Why can't we improve turnover time? A systematic review.

BACKGROUND: Despite substantial efforts to reduce operating room (OR) turnover time (TOT), delays remain a frustration to physicians, staff, and hospital leadership. These efforts have employed many systems and human factor-based approaches with variable results. A deeper dive into methodologies and their applicability could lead to successful and sustained change. The aim of this study was to conduct a systematic review to evaluate relevant research focused on improving OR TOT and clearly defining measures of successful intervention. MATERIAL AND METHODS: A systematic review of OR TOT interventions implemented between 1980 through October 2022 was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Research databases included: 1) PubMed; 2) Web of Science; and 3) OVID Medline. RESULTS: A total of 38 articles were appropriate for analysis. Most employed a pre/post intervention approach (29, 76.3%), the remaining utilized a control/intervention approach. Nine intervention methods were identified: the majority included a process redesign bundle (24, 63%), followed by overlapping induction, dedicated unit/team/space feedback, financial incentives, team training, education, practice guidelines, and redefinition of roles/responsibilities. Studies were further categorized into one of two groups: (1) those that utilized predetermined interventions based on anecdotal experience or prior literature (18, 47.4%) and (2) those that conducted a prospective analysis on baseline data to inform intervention development (20, 52.6%). DISCUSSION: There are significant variability in the methodologies utilized to improve OR TOT; however, the most effective solutions involved process redesign bundles developed from a prospective investigation of the clinical work-system.

Identifying Workflow Disruptions in Robotic-Assisted Bariatric Surgery: Elucidating Challenges Experienced by Surgical Teams.

PURPOSE: Bariatric surgery is an effective and durable treatment for weight loss for patients with extreme obesity. Although traditionally approached laparoscopically, robotic bariatric surgery (RBS) has unique benefits for both surgeons and patients. Nonetheless, the technological complexity of robotic surgery presents new challenges for OR teams and the wider clinical system. Further assessment of the role of RBS in delivering quality care for patients with obesity is necessary and can be done through a human factors approach. This observational study sought to investigate the impact of RBS on the surgical work system via the study of flow disruptions (FDs), or deviations from the natural workflow progression. MATERIALS AND METHODS: RBS procedures were observed between October 2019 and March 2022. FDs were recorded in real time and subsequently classified into one of nine work system categories. Coordination FDs were further classified into additional sub-categories. RESULTS: Twenty-nine RBS procedures were observed at three sites. An average FD rate of 25.05 (CI = ± 2.77) was observed overall. FDs were highest between insufflation and robot docking (M = 29.37, CI = ± 4.01) and between patient closing and wheels out (M = 30.00, CI = ± 6.03). FD rates due to coordination issues were highest overall, occurring once every 4 min during docking (M = 14.28, CI = ± 3.11). CONCLUSION: FDs occur roughly once every 2.4 min and happen most frequently during the final patient transfer and robot docking phases of RBS. Coordination challenges associated with waiting for staff/instruments not readily available and readjusting equipment contributed most to these disruptions.

A better way: training for direct observations in healthcare.

Direct observation is valuable for identifying latent threats and elucidating system complexity in clinical environments. This approach facilitates prospective risk assessment and reveals workarounds, near-misses and recurrent safety problems difficult to diagnose retrospectively or via outcome data alone. As observers are an instrument of data collection, developing effective and comprehensive observer training is critical to ensuring the reliability of the data collection and reproducibility of the research. However, methodological rigour for ensuring these data collection properties remains a key challenge in direct observation research in healthcare. Although prior literature has offered key considerations for observational research in healthcare, operationalising these recommendations may pose a challenge and unless guidance is also provided on observer training. In this article, we offer guidelines for training non-clinical observers to conduct direct observations including conducting a training needs analysis, incorporating practice observations and evaluating observers and inter-rater reliability. The operationalisation of these guidelines is described in the context of a 5-year multisite observational study investigating technology integration in the operating room. We also discuss novel tools developed during the course our project to support data collection and examine inter-rater reliability among observers in direct observation studies.

Human Factors Integration in Robotic Surgery.

OBJECTIVE: Using the example of robotic-assisted surgery (RAS), we explore the methodological and practical challenges of technology integration in surgery, provide examples of evidence-based improvements, and discuss the importance of systems engineering and clinical human factors research and practice. BACKGROUND: New operating room technologies offer potential benefits for patients and staff, yet also present challenges for physical, procedural, team, and organizational integration. Historically, RAS implementation has focused on establishing the technical skills of the surgeon on the console, and has not systematically addressed the new skills required for other team members, the use of the workspace, or the organizational changes. RESULTS: Human factors studies of robotic surgery have demonstrated not just the effects of these hidden complexities on people, teams, processes, and proximal outcomes, but also have been able to analyze and explain in detail why they happen and offer methods to address them. We review studies on workload, communication, workflow, workspace, and coordination in robotic surgery, and then discuss the potential for improvement that these studies suggest within the wider healthcare system. CONCLUSION: There is a growing need to understand and develop approaches to safety and quality improvement through human-systems integration at the frontline of care.Precis: The introduction of robotic surgery has exposed under-acknowledged complexities of introducing complex technology into operating rooms. We explore the methodological and practical challenges, provide examples of evidence-based improvements, and discuss the implications for systems engineering and clinical human factors research and practice.

Operative approach and case volume are associated with negative resection margins for adrenocortical carcinoma.

BACKGROUND: Surgical resection with negative margins is the treatment of choice for adrenocortical carcinoma (ACC). This study was undertaken to determine factors associated with negative resection margins. METHODS: National Cancer Database was queried from 2010 to 2016 to identify patients with AJCC/ENSAT Stage I-III ACC who underwent adrenalectomy. Patient, tumor, facility, and operative characteristics were compared by margin status (positive-PM or negative-NM) and operative approach (open-OA, laparoscopic-LA, or robotic-RA). Multivariable logistic regression was used to identify factors associated with PM. RESULTS: Eight hundred and eighty-one patients were identified, of which 18.4% had PM and 81.6% had NM. Patients with advanced pathologic T stage and pathologic N1 stage were more likely to have PM (vs. NM) (T3, 49.7% vs. 24.8%, p < 0.01; T4, 26.2% vs. 10.0%, p < 0.01; N1, 6.7% vs. 3.5%, p < 0.01). Patients undergoing OA (vs. LA and RA) were more likely to have advanced clinical T stage (T4, 16.6% vs. 5.7% vs. 7.8%, p < 0.01) and larger tumors (> 6 cm, 84.6% vs. 64.1% vs. 62.3%, p < 0.01). High-volume centers (≥ 5 cases) were more likely to utilize OA. Patients undergoing LA (vs. RA) were more likely to require conversion to open (20.3% vs. 7.8%, p = 0.011). On multivariable analysis, factors associated with higher odds of PM included T3 disease (OR 7.02, 95% CI 2.66-18.55), T4 disease (OR 10.22, 95% CI 3.66-28.53), and LA (OR 1.99, 95% CI 1.28-3.09). High-volume centers were associated with lower odds of PM (OR 0.67, 95% CI 0.45-0.98). There was no significant difference in margin status between OA and RA (OR 1.44, 95% CI 0.71-2.90). CONCLUSION: Centers with higher ACC case volumes have lower odds of PM and utilize OA more often. LA is associated with higher odds of PM, whereas RA is not. These factors should be considered when planning the operative approach for ACC.

The Application of Human Factors Engineering to Reduce Operating Room Turnover in Robotic Surgery.

BACKGROUND: Challenges associated with turnover time are magnified in robotic surgery. The introduction of advanced technology increases the complexity of an already intricate perioperative environment. We applied a human factors approach to develop systematic, data-driven interventions to reduce robotic surgery turnover time. METHODS: Researchers observed 40 robotic surgery turnovers at a tertiary hospital [20 pre-intervention (Jan 2018 to Apr 2018), 20 post-intervention (Jan 2019 to Jun 2019)]. Components of turnover time, including cleaning, instrument and room set-up, robot preparation, flow disruptions, and major delays, were documented and analyzed. Surveys and focus groups were used to investigate staff perceptions of robotic surgery turnover time. A multidisciplinary team of human factors experts and physicians developed targeted interventions. Pre- and post-intervention turnovers were compared. RESULTS: Median turnover time was 67 min (mean: 72, SD: 24) and 22 major delays were noted (1.1/case). The largest contributors were instrument setup (25.5 min) and cleaning (25 min). Interventions included an electronic dashboard for turnover time reporting, clear designation of roles and simultaneous completion of tasks, process standardization of operating room cleaning, and data transparency through monthly reporting. Post-intervention turnovers were significantly shorter (U = 57.5, p = .000) and ten major delays were noted. CONCLUSIONS: Human factors analysis generated interventions to improve turnover time. Significant improvements were seen post-intervention with a reduction in turnover time by a 26 min and decrease in major delays by over 50%. Future opportunities to intervene and further improve turnover time include targeting pre- and post-operative care phases.

Routine Versus Selective Liver Biopsy During Bariatric Surgery: Postoperative Outcomes and Preoperative Predictors of NASH.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is common in patients with obesity. Liver biopsy (LB) can be routinely or selectively performed during bariatric surgery to identify patients with NASH. METHODS: Patients undergoing bariatric surgery between 2016 and 2020 at our institution were identified. Chart review identified patients undergoing concurrent LB. LB results were compared between patients undergoing routine LB and selective LB. Patient demographics and postoperative outcomes were compared between those who received LB and those who did not (non-LB). In the LB cohort, preoperative characteristics of patients with NASH were compared to those without NASH, and multivariable regression was used to identify predictors of NASH. RESULTS: Two thousand three hundred ninety-three patients were identified, of which 400 (16.7%) had liver biopsies (LB) and 1,993 (83.3%) did not (non-LB). Three hundred thirty LB were performed routinely, and 70 were selective. Compared to selective LB, routine LB identified significantly higher rates of steatosis (83.6% vs. 4.5%, p < 0.01), periportal inflammation (67.0% vs. 3.2%, p < 0.01), fibrosis (65.8% vs. 2.1%, p < 0.01), and NASH (10.9% vs. 1.5%, p < 0.01). There were no differences in postoperative complications, blood transfusions, readmissions, or reoperations between LB and non-LB. On multivariable regression, highest BMI > 40 (OR 2.85, 95% CI 1.43-5.67) and insulin-dependent diabetes (OR 4.83, 95% CI 1.70-13.69) were associated with a higher odds of NASH, while Black race was associated with lower odds (OR 0.25, 95% CI 0.09-0.65). CONCLUSIONS: Routine liver biopsies during bariatric surgery identify higher rates of advanced NAFLD compared to selective biopsies, and can be safely performed without an increased risk of postoperative complications.

Adrenocortical Carcinoma: The Value of Lymphadenectomy.

BACKGROUND: Adrenocortical carcinoma (ACC) staging does not account for the number of positive nodes. The prognostic value of quantitative metastatic nodal burden is unknown. METHODS: The National Cancer Database was retrospectively queried from 2004-2016 to identify patients with Stage I-III ACC undergoing adrenalectomy. Patients who underwent lymphadenectomy (LAD) were further studied. Demographics, TNM staging, tumor characteristics, and surgical approach were analyzed. RESULTS: 386 LADs were identified. The median number of nodes examined was 2 (IQR 2-6), with no difference by surgical approach '[laparoscopic, 3 (1-3); robotic, 1.5 (1-4.5); open, 2 (1-7), p = 0.493]. In LADs with cN0 disease, positive nodes were seen in 17.5% of patients; an average of 6 (1-12) nodes were examined in patients who upstaged to pN1 disease compared with an average of 2 (1-6) nodes in those who remained pN0. Median survival was incrementally worse for patients with more positive nodes (62.8 vs. 21.9 vs. 13.7 vs. 11.3 vs. 10.7 months for 0, 1, 2, 3, and ≥ 4 positive nodes, respectively, p < 0.01). On multivariate analysis, significant prognostic factors for poor survival included older age, ≥ 2 comorbidities, pT3, and pT4. The strongest prognostic factor for poor survival was the number of positive nodes (1 node, hazards ratio [HR] 2.3, 95% confidence interval [CI] 1.5-3.6; 2 nodes, HR 1.3, 95% CI 0.6-3.0; 3 nodes, HR 3.0, 95% CI 1.1-8.0; ≥ 4 nodes, HR 4.0, 95% CI 2.5-6.2). Lymphadenectomy was associated with improved survival (HR 0.82, 95% CI 0.67-0.99). CONCLUSIONS: Higher quantitative metastatic nodal burden is a robust prognostic factor for worse survival in ACC.

Management of Postcholecystectomy Complications.

Cholecystectomy is one of the most common general surgery procedures performed worldwide. Complications include bile duct injury, strictures, bleeding, infection/abscess, retained gallstones, hernias, and postcholecystectomy syndrome. Obtaining a critical view of safety and following the other tenets of the Safe Cholecystectomy Task Force will aid in the prevention of bile duct injury and other morbidity associated with cholecystectomy.

Room Size Influences Flow in Robotic-Assisted Surgery.

The introduction of surgical technology into existing operating rooms (ORs) can place novel demands on staff and infrastructure. Despite the substantial physical size of the devices in robotic-assisted surgery (RAS), the workspace implications are rarely considered. This study aimed to explore the impact of OR size on the environmental causes of surgical flow disruptions (FDs) occurring during RAS. Fifty-six RAS procedures were observed at two academic hospitals between July 2019 and January 2021 across general, urologic, and gynecologic surgical specialties. A multiple regression analysis demonstrated significant effects of room size in the pre-docking phase (t = 2.170, df = 54, ß = 0.017, p = 0.035) where the rate of FDs increased as room size increased, and docking phase (t = -2.488, df = 54, ß = -0.017, p = 0.016) where the rate of FDs increased as room size decreased. Significant effects of site (pre-docking phase: p = 0.000 and docking phase: p = 0.000) were also demonstrated. Findings from this study demonstrate hitherto unrecognized spatial challenges involved with introducing surgical robots into the operating domain. While new technology may provide benefits towards patient safety, it is important to consider the needs of the technology prior to integration.

Factors Associated with Non-Operative Management of Resectable Adrenocortical Carcinoma.

INTRODUCTION: Surgery is the initial treatment of choice for patients with resectable adrenocortical carcinoma (ACC). We sought to determine factors associated with non-operative management of resectable ACC. METHODS: 2004-2016 National Cancer Database (NCDB) was queried to identify patients with AJCC/ENSAT Stage I-III ACC. Patients who underwent surgery (S) were compared to those who did not undergo surgery (NS). Multivariate logistic regression was used to identify factors associated with NS. Kaplan-Meier estimates used to assess survival. RESULTS: Two thousand-seventy patients with Stage I-III ACC were identified, of which 17.5% were NS. 85.9% of NS patients were not offered surgery; 69.9% of NS patients did not receive chemotherapy or radiation therapy. NS were older and less likely to receive care at an Academic center or high volume center (≥5 cases during the study period). NS patients were more likely to have advanced T stage and N1 disease. On multivariate regression, factors associated with lower odds of surgery include older age (OR 1.03, 95% CI 1.02-1.06), T4 disease (OR 3.34, 95% CI 1.05-10.68), and treatment at a community center (OR 2.92, 95% CI 1.58-5.40). Overall median survival was significantly poorer for NS patients (50.4 versus 78.4 months, P < 0.01). CONCLUSION: Patients with locally advanced ACC are less likely to undergo an operation, while those treated at centers with more operative experience or Academic facilities are more likely to undergo an operation. As the surgery-first approach is the current standard of care for resectable ACC, these patients may be best served at high volume Academic facilities.

Conversion of laparoscopic sleeve gastrectomy to Roux-en-Y gastric bypass: patterns predicting persistent symptoms after revision.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is the most common bariatric operation performed. However, it is not without its drawbacks and patients may develop gastroesophageal reflux (GERD) after LSG. There are limited data available to guide treatment choice for patients suffering these sequelae. OBJECTIVE: This study was undertaken to evaluate the success of conversion to Roux-en-Y gastric bypass (RYGB) in treating GERD symptoms after LSG. SETTING: Single bariatric center, United States. METHODS: Analysis of a prospectively maintained clinical database was performed. Outcomes studied included heartburn-related quality of life score (GERD-HRQL), anti-secretory usage, and body mass index (BMI). RESULTS: A total of 54 patients met inclusion criteria during the review period. Of these, 41 patients (76%) underwent conversion for indication including GERD. Mean BMI at conversion was 33.8 ± 5.61 and was found to be significantly reduced at 12 months after conversion (n = 26; 63%; P < .001) and at long-term follow-up (n = 37; 90%) (P ≤ .001; mean follow-up period: 33.3 mo). Mean GERD-HRQL at time of conversion was 31.5 ± 11.4. Conversion to RYGB produced a significant reduction of HRQL at 6 months after conversion (n = 30; 73%) (mean: 5.6, P < .001) and long-term follow-up (n = 38; 93%) (mean: 7.3, P < .001. mean follow-up period: 15.1 mo). Prior to conversion, 32 patients (78%) required antisecretory therapy for GERD and after conversion, 12 of these patients (38%) required antisecretory therapy (P < .001). These 12 patients were found to exhibit a significantly (P = .005) smaller decrease in GERD-HRQL after revision compared with their peers who were liberated from antisecretory therapy. Preoperative symptoms were compared between these 2 groups. Delayed onset of GERD symptoms after LSG (>3 mo) was found to be a significant risk factor for continued antisecretory dependence after conversion to RYGB. CONCLUSION: Conversion of LSG to RYGB quantitatively reduces GERD symptoms, and results in a modest but significant amount of weight loss. While there was a significant improvement in HRQL after revision, a subgroup of patients continued to be antisecretory-dependent and showed a limited improvement in HRQL. This limited response was predicted by a gradual onset of GERD symptoms prior to revision. An interval of 3 months or greater between LSG and onset of symptoms was found to be a significant risk factor for limited response to conversion.

Clinico-pathologic findings in patients with median arcuate ligament syndrome (celiac artery compression syndrome).

Median Arcuate Ligament Syndrome (MALS) is a rare entity characterized by severe post-prandial epigastric pain, nausea, vomiting, and/or weight loss. Symptoms have been attributed to vascular compression (celiac artery compression syndrome, CACS), but it remains controversial whether they could be secondary to neural compression. Literature review identified rare description of pathologic findings in surgery journals. The clinico-pathologic findings of four MALS patients who underwent robotic or laparoscopic surgery in our hospital are described. All our patients were female with a median age of 32.5 (range 25-55 years), and a median BMI of 23.5 kg/m2. They presented with chronic often post-prandial abdominal pain (4/4), nausea (3/4), emesis (2/4), anorexia (1/4), and weight loss (1/4). Two patients had a history of Crohn's disease. At intraoperative exploration, the celiac artery and adjacent nerves and ganglia were encased and partially compressed by fibrotic tissue in each patient. In each case laparoscopic excision of fibrotic tissue, celiac plexus and ligament division and was performed; celiac plexus nerve block was also performed in one patient. After surgical intervention, symptoms improved in three of the patients whose specimens show periganglionic and perineural fibrosis with proliferation of small nerve fibers. Our findings support neurogenic compression as a contributing factor in the development of pain and other MALS symptoms, and favor the use of MALS rather than CACS as diagnostic terminology. To further study the pathogenesis of this unusual syndrome, surgeons should submit all tissues excised during MALS procedures for histopathologic examination.

Using Flow Disruptions to Examine System Safety in Robotic-Assisted Surgery: Protocol for a Stepped Wedge Crossover Design.

BACKGROUND: The integration of high technology into health care systems is intended to provide new treatment options and improve the quality, safety, and efficiency of care. Robotic-assisted surgery is an example of high technology integration in health care, which has become ubiquitous in many surgical disciplines. OBJECTIVE: This study aims to understand and measure current robotic-assisted surgery processes in a systematic, quantitative, and replicable manner to identify latent systemic threats and opportunities for improvement based on our observations and to implement and evaluate interventions. This 5-year study will follow a human factors engineering approach to improve the safety and efficiency of robotic-assisted surgery across 4 US hospitals. METHODS: The study uses a stepped wedge crossover design with 3 interventions, introduced in different sequences at each of the hospitals over four 8-month phases. Robotic-assisted surgery procedures will be observed in the following specialties: urogynecology, gynecology, urology, bariatrics, general, and colorectal. We will use the data collected from observations, surveys, and interviews to inform interventions focused on teamwork, task design, and workplace design. We intend to evaluate attitudes toward each intervention, safety culture, subjective workload for each case, effectiveness of each intervention (including through direct observation of a sample of surgeries in each observational phase), operating room duration, length of stay, and patient safety incident reports. Analytic methods will include statistical data analysis, point process analysis, and thematic content analysis. RESULTS: The study was funded in September 2018 and approved by the institutional review board of each institution in May and June of 2019 (CSMC and MDRH: Pro00056245; VCMC: STUDY 270; MUSC: Pro00088741). After refining the 3 interventions in phase 1, data collection for phase 2 (baseline data) began in November 2019 and was scheduled to continue through June 2020. However, data collection was suspended in March 2020 due to the COVID-19 pandemic. We collected a total of 65 observations across the 4 sites before the pandemic. Data collection for phase 2 was resumed in October 2020 at 2 of the 4 sites. CONCLUSIONS: This will be the largest direct observational study of surgery ever conducted with data collected on 680 robotic surgery procedures at 4 different institutions. The proposed interventions will be evaluated using individual-level (workload and attitude), process-level (perioperative duration and flow disruption), and organizational-level (safety culture and complications) measures. An implementation science framework is also used to investigate the causes of success or failure of each intervention at each site and understand the potential spread of the interventions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25284.

Work-system interventions in robotic-assisted surgery: a systematic review exploring the gap between challenges and solutions.

BACKGROUND: The introduction of a robot into the surgical suite changes the dynamics of the work-system, creating new opportunities for both success and failure. An extensive amount of research has identified a range of barriers to safety and efficiency in Robotic Assisted Surgery (RAS), such as communication breakdowns, coordination failures, equipment issues, and technological malfunctions. However, there exists very few solutions to these barriers. The purpose of this review was to identify the gap between identified RAS work-system barriers and interventions developed to address those barriers. METHODS: A search from three databases (PubMed, Web of Science, and Ovid Medline) was conducted for literature discussing system-level interventions for RAS that were published between January 1, 1985 to March 17, 2020. Articles describing interventions for systems-level issues that did not involve technical skills in RAS were eligible for inclusion. RESULTS: A total of 30 articles were included in the review. Only seven articles (23.33%) implemented and evaluated interventions, while the remaining 23 articles (76.67%) provided suggested interventions for issues in RAS. Major barriers identified included disruptions, ergonomic issues, safety and efficiency, communication, and non-technical skills. Common solutions involved team training, checklist development, and workspace redesign. CONCLUSION: The review identified a significant gap between issues and solutions in RAS. While it is important to continue identifying how the complexities of RAS affect operating room (OR) and team dynamics, future work will need to address existing issues with interventions that have been tested and evaluated. In particular, improving RAS-associated non-technical skills, task management, and technology management may lead to improved OR dynamics associated with greater efficiency, reduced costs, and better systems-level outcomes.

A Human Factors Approach to Surgical Patient Safety.

This article explores the role of human factors engineering in patient safety in surgery. The authors discuss the history and evolution of human factors and the role of human factors in patient safety and provide a description of human factors methods used to study and improve patient safety.

Discovering the barriers to efficient robotic operating room turnover time: perceptions vs. reality.

Turnover time (TOT) has remained the subject of numerous research articles and operating room (OR) committee discussions. Inefficiencies associated with TOT are multiplied when complex technology, such as surgical robots, is involved. Using a human factors approach, this study investigated impediments to efficient robotic TOT and team members' perceptions surrounding this topic. Researchers observed 20 robotic turnovers over 2 months at a tertiary hospital. TOT, cleaning time, number of staff present, bed set-up time, instrument set-up time and any major delays were recorded. Additionally, 79 OR team members completed a questionnaire regarding perceptions of OR turnover. Average TOT was 72 min (s, 24 min). Overall, cleaning required the most time (average of 27.4 min, 37.96% of TOT), followed by instrument set-up (15.4 min, 21.34% of TOT) and RN retrieval of the patient from pre-op (12 min, 17.72% of TOT). OR team members estimated that turnovers require 60.36 min. Physicians believed the greatest contributor to TOT was "time to set up the OR", while OR staff rated "instrument availability" as the greatest issue, both of which were inaccurate. OR team members' perceptions of robotic TOT and contributing factors were different from reality based on observed contributors. Data demonstrated several areas of opportunity for process improvement. These data can be used to guide the implementation of targeted interventions to improve TOT efficiency.

Median Arcuate Ligament Syndrome and Its Associated Conditions.

The risk factors and associated conditions of median arcuate ligament syndrome (MALS) have not been well characterized in the literature. In this study, we aim to investigate the presentation and outcomes of MALS patients with an emphasis on the prevalence of other uncommon disorders. To this end, data of patients with MALS who underwent surgery between 2013 and 2018 were collected and compiled into a retrospective database and analyzed. Eleven patients were identified. Seven of these eleven patients underwent diagnostics to evaluate gastric emptying. Five of these seven patients (71.4%) had radiographic evidence of delayed gastric emptying. Four of the eleven patients (36.4%) were found to have anatomic abnormalities of their visceral vasculature. Two of the eleven patients (18.2%) were found to have connective tissue disorders, both with Ehlers-Danlos syndrome. Three of the eleven (27.3%) had a diagnosis of postural orthostatic tachycardia syndrome. This is the first case series reporting on an association between MALS and delayed gastric emptying. We also explored the relationship between MALS and visceral vascular abnormalities, Ehlers-Danlos syndrome, and postural orthostatic tachycardia syndrome. It is notable that these conditions are more prevalent in the MALS population than in the general population, suggesting a possible pathophysiologic relationship.

Hyaluronan synthase 2-mediated hyaluronan production mediates Notch1 activation and liver fibrosis.

Hyaluronan (HA), a major extracellular matrix glycosaminoglycan, is a biomarker for cirrhosis. However, little is known about the regulatory and downstream mechanisms of HA overproduction in liver fibrosis. Hepatic HA and HA synthase 2 (HAS2) expression was elevated in both human and murine liver fibrosis. HA production and liver fibrosis were reduced in mice lacking HAS2 in hepatic stellate cells (HSCs), whereas mice overexpressing HAS2 had exacerbated liver fibrosis. HAS2 was transcriptionally up-regulated by transforming growth factor-ß through Wilms tumor 1 to promote fibrogenic, proliferative, and invasive properties of HSCs via CD44, Toll-like receptor 4 (TLR4), and newly identified downstream effector Notch1. Inhibition of HA synthesis by 4-methylumbelliferone reduced HSC activation and liver fibrosis in mice. Our study provides evidence that HAS2 actively synthesizes HA in HSCs and that it promotes HSC activation and liver fibrosis through Notch1. Targeted HA inhibition may have potential to be an effective therapy for liver fibrosis.