bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the Use of Simulated Patients in Basic First Aid Training on Laypeople Knowledge, Skills, and Self-efficacy
Authors: Avau Bert , Vanhove Anne-Catherine , Scheers Hans , Stroobants Stijn , Lauwers Karen , Vandekerckhove Philippe , De Buck Emmy
Published: April 2022

Background

First aid training is a cost-effective way to improve public health, but the most effective methods to teach first aid are currently unclear. The aim of this research was to investigate the added value of simulated patients during first aid certification trainings.

Methods

Occupational first aid trainings organized by the Belgian Red Cross between September 2018 and August 2019 were allocated to either training with a simulated patient or regular training, for the topics “stroke” and “burns.” Participants' knowledge and self-efficacy related to these topics were assessed at baseline, directly after training and after 1 year. First aid skills for “stroke” and “burns” and participant satisfaction were assessed after training. Knowledge and self-efficacy were measured via a questionnaire, and skills were assessed during a practical skills test. Data were analyzed using generalized linear mixed model analyses.

Results

A total of 1113 participants were enrolled, 403 in the simulated patient group and 710 in the control group. First aid knowledge and self-efficacy increased strongly immediately after training. These increases did not differ between groups, nor did the level of practical skills. The simulated patient group had a significantly increased retention in first aid knowledge after 1 year, compared with control, while retention in self-efficacy did not differ. Participant satisfaction with training was similar between groups.

Conclusions

Using simulated patients during occupational first aid trainings for laypeople did not improve outcomes immediately after training but did improve retention of first aid knowledge after 1 year. These results support the use of simulated patients during first aid training.
Setting an Agenda
Authors: Gross Isabel T. , Clapper Timothy C. , Ramachandra Geethanjali , Thomas Anita , Ades Anne , Walsh Barbara , Kreuzer Florian , Elkin Rachel , Wagner Michael , Whitfill Travis , Chang Todd P. , Duff Jonathan P. , Deutsch Ellen S. , Loellgen Ruth M. , Palaganas Janice C. , Fayyaz Jabeen , Kessler David , Calhoun Aaron W.
Published: April 2022

Background

The COVID-19 pandemic forced rapid implementation and refinement of distance simulation methodologies in which participants and/or facilitators are not physically colocated. A review of the distance simulation literature showed that heterogeneity in many areas (including nomenclature, methodology, and outcomes) limited the ability to identify best practice. In April 2020, the Healthcare Distance Simulation Collaboration was formed with the goal of addressing these issues. The aim of this study was to identify future research priorities in the field of distance simulation using data derived from this summit.

Methods

This study analyzed textual data gathered during the consensus process conducted at the inaugural Healthcare Distance Simulation Summit to explore participant perceptions of the most pressing research questions regarding distance simulation. Participants discussed education and patient safety standards, simulation facilitators and barriers, and research priorities. Data were qualitatively analyzed using an explicitly constructivist thematic analysis approach, resulting in the creation of a theoretical framework.

Results

Our sample included 302 participants who represented 29 countries. We identified 42 codes clustered within 4 themes concerning key areas in which further research into distance simulation is needed: (1) safety and acceptability, (2) educational/foundational considerations, (3) impact, and (4) areas of ongoing exploration. Within each theme, pertinent research questions were identified and categorized.

Conclusions

Distance simulation presents several challenges and opportunities. Research around best practices, including educational foundation and psychological safety, are especially important as is the need to determine outcomes and long-term effects of this emerging field.
Building a sustainable Mil-Civ partnership to ensure a ready medical force: A single partnership site's experience
Authors: Stinner Daniel J. , Jahangir A. Alex , Brown Christopher , Bickett Christopher R. , Smith Joshua P. , Dennis Bradley M.
Published: April 2022

One of the challenges in military medicine is ensuring that the medical force deployed to the theater of combat operations is prepared to perform life, limb, and eyesight saving care at a level of care comparable to our top civilian Level I trauma centers. There is increasingly more evidence demonstrating that the majority of military physicians are not exposed to trauma or combat casualty care-relevant surgical cases on a consistent basis in their daily practice at their garrison military treatment facility (MTF). To prevent this widening skills and experience gap from become more of a reality, the 2017 National Defense Authorization Act called for the expansion of military and civilian (Mil-Civ) medical partnerships, working toward embedding military medical providers and surgical teams in busy civilian trauma centers. Vanderbilt University Medical Center is one of the busiest trauma centers in the country and being in close proximity to the local MTF at Fort Campbell, KY, it is primed to become one of the premier Mil-Civ partnerships. Creating a strategy that builds the partnership in a calculated and stepwise fashion through multiple avenues with centralized leadership has resulted in the early success of the program. However, Vanderbilt University Medical Center is not immune to challenges similar to those at other Mil-Civ partnerships, but only by sharing best practices can we continue to make progress.
A New Presenilin-1 Missense Variant Associated With a Progressive Supranuclear Palsy-like Phenotype
Authors: Thomas Quentin , Nambot Sophie , Béjot Yannick , Philippe Christophe , Faivre Laurence , Duffourd Yannis , Thauvin-Robinet Christel , Dupont Gwendoline
Published: April 2022

Early-onset forms of Alzheimer disease (AD) have been associated with pathogenic variants in the APP, PSEN1, and PSEN2 genes. Mutations in presenilin-1 (PSEN1) account for the majority of cases of autosomal dominant AD. Numerous phenotypes have been associated with PSEN1-pathogenic variants, including cerebellar ataxia and spastic paraplegia. Here, we describe a patient with early-onset AD presenting with extrapyramidal symptoms and supranuclear gaze palsy, mimicking progressive supranuclear palsy.
Prognostic Value of Water-Soluble Contrast Challenge for Nonadhesive Small Bowel Obstruction
Authors: Hunter Lanier M , Ludwig Daniel R , Ilahi Obeid , Mellnick Vincent
Published: April 2022

BACKGROUND:

There is little evidence supporting the use of a water-soluble contrast challenge (WSCC) for conservative management of nonadhesive small bowel obstruction (NASBO). Our objective was to evaluate the prognostic value of the WSCC in a diverse group of patients with NASBO in comparison with patients with adhesive small bowel obstruction (ASBO).

STUDY DESIGN:

Retrospective chart review of patients with ASBO or NASBO who underwent a WSCC during a 4-year time period was performed. The primary study endpoint was any intervention for small bowel obstruction during the initial admission or within 30 days of discharge.

RESULTS:

A total of 106 patients were included, 53 with ASBO (mean age 64 ± 13 years [SD]; 55% women) and 53 with NASBO (mean age 59 ± 13 years [SD]; 57% women). A higher rate of interventions during admission or within 30 days of discharge was seen in patients with NASBO compared with ASBO (24/53 [45%] vs 12/53 [23%]; p = 0.01), including those with colonic transit times of less than 36 hours (14/41 [34%] vs 5/43 [12%]; p = 0.01). Using multivariate analysis, transit time greater than 36 hours remained an independent predictor of an intervention during admission or within 30 days of discharge (p < 0.001, odds ratio 19.0), after controlling for the type of small bowel obstruction.

CONCLUSIONS:

A majority of patients with NASBO were successfully managed conservatively during a 30-day period, supporting the use of WSCC in patients with NASBO; however, patients with NASBO had a higher rate of interventions during admission or within 30 days of discharge.
Increasing Living Donor Liver Transplantation Using Liver Paired Exchange
Authors: Gunabushanam Vikraman , Ganesh Swaytha , Soltys Kyle , Mazariegos George , Ganoza Armando , Molinari Michele , Tevar Amit , Hughes Christopher , Humar Abhinav
Published: April 2022

BACKGROUND:

Living donor liver transplantation (LDLT) continues to be the primary modality of liver transplantation in Asia, but it accounts for about 5% of all liver transplantations in the US. ABO incompatibility is the primary reason motivated donors are declined. Although kidney paired exchanges are common, liver paired exchange (LPE) is still evolving in the US.

STUDY DESIGN:

This is a retrospective review (between January 1, 2019, and July 31, 2021) of our initial experience with LPE.

RESULTS:

A total of 10 LPEs (20 LDLTs) were performed during the study period. Seven LPEs were initiated by a nondirected O donor. The other 3 pair sets involved 1 ABO compatible and 1 ABO incompatible pair. Transplantations in a pair set were completed within a mean of 4.8 (range 1–14) days of each other. All 20 donors are doing well with no major complications at 12.7 (range 1–20) months. Seventeen of 20 recipients are alive and have good allograft function. One recipient died in the early postoperative period. Two late deaths of patients with functioning allografts were due to COVID-19 (at 8 months) and peritoneal carcinomatosis and gram-negative sepsis (at 9 months).

CONCLUSIONS:

LPE is feasible in a high-volume LDLT center and is a useful option to increase LDLT by overcoming ABO incompatibility. Nondirected donors can be utilized to initiate an LPE.
Incidence and Clinical Impact of Bile Leakage after Laparoscopic and Open Liver Resection: An International Multicenter Propensity Score-Matched Study of 13,379 Patients
Authors: Görgec Burak , Cacciaguerra Andrea Benedetti , Aldrighetti Luca A , Ferrero Alessandro , Cillo Umberto , Edwin Bjørn , Vivarelli Marco , Lopez-Ben Santiago , Besselink Marc G , Abu Hilal Mohammed ,   for the International Study Group of Bile Leakage after Liver Surgery
Published: April 2022

BACKGROUND:

Despite many developments, postoperative bile leakage (POBL) remains a relatively common postoperative complication after laparoscopic liver resection (LLR) and open liver resection (OLR). This study aimed to assess the incidence and clinical impact of POBL in patients undergoing LLR and OLR in a large international multicenter cohort using a propensity score–matched analysis.

STUDY DESIGN:

Patients undergoing LLR or OLR for all indications between January 2000 and October 2019 were retrospectively analyzed using a large, international, multicenter liver database including data from 15 tertiary referral centers. Primary outcome was clinically relevant POBL (CR-POBL), defined as Grade B/C POBL.

RESULTS:

Overall, 13,379 patients met the inclusion criteria and were included in the analysis (6,369 LLR and 7,010 OLR), with 6.0% POBL. After propensity score matching, a total of 3,563 LLR patients were matched to 3,563 OLR patients. In both groups, propensity score matching accounted for similar extent and types of resections. The incidence of CR-POBL was significantly lower in patients after LLR as compared with patients after OLR (2.6% vs 6.0%; p < 0.001). Among the subgroup of patients with CR-POBL, patients after LLR experienced less severe (non-POBL) postoperative complications (10.1% vs 20.9%; p = 0.028), a shorter hospital stay (12.5 vs 17 days; p = 0.001), and a lower 90-day/in-hospital mortality (0% vs 5.4%; p = 0.027) as compared with patients after OLR with CR-POBL.

CONCLUSION:

Patients after LLR seem to experience a lower rate of CR-POBL as compared with the open approach. Our findings suggest that in patients after LLR, the clinical impact of CR-POBL is less than after OLR.
Impact of Pretransplantation CT on Liver Donation in Potential Deceased Organ Donors
Authors: Robb Caroline L , Fowler Kathryn J , Bierhals Andrew J , Raptis Demetrios A , Majella Doyle Maria B , Chapman William C , Raptis Constantine A
Published: April 2022

BACKGROUND:

Computed tomography (CT) is routinely used to determine the suitability of potential living donor liver transplants, providing important information about liver size, vascular anatomy, and the presence of other diseases that would preclude it from safe donation. CT is not routinely used, however, when evaluating eligible deceased organ donors after brain death, a group which comprises most orthotopic liver transplants. After the installation of a CT scanner at a local procurement facility, CTs have been performed on potential deceased organ donors and used, in conjunction with other evaluative protocols, to help direct donation decisions and assist in procurement procedures.

STUDY DESIGN:

A retrospective analysis of data from 373 cases spanning 5 years was systematically collected and analyzed, including information pertaining to patient’s medical histories, biopsy results, operative findings, and CT results.

RESULTS:

CT findings directly impacted the directive decision-making process in 29% of cases in this patient cohort, likely an underestimate, and reliably evaluated important factors including variant vascular anatomy and the presence and severity of hepatic steatosis and cirrhosis.

CONCLUSION:

Overall, this study suggests that CT has the potential to play a significant role in procurement procedures and the directive decision-making process, thereby improving the efficiency and accuracy by which potential deceased organ donors are evaluated.
Emergency General Surgery Quality Improvement: A Review of Recommended Structure and Key Issues
Authors: Ross Samuel W , Reinke Caroline E , Ingraham Angela M , Holena Daniel N , Havens Joaquim M , Hemmila Mark R , Sakran Joseph V , Staudenmayer Kristan L , Napolitano Lena M , Coimbra Raul
Published: April 2022

Emergency general surgery (EGS) accounts for 11% of hospital admissions, with more than 3 million admissions per year and more than 50% of operative mortality in the US. Recent research into EGS has ignited multiple quality improvement initiatives, and the process of developing national standards and verification in EGS has been initiated. Such programs for quality improvement in EGS include registry formation, protocol and standards creation, evidenced-based protocols, disease-specific protocol implementation, regional collaboratives, targeting of high-risk procedures such as exploratory laparotomy, focus on special populations like geriatrics, and targeting improvements in high opportunity outcomes such as failure to rescue. The authors present a collective narrative review of advances in quality improvement structure in EGS in recent years and summarize plans for a national EGS registry and American College of Surgeons verification for this under-resourced area of surgery.
Long-Term Outcomes of Single-Incision Distal Gastrectomy Compared with Conventional Laparoscopic Distal Gastrectomy: A Propensity Score–Matched Analysis
Authors: Kang So Hyun , Lee Eunju , Lee Sangjun , Park Young Suk , Ahn Sang-Hoon , Park Do Joong , Kim Hyung-Ho
Published: April 2022

BACKGROUND

Single-incision laparoscopic surgery is gaining more attention due to advancements in surgical devices and techniques. Ten years have passed since the first report of single-incision distal gastrectomy. This study aims to analyze the long-term oncological safety of single-incision distal gastrectomy by comparing it with multiport distal gastrectomy.

STUDY DESIGN

Patients diagnosed with gastric cancer who underwent laparoscopic distal gastrectomy from January 2010 to December 2017 were enrolled. Palliative surgery, history of other malignancy, preoperative chemotherapy, and distant metastasis were excluded. The 5-year overall survival and 5-year disease-free survival were set as coprimary endpoints. Operative time, blood loss, postoperative outcome, and risk factors for survival were secondary endpoints. Propensity score matching of 1:1 ratio was performed to adjust for age, sex, body mass index, comorbidities, tumor size, operation history, and clinical stage.

RESULTS

A total of 3,097 patients were enrolled. After propensity score matching, 378 patients were allocated to each group. There was no difference in patient demographics after matching. Operation time was faster (170.8 ± 65.3 minutes vs 147.2 ± 44.1 minutes, p < 0.001), with less blood loss in the single-port group (84.1 ± 87.6 mL vs 34.9 ± 49.9 mL, p < 0.001). Administration of additional intravenous analgesics was less frequent in the single-port group (p = 0.043). There was no difference in long-term survival (5-year overall survival: multiport 94.2%, single-port 95.8%, p = 0.43; 5-year disease-free survival: multiport 94.1%, single-port 95.8%, p = 0.32).

CONCLUSIONS

Single-incision distal gastrectomy is safe and feasible with good long-term outcomes and less use of additional analgesics for patients diagnosed with early gastric cancer.
Transcutaneous Laryngeal Ultrasonography for Assessing Vocal Cord Twitch Response in Thyroid Operation during Predissection Vagus Nerve Stimulation
Authors: Kuo Ting-Chun , Chen Kuen-Yuan , Lai Chieh-Wen , Wang Yi-Chia , Lin Ming-Tsan , Chang Chin-Hao , Wu Ming-Hsun
Published: April 2022

BACKGROUND

In this study, we aimed to report our experience with the use of intraoperative transcutaneous laryngeal ultrasonography (TLUSG) to evaluate the vocal cord twitch response during predissection vagus nerve stimulation in thyroid surgeries and examine the reliability of this technique when compared with that of laryngeal twitch palpation (LTP).

STUDY DESIGN

The prospective data collection of consecutive patients who underwent open thyroidectomy with intraoperative neuromonitoring (IONM) was reviewed retrospectively. We recorded the electromyographic activity and assessed the vocal cord twitch response on LTP, TLUSG. We compared the accessibility, sensitivity, and specificity of the techniques.

RESULTS

A total of 110 patients (38 men and 72 women) with 134 nerves at risk were enrolled. The vocal cord was assessable by TLUSG in 103 (93.6%) patients and by LTP in 64 (59.1%) patients. Two patients showed negative predissection IONM signal but positive on TLUSG and the presence of laryngeal twitch response confirmed by laryngoscopy. Fourteen patients showed positive IONM signals and presence of the vocal cord twitch response on TLUSG but not on LTP. The sensitivity and specificity were 70.21% and 100%, respectively, for LTP, and those both were 100% for TLUSG. For patients who could be assessed using both techniques, TLUSG had better accuracy than LTP (100% vs 80.33%, p = 0.0005).

CONCLUSIONS

The innovative intraoperative application of TLUSG is better for evaluating the laryngeal twitch response than LTP. This technique provides practical troubleshooting guidance for patients with no IONM signals during predissection vagus nerve stimulation.
Multi-Institutional Quality Improvement Project to Minimize Opioid Prescribing in Children after Appendectomy Using NSQIP-Pediatric
Authors: Kelley-Quon Lorraine I , Ourshalimian Shadassa , Lee Justin , Russell Katie W , Kling Karen , Shew Stephen B , Mueller Claudia , Jensen Aaron R , Vu Lan , Padilla Benjamin , Ostlie Daniel , Smith Caitlin , Inge Thomas , Roach Jonathan , Ignacio Romeo , Lofberg Katrine , Radu Stephanie , Rohan Autumn , Wang Kasper S
Published: April 2022

BACKGROUND

There is wide variation in opioid prescribing after appendectomy in children and adolescents, with recent increases noted in opioid-related pediatric deaths from prescription and illicit opioids. The goal of this project was to minimize opioid prescribing at the time of discharge for children undergoing appendectomy by using Quality Improvement (QI) methodology.

STUDY DESIGN

Children (18 years of age or less) who underwent appendectomy were evaluated from January to December 2019 using NSQIP-Pediatric at 10 children’s hospitals within the Western Pediatric Surgery Research Consortium. Before project initiation, 5 hospitals did not routinely prescribe opioids after appendectomy (protocol). At the remaining 5 hospitals, prescribing was not standardized and varied by surgeon (no-protocol). A prospective multi-institutional QI project was used to minimize outpatient opioid prescriptions for children after appendectomy. The proportion of children at each hospital receiving an opioid prescription at discharge was compared for 6 months before and after the intervention using chi-square analysis.

RESULTS

Overall, 1,524 children who underwent appendectomy were evaluated from January to December 2019. After the QI intervention, overall opioid prescribing decreased from 18.2% to 4.0% (p < 0.001), with significant decreases in protocol hospitals (2.7% vs 0.8%, p = 0.038) and no-protocol hospitals (37.9% vs 8.8%, p < 0.001). The proportion of 30-day emergency room visits did not change after the QI intervention (8.9% vs 9.9%, p = 0.54) and mean postintervention pain management satisfaction scores were high.

CONCLUSION

Opioid prescribing can be minimized in children after appendectomy without increasing emergency room visits or decreasing patient satisfaction. Furthermore, NSQIP-Pediatric can be used as a platform for multi-institutional collaboration for successful implementation of QI projects.
Index Admission Cholecystectomy and Recurrence of Pediatric Gallstone Pancreatitis: Multicenter Cohort Analysis
Authors: Muñoz Abraham Armando S , Osei Hector , Bajinting Adam , Cowles Robert A , Greenspon Jose , Hosfield Brain D , Keller Martin S , Landman Matthew P , Owens Hawkins , Shaughnessy Matthew P , St. Peter Shawn D , Sujka Joseph , Vogel Adam M , Villalona Gustavo A
Published: April 2022

BACKGROUND

We aim to evaluate recurrence rates of gallstone pancreatitis in children undergoing early vs interval cholecystectomy.

STUDY DESIGN

A multicenter, retrospective review of pediatric patients admitted with gallstone pancreatitis from 2010 through 2017 was performed. Children were evaluated based on timing of cholecystectomy. Early cholecystectomy was defined as surgery during the index admission, whereas the delayed group was defined as no surgery or surgery after discharge. Outcomes, recurrence rates, and complications were evaluated.

RESULTS

Of 246 patients from 6 centers with gallstone pancreatitis, 178 (72%) were female, with mean age 13.5 ± 3.2 years and a mean body mass index of 28.9 ± 15.2. Most (90%) patients were admitted with mild pancreatitis (Atlanta Classification). Early cholecystectomy was performed in 167 (68%) patients with no difference in early cholecystectomy rates across institutions. Delayed group patients weighed less (61 kg vs. 72 kg, p = 0.003) and were younger (12 vs. 14 years, p = 0.001) than those who underwent early cholecystectomy. However, there were no differences in clinical, radiological, or laboratory characteristics between groups. There were 4 (2%) episodes of postoperative recurrent pancreatitis in the early group compared with 22% in the delayed group. More importantly, when cholecystectomy was delayed more than 6 weeks from index discharge, recurrence approached 60%. There were no biliary complications in any group.

CONCLUSIONS

Cholecystectomy during the index admission for children with gallstone pancreatitis reduces recurrent pancreatitis. Recurrence proportionally increases with time when patients are treated with a delayed approach.
Surgical Outcomes Improvement and Health Inequity in a Regional Quality Collaborative
Authors: Curran Thomas , Zhang Jingwen , Gebregziabher Mulugeta , Taber David J , Marsden Justin E , Booth Alexander , Magwood Gayenell S , Mauldin Patrick D , Baliga Prabhakar K , Lockett Mark A
Published: April 2022

BACKGROUND:

Surgical quality improvement initiatives may impact sociodemographic groups differentially. The objective of this analysis was to assess the trajectory of surgical morbidity by race and age over time within a Regional Collaborative Quality Initiative.

STUDY DESIGN:

Adults undergoing eligible general surgery procedures in South Carolina Surgical Quality Collaborative hospitals were analyzed for the presence of at least 1 of 22 morbidities between August 2015 and February 2020. Surgery-level multivariable logistic regression assessed the racial differences in morbidity over time, stratified by age group (18 to 64 years, 65 years and older), and adjusting for potential patient- and surgical-level confounders.

RESULTS:

A total of 30,761 general surgery cases were analyzed, of which 28.4% were performed in Black patients. Mean morbidity rates were higher for Black patients than non-Black patients (8.5% vs 6.0%, p < 0.0001). After controlling for race and other confounders, a significant decrease in monthly mean morbidity through time was observed in each age group (odds ratio [95% CI]: age 18 to 64 years, 0.986 [0.981 to 0.990]; age 65 years and older, 0.991 [0.986 to 0.995]). Comparing morbidity rates from the first 4 months of the collaborative to the last 4 months reveals older Black patients had an absolute decrease in morbidity of 6.2% compared with 3.6% for older non-Black patients. Younger Black patients had an absolute decrease in morbidity of 4.7% compared with a 3.0% decrease for younger non-Black patients.

CONCLUSIONS:

Black patients had higher morbidity rates than non-Black patients even when controlling for confounders. The reasons for these disparities are not apparent. Morbidity improved over time in all patients with older Black patients seeing a larger absolute decrease in morbidity.
Public Humiliation in the Surgical Clerkship: Qualitative Analysis of Responses to the Association of American Medical Colleges Graduation Questionnaire
Authors: Mullins Clarence , Callahan Edward , Hageman Heather , Chen Herbert , Lindeman Brenessa
Published: April 2022

BACKGROUND:

Nearly 1 in 5 medical students reports at least 1 incident of mistreatment, with many occurring in the perioperative environment. We aimed to further define the types of mistreatment occurring perioperatively in a national data set by using a mixed-methods approach.

STUDY DESIGN:

A sample of 2,224 responses to the general public humiliation free-text question on the 2015 Association of American Medical College’s Graduation Questionnaire were analyzed. Using grounded theory methodology, 4 raters independently created and refined the coding schema. Final coding was determined by majority rating. Descriptive statistics, interrater reliability, and chi-square analysis were performed where appropriate.

RESULTS:

Among responses, 2,411 events were identified. Interrater reliability was moderate (>0.41) on 94% of variables. Events occurring in a specific setting implicated the surgery clerkship and the operating room 53.2% and 21.8% of the time, respectively. Perioperative events accounted for nearly one-third of verbal abuse reports (30.5%, 324/1059), and almost half of events described yelling (47.0%, 178/379). Mistreatment involving physical contact was significantly more likely to occur in the operating room (59% vs 41%, p < 0.001). Events coded as possibly routine education (n = 379) were significantly less common perioperatively than nonsurgical settings (20.5% vs 79.4%, p = 0.007).

CONCLUSIONS:

A significant proportion of medical student mistreatment events occur in the context of surgery. Surgeons and trainees must play active roles in leading and instituting needed changes to improve the learning environment to support medical students and recruit a sufficient future surgical workforce.
Quality of Life Associated with Open vs Minimally Invasive Pancreaticoduodenectomy: A Prospective Pilot Study
Authors: Moris Dimitrios , Rushing Christel , McCracken Emily , Shah Kevin N , Zani Sabino , Perez Alexander , Allen Peter J , Niedzwiecki Donna , Fish Laura J , Blazer Dan G
Published: April 2022

BACKGROUND:

This prospective study was designed to compare quality of life (QoL) among patients who underwent open (O-PD) vs minimally invasive pancreaticoduodenectomy (MI-PD), using a combination of validated qualitative and quantitative methodologies.

STUDY DESIGN:

From 2017 to 2019, patients scheduled for pancreaticoduodenectomy (PD) were enrolled and presented with Functional Assessment of Cancer Therapy-Hepatobiliary surveys preoperatively, before discharge, at first postoperative visit and approximately 3 to 4 months after operation (“3 months”). Longitudinal plots of median QoL scores were used to illustrate change in each score over time. In a subset of patients, content analysis of semistructured interviews at postoperative time points (1.5 to 6 months after operation) was conducted.

RESULTS:

Among 56 patients who underwent PD, 33 had an O-PD (58.9%). Physical and functional scores decreased in the postoperative period but returned to baseline by 3 months. No significant differences were found in any domains of QoL at baseline and in the postoperative period between patients who underwent O-PD and MI-PD. Qualitative findings were concordant with quantitative data (n = 14). Patients with O-PD and MI-PD reported similar experiences with complications, pain, and wound healing in the postoperative period. Approximately half the patients in both groups reported “returning to normal” in the 6-month postoperative period. A total of 4 patients reported significant long-term issues with physical and functional well-being.

CONCLUSIONS:

Using a novel combination of qualitative and quantitative analyses in patients undergoing PD, we found no association between operative approach and QoL in patients who underwent O-PD vs MI-PD. Given the increasing use of minimally invasive techniques for PD and the steep learning curve associated with these techniques, continued assessment of patient benefit is critical.
Nuclear Factor Erythroid 2–Related Factor 2 Activation and Burn-Induced Cardiac Dysfunction
Authors: Wen Jake J , Mobli Keyan , Rontoyanni Victoria G , Cummins Claire B , Radhakrishnan Geetha L , Murton Andrew , Radhakrishnan Ravi S
Published: April 2022

BACKGROUND:

Our previous studies have found that burn injury induces cardiac dysfunction through interruption of the antioxidant-response element (ARE) pathway in cardiac mitochondria. Nuclear factor erythroid 2–related factor 2 (Nrf2) is a key regulator that activates many antioxidant enzymes. Oltipraz (Olti) is a Nrf2 activator and a well-known inducer of NQO1 along with other enzymes that comprise the Nrf2-associated antioxidants. We propose that Nrf2 activation will induce the ARE pathway, leading to abrogation of burn-induced cardiac dysfunction.

STUDY DESIGN:

In this study, we investigated the effect of Nrf2-deficiency in mice on burn-induced cardiac dysfunction. Wild-type (WT) and Nrf2-deficient mice received 30% total body surface area burn injury and were treated with or without Olti and then harvested at 3 hours and 24 hours post burn (3 hpb and 24 hpb).

RESULTS:

As expected, Nrf2-deficient mice exhibited exacerbated cardiac dysfunction after burn injury, as measured by Vevo 2100 echocardiography. Electron microscopy showed that Nrf2 depletion worsened burn injury–induced cardiac mitochondrial damage. In addition, Nrf2 depletion increased cardiac mitochondrial dysfunction and myocardial fibrosis after burn injury. Treatment with Olti ameliorated the heart dysfunction in burned Nrf2−/+ mice, improved cardiac mitochondrial structure and oxidative phosphorylation, as well as decreased cardiac fibrosis. These results suggest that Nrf2 and its downstream targets modulate cardiac function after burn injury.

CONCLUSIONS:

In summary, Nrf2 depletion worsens cardiac dysfunction after burn injury. Nrf2 activation, with a drug such as Olti, offers a promising therapeutic strategy for abrogating burn-induced cardiac dysfunction.
Identification and Genomic Assessment of Daptomycin-, Linezolid-, Vancomycin-resistant Enterococcus faecium During Protracted Infection
Authors: Pincus Nathan B. , Joshi Tejas , Gatesy Samuel W.M. , Al-Heeti Omar , Moore W. Justin , Bachta Kelly E. R.
Published: April 2022

Linezolid and daptomycin resistance among Enterococccus faecium (Efm) isolates, while rare, is a major challenge for clinicians who are often limited to broad-spectrum or combination antibiotic therapies for management. Combination therapy with a beta-lactam has been reported, but limited clinical evidence exists to support its use. We describe the clinical management of a prolonged Efm intraabdominal (IA) infection and subsequent bacteremia, along with observed multidrug resistance development and use of serial whole genome sequencing to better understand resistance mechanisms. Combination antimicrobial therapy with daptomycin (DAP) and ceftaroline (CPT) was used to treat the patient’s catheter-associated daptomycin-, linezolid-, vancomycin-resistant Efm (DLVRE) bloodstream infection. In vitro antimicrobial testing of this DLVRE revealed only minor synergy between daptomycin and ceftaroline; However, the patient’s bacteremia cleared following initiation of combination therapy in conjunction with catheter removal. Sequencing of the patient’s DLVRE revealed multiple genomic mutations which explain both linezolid and daptomycin resistance and the presence of a plasmid containing known resistance determinants for vancomycin. Daptomycin resistance was attributed to the presence of chromosomal mutations in liaS (Thr120Ala), liaR (Trp73Cys), and cls (Asp13Ile), while linezolid resistance was attributed to the presence of the G2576T variant allele in some of 23S rRNA gene copies. Sequential whole genome sequencing of two additional bacterial isolates from the same patient revealed protracted colonization with a single DLVRE clone and suggested the development of bacterial subpopulations. Pairing clinical isolate susceptibilities with whole genome sequencing should be encouraged in clinical practice to better inform antimicrobial management in cases of multidrug resistance.
The new normal? Dynamics and scale of the SARS-CoV-2 variant Omicron epidemic in England
Authors: Eales Oliver , de Oliveira Martins Leonardo , Page Andrew J. , Wang Haowei , Bodinier Barbara , Tang David , Haw David , Jonnerby Jakob , Atchison Christina , Ashby Deborah , Barclay Wendy , Taylor Graham , Cooke Graham , Ward Helen , Darzi Ara , Riley Steven , Elliott Paul , Donnelly Christl A. , Chadeau-Hyam Marc
Published: April 2022

The SARS-CoV-2 pandemic has been characterised by the regular emergence of genomic variants which have led to substantial changes in the epidemiology of the virus. With natural and vaccine-induced population immunity at high levels, evolutionary pressure favours variants better able to evade SARS-CoV-2 neutralising antibodies. The Omicron variant was first detected in late November 2021 and exhibited a high degree of immune evasion, leading to increased infection rates in many countries. However, estimates of the magnitude of the Omicron wave have relied mainly on routine testing data, which are prone to several biases. Here we infer the dynamics of the Omicron wave in England using PCR testing and genomic sequencing obtained by the REal-time Assessment of Community Transmission-1 (REACT-1) study, a series of cross-sectional surveys testing random samples of the population of England. We estimate an initial peak in national Omicron prevalence of 6.89% (5.34%, 10.61%) during January 2022, followed by a resurgence in SARS-CoV-2 infections in England during February-March 2022 as the more transmissible Omicron sub-lineage, BA.2 replaced BA.1 and BA.1.1. Assuming the emergence of further distinct genomic variants, intermittent epidemics of similar magnitude as the Omicron wave may become the ‘new normal’.
Comparing evolvability and pleiotropy across environments
Authors: Tarkington Jason , Zufall Rebecca
Published: April 2022

The environment can play an important role in determining evolutionary outcomes (Reboud and Bell 1997; Stanton et al. 2000; Gresham et al. 2008; Cooper and Lenski 2010; Becks and Agrawal 2012; Bailey et al. 2015). Populations may increase in fitness more after evolution in one environment than in another (Hegreness et al. 2008). This may be because the distance between the ancestral genotype and the top of the locally accessible fitness peak may be greater in one environment or the other. Additionally, the rate at which mutations occur and populations move up the peaks could differ. For this reason, comparing evolvability across environments presents an interesting problem. Here, we show an environment impacts evolvability in two ways, directly by impacting the rate of adaptative evolution, and indirectly by limiting the range of fitness outcomes that are possible. We show that correlated responses are often highly idiosyncratic, due to variation in the range of possible fitness outcomes in the environment and differences in pleiotropic effects across environments but can also be predicted from the ancestral growth rate regardless of the environment in which populations evolve. Interestingly, we also show a negative correlation between increase in an environment X following evolution in environment Y and the increase in environment Y following evolution in environment X. These results highlight the necessity to measure fitness in both environments when comparing the evolvability or repeatability of evolution across environments.
Decision heuristics in contexts exploiting intrinsic skill
Authors: Dundon Neil M. , Colas Jaron T. , Garrett Neil , Babenko Viktoriya , Rizor Elizabeth , Yang Dengxian , MacNamara Máirtín , Petzold Linda , Grafton Scott T.
Published: April 2022

Heuristics can inform human decision making in complex environments through a reduction of computational requirements (accuracy-resource trade-off) and a robustness to overparameterisation (less-is-more). However, tasks capturing the efficiency of heuristics typically ignore action proficiency in determining rewards. The requisite movement parameterisation in sensorimotor control questions whether heuristics preserve efficiency when actions are nontrivial. We developed a novel action selection-execution task requiring joint optimisation of action selection and spatio-temporal skillful execution. Optimal choices could be determined by a simple spatial heuristic, or by more complex planning. Computational models of action selection parsimoniously distinguished human participants who adopted the heuristic from those using a more complex planning strategy. Broader comparative analyses then revealed that participants using the heuristic showed combined decisional (selection) and skill (execution) advantages, consistent with a less-is-more framework. In addition, the skill advantage of the heuristic group was predominantly in the core spatial features that also shaped their decision policy, evidence that the dimensions of information guiding action selection might be yoked to salient features in skill learning.

Author Summary

We often must choose between actions and then execute them, e.g., a tennis player chooses between a forehand and backhand and then skilfully executes the shot. To select actions, the player might plan their action with either shot, and select whichever simulated outcome is more advantageous. However, a more efficient approach might instead be to use a “heuristic”, i.e., a simpler rule, such as, forehand always on one side of the court, and backhand on the other. In this work, we look at whether styles of planning are related to physical skill performing actions, e.g., would a more skillful tennis player be more likely to use planning or a heuristic? We use a new task that requires people to choose and execute complex actions. Regarding choices, we use computational modeling to identify which people use some degree of planning, and which people use a simpler heuristic. Then, regarding action execution, we reveal that heuristic decision makers are in fact more skilled. However, they are not superiorly skilled in all aspects of performance, showing an advantage solely in the aspect of skill most closely linked to the information (spatial) they use for their heuristic. We therefore reveal the first ever evidence that a relation exists between the complexity of our action-related decisions and how broadly we learn associated motor behaviour.
Factors regulating translation coupled mRNA degradation in yeast
Authors: Basu Sudipto , Maiti Raktim , Hait Suman , Chaudhuri Ashesh Ray , Kundu Sudip
Published: April 2022

Codon optimality is a major factor governing translation speed and efficiency, mRNA expression, and stability. Presence of optimal codons maintains a steady translation time, while non-optimal codons can lead to slow peptidyl transfer, prolonged translation time and frequent halt. Owing to this, there are co-translational surveillance protein complexes which monitor this process meticulously and can trigger the release of the mRNA transcript after prolonged halt. The surveillance protein complexes are closely associated with various degradation enzymes which can break down these released transcripts. Degradation of the released transcripts will be ensured if they contain amenable regions for enzyme binding and action. Here, we have used sequence data to estimate the relative abundance of non-optimal codons within a transcript. We found that transcripts with high relative abundance of non-optimal codon show reduced stability and half-life compared to transcripts with lower relative abundance of non-optimal codon. We have further integrated the relative abundance of non-optimal codons with internal unstructured segments for the transcripts, to show that the former is responsible for transcript release and the latter provides susceptible platform for endonuclease cleavage, which together is capable of destabilising and reducing the transcript’s half-life. Since this is a translational system, sequestration of mRNA into a dense forest of ribosomes is seen to prolong the transcript’s half-life even in the presence of destabilising factors.
Cellpose 2.0: how to train your own model
Authors: Stringer Carsen , Pachitariu Marius
Published: April 2022

Generalist models for cellular segmentation, like Cellpose, provide good out-of-the-box results for many types of images. However, such models do not allow users to adapt the segmentation style to their specific needs and may perform sub-optimally for test images that are very different from the training images. Here we introduce Cellpose 2.0, a new package which includes an ensemble of diverse pretrained models as well as a human-in-the-loop pipeline for quickly prototyping new specialist models. We show that specialist models pretrained on the Cellpose dataset can achieve state-of-the-art segmentation on new image categories with very little user-provided training data. Models trained on 500-1000 segmented regions-of-interest (ROIs) performed nearly as well as models trained on entire datasets with up to 200,000 ROIs. A human-in-the-loop approach further reduced the required user annotations to 100-200 ROIs, while maintaining state-of-the-art segmentation performance. This approach enables a new generation of specialist segmentation models that can be trained on new image types with only 1-2 hours of user effort. We provide software tools including an annotation GUI, a model zoo and a human-in-the-loop pipeline to facilitate the adoption of Cellpose 2.0.
GenMPI: Cluster Scalable Variant Calling for Short/Long Reads Sequencing Data
Authors: Ahmad Tanveer , Schuchart Joseph , Ars Zaid Al , Niethammer Christoph , Gracia José , Hofstee H. Peter
Published: April 2022

Rapid technological advancements in sequencing technologies allow producing cost effective and high volume sequencing data. Processing this data for real-time clinical diagnosis is potentially time-consuming if done on a single computing node. This work presents a complete variant calling workflow, implemented using the Message Passing Interface (MPI) to leverage the benefits of high bandwidth interconnects. This solution (GenMPI) is portable and flexible, meaning it can be deployed to any private or public cluster/cloud infrastructure. Any alignment or variant calling application can be used with minimal adaptation. To achieve high performance, compressed input data can be streamed in parallel to alignment applications while uncompressed data can use internal file seek functionality to eliminate the bottleneck of streaming input data from a single node. Alignment output can be directly stored in multiple chromosome-specific SAM files or a single SAM file. After alignment, a distributed queue using MPI RMA (Remote Memory Access) atomic operations is created for sorting, indexing, marking of duplicates (if necessary) and variant calling applications. We ensure the accuracy of variants as compared to the original single node methods. We also show that for 300x coverage data, alignment scales almost linearly up to 64 nodes (8192 CPU cores). Overall, this work outperforms existing big data based workflows by a factor of two and is almost 20% faster than other MPI-based implementations for alignment without any extra memory overheads. Sorting, indexing, duplicate removal and variant calling is also scalable up to 8 nodes cluster. For pair-end short-reads (Illumina) data, we integrated the BWA-MEM aligner and three variant callers (GATK HaplotypeCaller, DeepVariant and Octopus), while for long-reads data, we integrated the Minimap2 aligner and three different variant callers (DeepVariant, DeepVariant with WhatsHap for phasing (PacBio) and Clair3 (ONT)). All codes and scripts are available at: https://github.com/abs-tudelft/gen-mpi
A multiscale whole-cell theory for mechano-sensitive migration on viscoelastic substrates
Authors: Shu Wenya , Kaplan C. Nadir
Published: April 2022

Increasing experimental evidence validates that both the elastic stiffness and viscosity of the extracellular matrix regulate mesenchymal cell behavior, such as the rational switch between durotaxis (cell migration to stiffer regions), anti-durotaxis (migration to softer regions), and adurotaxis (stiffness-insensitive migration). To reveal the mechanisms underlying the crossover between these motility regimes, we have developed a multiscale chemo-mechanical whole-cell theory for mesenchymal migration. Our framework couples the sub-cellular focal adhesion dynamics at the cell-substrate interface with the cellular cytoskeletal mechanics and the chemical signaling pathways involving Rho GTPase proteins. Upon polarization by the Rho GTPase gradients, our simulated cell migrates by concerted peripheral protrusions and contractions, a hallmark of the mesenchymal mode. The resulting cell dynamics quantitatively reproduces the experimental migration speed as a function of the uniform substrate stiffness and explains the influence of viscosity on the migration efficiency. In the presence of stiffness gradients and absence of chemical polarization, our simulated cell can exhibit durotaxis, anti-durotaxis, and adurotaxis respectively with increasing substrate stiffness or viscosity. The cell moves toward an optimally stiff region from softer regions during durotaxis and from stiffer regions during anti-durotaxis. We show that cell polarization through steep Rho GTPase gradients can reverse the migration direction dictated by the mechanical cues. Overall, our theory demonstrates that opposing durotactic behaviors emerge via the interplay between intracellular signaling and cellmedium mechanical interactions in agreement with experiments, thereby elucidating complex mechano-sensing at the single-cell level.