Mara, Kristin

Objective The diagnosis of autoimmune pancreatitis (AIP) is challenging. Sonographic and cross-sectional imaging findings of AIP closely mimic pancreatic ductal adenocarcinoma (PDAC) and techniques for tissue sampling of AIP are suboptimal. These limitations often result in delayed or failed diagnosis, which negatively impact patient management and outcomes. This study aimed to create an endoscopic ultrasound (EUS)-based convolutional neural network (CNN) model trained to differentiate AIP from PDAC, chronic pancreatitis (CP) and normal pancreas (NP), with sufficient performance to analyse EUS video in real time. Design A database of still image and video data obtained from EUS examinations of cases of AIP, PDAC, CP and NP was used to develop a CNN. Occlusion heatmap analysis was used to identify sonographic features the CNN valued when differentiating AIP from PDAC. Results From 583 patients (146 AIP, 292 PDAC, 72 CP and 73 NP), a total of 1 174 461 unique EUS images were extracted. For video data, the CNN processed 955 EUS frames per second and was: 99% sensitive, 98% specific for distinguishing AIP from NP; 94% sensitive, 71% specific for distinguishing AIP from CP; 90% sensitive, 93% specific for distinguishing AIP from PDAC; and 90% sensitive, 85% specific for distinguishing AIP from all studied conditions (ie, PDAC, CP and NP). Conclusion The developed EUS-CNN model accurately differentiated AIP from PDAC and benign pancreatic conditions, thereby offering the capability of earlier and more accurate diagnosis. Use of this model offers the potential for more timely and appropriate patient care and improved outcome.

Abstract Background Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI. Methods We conducted a retrospective study of adults undergoing FMT for recurrent CDI. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, non-CDI antibiotic use, acid suppressant medications), and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure. Results Overall, 460 patients were included (median age, 57 years [18–94]; 65.2% female). Comorbidities included chronic liver disease, 12.8% (n = 59); cancer, 11.7% (n = 54); chronic kidney disease, 3.9% (n = 18); and inflammatory bowel disease, 21.9% (n = 101). Overall, 31.3% (n = 144) received antibiotics, 21.7% (n = 100) received acid suppressants, and 76.8% (n = 350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% (95% confidence interval [CI], 72.7%–84.0%) had durable response to FMT at 1 year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT (hazard ratio, 0.27; 95% CI, .15–.49; P < .001). Conclusions The majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics.

AbstractObjectiveOrthostatic intolerance (OI) and autonomic dysfunction (AD) are common in adolescents and young adults. Patients experience multisystem symptoms including gastrointestinal (GI), postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), or only symptoms of OI (SOI) without significant findings on 70‐degree head‐up tilt testing (HUT). We hypothesize that patients with POTS, OH, and SOI show differences in GI symptoms and motility test and that heart rate (HR) changes on HUT predict severity of GI dysmotility.Study designFrom medical records of patients (<18 years) with OI, we collected demographics, presenting symptoms, GI manifestations, and GI motility testing. Data were compared between the 3 groups (POTS, OH, and SOI). We assessed changes in HR on HUT with changes on GI motility evaluation.ResultsTwo hundred twenty‐nine patients were included (73% females). Abdominal pain (65%), nausea (49%), vomiting (18%), and constipation (24%) were the most common GI symptoms. In patients who had motility evaluation, there were 27% (53/193) with delayed gastric emptying (GE) at 4 hours, 35% (32/92) with delayed colonic transit (CT), 55% (17/31) with reduced gastric accommodation (GA), and 75% (21/28) with dyssynergic defecation (DD). Among 100 POTS, 34 OH, and 95 SOI patients, no significant differences in GI symptoms or motility tests were identified and HR changes on HUT were not associated with changes on motility tests.ConclusionGI symptoms are frequent in adolescents with OI and are associated with delayed GE, reduced GA, delayed CT, and presence of DD.

Objective. Osteochondral allograft (OCA) transplantation has demonstrated good long-term outcomes in treatment of cartilage defects. Viability, a key factor in clinical success, decreases with peri-implantation storage at 4°C during pathogen testing, matching logistics, and transportation. Modern, physiologic storage conditions may improve viability and enhance outcomes. Design. Osteochondral specimens from total knee arthroplasty patients (6 males, 5 females, age 56.4 ± 2.2 years) were stored in media and incubated at normoxia (21% O 2 ) at 22°C or 37°C, and hypoxia (2% O 2 ) at 37°C. Histology, live-dead staining, and quantitative polymerase chain reaction (qPCR) was performed 24 hours after harvest and following 7 days of incubation. Tissue architecture, cell viability, and gene expression were analyzed. Results. No significant viability or gene expression deterioration of cartilage was observed 1-week postincubation at 37°C, with or without hypoxia. Baseline viable cell density (VCD) was 94.0% ± 2.7% at day 1. At day 7, VCD was 95.1% (37°C) with normoxic storage and 92.2% (37°C) with hypoxic storage ( P ≥ 0.27). Day 7 VCD (22°C) incubation was significantly lower than both the baseline and 37°C storage values (65.6%; P < 0.01). COL1A1, COL1A2, and ACAN qPCR expression was unchanged from baseline ( P < 0.05) for all storage conditions at day 7, while CD163 expression, indicative of inflammatory macrophages and monocytes, was significantly lower in the 37°C groups ( P < 0.01). Conclusion. Physiologic storage at 37°C demonstrates improved chondrocyte viability and metabolism, and maintained collagen expression compared with storage at 22°C. These novel findings guide development of a method to optimize short-term fresh OCA storage, which may lead to improved clinical results.

AbstractBackgroundStudies have suggested transplantation using older donor livers results in similar short‐term outcomes as younger donor livers; however, little data exist on long‐term patient/graft outcomes of the octogenarian liver recipient.MethodsRetrospective data were collected from 2 centers, (Valencia, Spain and Rochester, MN, USA) of all recipients of octogenarian donor liver allografts from 2000 to 2011 with follow‐up to 2016. The aim was to compare long‐term patient/graft survival as well as metabolic outcomes of the recipient with the octogenarian liver vs younger than 60 years donor.Results78 recipients of older liver allografts were compared to 78 matched controls. No difference in 10‐year patient mortality was demonstrated (P = 0.074). Octogenarian livers were associated with 3‐fold higher likelihood of graft failure (P = 0.002) but no increase in the risk of post‐LT cardiovascular disease (P = 0.60), hypertension (P = 0.33), vascular complications (P = 0.53), or malignancy (P = 0.14). In multivariate analysis, elder livers remained a significant factor associated with rejection (P = 0.034) with a trend not reaching statistical significance for graft failure (P = 0.052).ConclusionsFor appropriately selected recipients, receiving an octogenarian liver does not clearly influence patient survival but does impact early graft survival with a notable increase in early posttransplant rejection rates and re‐transplantation. Over 1.5 decades, older allografts have not adversely affected metabolic outcomes.

Background. Acute kidney injury (AKI) is a common complication of treatment with liposomal amphotericin B (LAmB). The trajectory of renal recovery after LAmB-associated AKI has not been well described, nor has effect of LAmB dose on recovery of renal function been explored. Objective. Characterize the pattern of renal recovery after incident AKI during LAmB and determine potential influencing factors. Methods. This retrospective cohort study analyzed patients who developed a ≥50% increase in serum creatinine while on LAmB. Patients were followed up until complete renal recovery or death or for 30 days, whichever occurred first. The primary outcome was complete renal recovery, defined as serum creatinine convalescence to within 10% of the patient’s pretreatment baseline. Multivariable modeling was used to identify independent predictors of renal recovery. Results. Ninety-eight patients experienced nephrotoxicity during LAmB, 94% of which received doses <7 mg/kg/day. Fifty-one patients at least partially recovered renal function and, of these, 32 exhibited complete recovery after a mean 9.8 ± 7.8 days. No statistical relationship was found between LAmB dose at the time of AKI or cumulative exposure to LAmB and the likelihood of renal recovery. Concomitant nephrotoxins, age, and pretreatment renal function did not modify this effect in multivariable analysis. Conclusion and Relevance. Our data suggests that LAmB dose did not impact the likelihood of renal recovery. Additional investigation is needed to confirm these findings when aggressive dosing strategies are employe. Additional research is also warranted to further characterize the course of recovery after LAmB-associated nephrotoxicity and comprehensive spectrum of renal outcomes.

Background Hepatic steatosis is strongly associated with cardiovascular disease in the general population. Whether recurrent or de novo, it can occur in the allograft, but the impact on survival and long-term clinical outcomes remains unclear. In this study, we aim to determine both the frequency and impact of allograft steatosis on long-term posttransplant outcomes. Methods A retrospective review of 588 adult liver transplant (LT) recipients (1999-2006) was performed. Cox regression analysis (time-dependent) was used to evaluate differences in time to steatosis post-LT, patient survival, and cardiovascular outcomes. Results Mean age 51.9 ± 10.6 years, 64.6% males, underlying nonalcoholic steatohepatitis (NASH) (9.4%), previous tobacco (52%), pre-LT diabetes mellitus (30.3%), pre-LT hypertension (23.2%), and known cardiovascular disease (9.7%). Overall, 254 recipients developed allograft steatosis (at 10 years: 77.6% NASH recipients, 44.7% Non-NASH recipients). Risk factors for allograft steatosis were female sex (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.09-2.00; P = 0.014), hepatitis C virus diagnosis (HR, 2.49; 95% CI, 1.77-3.94; P < 0.001), and time-dependent BMI (per unit: HR, 1.08; 95% CI, 1.05-1.10; P < 0.001). Allograft steatosis was not associated with post-LT survival (P = 0.25) nor cardiovascular events (HR, 1.08; 95% CI, 0.73-1.59; P = 0.70). Underlying NASH associated with cardiovascular events (HR, 2.04; 95% CI, 1.37-3.04; P < 0.001). Conclusions Allograft steatosis is common but not associated with survival or cardiovascular events in this study. Larger prospective studies are needed to better define the natural history of allograft steatosis.

Abstract Background Sexual dysfunction is often complex and biopsychosocial. Traditional sexual health care management involves individual providers not in a multi-disciplinary setting. A multi-disciplinary team may consist of a medical provider, pelvic floor physical therapist, and sex therapist. Aim The aim was to explore the patient perceptions of benefit from management of their sexual dysfunction by a biopsychosocial multi-disciplinary team. Methods A survey was e-mailed to women patients seen by multi-disciplinary teams at 2 different settings: San Diego Sexual Medicine or Mayo Clinic Women's Health Clinic during a 27-month period. Data are reported using summary statistics for age and count for remaining survey responses. Cochran-Armitage tests for trend were used to compare pre- and post-comfort levels. Outcomes Main outcome measures included perceived benefit of being managed in a team-based model of care, level of benefit and satisfaction from each provider, and difference from pre-conceived level of comfort to actual comfort after each provider visit. Results 89 of 270 e-mailed surveys were analyzed. Patient populations (mean age 47.6, range 23–77 years) were similar between sites. Overall, 82% of respondents reported moderate/great benefit from the team-based model; 72.1% reported management by all 3 providers valuable/extremely valuable; and 84.3% were somewhat/very satisfied with the model. Women endorsed specific ways in which they benefitted from the team-based model including: improved sexual function (58.1%), feeling validated (72.1%) and listened to (62.8%), that they better understood their health concerns (65.1%), that their partner better understood their health concerns (46.5%), and feeling normal (46.5%). There were no significant differences between the 2 clinics in terms of patient-perceived benefit, value, or satisfaction. Conclusions The team-based model of care for management of sexual dysfunction in women including a medical provider, physical therapist, and sex therapist is associated with patient-perceived benefit, satisfaction, and value.

Background Malignancy after liver transplant (LT) is a leading cause of mortality, but data is limited. The aim of this study was to identify patients at higher risk for de novo malignancies after LT in a large multicenter database. Methods The Scientific Registry of Transplant Recipients database comprising all 108 412 LT recipients across the United States between 1987 and March 2015 was analyzed with a median follow-up of 6.95 years. Potential risk factors for malignancies after LT were assessed using Cox regression analysis for the outcome of time to first malignancy. Results Mean age 51.9 ± 10.8 years, 64.6% male, 74.5% white, and 15.8% with previous malignancy. Malignancies during follow-up were 4,483 (41.3%) skin, 1519 (14.0%) hematologic, and 4842 (44.7%) solid organ. The 10-year probability of de novo malignancy was 11.5% (11.3-11.8%). On multivariable analysis, age by decade (hazard ratio [HR], 1.52; P < 0.001), male sex (HR, 1.28; P < 0.001), white race (compared with other races: HR, 1.45-2.04; P < 0.001), multiorgan transplant (HR, 1.35; P < 0.001), previous malignancy (HR, 1.34; P < 0.001), and alcoholic liver disease, autoimmune, nonalcoholic steatohepatitis (HR, 1.35; P < 0.001), and primary sclerosing cholangitis pre-LT (compared with hepatitis C virus, P < 0.001) were associated with higher risk of post-LT malignancy, but type of immunosuppression was not (P = NS). Conclusions This large data set demonstrates the effects of ethnicity/race and etiologies of liver disease, particularly nonalcoholic steatohepatitis as additional risk factors for cancer after LT. Patients with these high-risk characteristics should be more regularly and diligently screened.