Recurrent melanoma 25 years after initial diagnosis, presenting as metastatic disease early after heart transplantation.

BACKGROUND: Cancer survivors (CS) comprise a particularly high-risk group for both de-novo and recurrent malignancies after solid organ transplantation. CASE PRESENTATION: We report a case of relapsed melanoma, presented as metastatic disease seven months after heart transplantation in a patient who had an early-stage melanoma resected 25 years prior. Treatment with a combination of dabrafenib, a BRAF inhibitor, and trametinib, a mitogen-activated protein kinase (MEK) inhibitor resulted in a near-complete metabolic response, without major adverse effects. CONCLUSION: This case demonstrates the increased risk of recurrence in CS with melanoma, which can persist decades after cancer diagnosis. These patients may be amenable to treatment using modern treatment modalities in oncology.

Clinical Utility of Donor-Derived Cell-Free DNA in Heart Transplant Recipients With Multi-Organ Transplants.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) has emerged as a reliable, noninvasive method for the surveillance of allograft rejection in heart transplantation (HT) patients, but its utility in multi-organ transplants (MOT) is unknown. We describe our experience using dd-cfDNA in simultaneous MOT recipients. METHODS: A single-center retrospective review of all HT recipients between 2018 and 2022 that had at least one measurement of dd-cfDNA collected. Patients who had simultaneous MOT were identified and included in this study. Levels of dd-cfDNA were paired with endomyocardial biopsies (EMB) performed within 1 month of blood testing if available. Acute cellular rejection (ACR) was defined as ISHLT (International Society for Heart and Lung Transplantation) grade ≥ 2R. and antibody-mediated rejection (AMR) was defined as pAMR grade > 0. The within-patient variability score of the dd-cfDNA was calculated by the variance/average. RESULTS: The study included 25 multiorgan transplant recipients: 13 heart-kidney (H-K), 8 heart-liver (H-Li), and 4 heart-lung (H-Lu). The median age was 55 years, 44% were female; the median time from HT until the first dd-cfDNA measurement was 4.5 months (IQR 2, 10.5). The median dd-cfDNA level was 0.18% (IQR 0.15%, 0.27%) for H-K, 1.15% (IQR 0.77%, 2.33%) for H-Li, and 0.69% (IQR 0.62%, 1.07%) for H-Lu patients (p < 0.001). Prevalence of positive dd-cfDNA tests (threshold of 0.20%) were 42.2%, 97.3%, and 92.3% in the H-K, H-Li, and H-Lu groups, respectively. The within-patient variability score was highest in the H-Li group (median of 0.45 [IQR 0.29, 0.94]) and lowest in the H-K group (median of 0.09 [IQR 0.06, 0.12]); p = 0.002. No evidence of cardiac ACR or AMR was found. Three patients experienced renal allograft ACR and/or AMR, two patients experienced rejection of the liver allograft, and one patient experienced an episode of AMR-mediated lung rejection. One person in the H-K group experienced an episode of cardiac allograft dysfunction that was not associated with biopsy-confirmed rejection. CONCLUSION: Dd-cfDNA is chronically elevated in most MOT recipients. There is a high degree of within-patient variability in levels (particularly for H-Li and H-Lu recipients), which may limit the utility of this assay in monitoring MOT recipients.

Pain Resilience and Coping Behaviors in Individuals in a Collectivist Social Context.

BACKGROUND/OBJECTIVES: Pain resilience (PR) may be associated with different coping skills, resulting in differences in pain outcomes. This study aimed to understand the role of PR in dictating the choice of coping methods. METHODS: This study completed a preliminary validation of the Mandarin Chinese version of the Pain Resilience Scale (PRS-C) with online survey data (n = 46). Further, we conducted interviews with individuals with chronic low back pain (n = 24). RESULTS: The PRS-C psychometric properties were assessed using a confirmatory factor analysis. The interviews explored pain history, treatment experiences, and coping strategies and were analyzed thematically. The validated PRS-C (10 items) demonstrated satisfactory psychometric properties. The interview results showed that participants who scored lower were more likely to adopt disengagement rather than engagement coping strategies. Qualitative data revealed three themes explaining why and how participants in this collectivist social framework chose their coping methods. CONCLUSIONS: The findings suggest that while participants tried to understand their pain and treatment experiences, the cognitive appraisal construct in PR influenced some of the coping experiences. However, deeply influenced by Confucianism and Buddhism, participants also expressed factors beyond the scope of individual fortitudes, such as the relationship with a higher power that significantly influenced their coping behaviors.

International Society for Diseases of the Esophagus consensus on management of the failed fundoplication.

Fundoplication is a durable, effective, and well-accepted treatment for gastroesophageal reflux disease. Nonetheless, troublesome postoperative symptoms do occasionally occur with management varying widely among centers. In an attempt to standardize definition and management of postfundoplication symptoms, a panel of international experts convened by the Guidelines Committee of the International Society for Diseases of the Esophagus devised a list of 33 statements across 5 domains through a Delphi approach, with at least 80% agreement to establish consensus. Eight statements were endorsed for the domain of Definitions, four for the domain of Investigations, nine for Dysphagia, nine for Heartburn, and four for Revisional surgery. This consensus defined as the treatment goal of fundoplication the resolution of symptoms rather than normalization of physiology or anatomy. Required investigations of all symptomatic postfundoplication patients were outlined. Further management was standardized by patients' symptomatology. The appropriateness of revisional fundoplication and the techniques thereof were described and the role of revisional surgery for therapies other than fundoplication were assessed. Fundoplication remains a frequently-performed operation, and this is the first international consensus on the management of various postfundoplication problems.

Combined Pericapsular Nerve Group Block and Intrapelvic Lateral Femoral Cutaneous Nerve Block Is Associated With Decreased Opioid Consumption After Hip Arthroscopy: A Retrospective Cohort Study.

Introduction: Ambulatory hip arthroscopies are associated with moderate-to-severe pain often requiring opioid analgesia. Novel motor-sparing blocks, the pericapsular nerve group (PENG) and lateral femoral cutaneous nerve (LFCN) block, have shown efficacy in hip surgery. Purpose: We sought to investigate the analgesic benefits of these novel blocks in terms of opioid-sparing and discharge efficiency. Methods: We conducted a retrospective cohort study with propensity score matching of 224 patients who underwent ambulatory elective unilateral hip arthroscopy. One group received a combined PENG and LFCN block (PENG/LFCN, n = 86), while a second group received only a PENG block (n = 26). A control group (n = 112) received no blocks. The primary outcome was postanesthesia care unit (PACU) mean opioid consumption. Secondary outcomes were maximum numeric rating scale (NRS) pain score, intravenous rescue analgesia, and PACU readiness-for-discharge times. Results: The PENG/LFCN-block group required significantly less opioids than the control group in the PACU (25.98 ± 13.04 vs 14.58 ± 5.77, respectively) and were discharged earlier 2.72 ± 1.16 vs 4.42 ± 1.63 hours, respectively). The combined PENG/LFCN group also used less intravenous rescue opioids than the control group (0.47 ± 1.18 vs 1.44 ± 2.1 mg, respectively) and showed a significant difference in the highest NRS pain scores than the control group (6.01 ± 2.38 vs 6.77 ± 2.1 respectively). The PENG block alone group did not show a significant difference in opioid reduction (21.95 ± 15.83 vs 27.72 ± 15.01, respectively). Conclusions: This retrospective study found that in patients who underwent ambulatory elective unilateral hip arthroscopy, a combined PENG and LFCN block was associated with expedited PACU discharge and a clinically significant reduction in postoperative opioid use. Further study is warranted.

Robotic compared with laparoscopic cholecystectomy: A National Surgical Quality Improvement Program comparative analysis.

BACKGROUND: Data demonstrating the clinical benefit of robotic cholecystectomy over the laparoscopic approach are lacking. Herein, we aim to evaluate whether robotic cholecystectomy is associated with improved surgical outcomes compared with laparoscopic cholecystectomy. STUDY DESIGN: This is a retrospective cohort study that used the American College of Surgeons National Surgical Quality Improvement Program to compare the outcomes of patients who underwent robotic or laparoscopic cholecystectomy for benign indications in 2022. RESULTS: Of the 59,216 patients identified, 53,746 underwent laparoscopic cholecystectomy and 5,470 robotic. Compared with the robotic cohort, the patients in the laparoscopic cholecystectomy group were older (50.4 vs 49.7 years), were of the male sex (32.7% vs 29.7%), and comprised a greater percentage of other races than White, African American, and Asian (28.6% vs 14.8%). Multivariable logistic regression revealed that robotic cholecystectomy compared with the laparoscopic approach was independently associated with a lower risk of Clavien-Dindo complications grade 3 or 4 (odds ratio, 0.82; 95% confidence interval, 0.69-0.98), a lower rate of conversion to open (odds ratio, 0.44; 95% confidence interval, 0.32-0.61), and lower odds of requiring hospitalization ≥24 hours (odds ratio, 0.76; 95% confidence interval, 0.71-0.81). There were no significant differences between the 2 approaches in terms of reoperation (odds ratio, 0.69; 95% confidence interval, 0.47-1.00) and readmission (odds ratio, 0.94; 95% confidence interval, 0.82-1.10). CONCLUSION: Robotic cholecystectomy was independently associated with a lower risk of serious complications, lower rate conversion to open, and hospitalization ≥24 hours compared with laparoscopic cholecystectomy. These findings suggest that new technologies might enhance the safety of minimally invasive surgery.

Full esophageal mobilization during hiatal hernia repair with concomitant sleeve gastrectomy improves postoperative reflux symptoms for patients with preexisting reflux.

BACKGROUND: Hiatal hernia repair (HHR) performed concurrently with vertical sleeve gastrectomy (VSG) has been shown to improve postoperative gastroesophageal reflux disease (GERD). However, data on the optimal extent of esophageal mobilization during repair are lacking. Mobilization techniques for HHR during VSG include partial (PM) or full (FM) mobilization of the esophagus. We hypothesize that patients who undergo full mobilization will be less likely to develop postoperative reflux. METHODS: A single-institution retrospective review of all patients who underwent a VSG with a HHR between 2014 and 2021 was conducted. The primary outcome was postoperative reflux symptoms defined by diagnosis in the medical record, utilization of anti-reflux medications, and GERD health-related quality of life (GERD-HRQL) scores obtained via patient surveys. RESULTS: There were 190 patients included with 80 patients (42.1%) undergoing PM and 110 (57.9%) undergoing FM. Rates of preoperative reflux were similar between the two groups (47.5% vs. 51.8%; p = 0.55). During the GERD-HRQL survey, there were 114 patients (60.0%) contacted with a participation rate of 91.2% (104 patients). Patients with preoperative reflux who underwent PM were found to have a higher rate of reported postoperative reflux (90.0% vs. 62.5%; p = 0.03) and higher GERD-HRQL scores (16.40 ± 9.95 vs. 10.84 ± 9.01; p = 0.04). Patients without preoperative reflux did not have a significant difference in reported reflux (55.0% vs. 51.7%; p = 0.82) or GERD-HRQL scores (12.35 ± 14.14 vs. 9.93 ± 9.46; p = 0.25). CONCLUSION: Our study found that postoperative GERD was higher in patients with preexisting reflux who underwent partial esophageal mobilization during concurrent hiatal hernia repair with vertical sleeve gastrectomy. In patients without preoperative GERD, our data suggest that postoperative reflux symptoms are not dependent on the extent of esophageal mobilization during hiatal hernia repair with vertical sleeve gastrectomy.

Clinical Utility of the Molecular Microscope Diagnostic System in a Real-World Transplant Cohort: Moving Towards a New Paradigm.

Objectives: To evaluate the clinical implications of adjunctive molecular gene expression analysis (MMDx ) of biopsy specimens in heart transplant (HT ) recipients with suspected rejection. Introduction: Histopathological evaluation remains the standard method for rejection diagnosis in HT. However, the wide interobserver variability combined with a relatively common incidence of "biopsy-negative" rejection has raised concerns about the likelihood of false-negative results. MMDx, which uses gene expression to detect early signs of rejection, is a promising test to further refine the assessment of HT rejection. Methods: Single-center prospective study of 418 consecutive for-cause endomyocardial biopsies performed between November 2022 and May 2024. Each biopsy was graded based on histology and assessed for rejection patterns using MMDx. MMDx results were deemed positive if borderline or definitive rejection was present. The impact of MMDx results on clinical management was evaluated. Primary outcomes were 1-year survival and graft dysfunction following MMDx-guided clinical management. Secondary outcomes included changes in donor-specific antibodies, MMDx gene transcripts, and donor-derived cell-free DNA (dd-cfDNA) levels. Results: We analyzed 418 molecular samples from 237 unique patients. Histology identified rejection in 32 cases (7.7%), while MMDx identified rejection in 95 cases (22.7%). Notably, in 79 of the 95 cases where MMDx identified rejection, histology results were negative, with the majority of these cases being antibody-mediated rejection (62.1%). Samples with rejection on MMDx were more likely to show a combined elevation of dd-cfDNA and peripheral blood gene expression profiling than those with borderline or negative MMDx results (36.7% vs 28.0% vs 10.3%; p<0.001). MMDx results led to the implementation of specific antirejection protocols or changes in immunosuppression in 20.4% of cases, and in 73.4% of cases where histology was negative and MMDx showed rejection. 1-year survival was better in the positive MMDx group where clinical management was guided by MMDx results (87.0% vs 78.6%; log rank p=0.0017). Conclusions: In our cohort, MMDx results more frequently indicated rejection than histology, often leading to the initiation of antirejection treatment. Intervention guided by positive MMDx results was associated with improved outcomes.

Attentional Bias for Opioids in Taiwanese Heavy Smokers with Chronic Noncancer Pain.

Background and Objectives: Attentional bias (AB) for addictive substances is a feature of attention found in individuals with substance misuse or diagnosed with substance use disorders. When AB exists, the attention of the addicted individual may be quickly oriented to cues related to the addictive substance or be maintained on these cues for a longer time. AB toward opioids was found in Western samples of smokers with chronic noncancer pain. The level of AB was dose-responsive. However, similar studies in the Taiwanese population are lacking. This study compared the patterns of AB for opioid analgesics in Taiwanese participants with chronic noncancer pain to that of individuals without pain. This study aimed to investigate if AB toward opioids is presented in Taiwanese heavy smokers who are on long-term opioid therapy for pain control. Materials and Methods: Participants were grouped into chronic noncancer pain smokers, chronic pain nonsmokers, and smokers without pain, according to smoking habits and whether or not on long-term opioid therapy for pain control. Each participant completed demographic questionnaires, mood scales, and the opioid-related visual probe task. Differences in AB among the groups were compared using a three-way analysis of covariance controlling for daily cigarette consumption. Results: Chronic noncancer pain smokers (n = 17) and chronic pain nonsmokers (n = 16) displayed more severe levels of depression, anxiety, and pain, compared to smokers without pain (n = 28). Only did chronic pain nonsmokers show significant AB for opioid cues that were displayed for a short time. Analysis on reaction time found that smokers without pain consistently responded faster to the tasks. No difference in reaction time was found between the pain groups. Conclusions: The current study did not fully replicate findings from studies that were based in Western countries. Formulary availability and regulatory limitations might have affected patient's perception of prescription opioids in Taiwan. However, chronic pain nonsmokers exhibited initial orientation toward opioid-related cues when daily cigarette consumption was accounted for. According to previous research, this AB for shortly displayed opioid cues can be associated with the expectation of pain relief. The current finding also indicated general psychomotor retardation in individuals who were on long-term use of opioids.

How does sleeve gastrectomy impact long-term eating-related symptoms, distress, and behavior? A cross-sectional study using the BODY-Q patient-reported outcome measures.

BACKGROUND: Patients undergoing sleeve gastrectomy (SG) experience transformative changes in eating-related experiences that include eating-related symptoms, emotions, and habits. Long-term assessment of these endpoints with rigorous patient-reported outcome measures (PROMs) is limited. We assessed patients undergoing SG with the Body-Q Eating Module PROMs. METHODS: All patients evaluated at the Emory Bariatric Center were given the Body-Q Eating Modules questionnaire at preoperative/postoperative clinic visits. Rasch scores and prevalence of relevant endpoints were assessed across six time-points of interest: preoperatively, post-operative months 0-6, 7-12, 12-24, 24-36, and over 36. Student's t-test and Chi-square test were used for analysis. RESULTS: Overall, 1,352 questionnaires were completed pre-operatively and 493 postoperatively. Survey compliance was 81%. Compared to the pre-operative group, the post-operative group had lower BMI (39.7 vs. 46.4, p < 0.001) and higher age (46.3 vs. 44.9, p = 0.019). Beginning one year after SG, patients experience more frequent eating-related pain, nausea and constipation compared to pre-operative baseline (p < 0.05). They also more frequently experience eating-related regurgitation and dumping syndrome-related symptoms beginning post-operative year two (p < 0.05). In the first year after SG, patients more rarely feel eating-related embarrassment, guilt, and disappointment compared to pre-operative baseline (p < 0.05). These improvements disappear one year after SG, after which patients more frequently experience feeling out of control, unhappy, like a failure, disappointed, and guilty (p < 0.05). In the first year after SG, patients experience an increased frequency in positive eating behaviors (ate healthy foods, showed self-control, stopped before full; (p < 0.05). Only two eating-related behavior improvements persist long-term: feeling in control and eating the right amount (p < 0.05). CONCLUSIONS: Patients undergoing SG may experience more frequent eating-related symptoms, distress, and behavior in the long-term. These findings can enhance the pre-operative informed consent and guide development of a more tailored approach to postoperative clinical management such as more frequent visits with the dietician.

Discovery and Preclinical Characterization of BIIB129, a Covalent, Selective, and Brain-Penetrant BTK Inhibitor for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic disease with an underlying pathology characterized by inflammation-driven neuronal loss, axonal injury, and demyelination. Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase and member of the TEC family of kinases, is involved in the regulation, migration, and functional activation of B cells and myeloid cells in the periphery and the central nervous system (CNS), cell types which are deemed central to the pathology contributing to disease progression in MS patients. Herein, we describe the discovery of BIIB129 (25), a structurally distinct and brain-penetrant targeted covalent inhibitor (TCI) of BTK with an unprecedented binding mode responsible for its high kinome selectivity. BIIB129 (25) demonstrated efficacy in disease-relevant preclinical in vivo models of B cell proliferation in the CNS, exhibits a favorable safety profile suitable for clinical development as an immunomodulating therapy for MS, and has a low projected total human daily dose.

Achieving durable compliance with venous thromboembolism prophylaxis in bariatric surgery: 3-year data from a major academic medical center.

BACKGROUND: Metabolic and bariatric surgery (MBS) venous thromboembolism (VTE) prescribing practices vary widely. Our institutional VTE prophylaxis protocol has historically been unstandardized. OBJECTIVES: To create a standardized MBS VTE prophylaxis protocol, track protocol compliance, and identify barriers to protocol compliance and address them with Plan-Do-Study-Act (PDSA) cycles. SETTING: Single Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program-accredited academic hospital. METHODS: We conducted a retrospective study for all patients undergoing MBS (January 2019 to September 2022). A multidisciplinary group of bariatric clinicians reviewed literature and developed the following standardized VTE prophylaxis protocol: 5000 units preoperative subcutaneous (SC) heparin within 60 minutes of anesthesia induction and postoperative 40 mg SC low molecular weight heparin (LMWH) within 24 hours of surgery. This protocol was distributed to relevant clinical stakeholders. We assessed monthly compliance rates through chart review. Goal compliance was ≥90%. We identified sources of noncompliance and addressed them with PDSA methodology. RESULTS: A total of 796 patients were included. Preoperative heparin administration increased from a mean of 47% (107/228) preintervention to 96% (545/568) postintervention (P < .0001), and postoperative LMWH administration increased from 71% (47/66) to 96% (573/597, P = .0002). These compliance rates were sustained for 3 years. Barriers to protocol noncompliance included order set timing errors (n = 45), surgeon error (n = 44), surgeon discretion (n = 40), and nursing error (n = 20). No change in bleeding or VTE rates was observed. CONCLUSIONS: Developing a standardized VTE prophylaxis protocol, monitoring process measures, and engaging relevant stakeholders in PDSA cycles resulted in drastic and durable improvement in VTE prophylaxis compliance rates.

Robotic versus laparoscopic gastrectomy for adenocarcinoma in the US: a propensity score-matching analysis of 11,173 patients on oncological adequacy.

INTRODUCTION: Surgery remains the cornerstone treatment for gastric cancer. Previous studies have reported better lymphadenectomy with minimally invasive approaches. There is a paucity of data comparing robotic and laparoscopic gastrectomy in the US. Herein, we examined whether oncological adequacy differs between laparoscopic and robotic approaches. METHODS: The National Cancer Database was utilized to identify patients who underwent gastrectomy for adenocarcinoma between 2010 and 2019. A propensity score-matching analysis between robotic gastrectomy (RG) versus laparoscopic gastrectomy (LG) was performed. The primary outcomes were lymphadenectomy ≥ 16 nodes and surgical margins. RESULTS: A total of 11,173 patients underwent minimally invasive surgery for gastric adenocarcinoma between 2010 and 2019. Of those 8320 underwent LG and 2853 RG. Comparing the unmatched cohorts, RG was associated with a higher rate of adequate lymphadenectomy (63.5% vs 57.1%, p < .0.0001), higher rate of negative margins (93.8% vs 91.9%, p < 0.001), lower rate of prolonged length of stay (26.0% vs 29.6%, p < .0.001), lower 90-day mortality (3.7% vs 5.0%, p < 0.0001), and a better 5-year overall survival (OS) (56% vs 54%, p = 0.03). A propensity score-matching cohort with a 1:1 ratio was created utilizing the variables associated with lymphadenectomy ≥ 16 nodes. The matched analysis revealed that the rate of adequate lymphadenectomy was significantly higher for RG compared to LG, 63.5% vs 60.4% (p = 0.01), respectively. There was no longer a significant difference between RG and LG regarding the rate of negative margins, prolonged length of stay, 90-day mortality, rate of receipt of postoperative chemotherapy, and OS. CONCLUSIONS: This propensity score-matching analysis with a large US cohort shows that RG was associated with a higher rate of adequate lymphadenectomy compared to LR. RG and LG had a similar rate of negative margins, prolonged length of stay, receipt of postoperative chemotherapy, 90-day mortality, and OS, suggesting that RG is a comparable surgical approach, if not superior to LG.

Development of a PET Tracer for OGA with Improved Kinetics in the Living Brain.

O-GlcNAcylation is thought to play a role in the development of tau pathology in Alzheimer's disease because of its ability to modulate tau's aggregation propensity. O-GlcNAcylation is regulated by 2 enzymes: O-GlcNAc transferase and O-GlcNAcase (OGA). Development of a PET tracer would therefore be an essential tool for developing therapeutic small-molecule inhibitors of OGA, enabling clinical testing of target engagement and dose selection. Methods: A collection of small-molecule compounds was screened for inhibitory activity and high-affinity binding to OGA, as well as favorable PET tracer attributes (multidrug resistance protein 1 efflux, central nervous system PET multiparameter optimization, etc.). Two lead compounds with high affinity and selectivity for OGA were selected for further profiling, including OGA binding to tissue homogenate using a radioligand competition binding assay. In vivo pharmacokinetics were established using a microdosing approach with unlabeled compounds in rats. In vivo imaging studies were performed in rodents and nonhuman primates (NHPs) with 11C-labeled compounds. Results: Two selected candidates, BIO-735 and BIO-578, displayed promising attributes in vitro. After radiolabeling with tritium, [3H]BIO-735 and [3H]BIO-578 binding in rodent brain homogenates demonstrated dissociation constants of 0.6 and 2.3 nM, respectively. Binding was inhibited, concentration-dependently, by homologous compounds and thiamet G, a well-characterized and structurally diverse OGA inhibitor. Imaging studies in rats and NHPs showed both tracers had high uptake in the brain and inhibition of binding to OGA in the presence of a nonradioactive compound. However, only BIO-578 demonstrated reversible binding kinetics within the time frame of a PET study with a 11C-labeled molecule to enable quantification using kinetic modeling. Specificity of tracer uptake was confirmed with a 10 mg/kg blocking dose of thiamet G. Conclusion: We describe the development and testing of 2 11C PET tracers targeting the protein OGA. The lead compound BIO-578 demonstrated high affinity and selectivity for OGA in rodent and human postmortem brain tissue, leading to its further testing in NHPs. NHP PET imaging studies showed that the tracer had excellent brain kinetics, with full inhibition of specific binding by thiamet G. These results suggest that the tracer [11C]BIO-578 is well suited for further characterization in humans.

The utilization of molecular microscope in management of heart transplant recipients in the era of noninvasive monitoring.

INTRODUCTION: Monitoring for graft rejection is a fundamental tenet of post-transplant follow-up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor-derived cell-free DNA (dd-cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB. METHODS: This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection. CONCLUSIONS: We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies.

Implementation of an Online Intraoperative Assessment of Technical Performance for Surgical Trainees.

INTRODUCTION: Assessment of surgical resident technical performance is an integral component of any surgical training program. Timely assessment delivered in a structured format is a critical step to enhance technical skills, but residents often report that the quality and quantity of timely feedback received is lacking. Moreover, the absence of written feedback with specificity can allow residents to seemingly progress in their operative milestones as a junior resident, but struggle as they progress into their postgraduate year 3 and above. We therefore designed and implemented a web-based intraoperative assessment tool and corresponding summary "dashboard" to facilitate real-time assessment and documentation of technical performance. MATERIALS AND METHODS: A web form was designed leveraging a cloud computing platform and implementing a modified Ottawa Surgical Competency Operating Room Evaluation instrument; this included additional, procedure-specific criteria for select operations. A link to this was provided to residents via email and to all surgical faculty as a Quick Response code. Residents open and complete a portion of the form on a smartphone, then relinquish the device to an attending surgeon who then completes and submits the assessment. The data are then transferred to a secure web-based reporting interface; each resident (together with a faculty advisor) can then access and review all completed assessments. RESULTS: The Assessment form was activated in June 2021 and formally introduced to all residents in July 2021, with residents required to complete at least one assessment per month. Residents with less predictable access to operative procedures (night float or Intensive Care Unit) were exempted from the requirement on those months. To date a total of 559 assessments have been completed for operations performed by 56 trainees, supervised by 122 surgical faculty and senior trainees. The mean number of procedures assessed per resident was 10.0 and the mean number per assessor was 4.6. Resident initiation of Intraoperative Assessments has increased since the tool was introduced and scores for technical and nontechnical performance reliably differentiate residents by seniority. CONCLUSIONS: This novel system demonstrates that an online, resident-initiated technical assessment tool is feasible to implement and scale. This model's requirement that the attending enter performance ratings into the trainee's electronic device ensures that feedback is delivered directly to the trainee. Whether this aspect of our assessment ensures more direct and specific (and therefore potentially actionable) feedback is a focus for future study. Our use of commercial cloud computing services should permit cost-effective adoption of similar systems at other training programs.

Does the use of a suction calibration system (SCS) reduce stapler load firings and operative time? A randomized controlled trial comparing use of endoscopic calibration vs. SCS in laparoscopic sleeve gastrectomy.

BACKGROUND: It is critical to ensure appropriate and consistent sleeve size and orientation during laparoscopic sleeve gastrectomy (LSG). Various devices are used to achieve this, including weighted rubber bougies, esophagogastroduodenoscopy (EGD), and suction calibration systems (SCS). Prior reports suggest that SCSs may decrease operative time and stapler load firings but are limited by single-surgeon experience and retrospective design. We performed the first randomized controlled trial comparing SCS against EGD in patients undergoing LSG to investigate whether the SCS decreases the number of stapler load firings. METHODS: This was a randomized, non-blinded study from a single MBSAQIP-accredited academic center. Appropriate LSG candidates ≥ 18 years of age were randomized to EGD or SCS calibration. Exclusion criteria included prior gastric or bariatric surgery, detection of hiatal hernia before surgery, and intraoperative hiatal hernia repair. A randomized block design was employed controlling for body mass index, gender, and race. Seven surgeons employed a standardized LSG operative technique. The primary endpoint was the number of stapler load firings. Secondary endpoints were operative duration, reflux symptoms, and change in total body weight (TBW). Endpoints were analyzed via t-test. RESULTS: A total of 125 LSG patients (84% female) underwent study enrollment, with an average age of 44 ± 12 years and average BMI of 49 ± 8 kg/m2. Overall, 117 patients were randomized to receive EGD (n = 59) or SCS (n = 58) calibration. No significant differences in baseline characteristics were identified. The mean number of stapler load firings for EGD and SCS groups were 5.43 ± 0.89 and 5.31 ± 0.81, respectively (p = 0.463). The mean operative times for EGD and SCS groups were 94.4 ± 36.5 and 93.1 ± 27.9 min, respectively (p = 0.83). There were no significant differences in post-operative reflux, TBW loss, or complications. CONCLUSION: Use of EGD and SCS resulted in a similar number of LSG stapler load firings and operative duration. Additional research is needed to compare LSG calibration devices in different patients and settings to optimize surgical technique.

Development of a Novel [11C]CO-Labeled Positron Emission Tomography Radioligand [11C]BIO-1819578 for the Detection of O-GlcNAcase Enzyme Activity.

Imaging O-GlcNAcase OGA by positron emission tomography (PET) could provide information on the pathophysiological pathway of neurodegenerative diseases and important information on drug-target engagement and be helpful in dose selection of therapeutic drugs. Our aim was to develop an efficient synthetic method for labeling BIO-1819578 with carbon-11 using 11CO for evaluation of its potential to measure levels of OGA enzyme in non-human primate (NHP) brain using PET. Radiolabeling was achieved in one-pot via a carbon-11 carbonylation reaction using [11C]CO. The detailed regional brain distribution of [11C]BIO-1819578 binding was evaluated using PET measurements in NHPs. Brain radioactivity was measured for 93 min using a high-resolution PET system, and radiometabolites were measured in monkey plasma using gradient radio HPLC. Radiolabeling of [11C]BIO-1819578 was successfully accomplished, and the product was found to be stable at 1 h after formulation. [11C]BIO-1819578 was characterized in the cynomolgus monkey brain where a high brain uptake was found (7 SUV at 4 min). A pronounced pretreatment effect was found, indicating specific binding to OGA enzyme. Radiolabeling of [11C]BIO-1819578 with [11C]CO was successfully accomplished. [11C]BIO-1819578 binds specifically to OGA enzyme. The results suggest that [11C]BIO-1819578 is a potential radioligand for imaging and for measuring target engagement of OGA in the human brain.

The financial impact of the COVID-19 pandemic on sleeve gastrectomy at a major academic institution.

INTRODUCTION: The COVID-19- pandemic significantly impacted metabolic and bariatric surgery (MBS) practices due to large-scale surgery cancellations along with staff and supply shortages. We analyzed sleeve gastrectomy (SG) hospital-level financial metrics before and after the COVID-19 pandemic. METHODS: Hospital cost-accounting software (MicroStrategy, Tysons, VA) was reviewed for revenues, costs, and profits per SG at an academic hospital (2017-2022). Actual figures were obtained, not insurance charge estimates or hospital projections. Fixed costs were obtained through surgery-specific allocation of inpatient hospital and operating-room costs. Direct variable costs were analyzed with sub-components including: (1) labor and benefits, (2) implants, (3) drug costs, and 4) medical/surgical supplies. The pre-COVID-19 period (10/2017-2/2020) and post-COVID-19 period (5/2020-9/2022) financial metrics were compared with student's t-test. Data from 3/2020 to 4/2020 were excluded due to COVID-19-related changes. RESULTS: A total of 739 SG patients were included. Average length of stay (LOS), Center for Medicaid and Medicare Case Mix Index (CMI), and percentage of patients with commercial insurance were similar pre vs. post-COVID-19 (p > 0.05). There were more SG performed per quarter pre-COVID-19 than post-COVID-19 (36 vs. 22; p = 0.0056). Pre-COVID-19 and post-COVID-19 financial metrics per SG differed significantly for, respectively, revenues ($19,134 vs. $20,983) total variable cost ($9457 vs. $11,235), total fixed cost ($2036 vs. $4018), total profit ($7571 vs. $5442), and labor and benefits cost ($2535 vs. $3734; p < 0.05). CONCLUSIONS: The post-COVID-19 period was characterized by significantly increased SG fixed cost (i.e., building maintenance, equipment, overhead) and labor costs (increased contract labor), resulting in precipitous profit decline that crosses the break-even in calendar year quarter (CQ) 3, 2022. Potential solutions include minimizing contract labor cost and decreasing LOS.

Gastric Cancer Surgery in the US: a Contemporary Trend Analysis of Lymphadenectomy and the Impact of Minimally Invasive Approaches.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend harvesting 16 or more lymph nodes for the adequate staging of gastric adenocarcinoma. This study examines the rate of adequate lymphadenectomy over recent years, its predictors, and its impact on overall survival(OS). STUDY DESIGN: The National Cancer Database was utilized to identify patients who underwent surgical treatment for gastric adenocarcinoma between 2006-2019. Trend analysis was performed for lymphadenectomy rates during the study period. Logistic regression, Kaplan-Meier survival plots, and Cox proportional hazard regression were utilized. RESULTS: A total of 57,039 patients who underwent surgical treatment for gastric adenocarcinoma were identified. Only 50.5% of the patients underwent a lymphadenectomy of ≥ 16 nodes. Trend analysis showed that this rate significantly improved over the years, from 35.1% in 2006 to 63.3% in 2019 (p < .0001). The main independent predictors of adequate lymphadenectomy included high-volume facility with ≥ 31 gastrectomies/year (OR: 2.71; 95%CI:2.46-2.99), surgery between 2015-2019 (OR: 1.68; 95%CI: 1.60-1.75), and preoperative chemotherapy (OR:1.49; 95%CI:1.41-1.58). Patients with adequate lymphadenectomy had better OS than patients who did not: median survival: 59 versus 43 months (Log-Rank: p < .0001). Adequate lymphadenectomy was independently associated with improved OS (HR:0.79; 95%CI:0.77-0.81). Laparoscopic and robotic gastrectomies were independently associated with adequate lymphadenectomy compared to open, OR: 1.11, 95%CI:1.05-1.18 and OR: 1.24, 95%CI:1.13-1.35, respectively. CONCLUSION: Although the rate of adequate lymphadenectomy improved over the study period, a large number of patients still lacked adequate lymph node dissection, negatively impacting their OS despite multimodality therapy. Laparoscopic and robotic surgeries were associated with a significantly higher rate of lymphadenectomy ≥ 16 nodes.