OBJECTIVE:While endoscopic laser wedge excision (LWE) for iSGS demonstrated lower surgical recurrence rates compared to endoscopic dilation (ED), ED remains the primary technique employed. Additionally, serial intralesional steroid injections (SILSIs) also demonstrate benefits in controlling disease. We aimed to compare surgical recurrence rates following ED, ED + SILSI, and LWE following a patient's first operation. METHODS:This was a two-center retrospective analysis of iSGS patients who underwent either ED, ED + SILSI, or LWE. Patients were followed to their last follow-up date or reoperation. Kaplan-Meier analysis and Cox proportional hazards were used to evaluate the recurrence times across the different surgical groups with additional stratification by age, compliance to medical adjuvant therapy, and percentage of stenosis rated at reoperation. RESULTS:A total of 126 patients from Institution 1 underwent LWE, while at Institution 2, ED and ED + SILSI were performed on 32 and 23 patients, respectively. One-year recurrence estimates were 9%, 53%, and 0% for LWE, ED, and ED + SILSI, respectively, while 5-year recurrence estimates were 45%, 90%, and 19%, respectively. Adjusted Cox-proportional hazard ratios demonstrated a greater risk of surgical recurrence with ED compared to LWE (2.25; 95% confidence interval [CI]: 1.31-3.88) and no difference between ED + SILSI and LWE (0.84; 95% CI: 0.32-2.25). CONCLUSION:LWE demonstrates reduced recurrence times compared to ED when controlling for surgery number, age, triple therapy compliance, and percentage of stenosis at reoperation. The application of postoperative SILSI appears to similarly reduce recurrence rates comparable to LWE and warrants further investigation.

Recent changes to allocation systems have increased the geographic distribution of pancreas offers, often originating from outside a transplant center's donor service area or region. The impact of this wider sharing on outcomes remains uncertain. This study analyzed outcomes of primary pancreas transplants (2000–2018) at a large transplant center, stratified retrospectively on the nautical miles distance from the donor hospital. Primary endpoints were death-censored graft survival (DC-GS), patient survival, and graft thrombosis at different time points. No significant differences were found in DC-GS or patient survival for recipients of simultaneous pancreas-kidney (SPK), pancreas after kidney (PAK), or pancreas transplant alone (PTA), regardless of the distance from the donor hospital to the transplant center. Thrombosis rates were comparable across groups. Imported pancreata were from younger donors with lower BMI compared to locally recovered grafts. These findings support the notion that importing pancreata for transplantation is a feasible and safe practice that benefits patients, increases organ utilization, while benefiting transplant center volume data and reducing waiting times for patients. Encouraging wider importation may reduce waiting times and improve access to pancreas transplantation.

OBJECTIVE:There is currently not a marker of disease severity in idiopathic subglottic stenosis (iSGS). Our objective was to characterize iSGS patients' disease severity using endoscopic surgery rates. METHODS:This was a two-center retrospective analysis of iSGS patients with a minimum of 4 years of follow up following an initial endoscopic procedure (laser wedge excision (LWE) or endoscopic dilation (ED)). Disease severity was classified into Groups A-C, based on whether patients had fewer (Group A), the same number (Group B), or more surgeries (Group C) in years 3-5 compared to years 1 and 2. Disease severity proportions were compared across institutions using chi-square analysis. Nonparametric testing compared clinical characteristics such as age, BMI, and GERD across severity groups. RESULTS:There were 104 patients from institution 1 and 53 patients from institution 2 that were all female and predominantly Caucasian. Both institutions had clinically and statistically similar proportions of patients in Group A (64% vs. 62%), Group B (20% vs. 19%), and Group C (16% vs. 19%) disease (p > 0.05). No clinical characteristic (e.g., age, sex, race, BMI, GERD) was associated with disease severity. CONCLUSION:Across tertiary care institutions there is a consistent proportion of iSGS patients who either demonstrate nonrecurrent/decelerating (Group A), stable but persistent (Group B), or rapidly recurring disease (Group C). Two-year surgery rates appear to be an important timepoint for providing expectations to patients on the likelihood of possessing severe disease. LEVEL OF EVIDENCE: 4:

Purpose: ​ Direct‐acting antiviral agents (DAAs) against hepatitis C virus (HCV) such as sofosbuvir/velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (GLE/PIB) are effective in treating recipients of organs infected with HCV. The objective of this project is to identify changes in tacrolimus pharmacokinetics throughout DAA therapy in recipients of abdominal transplants from nucleic acid testing‐positive (NAT+) donors. Methods: Adult kidney or liver transplant recipients transplanted between 4/22/2019 and 6/23/2022 were included. Recipients of HCV NAT+ organs were treated with DAAs based on institutional protocol and insurance preference. Recipients of HCV NAT− organs from donors who fit Public Health Service (PHS) risk criteria for HCV transmission were included in the comparator group. Tacrolimus doses and concentrations were collected at DAA initiation and cessation and at the time of sustained virologic response assessment at 12 weeks after treatment completion (SVR12); these time points were matched in the NAT− control group. The primary outcome was difference in concentration‐to‐dose ratio (C/D) change (ΔC/D) over time between NAT+ and NAT− organ recipients. Results: At DAA initiation, NAT+ organ recipients required a lower tacrolimus dose to reach goal than NAT− organ recipients (ΔC/D NAT+ = −0.41, ΔC/D NAT− 0.60, p = 0.01); however, a known tacrolimus interaction with fluconazole—administered to liver transplant recipients at high risk for invasive fungal infection (IFI)—represents a significant confounding factor. No differences in average C/D ratio between NAT+ and NAT− organ recipients were identified at any time point. Conclusion: These results do not support empiric dose adjustments based on donor HCV NAT status or antiviral therapy.

IntroductionParkinson disease (PD) is a neurodegenerative condition affecting multiple sensorimotor and cognitive systems. The Pink1−/− rat model exhibits vocal, cognitive, and limb use deficits seen in idiopathic PD. We sought to measure glucose metabolism in brain regions in Pink1−/− and wild type (WT) rats, and to associate these to measures of ultrasonic vocalization, cognition, and limb use behavior.MethodsPink1−/− (n = 12) and WT (n = 14) rats were imaged by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in a repeated measures design at approximately 10 months of age and 6 weeks later. Relative regional glucose metabolism was indexed by whole brain normalized FDG uptake, which was calculated for 18 regions identified a priori for comparison. Behavioral measures included tests of communication via ultrasonic vocalization, cognition with 5-Choice Serial Reaction Time Test (5-CSRTT), and limb use with Cylinder Test and Challenge Beam.ResultsRelative glucose metabolism was significantly different in Pink1−/− rats in prelimbic area, striatum, nucleus ambiguus, globus pallidus, and posterior parietal association cortex compared to WT controls. For behavioral measures, Pink1−/− rats demonstrated quieter vocalizations with a restricted frequency range, and they showed increased number of foot-faults and hindlimb steps (shuffling) in limb motor tests. Significant behavior vs. brain correlations included associations of ultrasonic vocalization parameters with glucose metabolism indices in locus coeruleus and substantia nigra.ConclusionFDG PET reveals abnormalities in relative regional brain glucose metabolism in Pink1−/− rats in brain regions that are important to cognition, vocalization, and limb motor control that are also impacted by Parkinson disease. This method may be useful for mechanistic studies of behavioral deficits and therapeutic interventions in translational studies in the Pink1−/− PD model.

IntroductionLiver transplant recipients are at a heightened risk for oropharyngeal dysphagia; identification of those who are at high risk for postoperative dysphagia could reduce hospital costs and length of stay. We sought to identify predictors of dysphagia, in a large cohort of patients who underwent liver transplantation.MethodsElectronic medical records were queried for patients undergoing liver transplantation, who underwent instrumental swallowing evaluations. Demographics, functional outcomes, and interventions were collected. Logistic regression analyses were performed to identify predictors of dysphagia.ResultsSeven hundred and ninety-five patients met inclusionary criteria. Multivariate analyses found ethnic group (p = .0191), MELD Score (p < 0001), cold ischemia time (p = .0123), and length of intubation (p < .0001) to be predictors of post-operative development of dysphagia. Pre-transplant dialysis (p < .0001), dysphagia related to end stage liver disease (p < .0001), Karnofsky Performance Status Scale (p < .0001), wait time to transplant (p = 0.0173), surgery time (p = 0.0095), tracheostomy (p < 0.0001), and transfusion of intraoperative RBC (p < .0001), intraoperative platelets (p = 0.0018), intraoperative FFP (p = 0.0495), perioperative FFP (p = 0.0002), perioperative platelets (p = 0.0151) and perioperative RBC (p = 0.0002) were variables of significance associated with the development of postoperative dysphagia from univariate analysis.ConclusionsOur results propose a set of predictors that should be considered when identifying post-operative critically ill patients at risk for dysphagia.

Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HRpancreas = 1.04, p = 0.93; HRkidney = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (ppancreas = 0.57; pkidney = 0.41). T2D had a significantly lower incidence of de novo DSA at 1 year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients.

INTRODUCTION:Twin reversed arterial perfusion (TRAP) sequence is a rare complication of monochorionic twin pregnancies characterized by placental anastomoses between a normally developed twin and an acardiac mass. Though several treatment modalities exist, the optimal management strategy is unclear. This study aimed to compare the various treatment strategies for TRAP sequence. METHODS:A systematic review of the literature was performed using PRISMA guidelines including PubMed, Scopus, Web of Science, and the Cochrane Library. Studies were imported into Covidence, where they were independently screened by two authors. Studies included described interventions for TRAP sequence. Those excluded were unavailable in English and lacked differentiation between intervention strategies for TRAP and other monochorionic twin pregnancies. Fisher's exact test and random effects modeling were used for statistical analysis. RESULTS:A total of 2,340 abstracts were screened, of which 218 articles progressed to full review and 120 qualified for data extraction. Overall, 757 twin pregnancies were described. Most were treated with radiofrequency ablation (RFA) (n = 363, 47.95%) and laser ablation (n = 220, 29.06%). Statistically significant differences among the modalities were seen in technical success (p = 0.005), gestational age at presentation (p < 0.01), intervention (p = 0.01), and delivery (p = 0.01), respectively, and time between treatment and delivery (p < 0.01). Notably, pump twin survival did not differ based on treatment modality used (p = 0.196). Overall, complication rates were low with no differences in preterm premature rupture of membranes (p = 0.66), preterm labor (p = 0.58), or maternal hemorrhage between modalities (p = 0.28). Suture cord ligation, however, had a greater hemorrhage rate than RFA (p = 0.03). CONCLUSIONS:This embodies the first meta-analysis comparing treatment modalities for TRAP sequence with outcomes and complications. RFA is the most technically successful strategy. Prospective data are required to further understand the optimal modality and gestational age at treatment to ensure best overall outcomes.

Purpose: This study aimed to determine if cervical bracing with a PMT collar increases risk of airway invasion and pharyngeal residue in elderly patients with dysphagia. Additionally, it aimed to identify patient preference for cervical bracing during deglutition. Method: Twenty-one patients underwent a videofluoroscopic swallow study. Thin liquid, nectar thick liquid, pudding, and cracker were administered with cervical collar on and off with order of condition randomized. The Penetration- Aspiration Scale (PAS) was used to grade swallows, with McNemar's test of symmetry used to determine whether the categorical PAS score was similar between conditions. Pharyngeal residue was measured following swallows. Patients were asked which condition they preferred, and which was more comfortable with "no difference" being a selection. Results: No significant difference in PAS categorization score was measured for any consistency ( p = .317-.919). Significantly more pyriform sinus residue was measured in the collar off condition ( p = .003), albeit amounts were within normative range, with no difference measured in vallecula residue between conditions ( p = .939). Forty-five percent of participants preferred to swallow with the collar off, while 55% indicated no preference. Forty-one percent of participants indicated increased comfort with collar off, while 59% indicated no difference in comfort. No participant preferred swallowing or indicated increased comfort with the collar on. Conclusions: Presence of a cervical collar in elderly patients with dysphagia did not result in a significant difference in airway invasion or total pharyngeal residue. There was significantly more residue in the pyriform sinuses when cervical bracing was removed. The majority of patients did not indicate a difference in preference or comfort between collar on/off conditions.

Existing literature offers conflicting conclusions about whether early acute cellular rejection influences long-term outcomes in liver transplantation. We retrospectively collected donor and recipient data on all adult, first-time liver transplants performed at a single center between 2008 and 2020. We divided this population into two cohorts based on the presence of early biopsy-proven acute cellular rejection (EBPR) within the first 90 days post-transplant and compared outcomes between the groups. There were 896 liver transplants that met inclusion criteria with 112 cases (12.5%) of EBPR. Recipients who developed EBPR had higher biochemical Model for End-Stage Liver Disease scores (28 vs. 24, p < .01), but other donor and recipient characteristics were similar. Recipients with EBPR had similar overall survival compared to patients without EBPR (p = .09) but had decreased graft survival (p < .05). EBPR was also associated with decreased time to first episode of late (> 90 days post-transplant) rejection (p < .0001) and increased vulnerability to bacterial and viral infection (p < .05). In subgroup analysis of recipients with autoimmune indications for liver transplantation, EBPR had a more pronounced association with patient death (hazard ratio [HR] 3.9, p < .05) and graft loss (HR 4.0, p < .01). EBPR after liver transplant is associated with inferior graft survival, increased susceptibility to late rejections, and increased vulnerability to infection.

Purpose Evaluate cytomegalovirus (CMV) post-prophylaxis surveillance in high-risk (D+/R-) kidney and liver transplant recipients. Methods Adult D+/R- patients were included if transplanted between 6/1/15 and 11/30/22 and divided into a pre-CMV-stewardship-era (6/1/15-5/31/18), CMV-stewardship-era (6/1/18-6/30/20), and a surveillance-era (7/1/2020-11/30/2022) then followed through 12 months. The primary objective was to evaluate CMV-related outcomes. The secondary objective was to assess graft and patient survival by era. Results There were 328 patients in the study period; 133 in the pre-stewardship-era, 103 in the stewardship-era, and 92 in the surveillance-era. Replication rates in the surveillance-era were significantly higher, as anticipated due to increased sampling (pre 38.4%, stewardship 33.0%, surveillance 52.2%, p = 0.02). Time from transplant to first replication was similar (pre 214.0 +/- 79.0 days, stewardship 231.1 +/- 65.5, surveillance 234.9 +/- 61.4, p = 0.29). CMV viral load (VL) at first detection, maximum-VL, and incidence of VL > 100 000 IU/mL were numerically lower in the surveillance era, although not statistically significant. CMV end-organ disease (p < 0.0001) and ganciclovir-resistance (p = 0.002) were significantly lower in the surveillance era than in both previous eras. Rejection was not different between eras (p = 0.4). Graft (p = 0.0007) and patient survival (p = 0.008) were significantly improved in the surveillance era. Conclusions Post-prophylaxis surveillance significantly reduced CMV end-organ disease and resistance. Despite observing increased replication rates in the surveillance era, rejection was not significantly different and there was no graft loss or patient mortality at 12 months.

Swallowing impairments resulting from stroke have few rehabilitative options. Prior evidence suggests lingual strengthening exercise may provide some benefit, but more randomized controlled trials are required. The purpose of this study was to examine efficacy of progressive lingual resistance training on lingual pressure generative capacity and swallowing outcomes for individuals with dysphagia after stroke. Participants with dysphagia within 6 months of acute stroke were randomly assigned to: (1) treatment: progressive resistance tongue exercise using pressure sensors for 12 weeks with usual care; or (2) control: usual care only. Outcomes were measured at baseline, 8 and 12 weeks to assess group differences in lingual pressure generation, swallow safety, efficiency, oral intake, and swallowing quality of life. Final sample included 19 participants [treatment (N = 9) and control (N = 10)] with 16 males and 3 females (mean age = 69.33). Functional Oral Intake Scale (FOIS) scores improved significantly (p = 0.04) in the treatment group from baseline to 8 weeks compared to usual care (control). No significant differences between treatment groups were identified for other outcomes; large effect sizes were detected for group differences in lingual pressure generative capacity from baseline to 8 weeks at the anterior sensor (d = .95) and posterior sensor (d = 0.96), and vallecular residue of liquids (baseline to 8-week d = 1.2). Lingual strengthening exercise resulted in significant improvements in functional oral intake for patients with post-stroke dysphagia as compared to usual care after 8 weeks. Future studies should include a larger sample size and address treatment impact on specific aspects of swallow physiology.

ObjectiveWe investigated the impact of body mass index (BMI) on post-operative outcomes and survival of patients with interstitial pulmonary fibrosis (IPF) undergoing lung transplantation.MethodsWe retrospectively reviewed 222 patients with IPF that underwent lung transplant (LT) at our institution from 2005 to 2019. Recipients were divided in 4 groups: group-1 consisted of underweight patients (BMI ≤18.5 kg/m2), group-2 of normal weight patients (BMI 18.5–25 kg/m2), group-3 of over-weight patients (BMI 25–29.9 kg/m2) and group-4 of obese patients (BMI ≥30 kg/m2).ResultsGroup-1 consisted of 13 (6%) patients, group-2 of 67 (30%) patients, group-3 of 79 (36%) patients, group-4 consisted of 63 (28%) patients. Median BMI for group-1 was 17 [interquartile range (IQR): 17, 18], for group-2 was 23 (22, 24), for group-3 was 29 (28, 29.5) and group-4 was 32 (31, 33). Patients in group-1 were significantly younger (p < 0.01). Single LT comprised the majority of operation type in group-2 to group-4 and it was significantly higher than group 1 (p < 0.01). Median follow-up time was 39 months (13–76). A total of 79 (35.5%) patients died by the end of study. Overall, five deaths occurred in group-1, 17 in group-2, 33 in group-3, and 24 in group-4. Kaplan–Meier analysis showed that mortality was not statistically significant between the groups (p = 0.24). Cox-regression analysis was used to assess other possible risk factors that could influence the effect of BMI on mortality, including transplant type (single, double), lung allocation score, and age, diabetes and creatinine levels at surgery. None of these factors were shown to affect patient mortality (p > 0.05). Overall reasons for death included graft failure (24%), infection (23%), respiratory failure (14%), and malignancy (13%).ConclusionsBody mass index does not impact long-term survival of patients with IPF undergoing lung transplantation.

Described details of Western blot, clonogenic assay, cell migration assay, ex-vivo imaging, IHC and etc.

Scratch of a gap for wound healing assay was generated and closure of the gap was evaluated 24 hours later in FTC236-Notch1 cells with or without doxycycline treatment. The cells with NICD induction by doxycycline exhibited slower closure of the gap than those without NICD induction. Images were taken immediately after scratching the cultures 0 hr and 24hr later. Representative images at 0 hr and 24 hr are shown in the upper panel. The bar graph represents the average percentage of the gap closure. Each bar represents mean{plus minus} SEM; "Dox" indicates doxycycline; ** indicates p< 0.01; Scale bar:200µm.