Critical review of the phytohemagglutinin assay for assessing amphibian immunity.

Infectious diseases are a major driver of the global amphibian decline. In addition, many factors, including genetics, stress, pollution, and climate change can influence the response to pathogens. Therefore, it is important to be able to evaluate amphibian immunity in the laboratory and in the field. The phytohemagglutinin (PHA) assay is an inexpensive and relatively non-invasive tool that has been used extensively to assess immunocompetence, especially in birds, and more recently in amphibians. However, there is substantial variation in experimental methodology among amphibian PHA studies in terms of species and life stages, PHA doses and injection sites, and use of experimental controls. Here, we compile and compare all known PHA studies in amphibians to identify knowledge gaps and develop best practices for future work. We found that research has only been conducted on a limited number of species, which may not reflect the diversity of amphibians. There is also a lack of validation studies in most species, so that doses and timing of PHA injection and subsequent swelling measurements may not effectively evaluate immunocompetence. Based on these and other findings, we put forward a set of recommendations to make future PHA studies more consistent and improve the ability to utilize this assay in wild populations, where immune surveillance is greatly needed.

Assessing the Accuracy of Responses by the Language Model ChatGPT to Questions Regarding Bariatric Surgery.

PURPOSE: ChatGPT is a large language model trained on a large dataset covering a broad range of topics, including the medical literature. We aim to examine its accuracy and reproducibility in answering patient questions regarding bariatric surgery. MATERIALS AND METHODS: Questions were gathered from nationally regarded professional societies and health institutions as well as Facebook support groups. Board-certified bariatric surgeons graded the accuracy and reproducibility of responses. The grading scale included the following: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. Reproducibility was determined by asking the model each question twice and examining difference in grading category between the two responses. RESULTS: In total, 151 questions related to bariatric surgery were included. The model provided "comprehensive" responses to 131/151 (86.8%) of questions. When examined by category, the model provided "comprehensive" responses to 93.8% of questions related to "efficacy, eligibility and procedure options"; 93.3% related to "preoperative preparation"; 85.3% related to "recovery, risks, and complications"; 88.2% related to "lifestyle changes"; and 66.7% related to "other". The model provided reproducible answers to 137 (90.7%) of questions. CONCLUSION: The large language model ChatGPT often provided accurate and reproducible responses to common questions related to bariatric surgery. ChatGPT may serve as a helpful adjunct information resource for patients regarding bariatric surgery in addition to standard of care provided by licensed healthcare professionals. We encourage future studies to examine how to leverage this disruptive technology to improve patient outcomes and quality of life.

Presence of refractory GERD-like symptoms following laparoscopic fundoplication is rarely indicative of true recurrent GERD.

BACKGROUND: Laparoscopic fundoplication (LF) is the gold standard for gastroesophageal reflux disease (GERD). Recurrent GERD is a known complication; however, the incidence of recurrent GERD-like symptoms and long-term fundoplication failure is rarely reported. Our objective was to identify the rate of recurrent pathologic GERD in patients with GERD-like symptoms following fundoplication. We hypothesized that patients with recurrent GERD-like symptoms refractory to medical management do not have evidence of fundoplication failure as indicated by a positive ambulatory pH study. METHODS: This is a retrospective cohort study of 353 consecutive patients undergoing LF for GERD between 2011 and 2017. Baseline demographics, objective testing, GERD-HRQL scores, and follow-up data were collected in a prospective database. Patients with return visits to clinic following routine post-operative visits were identified (n = 136, 38.5%), and those with a primary complaint of GERD-like symptoms (n = 56, 16%) were included. The primary outcome was the proportion of patients with a positive post-operative ambulatory pH study. Secondary outcomes included proportion of patients with symptoms managed with acid-reducing medications, time to return to clinic, and need for reoperation. P values < 0.05 were considered significant. RESULTS: Fifty-six (16%) patients returned during the study period for an evaluation of recurrent GERD-like symptoms with a median interval of 51.2 (26.2-74.7) months. Twenty-four patients (42.9%) were successfully managed expectantly or with acid-reducing medications. Thirty two (57.1%) presented with GERD-like symptoms and failure of management with medical acid suppression and underwent repeat ambulatory pH testing. Of these, only 5 (9%) were found to have a DeMeester score of > 14.7, and three (5%) underwent recurrent fundoplication. CONCLUSION: Following LF, the incidence of GERD-like symptoms refractory to PPI therapy is much higher than the incidence of recurrent pathologic acid reflux. Few patients with recurrent GI symptoms require surgical revision. Evaluation, including objective reflux testing, is critical to evaluating these symptoms.

Impact of a Body Mass Index Threshold on Abdominal Wall Hernia Repair at a Safety-Net Hospital.

BACKGROUND: Body mass index (BMI) thresholds are utilized as a preoperative optimization strategy for obese patients prior to elective abdominal wall hernia repair. The objectives of this study were to determine the proportion of patients at our institution who ultimately underwent hernia repair after initial deferral due to BMI and to evaluate outcomes of those who required emergent repair during the deferral period. METHODS: A retrospective review was performed from 2016 to 2018 to identify all patients with abdominal wall hernias who were deferred surgery due to BMI. Patient characteristics, hernia type, change in BMI, progression to surgery, acuity of surgery (elective or emergent), and postoperative outcomes were examined. RESULTS: 200 patients were deferred hernia repair due to BMI. Of these, 150 (75%) did not undergo repair over a mean period of 27 months. The remaining 50 patients ultimately underwent repair, 36 of which (72%) were elective and 14 (28%) emergent. The mean initial BMI of the elective group was 35.3 ± 1.8, compared to 39.1 ± 5.3 in the no surgery group and 40.6 ± 8.2 in the emergent group (P < .01). While the elective group lost weight before surgery, the other groups did not. Patients who required emergent surgery had worse outcomes than those repaired electively. CONCLUSIONS: Preoperative weight loss is unsuccessful in most obese patients presenting for abdominal wall hernia repair at our institution. Patients who required emergent hernia repair had worse outcomes than those who underwent elective repair. Our institution's BMI threshold is a failed optimization strategy that needs to be reconsidered.

Hernia-to-neck ratio is associated with emergent ventral hernia repair.

BACKGROUND: The ratio of hernia size to fascial defect size, termed the hernia-to-neck ratio (HNR), has been proposed as a novel predictive factor for umbilical hernia complications. HNR ≥ 2.5 has been suggested to warrant surgery due to association with bowel strangulation, incarceration, and necrosis. The aim of this study was to evaluate the association between HNR and emergent ventral hernia repair at our institution. METHODS: A retrospective cohort study was performed of consecutive patients with ventral hernias evaluated at a large safety-net hospital from 2017 to 2019. Patients who required emergent ventral hernia repair were compared to patients who did not require repair at latest follow-up. HNR was calculated using a previously described method: maximal hernia sac size and maximal fascial defect size (termed "hernia neck size") were measured in the sagittal plane on CT scan. Data are described as mean ± standard deviation and median (interquartile range). RESULTS: A total of 166 patients were included: 84 (51%) required emergent hernia repair and 82 (49%) did not undergo repair. Median follow-up was 19 (8-27) months. Patient groups were similar except the emergent repair group had more males (50% vs. 34%, p = 0.03), umbilical hernias (93% vs. 56%, p < 0.01), recurrent hernias (31% vs. 15%, p < 0.01), and lower mean BMI (34.3 ± 9.9 vs. 39.1 ± 6.5, p < 0.01). Hernia sac size did not differ between groups (5.8 [3.8-8.4] cm vs. 6.1 [3.5-11.8] cm, p = 0.45). Hernia neck size was significantly smaller in the emergent repair group (1.5 [2.3-3.5] cm vs. 3.4 [1.8-6.2] cm, p < 0.01). Hernia-to-neck ratio was significantly higher in the emergent repair group (2.4 [1.8-3.1] vs. 1.7 [1.1-2.9], p < 0.01). CONCLUSION: This study demonstrated an association between higher HNR and increased risk of emergent ventral hernia repair. Future studies will evaluate the use of HNR to risk-stratify patients with ventral hernias in a safety-net hospital.

Introducing a Bariatric Surgery Program at a Large Urban Safety Net Medical Center Serving a Primarily Hispanic Patient Population.

BACKGROUND: Few bariatric surgery programs exist at safety net hospitals which often serve patients of diverse racial and socioeconomic backgrounds. A bariatric surgery program was developed at a large urban safety net medical center serving a primarily Hispanic population. The purpose of this study was to evaluate safety, feasibility, and first-year outcomes to pave the way for other safety net bariatric programs. METHODS: The bariatric surgery program was started at a safety net hospital located in a neighborhood with over twice the national poverty rate. A retrospective review was performed for patient demographics, comorbidities, preoperative diet and exercise habits, perioperative outcomes, and 1-year outcomes including percent total weight lost (%TWL) and comorbidity reduction. RESULTS: A total of 153 patients underwent laparoscopic sleeve gastrectomy from May 2017 through December 2019. The average preoperative BMI was 47.9kg/m2, and 54% of patients had diabetes. The 1-year follow-up rate was 94%. There were no mortalities and low complication rates. The average 1-year %TWL was 22.8%. Hypertension and diabetes medications decreased in 52% and 55% of patients, respectively. The proportion of diabetic patients with postoperative HbA1c <6.0% was 49%. CONCLUSION: This is one of the first reports on the outcomes of a bariatric surgery program at a safety net hospital. This analysis demonstrates feasibility and safety, with no mortalities, low complication rates, and acceptable %TWL and comorbidity improvement. More work is needed to investigate the impacts of race, culture, and socioeconomic factors on bariatric outcomes in this population.

Effects of the GluN2B-selective antagonist Ro 63-1908 on acquisition and expression of methamphetamine conditioned place preference in male and female rats.

BACKGROUND: Methamphetamine abuse has increased significantly in recent years. Currently, there are no FDA-approved pharmacotherapies for the treatment of methamphetamine use disorder. The goal of the current study was to determine if the N-methyl-d-aspartate (NMDA) GluN2B-selective antagonist Ro 63-1908 can block the conditioned rewarding effects of methamphetamine as assessed in conditioned place preference (CPP). METHODS: Two main experiments were conducted. In the first experiment, male (n = 24) and female (n = 24) rats received either vehicle or Ro 63-1908 (1.0-10.0 mg/kg) 30 min prior to the posttest to determine if blocking the GluN2B subunit attenuates expression of methamphetamine CPP. In the second experiment, male (n = 18) and female (n = 18) rats received either vehicle or Ro 63-1908 (1.0 or 3.0 mg/kg) 30 min prior to each conditioning session to determine if blocking the GluN2B subunit attenuates acquisition of methamphetamine CPP. RESULTS: Ro 63-1908 (3.0 mg/kg) blocked acquisition of methamphetamine CPP in male rats, but only attenuated CPP in female rats. Ro 63-1908 did not alter expression of CPP in either sex. Increasing the dose of Ro 63-1908 (10.0 mg/kg) failed to block acquisition of CPP in an additional group of female rats (n = 6). A control experiment showed that Ro 63-1908 (3.0 mg/kg) did not produce CPP or conditioned place aversion in male rats (n = 6) or in female rats (n = 6). CONCLUSIONS: The results of this study show that Ro 63-1908 is able to decrease the conditioned rewarding effects of methamphetamine.

Development and emergency implementation of an online surgical education curriculum for a General Surgery program during a global pandemic: The University of Southern California experience.

BACKGROUND: Physical distancing required by coronavirus disease 2019 (COVID-19) has limited traditional in-person resident education. We present our novel online curriculum for incorporation into traditional surgical educational programs. METHODS: The online curriculum utilized weekly sub-specialty themed faculty and resident created lectures, ABSITE practice questions, and weekly sub-specialty synchronized readings. Attendance, resident and faculty surveys, and completed ABSITE practice questions evaluated for curriculum success. Curriculum was adapted as COVID-19 clinical restructuring ended. RESULTS: 77% and 80% of clinical residents attended faculty lectures and resident led topic discussions as compared to 66% and 48% attending traditional in-person grand rounds and SCORE curriculum (both p > 0.05). 71.9% of residents and 16.6% of faculty reported improved resident participation while none reported decreased levels of participation (p < 0.001). 87.1% of residents and 66.7% of faculty preferred the online curriculum (p = 0.374). Completed ABSITE practice questions per resident increased from 21 to 31 questions/week (p = 0.541). CONCLUSION: Our online educational curriculum demonstrates success and can serve as a model for online restructuring of resident education.

The use of nonsteroidal anti-inflammatory drugs after sleeve gastrectomy.

BACKGROUND: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is discouraged after bariatric surgery. The effect of NSAIDs on patients who have undergone sleeve gastrectomy (SG) is not well studied. Moreover, the rate of NSAID use after SG is unknown. OBJECTIVES: To determine the rate of NSAID use after SG, and its associated complications. SETTING: A single institution, multi-surgeon, academic, tertiary care hospital. METHODS: We performed a retrospective review of patients who underwent SG between January 1, 2014, and November 1, 2017. A phone interview was conducted with identified patients. The inclusion criteria were any patient who had undergone SG during the study period, and there were no exclusion criteria. RESULTS: We identified 421 SG patients for inclusion. There were 231 phone surveys completed, with 64.5% of respondents reporting some NSAID use after SG. Of the respondents who used NSAIDs, 40.3% reported that they used the drugs often (>once/wk), 28.2% reported occasional use (>once/mo but

Complications Following Brachial Arterial Catheterization in the Surgical Intensive Care Unit.

Clinically, complication rates of brachial arterial catheterization appear to far exceed those of the radial or common femoral arteries. The study objective was to define the complication rate after brachial arterial line insertion. All patients undergoing arterial line placement to the brachial artery in the surgical intensive care units (SICUs) at our institution were retrospectively identified and included in the study (January 2016-December 2018). Demographics, complications (distal ischemia, thrombosis/dissection, brachial sheath hematoma, catheter-related sepsis, and inadvertent dislodgement), and outcomes were collected and analyzed. Over the study period, 53 patients underwent brachial arterial catheterization. Common admitting services were cardiothoracic surgery (n = 31, 58%), transplant surgery (n = 7, 13%), and neurosurgery (n = 4, 7%). The mean age was 55 ± 17 58 (24-84) years, and 58% (n = 31) were male. The hospital length of stay (LOS) was 37 ± 35 23 (1-132) days, and ICU LOS was 30 ± 27 20 (1-127) days. Mortality was 57% (n = 30). Complications of brachial arterial line placement occurred in 21 patients (40%). In summary, brachial arterial catheters were associated with high mortality and prolonged ICU length of stay. This likely reflects the critically ill nature of patients in whom conventional-site arterial line placement is not possible. Complications following brachial arterial catheterization were unacceptably high. On this basis, we recommend that the brachial artery be avoided whenever possible for arterial line placement in the SICU.

Outcomes associated with trial of labor after cesarean in women with one versus two prior cesarean deliveries after a change in clinical practice guidelines in an academic hospital.

Objective: In 2010, the American College of Obstetricians & Gynecologists (ACOG) published a new clinical practice guideline on trial of labor after cesarean (TOLAC) that was considered less restrictive. It allowed for offering TOLAC to women with two prior cesarean deliveries, even without a prior vaginal delivery, and for labor induction. As a result, our hospital, a public tertiary care academic center, updated our TOLAC practice guideline to reflect ACOG's new recommendations. We thus aim to evaluate maternal and neonatal outcomes for women undergoing TOLAC with 1 versus 2 prior cesareans, with and without a prior vaginal delivery, following these clinical practice changes at our hospital.Study design: This was a secondary analysis of a 2-year retrospective cohort following implementation of a hospital guideline in women undergoing TOLAC with a live, cephalic, singleton without lethal anomaly ≥24 0/7 weeks and 1 or 2 prior cesarean deliveries. Maternal and neonatal outcomes in women with one prior cesarean were compared to women with two prior cesareans. The primary outcome was composite maternal morbidity (uterine rupture, uterine dehiscence, hysterectomy, transfusion, postpartum venous thromboembolism, delivery/surgical injury, chorioamnionitis or endometritis, shoulder dystocia, death). Secondary outcomes included neonatal morbidity. The analysis was performed in SAS; p < .05 was considered significant.Results: Seven hundred women with one prior cesarean and 73 women with two prior cesareans underwent TOLAC after the 2011 guideline implementation. Post guideline maternal demographics, labor length, comorbid conditions, simplified Bishop score, and induced labor were similar between groups. Composite maternal morbidity was similar between groups (18.3 versus 23.3%, p = .30 for women with 1 versus 2 prior cesarean deliveries, respectively). The same was true when comparing women with 1 versus 2 prior cesareans who had never had a prior vaginal delivery (25.5 versus 33.3%, p = .28 for 1 versus 2 prior cesarean deliveries, respectively). There were no differences in neonatal outcomes. Vaginal birth after cesarean (VBAC) success rates were similar between groups (78.9% in women with 1 prior cesarean versus 74.0% in women with 2 prior cesareans, p=.33), even when only analyzing women without a prior vaginal delivery (69.4% in women with 1 prior cesarean versus 71.4% in women with 2 prior cesareans, p = .78).Conclusion: Adoption of ACOG's TOLAC practice changes, specifically offering TOLAC to women with two prior cesareans even without a prior vaginal delivery, and offering induction of labor regardless of cervical favorability, may increase VBAC rates without increasing maternal or neonatal morbidity from TOLAC.

Comparison of induction of labor methods for unfavorable cervices in trial of labor after cesarean delivery.

OBJECTIVE: To compare induction of labor methods in patients attempting a trial of labor after cesarean (TOLAC) with an unfavorable cervix. METHODS: This is a retrospective cohort study from patients attempting TOLAC from 2009 to 2013. Patients with a simplified Bishop score of three or less where labor was initiated with either a Cook balloon or oxytocin were included. Our primary outcome was mode of delivery. Our secondary outcomes included duration of labor and multiple maternal and neonatal morbidities. RESULTS: Two-hundred and fourteen women met inclusion criteria: 150 received oxytocin and 64 had the Cook balloon placed. The vaginal birth after cesarean delivery rate was significantly higher in the oxytocin group at 70.7% versus 50.0% in the Cook balloon group (p = 0.004). In the multivariable analysis, odds for cesarean delivery were two times higher with the Cook balloon than with oxytocin (Adjusted OR = 2.09, 95% CI = 1.05-4.18, p = 0.036). The duration of labor was longer with the Cook balloon versus oxytocin (21.9 versus 16.3 hours, p = 0.0002). There were no significant differences in maternal and neonatal health outcomes. CONCLUSION: Oxytocin induction of labor was associated with a higher rate of vaginal delivery and a shorter duration of labor compared to the Cook balloon in women undergoing TOLAC with an unfavorable cervix.

Evaluation of outcomes associated with trial of labor after cesarean delivery after a change in clinical practice guidelines in an academic hospital.

OBJECTIVE: To evaluate maternal-neonatal morbidity for women undergoing trial of labor after cesarean (TOLAC) following clinical practice changes based upon ACOG's 2010 VBAC guideline. STUDY DESIGN: Four-year retrospective cohort analysis around implementation of a hospital guideline in women undergoing TOLAC with a live, cephalic, singleton without lethal anomaly ≥24 weeks and ≥1 prior cesarean. Maternal-neonatal outcomes pre- and post-guideline implementation were compared. Primary outcome was composite maternal morbidity (uterine rupture or dehiscence, hysterectomy, transfusion, thromboembolism, operative/delivery injury, chorioamnionitis/endometritis, shoulder dystocia, death). Secondary outcomes included neonatal morbidity. RESULTS: Four hundred and fifty women underwent TOLAC before and 781 after guideline implementation. Post-guideline, there was a significant increase in age, body mass index, labor length, women with >1 cesarean, comorbid condition and induced labor. Composite maternal morbidity was significantly higher after the guideline (13.78% versus 18.82%, p = 0.02), possibly due to an increased rate of chorioamnionitis/endometritis, which was no longer significant after control for potential confounders in multivariable analysis. There were no differences in neonatal outcomes. Vaginal birth after cesarean (VBAC) success rates were unchanged (78.9% before versus 78.1% after, p = 0.75), however hospital VBAC rates increased after the guideline (26% versus 33%, p < 0.0001). CONCLUSIONS: Adoption of ACOG's TOLAC practice changes can increase VBAC rates without increasing maternal-neonatal morbidity from TOLAC.

Analysis of phosphotyrosine signaling in glioblastoma identifies STAT5 as a novel downstream target of ΔEGFR.

An in-frame deletion mutation in Epidermal Growth Receptor (EGFR), ΔEGFR is a common and potent oncogene in glioblastoma (GBM), promoting growth and survival of cancer cells. This mutated receptor is ligand independent and constitutively active. Its activity is low in intensity and thought to be qualitatively different from acutely ligand stimulated wild-type receptor implying that the preferred downstream targets of ΔEGFR play a significant role in malignancy. To understand the ΔEGFR signal, we compared it to that of a kinase-inactivated mutant of ΔEGFR and wild-type EGFR with shotgun phosphoproteomics using an electron-transfer dissociation (ETD) enabled ion trap mass spectrometer. We identified and quantified 354 phosphopeptides corresponding to 249 proteins. Among the ΔEGFR-associated phosphorylations were the previously described Gab1, c-Met and Mig-6, and also novel phosphorylations including that of STAT5 on Y694/9. We have confirmed the most prominent phosphorylation events in cultured cells and in murine xenograft models of glioblastoma. Pathway analysis of these proteins suggests a preference for an alternative signal transduction pathway by ΔEGFR compared to wild-type EGFR. This understanding will potentially benefit the search for new therapeutic targets for ΔEGFR expressing tumors.