BF170 hydrochloride enhances the emergence of hematopoietic stem and progenitor cells.

Generation of hematopoietic stem and progenitor cells (HSPCs) ex vivo and in vivo, especially the generation of safe therapeutic HSPCs, still remains inefficient. In this study, we have identified compound BF170 hydrochloride as a previously unreported pro-hematopoiesis molecule, using the differentiation assays of primary zebrafish blastomere cell culture and mouse embryoid bodies (EBs), and we demonstrate that BF170 hydrochloride promoted definitive hematopoiesis in vivo. During zebrafish definitive hematopoiesis, BF170 hydrochloride increases blood flow, expands hemogenic endothelium (HE) cells and promotes HSPC emergence. Mechanistically, the primary cilia-Ca2+-Notch/NO signaling pathway, which is downstream of the blood flow, mediated the effects of BF170 hydrochloride on HSPC induction in vivo. Our findings, for the first time, reveal that BF170 hydrochloride is a compound that enhances HSPC induction and may be applied to the ex vivo expansion of HSPCs.

Collaborative Development and Implementation of a Hybrid Virtual Surgery Clerkship Curriculum in a Vietnamese Medical School.

OBJECTIVE: To collaboratively develop a hybrid virtual curriculum for a medical school surgery clerkship within an emerging medical university in Vietnam. DESIGN: A hybrid virtual surgery clerkship curriculum was collaboratively developed by Vietnamese and American surgeons as part of an international partnership between their respective universities. A set of 25 virtual lectures with associated materials were created and deployed in tandem with live, in-person review and skills sessions. Student quantitative and qualitative evaluation methods were developed and deployed to allow continuous iteration. A 6-month course was deployed to develop surgical faculty into effective teachers. SETTING: The curriculum was deployed at VinUniversity College of Health Sciences, the youngest medical university in Vietnam. It was developed in collaboration with the University of Pennsylvania Perelman School of Medicine. Each cohort of 12 students in the surgical clerkship will participate in the curriculum. CONCLUSIONS: The development of this hybrid surgical clerkship in Vietnam leveraged local resources and expertise with those available remotely. Lessons learned are directly applicable to future collaborative curriculum development efforts at other emerging medical schools.

Teaching Airway Management Using Virtual Reality: A Scoping Review.

Airway management, a defined procedural and cognitive skillset embracing routine tracheal intubation and emergency airway rescue, is most often acquired through an apprenticeship model of opportunistic learning during anesthesia or acute care residency training. This training engages a host of modalities to teach and embed skill sets but is generally time- and location-constrained. Virtual reality (VR)-based simulation training offers the potential for reproducible and asynchronous skill acquisition and maintenance, an advantage that may be important with restricted trainee work hours and low frequency but high-risk events. In the absence of a formal curriculum from training bodies-or expert guidance from medical professional societies-local initiatives have filled the VR training void in an unstructured fashion. We undertook a scoping review to explore current VR-based airway management training programs to assess their approach, outcomes, and technologies to discover programming gaps. English-language publications addressing any aspect of VR simulation training for airway management were identified across PubMed, Embase, and Scopus. Relevant articles were used to craft a scoping review conforming to the Scale for quality Assessment of Narrative Review Articles (SANRA) best-practice guidance. Fifteen studies described VR simulation programs to teach airway management skills, including flexible fibreoptic bronchoscopic intubation (n = 10), direct laryngoscopy (n = 2), and emergency cricothyroidotomy (n = 1). All studies were single institution initiatives and all reported different protocols and end points using bespoke applications of commercial technology or homegrown technologic solutions. VR-based simulation for airway management currently occurs outside of a formal curriculum structure, only for specific skill sets, and without a training pathway for educators. Medical educators with simulation training and medical professional societies with content expertise have the opportunity to develop consensus guidelines that inform training curricula as well as specialty technology use.

A Systematic Review of Immersive Virtual Reality for Nontechnical Skills Training in Surgery.

OBJECTIVE: Immersive virtual reality (IVR) can be utilized to provide low cost and easily accessible simulation on all aspects of surgical education. In addition to technical skills training in surgery, IVR simulation has been utilized for nontechnical skills training in domains such as clinical decision-making and pre-operative planning. This systematic review examines the current literature on the effectiveness of IVR for nontechnical skill acquisition in surgical education. DESIGN: A literature search was performed using MEDLINE, EMBASE, and Web of Science for primary studies published between January 1, 1995 and February 9, 2022. Four reviewers screened titles, abstracts, full texts, extracted data, and analyzed included studies to answer 5 key questions: How is IVR being utilized in nontechnical skills surgical education? What is the methodological quality of studies? What technologies are being utilized? What metrics are reported? What are the findings of these studies? RESULTS: The literature search yielded 2340 citations, with 12 articles included for qualitative synthesis. Of included articles, 33% focused on clinical decision-making and 67% on anatomy/pre-operative planning. Motion sickness was a recorded metric in 25% of studies, with an aggregate incidence of 13% (11/87). An application score was reported in 33% and time to completion in 16.7%. A commercially developed application was utilized in 25%, while 75% employed a noncommercial application. The Oculus Rift was used in 41.7% of studies, HTC Vive in 25%, Samsung Gear in 16.7% of studies, Google Daydream in 8%, and 1 study did not report. The mean Medical Education Research Quality Instrument (MERSQI) score was 10.3 ± 2.3 (out of 18). In all studies researching clinical decision-making, participants preferred IVR to conventional teaching methods and in a nonrandomized control study it was found to be more effective. Averaged across all studies, mean scores were 4.33 for enjoyment, 4.16 for utility, 4.11 for usability, and 3.73 for immersion on a 5-point Likert scale. CONCLUSIONS: The IVR nontechnical skills applications for surgical education are designed for clinical decision-making or anatomy/pre-operative planning. These applications are primarily noncommercially produced and rely upon a diverse array of HMDs for content delivery, suggesting that development is primarily coming from within academia and still without clarity on optimal utilization of the technology. Excitingly, users find these applications to be immersive, enjoyable, usable, and of utility in learning. Although a few studies suggest that IVR is additive or superior to conventional teaching or imaging methods, the data is mixed and derived from studies with weak design. Motion sickness with IVR remains a complication of IVR use needing further study to determine the cause and means of mitigation.

Factors associated with conversion in laparoscopic surgery in a low-resource setting: a single-center prospective study.

INTRODUCTION: Laparoscopy has a clear patient benefit related to postoperative morbidity but may not be as commonly performed in low-and middle-income countries. The decision to convert to laparotomy can be complex and involve factors related to the surgeon, patient, and procedure. The objective of this work is to analyze the factors associated with conversion in laparoscopic surgery in a low-resource setting. METHODS: This is a single-center prospective study of patients who underwent laparoscopic surgery between May 1, 2018 and October 31, 2021. The parameters studied were age, sex, body mass index (BMI), intraoperative complication (e.g., accidental enterotomy, hemorrhage), equipment malfunction (e.g., technical failure of the equipment, break in CO2 supply line), operating time, and conversion rate. RESULTS: A total of 123 laparoscopic surgeries were performed. The average age of patients was 31.2 years (range 11-75). The procedures performed included appendix procedures (48%), followed by gynecological (18.7%), gallbladder (14.6%), digestive (10.56%), and abdominal procedures (4%). The average length of hospitalization was 3 days (range 1-16). Conversion to laparotomy was reported in 8.9% (n = 11) cases. Equipment malfunction was encountered in 9.8% (n = 12) cases. Surgical complications were noted in 11 cases (8.9%). Risk factors for conversion were shown to be BMI > 25 kg/m2 (OR 4.6; p = 0.034), intraoperative complications (OR 12.6; p = 0.028), and equipment malfunction (OR 9.4; p = 0.002). CONCLUSION: A better understanding of the underlying factors associated with high conversion rates, such as overweight/obesity, intraoperative complications, and equipment failure, is the first step toward surgical planning to reduce postoperative morbidity in low-resource settings.

Evolution of laparoscopic surgery in a sub-Saharan African country: a 30-year literature review in Senegal.

INTRODUCTION: The advent of laparoscopy has significantly reduced the morbidity associated with the majority of abdominal surgeries. In Senegal, the first studies evaluating this technique were published in the 1980s. The objective of this systematic review is to assess the evolution of laparoscopy research in Senegal. METHODS: A search of PubMed and Google Scholar was carried out without limit of publication date. The keywords used were "senegal" AND "laparoscop*". Duplicates were removed, and remaining articles were assessed for selection criteria. We included all articles about laparoscopy published in Senegal. The parameters studied in each included article were the place and year of study, average age, sex ratio, assessed indications and results. RESULTS: 41 Studies published between 1984 and 2021 met selection criteria. The average age of patients was 33 years (range 4.7-63). The sex ratio was 0.33. The main indications for laparoscopy according to the studies were: benign gastrointestinal disorders in 11 studies (26.8%), abdominal emergencies in 9 studies (22%), gallbladder surgery in 5 studies (12.2%), benign gynecological pathology in 6 studies (14.6%), malignant gynecological pathology in 2 studies (4.9%), diagnostic laparoscopy in 2 studies (4.9%), groin hernia repair in 2 studies (4.9%) and testicular pathology in 1 study (2.4%). Overall mortality was estimated at 0.9% (95% CI 0.6-1.3) and overall morbidity for all complications was estimated at 5% (95% CI 3.4-6.9). CONCLUSIONS: This systematic review showed a predominance of the laparoscopy publications from the capital in Dakar with favorable outcomes. This technique should be popularized in the different regions of the country and its indications expanded.

Evaluation of the educational quality of publicly available online videos on laparoscopic jejunostomy by utilizing the LAP-VEGaS guidelines.

BACKGROUND: Despite its common nature, there is no data on the educational quality of publicly available laparoscopic jejunostomy training videos. The LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool, released in 2020, has been developed to ensure that teaching videos are of appropriate quality. This study applies the LAP-VEGaS tool to currently available laparoscopic jejunostomy videos. METHODS: A retrospective review of YouTube® videos was conducted for "laparoscopic jejunostomy." Included videos were rated by three independent investigators using LAP-VEGaS video assessment tool (0-18). Wilcoxon rank-sum test was used to evaluate differences in LAP-VEGaS scores between video categories and date of publication relative to 2020. Spearman's correlation test was performed to measure association between scores and length, number of views and likes. RESULTS: 27 unique videos met selection criteria. Academic and physician video walkthroughs did not demonstrate a significant difference in median scores (9.33 IQR 6.33, 14.33 vs. 7.67 IQR 4, 12.67, p = 0.3951). Videos published after 2020 demonstrated higher median scores than those published before 2020 (13 IQR 7.5, 14.67 vs. 5 IQR 3, 9.67, p = 0.0081). A majority of videos failed to provide patient position (52%), intraoperative findings (56%), operative time (63%), graphic aids (74%), and audio/written commentary (52%). A positive association was demonstrated between scores and number of likes (rs = 0.59, p = 0.0011) and video length (rs = 0.39, p = 0.0421), but not number of views (rs = 0.17, p = 0.3991). CONCLUSION: The majority of available YouTube® videos on laparoscopic jejunostomy fail to meet the basic educational needs of surgical trainees, and there is no difference between those produced by academic centers or independent physicians. However, there has been improvement in video quality following the release of the scoring tool. Standardization of laparoscopic jejunostomy training videos with the LAP-VEGaS score can ensure that videos are of appropriate educational value with logical structure.

What are trainees watching? Assessing the educational quality of online laparoscopic cholecystectomy training videos using the LAP-VEGaS guidelines.

BACKGROUND: Laparoscopic cholecystectomy is the most common laparoscopic procedure performed in the US and a key component of general surgery training. Surgical trainees frequently access YouTube for educational walkthroughs of surgical procedures. This study aims to evaluate the educational quality of YouTube video walkthroughs on laparoscopic cholecystectomy by using the LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS) video assessment tool. METHODS: A YouTube search was conducted using "laparoscopic cholecystectomy." Results were sorted by relevance, and the top 100 videos were gathered. Videos with patient education or concomitant procedures were excluded. Included videos were categorized as Physician (produced by an individual physician), Academic (produced by a university or medical school), Commercial (produced by a surgical company), and Society (produced by a professional surgical society) and were rated by 3 investigators using the LAP-VEGaS video assessment tool (0-18). RESULTS: In all, 33 videos met the selection criteria. The average LAP-VEGaS score was 7.96 ± 3.95, and inter-rater reliability was .86. Academic videos demonstrated a significantly higher mean LAP-VEGaS score than Commercial (10.69 ± 3.54 vs 5.25 ± 2.38, P = .033). Most academic videos failed to provide formal case presentations (63%), patient positioning (50%), intraoperative findings (50%), graphic aids (63%), and operative time (75%). CONCLUSION: This is the first study to evaluate the quality of YouTube video walkthroughs on LC using the LAP-VEGaS tool. Despite demonstrating higher LAP-VEGaS scores than other categories, video walkthroughs provided by academic institutions still lack several essential educational criteria for this procedure, highlighting areas of improvement for educators.

Promoting a Culture of Safety in Cholecystectomy (COSIC) over a decade at a Philippine public regional hospital after the SAGES International Proctoring Course in Laparoscopic Cholecystectomy Course.

BACKGROUND: The SAGES International Proctoring Course for Laparoscopic Cholecystecomy accepts applications from low to middle-income countries for SAGES faculty to train local surgeons. A regional public hospital in the 10th most populous city in the Philippines was one of the chosen sites for the 1-week course in 2010. Two SAGES surgeons and one nurse trained two local surgeons and four nurses identified by the hospital director. METHODS: All patients seen in the out-patient clinic at the Zamboanga City Medical Center in the Philippines and scheduled for elective laparoscopic cholecystectomy from the first day of the course in August 2010 until December 2018 were entered into a prospectively collected database including demographics, pre-op diagnosis, operative findings, histopathologic diagnosis, conversion rates and 30-day complications including re-operations. RESULTS: 521 patients underwent laparoscopic cholecystectomy. Majority were female (63.7%) with a mean age of 45.9 years. Most procedures were completed laparoscopically with an open conversion rate of 3.3%. Three patients underwent laparoscopic subtotal cholecystectomy. Reported complications requiring reoperation included one stump necrosis, two incisional hernias and one retained stone. One serosal injury and one surgical site infection were also reported for an overall morbidity rate of 4.6%. Pathology showed chronic calculous cholecystitis in 92.8% of specimens. No 30-day mortality was recorded. CONCLUSION: The SAGES International Proctoring Course for Laparoscopic Cholecystectomy has been shown to be a successful method for global surgery training. A focused 1-week direct proctoring model in the Philippines showed a sustained culture of safety in cholecystectomy with low 30-day morbidity, complication and conversion rates over a decade following participation in this program.

Letting the sun set on small bowel obstruction: can a simple risk score tell us when nonoperative care is inappropriate?

Controversy remains as to which patients with small bowel obstruction (SBO) need immediate surgery and which may be managed conservatively. This study evaluated the ability of clinical risk factors to predict the failure of nonoperative management of SBO. The electronic medical record was used to identify all patients with SBO over one year. Clinical, laboratory, and imaging data were recorded. Univariate and multivariable analyses were performed to identify risk factors predicting need for surgery. Cox proportional hazards regression was used to identify risk factors that influence need and timing for surgery. Two hundred nineteen consecutive patients were included. Most patients did not have a prior history of SBO (75%), radiation therapy (92%), or cancer (70%). The majority had undergone previous abdominal or pelvic surgery (82%). Thirty-five per cent of patients ultimately underwent laparotomy. Univariate analysis showed that persistent abdominal pain, abdominal distention, nausea and vomiting, guarding, obstipation, elevated white blood cell count, fever present 48 hours after hospitalization, and high-grade obstruction on computed tomography (CT) scan were significant predictors of the need for surgery. Multivariable analysis revealed that persistent abdominal pain or distention (hazard ratio [HR], 3.04; P = 0.013), both persistent abdominal pain and distention (HR, 4.96; P < 0.001), fever at 48 hours (HR, 3.66; P = 0.038), and CT-determined high-grade obstruction (HR, 3.45; P = 0.017) independently predicted the need for surgery. Eighty-five per cent of patients with none of these four significant risk factors were successfully managed nonoperatively. Conversely, 92 per cent of patients with three or more risk factors required laparotomy. This analysis revealed four readily evaluable clinical parameters that may be used to predict the need for surgery in patients presenting with SBO: persistent abdominal pain, abdominal distention, fever at 48 hours, and CT findings of high-grade obstruction. These factors were combined into a predictive model that may of use in predicting failure of nonoperative SBO management. Early operation in these patients should decrease length of stay and diagnostic costs.

Localization and definitive control of lower gastrointestinal bleeding with angiography and embolization.

Angiography has long been a mainstay of lower gastrointestinal bleeding localization. More recently, angioembolism has been used therapeutically for bleeding control, but there are limited data on its efficacy. This study was designed to evaluate the efficacy of angiography and embolization for localizing and treating lower gastrointestinal bleeding as well evaluate the occurrence of bowel ischemia after embolization. This study is a retrospective descriptive review of all patients undergoing mesenteric angiography at a tertiary hospital over an eight-year period. Clinical data were recorded including patient demographics, causes of bleeding, procedures, and outcomes. Patients were excluded if the cause of bleeding was upper gastrointestinal bleeding or the medical record was missing data. Localization and definitive control of bleeding was the primary end point. One hundred fifty-nine angiograms were performed on 152 patients. Mean age was 72 years. Angiographic localization was successful in 23.7 per cent of patients. Although embolization after angiographic localization achieved definitive control of bleeding in 50 per cent of patients, the success rate was only 8.6 per cent of all patients who had angiography. One patient developed postembolization ischemia requiring laparotomy. Angiographic localization of lower gastrointestinal bleeding is successful in only 23.7 per cent of patients. Definitive hemostasis through embolization was successful in only 8.6 per cent of patients who underwent angiography for lower gastrointestinal bleeding.

Effects of night-float and 24-h call on resident psychomotor performance.

INTRODUCTION: Night-float work schedules were designed to address growing concerns of the affect of fatigue on resident psychomotor and cognitive skills after traditional 24-h call work schedules. Whether this transition has achieved these results is debatable. This study was designed to compare the psychomotor performance of general surgery residents on both work schedule types. We hypothesized that when measured with novel laparoscopic simulator tasks, residents on a 24-h call schedule would exhibit worse psychomotor performance compared with those on a night-float work schedule. METHODS: Nine general surgery residents at the post-graduate year (PGY) 2, 3, and 5 levels were recruited and trained on the Simbionix LAP Mentor Simulator (Simbionix, Cleveland, OH). Performance on two tasks was tested before and after a 24-h call work shift and a night-float shift. A survey assessing levels of work shift activity and fatigue were administered after all work shifts. RESULTS: There was no statistically significant difference in resident accuracy, speed of movement, economy of movement, and time to completion of the two simulation tasks. The only measures of work shift activity achieving statistically significant difference were number of patients seen and numbers of steps walked on call. There was no statistically significant difference in subjective evaluation of fatigue. CONCLUSIONS: In this study of general surgery residents, a statistically significant difference in psychomotor performance between residents working 24-h call shift versus a 12-h night-float shift could not be found. Psychomotor performance does not appear to suffer after a work shift. Additionally, post-shift subjective evaluations of fatigue are comparable regardless of shift type.

Watch and wait: conservative management of lower gastrointestinal bleeding.

BACKGROUND: Although indications for surgery in lower gastrointestinal bleeding (LGIB) are widely described, practice varies. This study was designed to assess outcomes of patients allowed to exceed traditional triggers for surgery because of LGIB. METHODS: This is a retrospective review of patients at an urban tertiary hospital over a 3-y period that had LGIB necessitating (99m)Tc-labeled red blood cell scintigraphy. Traditional indications for operative treatment of LGIB were defined as transfusion of >6U of packed red blood cells, hemodynamic instability, bleeding lasting >72h, and rebleeding after cessation of bleeding for >24h. RESULTS: One hundred ninety-four LGIB patients had scintigraphy during the period of study with 180 meeting inclusion criteria. Fifty-six (31%) patients had at least one operative indication, and 32 (60%) were managed nonoperatively without a mortality. There were two (8.3%) mortalities in those who had operative management, one of which was because of exsanguination. Eighteen (32%) patients who met operative criteria were unlocalized. CONCLUSIONS: Patients with LGIB can be safely managed nonoperatively, even when the bleed is unlocalized and traditional indications for surgery are met. Exsanguinations because of LGIB treated nonoperatively are rare except in patients deemed not to be surgical candidates.

Ovarian carcinomas: CCN genes are aberrantly expressed and CCN1 promotes proliferation of these cells.

PURPOSE: The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family consists of six matricellular proteins that are involved in various cellular functions, such as proliferation, development, and angiogenesis. The purpose of this study was to explore the possibility that CCN genes are involved in ovarian cancers. EXPERIMENTAL DESIGN: We quantified CCN expression in a series of 59 ovarian cancers using quantitative real-time reverse transcription-PCR. CCN1 protein levels were further determined by immunohistochemistry and Western blot analysis. Overexpression and inhibition of CCN1 expression by small interfering RNA were used to examine its role in ovarian cancer cell proliferation in vitro and in vivo. RESULTS: We found dysregulation of levels of the various CCN mRNAs in ovarian cancers compared with their expression in normal whole ovaries. Expression of CCN1 protein was detected in normal ovarian epithelial cells and ovarian tumors as well as in ovarian cancer cell lines. Furthermore, estrogen increased CCN1 mRNA and protein levels in ovarian cancer cells. Ectopic expression of CCN1 enhanced the growth of ovarian cancer cells in liquid culture, whereas inhibition of its expression decreased proliferation and increased apoptosis in these cells. The observed changes in cell growth were accompanied with activation of Akt and extracellular signal-regulated kinase (ERK) signaling pathways. Stable expression of CCN1 in SKOV3 cells significantly increased tumorigenicity in nude mice. Finally, overexpression of CCN1 conferred resistant to carboplatin-induced apoptosis in SKOV3 cells. CONCLUSIONS: This is the first study to show abnormalities in CCN expression in ovarian carcinomas. Furthermore, our results suggest that CCN1 may play a role in ovarian carcinogenesis by stimulating survival and antiapoptotic signaling pathways.

Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia.

CCAAT/enhancer-binding proteins (C/EBPs) are a family of transcription factors that regulate cell growth and differentiation in numerous cell types. To identify novel C/EBP-target genes, we performed transcriptional profiling using inducible NIH 3T3 cell lines expressing 1 of 4 members of the C/EBP family. Functional analysis revealed a previously unknown link between C/EBP proteins and circadian clock genes. Our microarray data showed that the expression levels of 2 core components of the circadian network, Per2 and Rev-Erbalpha, were significantly altered by C/EBPs. Recent studies suggested that Per2 behaves as a tumor suppressor gene in mice. Therefore, we focused our additional studies on Per2. We showed that Per2 expression is up-regulated by C/EBPalpha and C/EBPepsilon. Per2 levels were reduced in lymphoma cell lines and in acute myeloid leukemia (AML) patient samples. In addition, we generated stable K562 cells that expressed an inducible Per2 gene. Induction of Per2 expression resulted in growth inhibition, cell cycle arrest, apoptosis, and loss of clonogenic ability. These results suggest that Per2 is a downstream C/EBPalpha-target gene involved in AML, and its disruption might be involved in initiation and/or progression of AML.