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Canonically, MST1/2 functions as a core kinase of the Hippo pathway and noncanonically during both apoptotic signaling and with RASSFs in T-cells. Faithful signal transduction by MST1/2 relies on both appropriate activation and regulated substrate phosphorylation by the activated kinase. Considerable progress has been made in understanding the molecular mechanisms regulating the activation of MST1/2 and identifying downstream signaling events. Here, we investigated the ability of MST2 to phosphorylate a peptide substrate and how that activity is regulated. Using a steady-state kinetic system, we parse the contribution of different factors to substrate phosphorylation, including the domains of MST2, phosphorylation, caspase cleavage, and complex formation. We found that in the unphosphorylated state, the SARAH domain stabilizes interactions with a peptide substrate and promotes turnover. Phosphorylation drives the activity of MST2, and once activated, MST2 is not further regulated by complex formation with other Hippo pathway components (SAV1, MOB1A, and RASSF5). We also show that the phosphorylated, caspase-cleaved MST2 is as active as the full-length one, suggesting that caspase-stimulated activity arises through noncatalytic mechanisms. The kinetic analysis presented here establishes a framework for interpreting how signaling events and post-translational modifications contribute to the signaling of MST2 in vivo.

Background: Coronavirus disease-2019 (COVID-19) is associated with thromboembolism. Antiphospholipid antibody (APLa) formation is one of the mechanisms. Vitamin D deficiency has been associated with thrombosis in antiphospholipid antibody syndrome., Objective: Measure APLa and vitamin D in hospitalized COVID-19 patients with and without thrombosis to evaluate if thromboembolism is associated with concomitant APLa and vitamin D deficiency., Methods: Case-control study. Hospitalized COVID-19 patients with a thromboembolic event (ischemic stroke, myocardial infarction, deep venous thrombosis/pulmonary embolism, Cases n = 20). Controls (n = 20): Age, sex-matched without thromboembolic events. Patients with autoimmune disorders, antiphospholipid antibody syndrome, thrombophilia, anticoagulation therapy, prior thromboembolism, chronic kidney disease 3b, 4, end-stage renal disease, and malignancy were excluded. Given the limited current literature on the role of concomitant antiphospholipid antibodies and vitamin D deficiency in causing venous and/or arterial thrombosis in hospitalized COVID-19 patients, we enrolled 20 patients in each arm. Anti-cardiolipin IgG/IgM, beta-2 glycoprotein-1 IgG/IgM, lupus anticoagulant and vitamin D levels were measured in both groups., Results: Cases were 5.7 times more likely to be vitamin D deficient (OR:5.7, 95% CI:1.3-25.6) and 7.4 times more likely to have any one APLa (OR:7.4, 95% CI: 1.6-49.5) while accounting for the effects of sex. Patients with both APLa and vitamin D deficiency had significantly more thrombosis compared to patients who were antibody positive without vitamin D deficiency (100% vs 47.4%; p = 0.01)., Conclusions: Thrombosis in COVID-19 was associated with concomitant APLa and vitamin D deficiency. Future studies in COVID-19 should assess the role of vitamin D in reducing thrombosis., Competing Interests: The authors have declared that no competing interests exist.

Background: Neurocritical care (NCC) and neuropalliative care (NPC) clinicians provide care in specialized intensive care units (ICU). There is a paucity of data regarding the impact of NCC and NPC collaboration in smaller, community-focused settings., Objective: To determine the clinical impact of introducing a NCC/NPC collaborative model in a mixed ICU community-based teaching hospital., Design: Retrospective pre/post cohort study., Subjects: Patients ≥18 years of age admitted to the ICU who received neurology and palliative care consultations between September 1, 2015 and August 31, 2017 at a 300 bed community-focused hospital were included., Intervention: The addition of a NCC/NPC collaborative model took place in September of 2016. The time periods before (9/1/2015 to 8/31/2016) and after (9/1/2016 to 8/31/2017) the addition were compared., Results: A total of 274 admissions (pre: 130, post: 144) were included. There were significantly more NCC consultations provided in the post-period (44.6% vs 57.6%; P = .03). NPC consultation increased (55.4% vs 66.7%; P = .056) Median LOS was significantly shorter after implementation of the collaborative model (11 vs 8 days; P = .01). Median ICU LOS was also shorter by 1 ICU-day in the post-period, though this was not statistically significant ( P = .23). Mortality rates were similar ( P = .95)., Conclusions: Our findings suggest NCC/NPC collaboration in a community-focused teaching hospital was associated with more NCC consultations, as well as shorter LOS without increasing mortality. These data highlight the importance of supporting collaborative models of care in community settings. Further research is warranted.

Objective: Tranexamic acid (TXA) has demonstrated a reduction in all-cause mortality in trauma patients with hemorrhage. Administering TXA in the prehospital setting presents unique challenges because the identification of bleeding is based on clinical suspicion without advanced imaging or diagnostic tools. The objective of this study was to examine whether prehospital suspicion of bleeding is validated by in-hospital computed tomographic imaging and examination and to determine if patients received TXA in the absence of hemorrhage. The study was conducted at a level 1 trauma center supported by air medical transport services., Methods: This is a retrospective cohort study examining 88 trauma patients receiving prehospital TXA to treat suspected hemorrhage. Adult trauma patients who received TXA during the study period and were transported to our level 1 trauma center were included. A panel of trauma surgeons reviewed CT imaging and examination findings to retrospectively identify significant hemorrhage., Results: Forty-three percent of patients who received TXA during air medical transport did not have confirmed hemorrhage upon arrival., Conclusion: TXA was given to a significant number of patients who did not have confirmed hemorrhage upon arrival. We recommend that institutions using TXA perform this internal validation to ensure they are accurately identifying hemorrhage in the prehospital setting., (Copyright © 2021 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Introduction: Firearm-related deaths and injuries are ongoing public health issues in the United States. We reviewed a series of gun violence- and firearm-related injuries treated at a multi-campus community healthcare system in West Michigan to better understand the demographic and clinical characteristics of these injuries. We also studied hospital charges, and payers responsible, in an effort to identify stakeholders and opportunities for community- and hospital-based prevention., Methods: We performed a retrospective review of firearm injuries treated at Mercy Health Muskegon (MHM) between May 1, 2015 and June 30, 2019. Demographic data, injury type, Injury Severity Score (ISS), anatomic location and organ systems involved, length of stay (LOS), mortality, time of year, and ZIP code in which the injury occurred were reviewed, as were hospital charges and payers responsible., Results: Of those reviewed, 307 firearm-related injuries met inclusion criteria for the study. In 69.4% of cases the injury type was attempted murder or intent to do bodily harm. Accidental and self-inflicted injuries accounted for 25% of cases. There was a statistically significant difference in the mechanism of injury between Black and White patients with a higher proportion of Black men injured due to gun violence (P < 0.001). Median ISS was 8 and the most commonly injured organ system was musculoskeletal. Median LOS was one day. Self-inflicted firearm injuries had the highest rate of mortality (50%) followed by attempted murder (7%) and accidental discharge (3.1%; P < 0.001). Median hospital charge was $8,008. In 68% of cases, Medicaid was the payer. MHM received $4.98 million dollars in reimbursement from Medicaid; however, when direct and indirect costs were taken into account, a loss of $12,648 was observed., Conclusion: Findings from this study reveal that young, Black men are the primary victims of gun violence-related injuries in our West Michigan service area. Hospital care of firearm-related injuries at MHM was predominantly paid for by Medicaid. Multiple stakeholders stand to benefit from funding and supporting community- and hospital-based prevention programs designed to reduce gun violence and firearm-related injuries in our service area.

Background: As the cost of health care increases in the US, focus has been placed upon efficiency, cost reduction, and containment of spending. Operating room costs play a significant role in this spending. We investigated whether surgeon education and universal preference cards can have an impact on reducing the disposable supply costs for common laparoscopic general surgery procedures., Methods: General surgeons at two institutions participated in an educational session about the costs of the operative supplies used to perform laparoscopic appendectomies and cholecystectomies. All the surgeons at one institution agreed upon a universal preference card, with other supplies opened only by request. At the other, no universal preference cards were created, and surgeons were free to modify their own existing preference cards. Case cost data for these procedures were collected for each institution pre- (July 2014-December 2014) and post-intervention (February 2015-November 2017)., Results: At the institution with an education only program, there was no statistically significant change in supply costs after the intervention. At the institution that intervened with the combined education and universal preference card program, there was a statistically significant supply cost decrease for these common laparoscopic procedures combined. This significant cost decrease persisted for each appendectomies and cholecystectomies when analyzed independently as well (p = 0.001 and p < 0.001 respectively)., Conclusions: In this study, surgeon education alone was not effective in reducing operating room disposable supply costs. Surgeon education, combined with the implementation of universal preference cards, significantly maintains reductions in operating room supply costs. As health care costs continue to increase in the US and internationally, universal preference cards can be an effective tool to contain cost for common laparoscopic general surgery procedures.

Background: Nasogastric tube placement is widely taught, and tube maintenance relies on astute nursing care with adherence to both institutional and evidence-based recommendations. However, precise adherence to current recommendations relies on knowledge base regarding the identification of malfunctioning gastric drainage tubes. Troubleshooting skills are crucial in maintaining patient safety and recognizing malfunction., Method: Educational sessions on nasogastric and orogastric decompression tube management, led by a surgical intensive care fellow at a level 1 trauma center, were offered to critical care nurses. A presession and postsession survey evaluated the nurses' subjective and objective knowledge and comfort with naso/orogastric decompression tube management., Results: Ninety-seven critical care RNs participated. For all questions, the proportion of correct answers significantly increased from presession survey to postsession survey (p < .001). Ninety-seven percent of all participants found the session to be very helpful., Conclusion: Physician-led educational sessions on naso/orogastric decompression tube management were well-received and improved subjective and objective measurements of nurses' knowledge and comfort level with gastric decompression tubes. [J Contin Educ Nurs. 2020;51(10):484-488.]., (Copyright 2020, SLACK Incorporated.)

Background and Purpose: Recent trials have shown benefit of thrombectomy in patients selected by penumbral imaging in the late (>6 hours) window. However, the role penumbral imaging is not clear in the early (0-6 hours) window. We sought to evaluate if time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on CT perfusion (CTP)., Methods: We retrospectively analyzed consecutive patients who underwent thrombectomy in a single center. Demographics, comorbidities, National Institute of Health Stroke Scale (NIHSS), rtPA administration, ASPECTS, core infarct volume, onset to skin puncture time, recanalization (mTICI IIb/III), final infarct volume were compared between patients with good and poor 90-day outcomes (mRS 0-2 vs. 3-6). Multivariable logistic regression analyses were used to identify independent predictors of a good (mRS 0-2) 90-day outcome., Results: A total of 235 patients were studied, out of which 52.3% were female. Univariate analysis showed that the groups (early vs. late) were balanced for age (P = .23), NIHSS (P = .63), vessel occlusion location (P = .78), initial core infarct volume (P = .15), and recanalization (mTICI IIb/III) rates (P = .22). Favorable outcome (mRS 0-2) at 90 days (P = .30) were similar. There was a significant difference in final infarct volume (P = .04). Shift analysis did not reveal any significant difference in 90-day outcome (P = .14). After adjustment; age (P < .001), NIHSS (P = .01), recanalization (P = .008), and final infarct volume (P < .001) were predictive of favorable outcome., Conclusions: Penumbral imaging-based selection of patients for thrombectomy is effective regardless of onset time and yields similar functional outcomes in early and late window patients., (© 2020 by the American Society of Neuroimaging.)

Hippo pathway signaling limits cell growth and proliferation and maintains the stem-cell niche. These cellular events result from the coordinated activity of a core kinase cassette that is regulated, in part, by interactions involving Hippo, Salvador, and dRassF. These interactions are mediated by a conserved coiled-coil domain, termed SARAH, in each of these proteins. SARAH domain-mediated homodimerization of Hippo kinase leads to autophosphorylation and activation. Paradoxically, SARAH domain-mediated heterodimerization between Hippo and Salvador enhances Hippo kinase activity in cells, whereas complex formation with dRassF inhibits it. To better understand the mechanism by which each complex distinctly modulates Hippo kinase and pathway activity, here we biophysically characterized the entire suite of SARAH domain-mediated complexes. We purified the three SARAH domains from Drosophila melanogaster and performed an unbiased pulldown assay to identify all possible interactions, revealing that isolated SARAH domains are sufficient to recapitulate the cellular assemblies and that Hippo is a universal binding partner. Additionally, we found that the Salvador SARAH domain homodimerizes and demonstrate that this interaction is conserved in Salvador's mammalian homolog. Using native MS, we show that each of these complexes is dimeric in solution. We also measured the stability of each SARAH domain complex, finding that despite similarities at both the sequence and structural levels, SARAH domain complexes differ in stability. The identity, stoichiometry, and stability of these interactions characterized here comprehensively reveal the nature of SARAH domain-mediated complex formation and provide mechanistic insights into how SARAH domain-mediated interactions influence Hippo pathway activity., (© 2020 Cairns et al.)

Background: Despite concerns regarding the increasing obesity epidemic, little is known regarding obesity curricula in medical education. Medical school family medicine clerkships address common primary care topics during clinical training. However, studies have shown that many family physicians feel unprepared at addressing obesity. The purpose of this study was to evaluate factors related to obesity education provided during family medicine clerkships as well as identify future plans regarding obesity education., Methods: Data were collected through the 2017 Educational Research Alliance (CERA) survey of Family Medicine Clerkship Directors (CDs) in the United States and Canada. Survey items included the level of importance of obesity education, teaching methods, barriers to teaching, and obesity related topics taught during the clerkship. Survey data were summarized and analyzed., Results: The survey response rate was 71.2%. The most frequent barrier to teaching obesity related topics was time constraints (89%). The most commonly taught topics were co-morbid conditions (82.1%), diet (76.9%), and exercise (76.9%). The least commonly taught topics were addressed less than 30% of the time, and included cultural aspects, obesity bias, medications than can cause weight gain, medications to treat obesity, and bariatric surgery. Over half of CDs (59%) are not planning to change existing curriculum, with 39% planning to add to the current curriculum. The CDs' perceptions of the importance of obesity education were significantly associated with the number of topics covered during clerkship (p <  0.001). No relationship was found between clerkship duration and the number of obesity topics taught., Conclusion: The majority of clerkship directors are planning no changes to their existing curricula which consist of three common topics: obesity related co-morbid conditions, diet, and exercise. While time was the largest self-rated barrier in teaching obesity related topics, clerkship duration didn't impact the number of topics taught. However, the relative amount of importance placed by CDs upon obesity education was significantly associated with the number of topics covered during clerkship.

Background and Purpose: Infarct core assessment on presentation is important to evaluate salvageable tissue to select patients for thrombectomy. Our study aims to evaluate the correlation between infarct core volume measured by computed tomography (CT) perfusion (CTP) and magnetic resonance diffusion-weighted imaging (MR-DWI) in patients with acute large-vessel occlusion., Methods: We studied patients who underwent CTP on presentation to the emergency department for stroke symptoms. National Institute of Health Stroke Scale (NIHSS), collateral status, symptomatic vessels, and modified Rankin scale (mRS) at 90 days were collected. Admission infarct core volume was measured on initial relative cerebral blood volume and final infarct core volume on follow-up DWI. The correlation between two measures was assessed using Pearson's correlation coefficient., Results: Seventy-four patients were studied of which 41.9% were female. Median NIHSS was 13 (2-30). Middle cerebral artery occlusion was present in 53 (71.6%) patients and 54 (72.9%) had good collaterals. Good functional outcome of mRS 0-2 was achieved by 60.8% at 90 days. There was a strong correlation between CTP and MR-DWI (r = .94). There was no significant difference between volume (in milliliters) on CTP (54.1 ± 69.8) and volume on DWI (50.3 ± 59.7; P = .18) using the paired t-test., Conclusion: CTP provides a good estimation of the core infarct volume. It performs well within the clinically relevant thresholds for patient selection for thrombectomy., (© 2019 by the American Society of Neuroimaging.)

Background: Immediately fatal motorcycle crashes have not been well characterized. This study catalogues injuries sustained in fatal motorcycle crashes and assesses the impact of crash conditions on injury patterns., Methods: Autopsy records from the office of the medical examiner of Kent County, MI and publicly available traffic reports were queried for information pertaining to motorcyclists declared dead on-scene between January 1, 2007, and December 31, 2016., Results: A total of 71 autopsies of on-scene motorcycle crash fatalities were identified. The two most prevalent injuries were traumatic brain injury (TBI) (85%) and rib fractures (79%). The majority of fatalities occurred in daylight hours (54.3%) and in a 55 mph speed limit zone (63.8%)., Conclusions: This study provides a catalogue of the injuries sustained in immediately fatal motorcycle crashes and the associated conditions. Advocacy efforts that highlight the risks associated with motorcycle riding and that promote safe riding practices are warranted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Clostridium difficile infection (CDI) is one of the most common nosocomial infections in the United States, with an increasing incidence in children. Approximately 20% of pediatric patients develop recurrent infections. It's imperative to further analyze the incidence of recurrent CDI in the pediatric population and determine the most effective treatments. The primary goal of this study is to characterize children with recurrent CDI at our institution, including both hospital-acquired CDI (HA-CDI) and community-acquired CDI (CA-CDI) cases, summarize the various treatments utilized, including fecal microbiota transplant (FMT) and compare their success rates., Methods: A retrospective cohort study of pediatric patients 1-21 years of age treated for CDI at a single institution from January 2010 to December 2014 was performed., Results: There were 175 subjects with 215 separate episodes of CDI. Oral metronidazole was the most common initial treatment (145/207, 70%) followed by oral vancomycin (30/207, 15%), with recurrence rates of 30% (42/145) and 37% (11/30), respectively. Twenty-nine percent (63/215) of all initial CDI cases had at least 1 documented recurrence. Using multivariate analysis, subjects with HA-CDI were 2.6 times less likely to recur than those with CA-CDI (odds ratio: 0.39; 95% confidence interval: 0.18-0.85; P = 0.018). The overall success rate for FMT at our institution was 10/12 (83%)., Conclusions: Our data show that cases of HA-CDI were less likely to recur compared with CA-CDI. Although currently reserved for multiply-recurrent cases, FMT was highly successful in our small cohort. More studies on FMT should be conducted to further evaluate its usefulness in the treatment of recurrent CDI in children.

Background: Adrenocortical oncocytic neoplasms are rare tumors, generally regarded as benign and hormonally nonfunctional. We performed a systematic review to update the literature on adrenocortical oncocytic neoplasms by reviewing patient and tumor characteristics, as well as management trends, because the literature is composed of predominately single-case reports., Methods: A systematic search was performed in PubMed, Embase, and Cochrane Library through June 2017. Malignant potential was determined by applying the Lin-Weiss-Bisceglia criteria to cases., Results: Included for analysis were 84 citations describing 140 adrenocortical oncocytic neoplasms, including our own case. These were diagnosed predominantly in females (66%), on the left side (64%), and were nonfunctional (66%). Average age at diagnosis was 44 years (2.5-77), and median tumor size was 80 mm (16-285). A total of 35% of adrenocortical oncocytic neoplasms were benign, 41% borderline, and 24% malignant. Male patients were more likely to have a malignant tumor compared with females (36% versus 18%, P = .035). The 5-year overall survival for benign adrenocortical oncocytic neoplasms was 100%, borderline 88%, and malignant 47%. Hormonal function did not discriminate malignant from benign lesions. Adrenocortical oncocytic neoplasms that stained positive for synaptophysin (50%, P < .001) and negative for vimentin (62%, P = .009) are more often benign., Conclusion: We found that the majority of adrenocortical oncocytic neoplasms (65%) were either malignant or had malignant potential, contrary to the previous literature. The Lin-Weiss-Bisceglia criteria are useful in identifying those patients for whom closer surveillance is warranted, because their prognosis is dependent on the Lin-Weiss-Bisceglia diagnosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: The Choosing Wisely guidelines advise against ordering routine blood tests for hospitalised patients unless they change management. Unnecessary testing can lead to adverse effects (eg, iatrogenic anaemia, poor sleep quality, risk for infections and increased cost of care)., Methods: An 8-week quality initiative aimed at reducing unnecessary blood tests was implemented in three internal medicine resident inpatient services. The initiative included a 30 min educational session, reminders prior to rotation and midrotation and posters in work areas that displayed lab pricing and urged judicious testing. Residents were encouraged to justify the purpose of ordering tests in their daily progress notes. Attending physicians were made aware of the initiative. Preintervention and postintervention time points were used to compare key metrics. A >10% decrease between time periods was used as an evaluation criterion., Results: There were 293 patient records reviewed in the preintervention period and 419 in the postintervention period. The two groups were similar in terms of age and gender. Median blood test count (complete blood count/basic metabolic profile/comprehensive metabolic profile) decreased from 4 to 2 tests per patient per day (50 % decrease) after the intervention. The median length of hospital stay decreased from 4.9 to 3.9 days (21% decrease). A decreased percentage of people requiring transfusions was also noted (2016: 6.1%, 2017: 2.9%)., Conclusion: The frequency of unnecessary routine blood tests ordered in the hospital can be decreased by educating resident physicians, making them cost conscious and aware of the indications for ordering routine labs. Frequent reminders are needed to sustain the educational benefit., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Over the past 10 years, three new MD schools have been created in the state of Michigan, while the Michigan State University College of Human Medicine (MSU-CHM) has increased their class size to 850 students. The aim of this study was to determine if MSU-CHM alumni who graduate from an MSU-affiliated primary care residency from a single graduate medical education (GME) training program in Michigan are more likely to go on to practice in close proximity to the location of their training program immediately after graduation compared to non MSU-CHM alumni. Changes over time in the proportion of primary care graduates who received fellowship training immediately following residency were also compared between these groups., Methods: A review of historical data was performed for all 2000-2016 primary care (Family Medicine, FM; Internal Medicine, IM; Internal Medicine-Pediatrics, IMP; Pediatrics, Peds) program graduates sponsored by Grand Rapids Medical Education Partners (GRMEP). Study variables included primary care program, gender, age at graduation, fellowship training, practice location immediately after graduation and undergraduate medical education location. Summary statistics were calculated for the data. Comparisons were made using the chi-square test or Fisher's Exact test when appropriate. Significance was assessed at p < 0.05., Results: There were 478 primary care program graduates who went into practice immediately following graduation, 102 of whom also graduated from MSU-CHM. Just over half of the graduates were female and the average age at graduation was 32 years. There were 152 FM, 150 IM, 50 IMP and 126 Peds graduates. Those that graduated from both MSU-CHM and GRMEP were more likely to practice in Michigan immediately after residency training (79.4% vs 52.0%; p < 0.001), as well as within 100 miles of GRMEP (71.6% vs 46.4%; p < 0.001). There were 8% of MSU-CHM primary care graduates who went on to fellowship training from 2000 to 2009, increasing to 34% from 2010 to 2016 (p < 0.001)., Conclusion: Medical school graduates of MSU-CHM who receive GME training in primary care are more likely to practice medicine within close proximity to their training site than non MSU-CHM graduates. However, plans for fellowship after training may add one caveat to this finding.

Background: In April of 2012, Michigan repealed its 35-year-old universal motorcycle helmet law in favor of a partial helmet law, which permits motorcyclists older than 21 years old with sufficient insurance and experience to drive un-helmeted. We evaluated the clinical impact of the repeal., Methods: The Michigan Trauma Quality Improvement Program's trauma database was queried for motorcycle crash patients between 1/1/09-4/12/12 and between 4/13/12-12/31/14., Results: There were 1970 patients in the pre-repeal analysis and 2673 patients in the post-repeal analysis. Following the repeal, patients were more likely to be un-helmeted (p < 0.001) and to have a traumatic brain injury (p < 0.001). Patients were also more likely to require neurosurgical interventions (relative risk 1.4, p = 0.011)., Conclusion: Following the repeal of the universal helmet law, there has been a significant increase in traumatic brain injuries and neurosurgical interventions. This analysis highlights another detrimental impact of the repeal of the universal helmet law., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to compare patient outcomes for thoracic epidural anesthesia (TEA) with transversus abdominis plane (TAP) blocks., Methods: A prospective, randomized trial was performed for patients undergoing abdominal oncologic surgeries., Results: There were 32 TAP and 35 TEA subjects. The TEA group demonstrated increased episodes of hypotension in the first 24 h (3 v 0.6, p = 0.02). There was no difference in 24-48 h fluid balance between the groups. Overall parenteral morphine equivalents of opioids administered for the TEA group were higher for each postoperative day (p < 0.05). The post-operative survey did not demonstrate any difference in subjective pain between the TAP and TEA groups (6 v 6 p = 0.35). There was no attributable morbidity associated with either technique., Conclusions: TAP block use was associated with lower parenteral morphine equivalent usage and decreased incidence of hypotension in the early post-operative period compared to TEA., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Interferon alpha 2B (IFN-α) therapy in malignant melanoma has improved relapse free survival and overall survival but is considerably toxic and lowers the overall quality of life (QoL) substantially. A significant number of patients do not complete the full duration (one year) of therapy., Objective: The aim of this study was to evaluate patients' ability to tolerate IFN-α therapy and to compare our results to reported data in the literature., Methods: We conducted a retrospective review of patients diagnosed with cutaneous malignant melanoma who received IFN therapy after surgical resection. Patients were divided into two groups: patient who completed therapy (CIT) and those who did not (incomplete therapy, IIT). Duration of therapy was calculated. Reason for discontinuation and experienced side effects were reported. Statistical significance was determined at p &#60; 0.05., Results: A total of 64 patients were included in the review. There were 16 (25%) patients were able to complete therapy. The most common reasons for discontinuing IFN-α therapy was fatigue (81.3%), fever (40.6%), depression (28.1%) and nausea (18.8%). Patients in the CIT group were younger than those in the IIT group (47.4 ± 14.2 vs 57.8 ± 11.9 years, mean ± SD; p = 0.011). There also seemed to be an association that those with the presence of advanced disease may have been more likely to complete therapy (node positive disease at the time of diagnosis, p = 0.07)., Limitations: It is a retrospective study and has to rely on physician notes for the subjective data. For the survival analyses, the median follow-up times for both of the groups were less than 3.5 years., Conclusions: Younger patients were more likely to complete therapy. There was a trend towards an association between more advanced disease and the completion of therapy. Most common causes of discontinuation of therapy were fatigue, fever, depression, and nausea.

Setting: Spectrum Blodgett and Mercy Health St. Mary's hospitals in Grand Rapids, Michigan OBJECTIVE: To compare the 30-day outcomes of laparoscopic biliopancreatic diversion with duodenal switch (BPD/DS) to laparoscopic sleeve gastrectomy (SG)., Background: Laparoscopic BPD/DS has been shown to be superior to SG in terms of excess weight loss. Despite this superiority, BPD/DS accounts for a small percentage of all metabolic surgeries due partly to the perception that BPD/DS has a higher complication rate than SG., Methods: Retrospective review of all patients who underwent BPD/DS or SG from January 2008 to August 2014 by 1 surgeon was completed. These patients were used to construct cohorts matched via propensity score matching and compared by surgical type. Data collected included patient demographic characteristics; hospital length of stay (LOS); and 30-day rates of leak, bleed, reoperation, readmission, and mortality., Results: Of the 741 patients who underwent BPD/DS or SG, 2 cohorts of 167 patients each were matched for age, sex, and BMI. LOS was longer in the BPD/DS cohort (2.5±.9 days versus 2.1±.7 days, P<.001). There were no significant differences between the groups in relation to 30-day postoperative rates of leak (.3% versus .6%, P>.99), bleed (0% versus .3%, P>.99), reoperation (1.2% versus .6%, P>.99), or readmission (3% versus 1.2%, P = .45). There were no mortalities., Conclusion: After matching for age, sex, and BMI, BPD/DS found no significant differences from SG with regard to 30-day postoperative rates of leak, bleed, reoperation, readmission, or mortality., (Copyright © 2017 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: There is a paucity of literature when it comes to identifying predictors of in-state retention of graduate medical education (GME) graduates, such as the demographic and educational characteristics of these physicians., Objective: The purpose was to use demographic and educational predictors to identify graduates from a single Michigan GME sponsoring institution, who are also likely to practice medicine in Michigan post-GME training., Methods: We included all residents and fellows who graduated between 2000 and 2014 from 1 of 18 GME programs at a Michigan-based sponsoring institution. Predictor variables identified by logistic regression with cross-validation were used to create a scoring tool to determine the likelihood of a GME graduate to practice medicine in the same state post-GME training., Results: A 6-variable model, which included 714 observations, was identified. The predictor variables were birth state, program type (primary care versus non-primary care), undergraduate degree location, medical school location, state in which GME training was completed, and marital status. The positive likelihood ratio (+LR) for the scoring tool was 5.31, while the negative likelihood ratio (-LR) was 0.46, with an accuracy of 74%., Conclusions: The +LR indicates that the scoring tool was useful in predicting whether graduates who trained in a Michigan-based GME sponsoring institution were likely to practice medicine in Michigan following training. Other institutions could use these techniques to identify key information that could help pinpoint matriculating residents/fellows likely to practice medicine within the state in which they completed their training., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Background: In a time of threats to the funding for graduate medical education (GME) and projected physician shortages, drawing attention to the value of physician training programs may be useful. One approach is to study the number and percentage of physicians who enter practice in the state in which they trained., Objective: We sought to examine the percentage of graduates from a single Michigan-based GME institution over a 15-year period, who practiced medicine in Michigan during their career., Methods: We performed a retrospective review of historical data for all graduates currently in practice, derived from 18 GME training programs from 2000 through 2014. Practice location data were collected and confirmed using multiple sources for accuracy., Results: Data were available for 1168 graduates. The average age at the time of graduation was 32.6 ± 4.4 years (mean and standard deviation [SD]), and 60.2% were men (703 of 1168). There were 546 graduates (46.7%) who practiced in Michigan after graduation. Almost 80% of the graduates (279 of 358) who completed medical school and GME in Michigan also practiced in Michigan. Of those, 87.8% (245 of 279) also completed a bachelor's degree in Michigan., Conclusions: The findings show that graduates from our GME programs were highly likely to practice in Michigan if they completed their pre-GME education in Michigan., Competing Interests: The authors declare they have no competing interests.

Background: Assessing the degree of involvement of caregivers for children with type 1 diabetes mellitus (T1DM) in their diabetes care, differences in the degree of involvement based on the method of insulin administration (multiple daily injections: MDI/continuous subcutaneous insulin infusion: CSII), and its effect on glycemic control., Methods: This was a cross-sectional study with T1DM patients, ages 6-13 years using a six question survey derived from the Diabetes Family Responsibility Questionnaire (DFRQ). All caregivers (n=140) and participants between ages 11 and 13 (n=60) completed the survey., Results: Significant differences between MDI and CSII caregiver responses were found for responsibility for giving insulin boluses, as well as for rotation of infusion/injection sites (p<0.001 and p=0.03, respectively). A sub-analysis of caregiver responses for caregiver versus child responsibility for giving infusion boluses (excluding shared responsibility) showed that 36% of children in the CSII group had primary responsibility for giving insulin boluses, compared to 17% in the MDI group (p<0.001). The median agreement for all questions combined between participants and caregivers for ages 11-13 (n=60 pairs) was "poor" (κ=0.18). No significant effect of parental involvement on last 2-year average HbA1C was found for CSII or MDI groups (p>0.20)., Conclusions: Caregiver reported diabetes care responsibility (mostly parent, mostly child, shared between parent and child) varies for certain aspects of diabetes related care for children ages 6-13, depending upon the mode of insulin administration. Based on the reported degree of parental collaboration, HbA1C did not differ significantly. However, long-term effects are yet to be determined in longitudinal studies.

Objective: To assess the prevalence of fear of needles and its effect on glycemic control in children with type 1 diabetes mellitus (T1DM) on multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII)., Methods: Patients aged 6 to 17 years with T1DM on MDI or CSII (n = 150) were enrolled. All caregivers and patients aged ≥11 years completed a "Diabetes Fear of Injecting and Self-testing Questionnaire" (D-FISQ). Needle phobia was defined as a score ≥6 for fear of self-testing (FST), fear of injections (FI), and fear of infusion-site changes (FISC)., Results: Positive FST scores were noted in 10.0% and positive FI or FISC scores in 32.7% (caregivers' responses). Patients aged 6 to 10 years on CSII had greater fear (FISC) than those on MDI (FI) (P = .010). FST was inversely related to the number of daily blood sugar checks (P = .003). Patients with positive scores for FI/FISC or FST had significantly higher glycated hemoglobin (HbA1c) levels than those without. An inverse association was noted between positive FI/FISC scores and age of the patient (P = .029). Based on patient responses, FST severity was directly related to the age of the patient (P = .013)., Conclusion: Needle phobia is common in children with T1DM. Although FI/FISC are more common in younger children, especially in those on CSII, FST is more often encountered in older patients. Patients with a more intense fear of needles have higher HbA1c levels and less frequent blood sugar monitoring. Identifying these patients may help improve glycemic control.

Purpose: Laparoscopic treatment of perforated peptic ulcer disease (perfPUD) has demonstrated comparable operative outcomes with an open approach though the cost-efficiency of this method has not been studied., Methods: Data were obtained from the Nationwide Inpatient Sample (2007-2010). Patients who underwent operation for perfPUD were divided on the basis of laparoscopic or open approach. The primary outcome measures were hospital duration of stay, mortality, and total charges., Results: A total of 5,361 patients with perfPUD were identified: 5,219 in the open group and 142 in the laparoscopic group. Patients in the laparoscopic group were younger (50.5 vs 60.0, P < .001) and had a lesser incidence at presentation of sepsis (8.5 vs 14.8%, P = .034) and shock (2.1 vs 7.7%, P = .012). On univariate analysis, the laparoscopic group had decreased duration of stay (7.0 vs 8.0 days, P < .001), lesser rates of mortality (3.5 vs 8.1%, P = .048), and were discharged to home more frequently (79.6 vs 68.1%, P = .025). Mean total charges were less in the laparoscopic group ($44,095 vs $52,055, P = .019). Multivariate analyses failed to show a difference between groups for any of the outcome variables., Conclusion: The laparoscopic treatment of perfPUD is associated with equivalent costs and outcomes compared with the open technique when we corrected for presentation variables., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Metaplastic breast cancer is a rare histologic variant among breast cancers. We sought to investigate the impact of hormone receptor status in metaplastic breast cancer and compare outcomes with common histologic variants of breast cancer., Methods: The study was performed utilizing the Surveillance, Epidemiology, and End Results database. A query was made for patients with metaplastic breast cancer from 2000 to 2010. A separate query identified all patients with infiltrating ductal (IDC) or lobular (ILC) carcinoma during the same period. Effect of hormone receptor status was evaluated using Cox regression analysis. Significance was assessed for p < 0.05., Results: A total of 2,338 patients with metaplastic breast cancer were available for study. Most tumors were hormone receptor negative (79.0 %) and greater than or equal to grade 3 (82.9 %). For comparison, 382,667 and 44,813 patients with IDC and ILC, respectively, were obtained. Overall 5-year survival for metaplastic breast cancer was 62.2 % compared with 81.2 % for IDC (p < 0.001) and 80.2 % for ILC (p < 0.001). For metaplastic cases, no difference in 5-year survival was found between hormone-positive and hormone-negative tumors (65.7 vs. 63.5 %; p = 0.70). Multivariate analysis demonstrated metaplastic histology as an independent risk factor for cancer-related mortality both among hormone-positive (hazard ratio [HR] 2.4; 95 % confidence interval [CI] 1.8-3.0; p < 0.001) and hormone-negative (HR 1.7; 95 % CI 1.5-1.9; p < 0.001) breast cancers., Conclusion: Metaplastic breast cancer is an aggressive histologic variant that portends a poor prognosis compared with common breast cancer subtypes. Contrary to other breast cancers, hormone receptor positivity does not improve prognosis in metaplastic breast cancer.

Background and Objectives: Given the high incidence of postoperative morbidity following pancreaticoduodenectomy (PD), efforts at improving patient outcomes are vital. We sought to determine the impact of perioperative fluid balance on outcomes following PD in order to identify a targeted strategy for reducing morbidity., Methods: A retrospective review of consecutive PDs from 2008 to 2012 was completed. Cumulative fluid balances were recorded at 0, 24, 48, and 72 hr postoperatively and patients were divided into quartiles. Multivariate analyses were performed accounting for age, gender, diagnosis, ASA class, estimated blood loss, colloid and blood product use, and hemoglobin nadir. The predefined primary outcome measures were 90-day morbidity (Clavien grade ≥ III), mortality, and hospital readmission., Results: One hundred sixty-nine PDs were performed during the study period. The 90-day morbidity and mortality rates for the cohort were 40.2% and 3.0%, respectively, while hospital length of stay was 13.6 ± 6.7 days (mean ± SD). Higher fluid balance at 48 and 72 hr postoperatively was an independent predictor of morbidity and length of stay on multivariate analysis., Conclusions: Higher postoperative fluid balance is associated with increased postoperative morbidity and longer hospital stay following PD. Efforts at maintaining a fluid-restrictive strategy should be emphasized in this population., (© 2014 Wiley Periodicals, Inc.)

Objective: Children who are given unsupervised responsibility for their diabetes care prior to developmental and/or emotional readiness may have poorer glycemic control. The purpose of this study was to assess the age-related expectations of children and caregivers for independence in diabetes care-related tasks., Methods: A total of 150 participants with type 1 diabetes mellitus (T1DM) receiving multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) were enrolled in this study. All caregivers and participants older than 10 years of age completed questionnaires evaluating the expected age of independence for different diabetes care-related tasks., Results: The participants expected independence with no direct supervision in most diabetes care-related tasks at a younger age than their caregivers (P<.05). The difference was more prominent for those on CSII compared to MDI (P<.01). There was a positive correlation between the age when caregivers expect independence for most of the diabetes-related tasks and the age at diagnosis, regardless of the use of MDI or CSII (P<.01)., Conclusion: Children with T1DM expect to assume independence at a younger age than their caregivers do. The younger the children are at diagnosis, the younger they are expected by their caregivers to be independent, especially those on CSII.

Objective: To (a) determine if converting patients on simvastatin to lovastatin affects whether they meet their low-density lipoprotein cholesterol (LDL-C) goals as defined by the National Cholesterol Education Program Adult Treatment Panel III (ATP III) clinical practice guidelines and (b) assess the change in health care expenditures associated with such a conversion., Methods: Primary and secondary prevention patients receiving simvastatin 10 mg to 40 mg daily between September 1, 2001, and February 28, 2002, were offered lovastatin at a therapeutically equivalent dose. Fasting lipid profiles and alanine aminotransferase (ALT) levels were measured and recorded at least 6 weeks after starting lovastatin. A clinical pharmacy staff member, in collaboration with the subject's primary care provider, subsequently adjusted lipid-lowering therapy as needed to attain target LDL-C goals, as determined by the ATP III clinical practice guidelines., Results: Of 5,286 patients converted to lovastatin and for whom follow-up laboratory tests were drawn, 5,046 (95.5%) were converted successfully, and 240 (4.5%) had to be converted back to simvastatin due to intolerance (N=164, 3.1%) or failure to achieve LDL-C goal (N=76, 1.4%). The proportion of patients with LDL-C at or less than their target goal increased from 75.9% before the intervention to 79.1% after conversion to lovastatin (P <0.001). ALT levels did not change significantly. The mean ALT value, a proxy measure of safety before and after conversion for all patients, was 26.9 IU/L and 26.4 IU/L, respectively (P=0.134). For the 2,235 patients converted from lovastatin 80 mg to simvastatin 40 mg, the mean pre-ALT and post-ALT values were 26.9 IU/L and 26.5 IU/L (P=0.498). The annualized cost savings due to the conversions, expressed across the entire membership of this health maintenance organization (HMO), was 4.14 US dollars per member per year (PMPY), with no change in ALT levels. Patient savings in reduced copayments in the conversion from brand simvastatin to generic lovastatin were an average of 145.29 US dollars (62%) per patient (95% confidence interval, 143-149 US dollars, P <0.001)., Conclusion: A clinical pharmacy-directed program designed to convert patients from simvastatin to lovastatin resulted in substantial expenditure reductions for this HMO and 62% copayment savings for members, without compromise in clinical outcomes as measured by lipid control (effectiveness) and ALT levels (safety). The proportion of patients at or less than their LDL-C goal increased coincident with the conversion from simvastatin to lovastatin.