.106 encuestados de 50 a 75 años. Antes del ajuste, todos los grupos étnicos y raciales minoritarios demostraron probabilidades significativamente más bajas de detección en comparación con los encuestados blancos no hispanos. Después del ajuste por demografía, factores conductuales y determinantes sociales de la salud, en comparación con los encuestados blancos no hispanos, las probabilidades de detección aumentaron entre los encuestados negros no hispanos (OR 1,10, p = 0,02); más bajo pero atenuado entre los encuestados hispanos (OR 0,73, p < 0,001), los encuestados indios americanos/nativos de Alaska no hispanos (OR 0,85, p = 0,048) y los encuestados no hispanos de otras razas (OR 0,82, p = 0,01); y menor pero no atenuado entre los encuestados asiáticos no hispanos (OR 0,68, p < 0,001).LIMITACIONES: Sesgo de recuerdo y sesgo de participante, así como confusión residual.CONCLUSIONES: El ajuste para los determinantes sociales de la salud redujo las disparidades raciales y étnicas en la detección del cáncer colorrectal entre todos los grupos étnicos y raciales minoritarios, excepto las personas asiáticas no hispanas; sin embargo, es probable que existan otros factores de confusión no medidos. Consulte Video Resumen en http://links.lww.com/DCR/B977 . (Traducción-Dr. Felipe Bellolio ).

Effect of Operative Time on Outcomes of Minimally Invasive Versus Open Pancreatoduodenectomy.

OBJECTIVE: To evaluate how operative time interacts with outcomes among different approaches to pancreaticoduodenectomy (PD). Minimally invasive PDs (MIPD), which include laparoscopic (LPD) and robotic (RPD) approaches, are increasingly performed in the USA. MIPD are generally associated with longer operative times (OT) compared to open PD (OPD). Increased OT is associated with inferior outcomes for OPD; however, the effect of OT on MIPD is not well understood. METHODS: National Surgical Quality Improvement Program (NSQIP)-targeted pancreatectomy dataset was utilized (2014-2019). Propensity score matching, logistic regression, and mixed effect modeling were performed to determine the effect of OT on outcomes following PD. OTs were stratified by quartiles for each approach, and outcomes were subsequently compared. RESULTS: Among 23,988 PDs, 22,185 were OPD and 1803 MIPD. Increased OT was associated with greater overall morbidity in all approaches. When comparing OT quartiles, MIPD was consistently associated with improved overall morbidity compared to OPD in matched cohorts. However, for upper quartiles, prolonged OT in MIPD was associated with significantly increased reoperation rates and mortality. The effect of OT on overall morbidity and other outcomes was comparable among LPD and RPD. CONCLUSIONS: In this study, increased OT was associated with incremental increases in overall morbidity after PD, irrespective of approach. While MIPD was associated with improved overall morbidity compared to OPD when stratified by OT quartile, higher mortality rates were observed with prolonged OT only with MIPD. Those data suggest that MIPD is a safe alternative to OPD when OT is optimized. NSQIP was used to compare the effect of operative time (OT) on outcomes following pancreaticoduodenectomy (PD), stratified by approach. Increased OT was associated with inferior outcomes following open, laparoscopic, and robotic PD. Surgeons should attempt to optimize OT, regardless of the approach to PD.

Identifying individual social risk factors using unstructured data in electronic health records and their relationship with adverse clinical outcomes.

Objective: To determine the prevalence of individual-level social risk factors documented in unstructured data from electronic health records (EHRs) and the relationship between social risk factors and adverse clinical outcomes. Study setting: Inpatient encounters for adults (≥18 years) at the University of Virginia Medical Center during a 12-month study period between July 2018 and June 2019. Inpatient encounters for labor and delivery patients were excluded, as well as encounters where the patient was discharged to hospice, left against medical advice, or expired in the hospital. The study population included 21,402 inpatient admissions, representing 15,116 unique patients who had at least one inpatient admission during the study period. Study design: We identified measures related to individual social risk factors in EHRs through existing workflows, flowsheets, and clinical notes. Multivariate binomial logistic regression was performed to determine the association of individual social risk factors with unplanned inpatient readmissions, post-discharge emergency department (ED) visits, and extended length of stay (LOS). Other predictors included were age, sex, severity of illness, location of residence, and discharge destination. Results: Predictors of 30-day unplanned readmissions included severity of illness (OR = 3.96), location of residence (OR = 1.31), social and community context (OR = 1.26), and economic stability (OR = 1.37). For 30-day post-discharge ED visits, significant predictors included location of residence (OR = 2.56), age (OR = 0.60), economic stability (OR = 1.39), education (OR = 1.38), social and community context (OR = 1.39), and neighborhood and built environment (OR = 1.61). For extended LOS, significant predictors were age (OR = 0.51), sex (OR = 1.18), severity of illness (OR = 2.14), discharge destination (OR = 2.42), location of residence (OR = 0.82), economic stability (OR = 1.14), neighborhood and built environment (OR = 1.31), and education (OR = 0.79). Conclusions: Individual-level social risk factors are associated with increased risk for unplanned hospital readmissions, post-discharge ED visits, and extended LOS. While individual-level social risk factors are currently documented on an ad-hoc basis in EHRs, standardized SDoH screening tools using validated metrics could help eliminate bias in the collection of SDoH data and facilitate social risk screening.

Two unique cases of Bouveret syndrome with review of literature.

Bouveret syndrome is a rare form of gallstone ileus in which a proximally lodged gallstone in the duodenum causes a gastric outlet obstruction. It is a rare condition that can be challenging to manage. Although endoscopic management remains first line, a surgical approach can be needed. We present two cases of Bouveret syndrome. A 65-year-old man with oral squamous cell carcinoma treated with endoscopic management and a 63-year-old woman treated with surgery.

Early Experience Using Donor-derived Cell-free DNA for Surveillance of Rejection Following Simultaneous Pancreas and Kidney Transplantation.

Background: Allograft biopsy is the gold standard for diagnosing graft rejection following simultaneous pancreas and kidney (SPK) transplant. Intraperitoneal biopsies are technically challenging and can be burdensome to patients and the healthcare system. Donor-derived cell-free DNA (dd-cfDNA) is well-studied in kidney transplant recipients; however, it has not yet been studied in the SPK population. Methods: We hypothesized that dd-cfDNA could be utilized for rejection surveillance following SPK transplant. We prospectively collected dd-cfDNA in 46 SPK patients at a single institution. Results: There were 10 rejection events, 5 of which were confirmed with biopsy. The other 5 were treated based on dd-cfDNA and clinical data alone with favorable outcomes. Among all patients who did not have rejection, 97% had dd-cfDNA <0.5%. Dd-cfDNA may also help differentiate rejection from graft injury (ie, pancreatitis) with median values in rejection 2.25%, injury 0.36%, and quiescence 0.18% (P = 0.0006). Conclusions: Similar to kidneys, dd-cfDNA shows promise for rejection surveillance in SPK transplant recipients.

A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial Cells.

BACKGROUND & AIMS: Pancreatic islet ß-cells are factories for insulin production; however, ectopic expression of insulin also is well recognized. The gallbladder is a next-door neighbor to the developing pancreas. Here, we wanted to understand if gallbladders contain functional insulin-producing cells. METHODS: We compared developing and adult mouse as well as human gallbladder epithelial cells and islets using immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assays, RNA sequencing, real-time polymerase chain reaction, chromatin immunoprecipitation, and functional studies. RESULTS: We show that the epithelial lining of developing, as well as adult, mouse and human gallbladders naturally contain interspersed cells that retain the capacity to actively transcribe, translate, package, and release insulin. We show that human gallbladders also contain functional insulin-secreting cells with the potential to naturally respond to glucose in vitro and in situ. Notably, in a non-obese diabetic (NOD) mouse model of type 1 diabetes, we observed that insulin-producing cells in the gallbladder are not targeted by autoimmune cells. Interestingly, in human gallbladders, insulin splice variants are absent, although insulin splice forms are observed in human islets. CONCLUSIONS: In summary, our biochemical, transcriptomic, and functional data in mouse and human gallbladder epithelial cells collectively show the evolutionary and developmental similarities between gallbladder and the pancreas that allow gallbladder epithelial cells to continue insulin production in adult life. Understanding the mechanisms regulating insulin transcription and translation in gallbladder epithelial cells would help guide future studies in type 1 diabetes therapy.

Can Donor-Derived Cell-Free DNA Detect Graft-Versus-Host Disease in Solid Organ Transplantation: A Case Report.

Graft-versus-host disease (GVHD) is a rare complication after solid organ transplant. We present a case of GVHD after simultaneous pancreas kidney transplant. The patient was diagnosed with a cutaneous biopsy after developing the classic symptoms of maculopapular rash, diarrhea, and pancytopenia. However, this patient had unexplained elevations in donor-derived cell-free DNA (dd-cfDNA) for months before the onset of GVHD symptoms. We hypothesize that GVHD may be associated with elevated dd-cfDNA as a result of massive donor lymphocyte proliferation and turnover. Further investigation is warranted because earlier diagnosis and treatment could improve outcomes in an otherwise lethal disease.

Variation in bariatric surgery utilization by state from 2010 to 2019: analysis of the PearlDiver Mariner database.

BACKGROUND: Bariatric surgery is the most effective treatment for severe obesity and its associated complications, but it remains underutilized. The degree to which bariatric surgery utilization varies by state is unclear. OBJECTIVES: The aim of this study was to quantify variation in bariatric surgery utilization across U.S. states. SETTING: United States. METHODS: Patients who underwent sleeve gastrectomy or gastric bypass and patients with body mass index (BMI) >40 or BMI >35 with comorbidities between 2010 and 2019 were identified with Current Procedural Terminology, International Classification of Diseases-9 and -10 codes using the PearlDiver Mariner insurance claims database. Patients living in Puerto Rico and other U.S. territories were excluded. RESULTS: A total of 99,173 bariatric surgery patients were identified out of 1,789,457 patients eligible for bariatric surgery between 2010 and 2019 (5.5%). Bariatric surgery patients were more likely to be female (78.8% versus 65.6%) and have commercial insurance (81.4% versus 69.6%) compared with eligible patients who did not undergo bariatric surgery. Bariatric surgery utilization varied widely between states, from 10.4% in New Jersey to 2.1% in Vermont. The Northeast region had the highest rates at 7.95%, and the Midwest had the lowest at 4.47%. The proportion of bariatric surgeries that were sleeve gastrectomies also varied from <30% in Alaska, North Dakota, and Rhode Island to >80% in New Jersey, Nevada, and Mississippi. CONCLUSION: There is significant variation in bariatric surgery utilization between states, with almost a 5-fold difference between the states with the highest and lowest utilization.

The effect of bariatric surgery on ischemic stroke risk.

BACKGROUND: Metabolic and bariatric surgery (MBS) has demonstrated improvements in diabetes and cardiovascular health. The effect of MBS on the risk of ischemic stroke remains unclear. OBJECTIVES: The goal of this study was to determine the risk of stroke following MBS compared with patients with obesity who qualified for but did not undergo MBS. SETTING: The Mariner Database, a national claims database. METHODS: We identified patients with body mass index (BMI) ≥40 or those with a BMI and a qualifying co-morbidity, who underwent MBS between 2010 to 2019. Similar patients who did not undergo MBS served as controls. Coarsened exact matching was performed followed by logistic regression analysis to determine the effect of BMS on stroke risk. RESULTS: A total of 70 622 BMS patients and 1 320 182 MBS-eligible controls were identified. After matching, the 1-year stroke risk among MBS patients (n = 56 514) versus controls (n = 56 514) was .6% versus 1.2% (OR .54, 95% CI .47-.61). The 5-year stroke risk for MBS (n = 27619) versus control (n = 27619) was 2.8% versus 3.6% (OR .78, 95% CI .65-.90). CONCLUSION: MBS appears to reduce the risk of stroke following surgery. To our knowledge, this is the largest sample size in a study of ischemic cerebrovascular disease in bariatric surgery.