Development of an in vitro ventricular shunt material testing model and utility of PEG as antifouling coating.

OBJECTIVE: CSF shunts, most commonly the ventriculoperitoneal shunt, remain a first and last line of management for children and adults with hydrocephalus. However, the failure rates of these shunts are extremely high, leaving many patients with the need for revision surgical procedures. The objective of this study was to develop a model to assess the efficacy of a nonfouling ventricular catheter. A second objective was to test polyethylene glycol (PEG) as an antifouling coating. METHODS: Microglial cells were grown on medical-grade catheter silicone with biofouling simulated by collagen incubation over a range of concentrations from 31 to 103 µg/ml and durations from 2 to 18 hours. After ideal fouling conditions were identified, catheter silicone was then coated with PEG as an antifouling surface, and cell growth on this surface was compared to that on uncoated standard catheter silicone. RESULTS: Collagen biofouling increased cell growth on silicone surfaces with an ideal concentration of 69 µg/ml and incubation of 6 hours. PEG coating of silicone catheter material yielded 70-fold lower cell growth (p < 0.0001), whereas collagen-fouled PEG-coated silicone yielded 157-fold lower cell growth (p < 0.0001). CONCLUSIONS: Catheter coating significantly reduced cell growth, particularly in the setting of biofouling. The application of antifouling surfaces to ventricular shunts shows considerable promise for improving efficacy.

A National Study on Training Innovation in US Medical Education.

Introduction Traditional medical education has leaned heavily on memorization, pattern recognition, and learned algorithmic thinking. Increasingly, however, creativity and innovation are becoming recognized as a valuable component of medical education. In this national survey of Association of American Medical Colleges (AAMC) member institutions, we seek to examine the current landscape of exposure to innovation-related training within the formal academic setting. Methods Surveys were distributed to 168 of 171 AAMC-member institutions (the remaining three were excluded from the study for lack of publicly available contact information). Questions assessed exposure for medical students among four defined innovation pillars as follows: (1) medical humanities, (2) design thinking, (3) entrepreneurship, or (4) technology transfer. Chi-squared analysis was used to assess statistical significance between schools, comparing schools ranked in the top 20 by the US News and World Report against non-top 20 respondents, and comparing schools that serve as National Institutes of Health (NIH) Clinical and Translational Science Awards (CTSA) program hubs against non-CTSA schools. Heat maps for geospatial visualization of data were created using ArcGIS (ArcMAP 10.6) software (Redlands, CA: Environmental Systems Research Institute). Results The overall response rate was 94.2% with 161 schools responding. Among respondents, 101 (63%) reported having medical humanities curricula at their institution. Design thinking offerings were noted at 51/161 (32%) institutions. Support for entrepreneurship was observed at 51/161 institutions (32%), and technology transfer infrastructure was confirmed at 42/161 (26%) of institutions. No statistically significant difference was found between top 20 schools and lower 141 schools when comparing schools with no innovation programs or one or more innovation programs (p=0.592), or all four innovation programs (p=0.108). CTSA programs, however, did show a statistically significant difference (p<0.00001) when comparing schools with no innovation programs vs. one or more programs, but not when comparing to schools with all four innovation programs (p=0.639). Conclusion This study demonstrated an overwhelming prevalence of innovation programs in today's AAMC medical schools, with over 75% of surveyed institutions offering at least one innovation program. No statistically significant trend was seen in the presence of zero programs, one or more, or all four programs between top 20 programs and the remaining 141. CTSA hub schools, however, were significantly more likely to have at least one program vs. none compared to non-CTSA hub schools. Future studies would be valuable to assess the long-term impact of this trend on medical student education.

SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages.

Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet the underlying mechanism is unknown. To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of adipose tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled the response of adipose tissue to SARS-CoV-2 infection in vitro. In COVID-19 autopsy cases, we identified SARS-CoV-2 RNA in adipocytes with an associated inflammatory infiltrate. We identified two distinct cellular targets of infection: adipocytes and a subset of inflammatory adipose tissue-resident macrophages. Mature adipocytes were permissive to SARS-CoV-2 infection; although macrophages were abortively infected, SARS-CoV-2 initiated inflammatory responses within both the infected macrophages and bystander preadipocytes. These data suggest that SARS-CoV-2 infection of adipose tissue could contribute to COVID-19 severity through replication of virus within adipocytes and through induction of local and systemic inflammation driven by infection of adipose tissue-resident macrophages.

Literature review on antiobesity medication use for metabolic and bariatric surgery patients from the American Society for Metabolic and Bariatric Surgery Clinical Issues Committee.

The following literature search is in response to inquiries made to the American Society for Metabolic and Bariatric Surgery (ASMBS) regarding antiobesity medication (AOM) use in patients who are having or have already had metabolic and bariatric surgery (MBS). These recommendations are based on current clinical knowledge, expert opinion, and published peer-reviewed scientific evidence available at this time. This paper is not intended to establish a local, regional, or national standard of care. The paper will be revised in the future as additional evidence becomes available.

Pilot study of responsive nucleus accumbens deep brain stimulation for loss-of-control eating.

Cravings that precede loss of control (LOC) over food consumption present an opportunity for intervention in patients with the binge eating disorder (BED). In this pilot study, we used responsive deep brain stimulation (DBS) to record nucleus accumbens (NAc) electrophysiology during food cravings preceding LOC eating in two patients with BED and severe obesity (trial registration no. NCT03868670). Increased NAc low-frequency oscillations, prominent during food cravings, were used to guide DBS delivery. Over 6 months, we observed improved self-control of food intake and weight loss. These findings provide early support for restoring inhibitory control with electrophysiologically-guided NAc DBS. Further work with increased sample sizes is required to determine the scalability of this approach.

Beyond 5 years: a matched cohort of sleeve gastrectomy versus gastric bypass.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has demonstrated excellent short-term outcomes. However, existing studies suffer from loss to follow-up, and most long-term data focus on laparoscopic Roux-en-Y gastric bypass (LRYGB). This study compares weight loss in patients ≥5 years from LSG with that in matched patients who underwent LRYGB. OBJECTIVES: The purpose of this study was to compare long-term weight loss in patients undergoing LRYGB and LSG. SETTING: University hospital, United States. METHODS: We retrospectively evaluated patients who underwent LSG before August 2012 with follow-up data ≥5 years. LSG patients were matched 1:1 with LRYGB patients by sex, age at surgery, and preoperative body mass index. Univariate and multivariate analyses were performed with weight loss at the longest duration the primary outcome. RESULTS: One-hundred and sixty-five patients underwent LSG during the study period. Long-term follow-up data (≥5 years) were available for 85 patients (52%). There were no preoperative differences between those with and without follow-up data. Six LSG patients (7%) were excluded because they underwent reoperation that altered intestinal anatomy. Of the 79 patients remaining, 75 were matched with post-LRYGB patients. The average follow-up period was 6.4 years for LSG patients and 6.5 years for LRYGB patients (P = .08, not significant). Change in body mass index was 6.81 kg/m2 for LSG patients and 13.11 kg/m2 for LRYGB patients. Percentage of total body weight loss was 15.25% for LSG patients and 28.73% for LRYGB patients. Percentage of excess body weight loss was 37% for LSG patients and 67% for LRYGB patients (P < .0001). Weight loss for LSG patient follow-up in clinic versus outside the clinic was 46% versus 34% (P = .18, not significant). CONCLUSIONS: LSG is now the most common bariatric surgery in the United States. Long-term data are needed to confirm that observed short-term favorable outcomes are maintained. Recent studies have produced divergent results. We observed significantly less weight loss at ≥5 years in LSG patients compared with matched LRYGB patients.

Can responsive deep brain stimulation be a cost-effective treatment for severe obesity?

OBJECTIVE: A first-in-human responsive deep brain stimulation (rDBS) trial (NCT03868670) for obesity is under way, which is based on promising preclinical evidence. Given the upfront costs of rDBS, it is prudent to examine the success threshold for cost-effectiveness compared with laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Efficacy and safety data on LRYGB and safety data on rDBS were collected for established indications through a literature search. The success threshold was defined as minimum BMI reduction. Treatment costs were calculated via Medicare national reimbursement data. RESULTS: LRYGB had a mean BMI reduction of 13.75 kg/m2 . Based on adverse events, LRYGB was a less-preferred health state (overall adverse event utility of 0.96 [0.02]) than rDBS (0.98 [0.01]), but LRYGB ($14,366 [$6,410]) had a significantly lower treatment cost than rDBS ($29,951 [$4,490]; p < 0.0001). Therefore, for rDBS to be cost-effective compared with LRYGB, the multiple models yielded a success threshold range of 13.7 to 15.2 kg/m2 . CONCLUSIONS: This study established a preliminary efficacy success threshold for rDBS to be cost-effective for severe obesity, and results from randomized controlled trials are needed. This analysis allows for interpretation of the economic impact of advancing rDBS for obesity in light of ongoing trial results and suggests an attainable threshold is needed for cost-effectiveness.

Gastroesophageal Reflux Disease and the Patient with Obesity.

Patients with obesity who present with gastroesophageal reflux disease (GERD) require a nuanced approach. Those with lower body mass index (BMI) (less than 33) can be counseled on weight loss, and if successful may be approached with laparoscopic fundoplication. Those who are unable to achieve weight loss or those who present with a BMI greater than or equal to 35 should proceed with laparoscopic Roux-en-Y gastric bypass (LRYGB). Conversion to LRYGB from sleeve gastrectomy is a safe and effective way to manage GERD after sleeve gastrectomy.

Innovation in hemodialysis: Using the Biodesign process to identify unmet needs.

There is renewed demand to accelerate innovation in nephrology; public and private sectors are creating programs to support its growth. The Stanford Biodesign innovation process, first developed in 2000, provides a roadmap for health technology and device innovation. There is insufficient published guidance on the application of the Biodesign process in the generation of novel devices to address nephrology- and/or dialysis-related clinical unmet needs. We present "needs finding," the initial part of the identify phase in the Biodesign innovation process and how it may be utilized for nephrology- and/or dialysis-related innovation. We describe here how to apply the Biodesign process to identify unmet dialysis-related needs, with the use of specific case-based examples based on observations within a hemodialysis unit. We then explore how to develop these needs using background research, direct clinical observations, interviews, documentation of observations and interview findings, and development of multiple needs statements. We conclude that there is an opportunity for nephrology innovators to use this methodology broadly in order to identify areas for innovation and initiated the development on novel solutions to be introduced into patient care.

Long-term outcomes of per-oral endoscopic myotomy compared to laparoscopic Heller myotomy for achalasia: a single-center experience.

INTRODUCTION: Many centers have reported excellent short-term efficacy of per-oral endoscopic myotomy (POEM) for the treatment of achalasia. However, long-term data are limited and there are few studies comparing the efficacy of POEM versus Heller Myotomy (HM). AIMS: To compare the long-term clinical efficacy of POEM versus HM. METHODS: Using a retrospective, parallel cohort design, all cases of POEM or HM for achalasia between 2010 and 2015 were assessed. Clinical failure was defined as (a) Eckardt Score > 3 for at least 4 weeks, (b) achalasia-related hospitalization, or (c) repeat intervention. All index manometries were classified via Chicago Classification v3. Pre-procedural clinical, manometric, radiographic data, and procedural data were reviewed. RESULTS: 98 patients were identified (55 POEM, 43 Heller) with mean follow-up of 3.94 years, and 5.44 years, respectively. 83.7% of HM patients underwent associated anti-reflux wrap (Toupet or Dor). Baseline clinical, demographic, radiographic, and manometric data were similar between the groups. There was no statistical difference in overall long-term success (POEM 72.7%, HM 65.1% p = 0.417, although higher rates of success were seen in Type III Achalasia in POEM vs Heller (53.3% vs 44.4%, p < 0.05). Type III Achalasia was the only variable associated with failure on a univariate COX analysis and no covariants were identified on a multivariate Cox regression. There was no statistical difference in GERD symptoms, esophagitis, or major procedural complications. CONCLUSION: POEM and HM have similar long-term (4-year) efficacy with similar adverse event and reflux rates. POEM was associated with greater efficacy in Type III Achalasia.

Achalasia: physiology and diagnosis.

Achalasia is a rare motility disorder with incomplete relaxation of the lower esophageal sphincter and ineffective contractions of the esophageal body. It has been hypothesized that achalasia does not result from only one pathway but rather involves a combination of infectious, autoimmune, and familial etiological components. On the basis of other observations, a novel hypothesis suggests that a muscular form of eosinophilic esophagitis is involved in the pathophysiology of achalasia in some patients. This appears to progressively diminish the myenteric plexus at stage III, gradually destroy it at stage II, and finally eliminate it at stage I, the most advanced and final stage of achalasia. Although high-resolution manometry has identified these three different types of achalasia, another subset of patients with a normal-appearing sphincter relaxation has been proposed. Provocative maneuvers, such as the rapid drinking challenge, have recently been demonstrated to improve diagnosis in certain borderline patients, but have to be studied in more detail. However, whether the different types of achalasia will have a long-term impact on tailored therapies is still a matter of debate. Additionally, novel aspects of the standard timed barium swallow appear to be an important adjunct of diagnosis, as it has been shown to have a diagnostic as well as a predictive value.

Brain-Responsive Neurostimulation for Loss of Control Eating: Early Feasibility Study.

BACKGROUND: Loss of control (LOC) is a pervasive feature of binge eating, which contributes significantly to the growing epidemic of obesity; approximately 80 million US adults are obese. Brain-responsive neurostimulation guided by the delta band was previously found to block binge-eating behavior in mice. Following novel preclinical work and a human case study demonstrating an association between the delta band and reward anticipation, the US Food and Drug Administration approved an Investigational Device Exemption for a first-in-human study. OBJECTIVE: To assess feasibility, safety, and nonfutility of brain-responsive neurostimulation for LOC eating in treatment-refractory obesity. METHODS: This is a single-site, early feasibility study with a randomized, single-blinded, staggered-onset design. Six subjects will undergo bilateral brain-responsive neurostimulation of the nucleus accumbens for LOC eating using the RNS® System (NeuroPace Inc). Eligible participants must have treatment-refractory obesity with body mass index ≥ 45 kg/m2. Electrophysiological signals of LOC will be characterized using real-time recording capabilities coupled with synchronized video monitoring. Effects on other eating disorder pathology, mood, neuropsychological profile, metabolic syndrome, and nutrition will also be assessed. EXPECTED OUTCOMES: Safety/feasibility of brain-responsive neurostimulation of the nucleus accumbens will be examined. The primary success criterion is a decrease of ≥1 LOC eating episode/week based on a 28-d average in ≥50% of subjects after 6 mo of responsive neurostimulation. DISCUSSION: This study is the first to use brain-responsive neurostimulation for obesity; this approach represents a paradigm shift for intractable mental health disorders.

Analysis of Gender Perceptions in Health Technology: A Call to Action.

Gender diversity has been linked to positive business results. Yet limited data exist to characterize the gender landscape in health technology, a field that draws employees from both biomedical engineering and medicine. To better understand the state of gender diversity in this industry, we developed a survey to explore leadership representation and perceptions of workplace equality, job satisfaction, and work-life balance. Data from 400 + health technology professionals revealed that women are significantly underrepresented in senior leadership and that men and women experience the workplace differently. Men believe in greater numbers than females that senior leaders are focused on recruiting and promoting women, promotion criteria are equitable, and the major barrier to leadership roles for women is work/family balance. In contrast, women perceive a less meritocratic and inclusive workplace in which their ability to rise is hampered by exclusion from influential communication networks and stereotyping/bias. Perhaps as a result, more than one-third of female respondents are considering leaving their current jobs, citing dissatisfaction with management and a desire for greater advancement opportunities. This study highlights significant gender perception differences in health technology that require further study and proactive remediation for the field to fully realize the benefits of gender diversity.

Stanford's Biodesign Innovation program: Teaching opportunities for value-driven innovation in surgery.

The Stanford Biodesign Innovation process, which identifies meaningful clinical needs, develops solutions to meet those needs, and plans for subsequent implementation in clinical practice, is an effective training approach for new generations of healthcare innovators. Continued success of this process hinges on its evolution in response to changes in healthcare delivery and an ever-increasing demand for economically viable solutions. In this article, we provide perspective on opportunities for value-driven innovation in surgery and relate these to value-related teaching elements currently integrated in the Stanford Biodesign process.

Situating Artificial Intelligence in Surgery: A Focus on Disease Severity.

OBJECTIVES: Artificial intelligence (AI) has numerous applications in surgical quality assurance. We assessed AI accuracy in evaluating the critical view of safety (CVS) and intraoperative events during laparoscopic cholecystectomy. We hypothesized that AI accuracy and intraoperative events are associated with disease severity. METHODS: One thousand fifty-one laparoscopic cholecystectomy videos were annotated by AI for disease severity (Parkland Scale), CVS achievement (Strasberg Criteria), and intraoperative events. Surgeons performed focused video review on procedures with ≥1 intraoperative events (n = 335). AI versus surgeon annotation of CVS components and intraoperative events were compared. For all cases (n = 1051), intraoperative-event association with CVS achievement and severity was examined using ordinal logistic regression. RESULTS: Using AI annotation, surgeons reviewed 50 videos/hr. CVS was achieved in ≤10% of cases. Hepatocystic triangle and cystic plate visualization was achieved more often in low-severity cases (P < 0.03). AI-surgeon agreement for all CVS components exceeded 75%, with higher agreement in high-severity cases (P < 0.03). Surgeons agreed with 99% of AI-annotated intraoperative events. AI-annotated intraoperative events were associated with both disease severity and number of CVS components not achieved. Intraoperative events occurred more frequently in high-severity versus low-severity cases (0.98 vs 0.40 events/case, P < 0.001). CONCLUSIONS: AI annotation allows for efficient video review and is a promising quality assurance tool. Disease severity may limit its use and surgeon oversight is still required, especially in complex cases. Continued refinement may improve AI applicability and allow for automated assessment.

Preoperative weight loss: is waiting longer before bariatric surgery more effective?

BACKGROUND: Many insurance companies require patients to undergo supervised weight loss programs lasting several months. However, the association between time to surgery (TTS)-the wait time between the initial consultation visit and the immediate preoperative visit-and weight loss is not well documented. OBJECTIVES: To investigate whether TTS affects pre- or postoperative weight loss or complication rates. SETTING: University hospital, United States. METHODS: Data from 415 patients undergoing laparoscopic Roux-en-Y gastric bypass (n = 263) or sleeve gastrectomy (n = 152) at a single academic institution between 2014 and 2015 were retrospectively reviewed. TTS was compared with the percentage of total weight lost, change in body mass index, and adverse surgical events. RESULTS: Participants had an average body mass index of 47.42 kg/m2 at the consultation visit and TTS ranged from 7 to 1813 days with an average wait of 209.23 days. There was a statistically significant negative correlation between TTS and preoperative percentage of total weight lost among gastric bypass patients (b = -.005; P = .0492 2-tailed). A similar inverse relationship was identified among sleeve gastrectomy patients. Extended TTS provided no significant long-term benefits in weight loss by 24 months. No significant difference in rates of complications or readmissions was identified. CONCLUSIONS: Longer preoperative wait times do not result in improved weight loss or reduced adverse events. Determination of patient eligibility for bariatric surgery should rest with the health team and delay of treatment should be minimized.