Effect of antiplatelet and anticoagulant therapy on bleeding complications following ventral hernia repair: An ACHQC analysis.

BACKGROUND: We investigate the effect of antiplatelet and anticoagulant medications on bleeding complications in patients undergoing ventral hernia repair. METHODS: The Abdominal Core Health Quality Collaborative registry was queried from 2013 to 2022 for patients who underwent ventral hernia repair, evaluating the association between antiplatelet or anticoagulant use and bleeding complications. RESULTS: 37,973 patients underwent ventral hernia repair: 11.5 â€‹% on antiplatelet therapy alone and 5.8 â€‹% on anticoagulation alone. Despite being held, an adjusted regression analysis showed that anticoagulation was associated with an increased risk for postoperative bleeding requiring transfusion (OR 2.4 [1.7-3.4], p â€‹< â€‹0.0001), reoperation for postoperative bleeding (OR 6.3 [3.9-10.0], p â€‹< â€‹0.0001), and readmission for bleeding complications (OR 4.9 [2.9-8.2], p â€‹< â€‹0.0001). Antiplatelet use was not a risk factor for any postoperative bleeding complication. CONCLUSION: Despite being held preoperatively, patients on anticoagulants are at an increased risk for postoperative hemorrhagic complications. Antiplatelet therapy does not pose the same risk.

Needle Decompression Complicated by Cardiac Injury in a Prehospital Environment.

Needle decompression is a mainstay intervention for tension pneumothorax in trauma medicine. It is used in combat and prehospital medicine when definitive measures are often not available or ideal. It can temporarily relieve increased intrathoracic pressure and treat a collapsed lung or great vessel obstruction. However, when done incorrectly, it can result in underlying visceral organ and vessel trauma. This is a case of an adult male who presented to the emergency department after sustaining multiple stab wounds during an altercation. On arrival, the patient had a 14-gauge angiocatheter inserted at the 4th intercostal space (ICS), left of the parasternal line traversing the right ventricle and interventricular septum and terminating in the left ventricle. The case emphasizes the importance of understanding the landmarks of performing needle decompression in increasing the procedure's efficacy and reducing iatrogenic complications.

Combining total synthesis and genetic engineering to probe dihydropyran formation in ambruticin biosynthesis.

The ambruticins are a family of potent antifungal polyketide derived natural products isolated from the myxobacterium Sorangium cellulosum. Their unusual structures include a trisubstituted cyclopropyl group and two oxygen heterocycles, a tetrahydropyran (THP) and dihydropyran (DHP). Herein we report a flexible modular approach for the total synthesis of ambruticins which is used to prepare ambruticins F and S as well as in the first total synthesis of 20,21-dihydroambruticin F. The flexible strategy unites 3 fragments via Julia-Kocienski olefinations and provides important standards for investigation of dihydropyran formation in ambruticin biosynthesis. Cultures of wild-type S. cellulosum So ce10 produce mainly ambruticin S and the VS series of metabolites. An efficient electroporation method enabled gene knockout experiments which revealed that the ΔambP-S mutant of S. cellulosum accumulated the bisTHP polyketide 20,21-dihydroambruticin F. In contrast, the ΔambN-S mutant gave ambruticin F with the 20,21-alkene as the major metabolite confirming that AmbP and AmbO (a Rieske enzyme and flavin-dependent monooxygenase respectively) are implicated in 20,21-alkene formation. The results of feeding studies to a Sorangium strain containing only ambP and ambO are in accord with formation of the 20,21-alkene occurring prior to generation of the C3 to C7 dihydroxylated tetrahydropyran in ambruticin biosynthesis.

Defining digital surgery: a SAGES white paper.

BACKGROUND: Digital surgery is a new paradigm within the surgical innovation space that is rapidly advancing and encompasses multiple areas. METHODS: This white paper from the SAGES Digital Surgery Working Group outlines the scope of digital surgery, defines key terms, and analyzes the challenges and opportunities surrounding this disruptive technology. RESULTS: In its simplest form, digital surgery inserts a computer interface between surgeon and patient. We divide the digital surgery space into the following elements: advanced visualization, enhanced instrumentation, data capture, data analytics with artificial intelligence/machine learning, connectivity via telepresence, and robotic surgical platforms. We will define each area, describe specific terminology, review current advances as well as discuss limitations and opportunities for future growth. CONCLUSION: Digital Surgery will continue to evolve and has great potential to bring value to all levels of the healthcare system. The surgical community has an essential role in understanding, developing, and guiding this emerging field.

Initial report on special operations clinical training at a civilian academic medical center.

BACKGROUND: Military-civilian partnerships for combat casualty care skills training have mostly focused on traditional, combat surgical team training. We sought to better understand US Special Forces (SF) Medics' training at West Virginia University in Morgantown, West Virginia, a Level 1 trauma center, via assessments of medical knowledge, clinical skills confidence, and technical performance. METHODS: Special Forces Medics were evaluated using posttraining medical knowledge tests, procedural skills confidence surveys (using a 5-point Likert scale), and technical skills assessments using fresh perfused cadavers in a simulated combat casualty care environment. Data from these tests, surveys, and assessments were analyzed for 18 consecutive SF medic rotations from the calendar years 2019 through 2021. RESULTS: A total of 108 SF Medics' tests, surveys, and assessments were reviewed. These SF Medics had an average of 5.3 years of active military service; however, deployed experience was minimal (73% never deployed). Review of knowledge testing demonstrated a slight increase in mean test score between the precourse (80% ± 14%; range, 50-100%) when compared with the postcourse (82% ± 14%; range, 50-100%). Skills confidence scores increased between courses, specifically within the point of injury care ( p = 0.09) and prolonged field care ( p < 0.001). Technical skills assessments included cricothyroidotomy, chest tube insertion, and tourniquet placement. CONCLUSION: This study provides preliminary evidence supporting military-civilian partnerships at an academic Level 1 trauma center to provide specialty training to SF Medics as demonstrated by increase in medical knowledge and confidence in procedural skills. Additional opportunities exist for the development technical skills assessments. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Preoperative Weight Loss as a Predictor of Short and Midterm Postoperative Weight Loss in Patients Undergoing Bariatric Surgery.

Objective: To examine if preoperative weight loss correlates to postoperative weight loss 2 and 3 years after surgery. Methods: A review was conducted of bariatric surgery patients who underwent either gastric bypass or sleeve gastrectomy during 2015-2018 and had 3-year follow-up data. Demographic and outcome data were collected. A best-fit regression model for weight loss was constructed. Results: Eight hundred fifty-nine patients underwent surgery during the selected period, of which 199 patients (23%) were analyzed. Eighty-two percent of patients had gastric bypass and 82% were female. Preoperative percent excess weight loss (%EWL) was not significantly associated with 2- and 3-year postoperative %EWL (p = 0.18). Patients demonstrated significant weight regain at 3 years postoperatively versus 1 year (p < 0.01). Higher preoperative weight loss was associated with lower %EWL 3 years postoperatively versus 1 year (p = 0.04). Postoperative %EWL had a significant negative association with higher preoperative weight, diabetes, baseline use of a mobility device, and sleeve gastrectomy. Conclusions: In a cohort of bariatric surgery patients, there was no statistically significant association between preoperative and midterm postoperative %EWL. Postoperative %EWL was negatively associated with several patient-specific factors and increasing time since operation.

The use of an activity tracker to objectively measure inpatient activity after bariatric surgery.

BACKGROUND: Early postoperative ambulation reduces length of stay and prevents postoperative complications after bariatric surgery. Rarely is postoperative inpatient activity objectively measured despite readily available commercial activity trackers. OBJECTIVES: Evaluate the impact of using activity trackers to record number of inpatient steps taken after bariatric surgery and assess how patient characteristics may affect the number of steps recorded. SETTING: University Hospital, United States. METHODS: Using an activity tracker, the number of steps taken during the postoperative hospital stay was recorded for 235 patients undergoing either laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy. Patients were randomly assigned to either being informed about the devices' ability to record the number of steps taken or blinded to the purpose of the devices. Descriptive statistics were used to summarize study sample, a t test was used to compare number of steps recorded between groups, and a multivariate regression model was used to examine the effect of age, sex, preoperative body mass index (BMI), types of surgery, and length of stay on number of steps recorded. RESULTS: One hundred twenty-five patients (52.8%) were randomized to the blinded group while 111 (47.2%) were informed that the device would record the number of steps taken. There were no differences in the number of steps recorded between the 2 groups. Patients with prolonged length of stay recorded lower numbers of steps taken on postoperative day 0. Increasing age was seen to reduce the number of steps recorded on postoperative day number 1. There were no significant differences in number of steps recorded based on sex, preoperative BMI, or surgery type. CONCLUSION: The present study found that knowledge of an activity tracker being used did not affect the patient's activity level as measured by steps recorded. Increasing age correlated to reduced number of steps recorded on postoperative day 1 after bariatric surgery.

Emergency Laparoscopic Repair of an Iatrogenic Gastric Perforation in a Hiatal Hernia following a Failed Endoscopic Closure.

Iatrogenic gastrointestinal perforation is a rare, life-threatening complication of endoscopic procedures, which requires either endoscopic or surgical repair. We report the account of an 82-year-old woman with an iatrogenic gastric perforation of a hiatal hernia secondary to an endoscopic retrograde cholangiopancreatography (ERCP) procedure. Despite immediate recognition of the complication and endoscopic closure with through-the-scope (TTS) clips, the patient developed mediastinitis, peritonitis, and sepsis. She subsequently underwent an emergency laparoscopic hiatal hernia dissection and repair of the perforation with mediastinal and peritoneal washout. Given the patient's age and the degree of insult, subdiaphragmatic anchoring with abdominal drain placement was performed, and the hiatus was left open for additional drainage. The use of a side-viewing duodenoscope with the presence of a large hiatal hernia contributed to the risk of gastric perforation. We conclude that performing endoscopic procedures in patients with a known hiatal hernia should be carefully undertaken. If a perforation in such patients occurs, laparoscopic repair of such complications is feasible as demonstrated in this case video.

The Impact of Maternal Antibiotics on Neonatal Disease.

OBJECTIVES: We examined the impact of prenatal exposure to maternal antibiotics on risk of necrotizing enterocolitis (NEC), late onset sepsis (LOS), and death in infants born preterm. STUDY DESIGN: Secondary data analysis was conducted via an extant cohort of 580 infants born <32 weeks of gestation and enrolled in 3 level III neonatal intensive care units. Prenatal antibiotic exposure was defined as antibiotics received by the mother within 72 hours before delivery. Postnatal empiric antibiotic exposure was defined as antibiotic initiated within the first day of life without documented infection, categorized as low (<5 days) or high (>5 days) duration. RESULTS: Two-thirds of mothers received antibiotics within 72 hours before delivery, of whom 59.8% received >1 antibiotic. Ampicillin (37.6%) and azithromycin (26.4%) were the most common antibiotics given. NEC occurred in 7.5%, LOS in 11.1%, death in 9.6%, and the combined outcome of NEC, LOS, or death in 21.3% of study infants. In multiple logistic regression models adjusted for gestational age, postnatal empiric antibiotic exposure, and other factors, prenatal antibiotic exposure was associated with reduced risk of NEC (OR 0.28; 95% CI 0.14-0.56; P < .001), death (OR 0.29; 95% CI 0.14-0.60; P = .001), but not LOS (OR 1.59; 95% CI 0.84-2.99; P = .15), although protection was significant for the combined outcome (OR 0.52, P < .001). High postnatal empiric antibiotic exposure was associated with greater risk of death but not other outcomes in multiple regression models (OR 3.18, P = .002). CONCLUSIONS: Prenatal antibiotic exposure was associated with lower rates of NEC or death of infants born preterm, and its impact on infant outcomes warrants further study.

Clinician, patient and general public beliefs about diagnostic imaging for low back pain: protocol for a qualitative evidence synthesis.

INTRODUCTION: Little is known about how to reduce unnecessary imaging for low back pain. Understanding clinician, patient and general public beliefs about imaging is critical to developing strategies to reduce overuse. OBJECTIVE: To synthesise qualitative research that has explored clinician, patient or general public beliefs about diagnostic imaging for low back pain. METHODS AND ANALYSIS: We will perform a qualitative evidence synthesis of relevant qualitative research exploring clinician, patient and general public beliefs about diagnostic imaging for low back pain. Exclusions will be studies not using qualitative methods and studies not published in English. Studies will be identified using sensitive search strategies in MEDLINE, EMBASE, CINAHL, AMED and PsycINFO. Two reviewers will independently apply inclusion and exclusion criteria, extract data, and use the Critical Appraisal Skills Programme quality assessment tool to assess the quality of included studies. To synthesise the data we will use a narrative synthesis approach that involves developing a theoretical model, conducting a preliminary synthesis, exploring relations in the data, and providing a structured summary. We will code the data using NVivo. At least two reviewers will independently apply the thematic framework to extracted data. Confidence in synthesis findings will be evaluated using the GRADE Confidence in the Evidence from Reviews of Qualitative Research tool. ETHICS AND DISSEMINATION: Ethical approval is not required to conduct this review. We will publish the results in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42017076047.

Characterization of DNA Binding by the Isolated N-Terminal Domain of Vaccinia Virus DNA Topoisomerase IB.

Vaccinia TopIB (vTopIB), a 314-amino acid eukaryal-type IB topoisomerase, recognizes and transesterifies at the DNA sequence 5'-(T/C)CCTT↓, leading to the formation of a covalent DNA-(3'-phosphotyrosyl274)-enzyme intermediate in the supercoil relaxation reaction. The C-terminal segment of vTopIB (amino acids 81-314), which engages the DNA minor groove at the scissile phosphodiester, comprises an autonomous catalytic domain that retains cleavage specificity, albeit with a cleavage site affinity lower than that of the full-length enzyme. The N-terminal domain (amino acids 1-80) engages the major groove on the DNA face opposite the scissile phosphodiester. Whereas DNA contacts of the N-terminal domain have been implicated in the DNA site affinity of vTopIB, it was not known whether the N-terminal domain per se could bind DNA. Here, using isothermal titration calorimetry, we demonstrate the ability of the isolated N-terminal domain to bind a CCCTT-containing 24-mer duplex with an apparent affinity that is ∼2.2-fold higher than that for an otherwise identical duplex in which the pentapyrimidine sequence is changed to ACGTG. Analyses of the interactions of the isolated N-terminal domain with duplex DNA via solution nuclear magnetic resonance methods are consistent with its DNA contacts observed in DNA-bound crystal structures of full-length vTopIB. The chemical shift perturbations and changes in hydrodynamic properties triggered by CCCTT DNA versus non-CCCTT DNA suggest differences in DNA binding dynamics. The importance of key N-terminal domain contacts in the context of full-length vTopIB is underscored by assessing the effects of double-alanine mutations on DNA transesterification and its sensitivity to ionic strength.

Selective nonoperative management of abdominal gunshot wounds with isolated solid organ injury.

OBJECTIVE: To review selective nonoperative management (SNOM) of gunshot wound (GSW) patients with isolated abdominal solid organ injury. METHODS: Patients who sustained isolated solid organ injury secondary to GSW from 2003 to 2014 were studied. The use of SNOM over time was analyzed, and comparisons of initial SNOM and operative management (OM) groups were performed. RESULTS: Of 127 patients, 63 (50%) underwent SNOM. There were no significant differences between the early/late or SNOM/OM groups in demographics, physiologic presentation, or Injury Severity Score. SNOM increased from the early to late cohorts (31%-67%, p < 0.001), without any change in outcomes. SNOM patients had shorter hospital stays (5.8 vs. 10.0 days, p < 0.001), received fewer PRBCs (0.8 vs. 4 units, p < 0.001), and suffered fewer complications (13% vs. 28%, p < 0.05) than the OM group. CONCLUSION: An increase in SNOM vs. OM was associated with equivalent outcomes. Patients undergoing SNOM received fewer PRBCs and had shorter LOS.

Real-time imaging of intracellular hydrogen peroxide in pancreatic islets.

A real-time method to measure intracellular hydrogen peroxide (H2O2) would be very impactful in characterizing rapid changes that occur in physiologic and pathophysiologic states. Current methods do not provide the sensitivity, specificity and spatiotemporal resolution needed for such experiments on intact cells. We developed the use of HyPer, a genetic indicator for H2O2 that can be expressed in the cytosol (cyto-HyPer) or the mitochondria (mito-HyPer) of live cells. INS-1 cells or islets were permeabilized and the cytosolic HyPer signal was a linear function of extracellular H2O2, allowing fluorescent cyto-HyPer signals to be converted into H2O2 concentrations. Glucose increased cytosolic H2O2, an effect that was suppressed by overexpression of catalase. Large perturbations in pH can influence the HyPer signal, but inclusion of HEPES [4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid] in the perfusate prevented pH changes, but did not affect glucose-induced cyto-HyPer signals, suggesting that this effect is largely pH-independent. Using the assay, two fundamental questions were addressed. Knockdown of superoxide dismutase 2 (SOD2), the mitochondrial form of SOD, completely suppressed glucose-induced H2O2 Furthermore, glucose also induced mitochondrial superoxide and H2O2 production, which preceded the appearance of cytosolic H2O2 Therefore, glucose-induced H2O2 largely originated from mitochondria. Finally, the glucose-induced HyPer signal was less than 1/20th of that induced by toxic levels of H2O2 Overall, the use of HyPer for real-time imaging allowed resolution of acute changes in intracellular levels of H2O2 and will have great utility for islet studies involving mechanisms of H2O2-mediated signaling and oxidative stress.

Retrieving the real refractive index of mono- and polydisperse colloids from reflectance near the critical angle.

We investigate the accuracy in retrieving the real refractive index of submicron aerosol particles, at a visible wavelength, from near critical angle reflectance measurements of a dilute suspension of the aerosol. A coherent scattering model (CSM) is used to model the coherent reflectance from the colloidal suspension. We use an extension of the model for polydisperse particles to properly account for the modified size distribution close to the incident medium to colloid interface. We perform a rigorous sensitivity analysis, for both the monodisperse and polydisperse models, to determine how experimental uncertainties propagate into uncertainty in the retrieval of real refractive index. The effect of non-spherical scattering was included in the sensitivity analysis by using T-matrix methods. Experimental reflectance data, at a wavelength of 635 nm, were obtained for monodisperse spherical latex particles, a polydisperse sand sample and a polydisperse volcanic ash sample. We show that the retrieved real refractive index for these particles is consistent with values obtained using other techniques.

Dynamic Sumoylation of a Conserved Transcription Corepressor Prevents Persistent Inclusion Formation during Hyperosmotic Stress.

Cells are often exposed to physical or chemical stresses that can damage the structures of essential biomolecules. Stress-induced cellular damage can become deleterious if not managed appropriately. Rapid and adaptive responses to stresses are therefore crucial for cell survival. In eukaryotic cells, different stresses trigger post-translational modification of proteins with the small ubiquitin-like modifier SUMO. However, the specific regulatory roles of sumoylation in each stress response are not well understood. Here, we examined the sumoylation events that occur in budding yeast after exposure to hyperosmotic stress. We discovered by proteomic and biochemical analyses that hyperosmotic stress incurs the rapid and transient sumoylation of Cyc8 and Tup1, which together form a conserved transcription corepressor complex that regulates hundreds of genes. Gene expression and cell biological analyses revealed that sumoylation of each protein directs distinct outcomes. In particular, we discovered that Cyc8 sumoylation prevents the persistence of hyperosmotic stress-induced Cyc8-Tup1 inclusions, which involves a glutamine-rich prion domain in Cyc8. We propose that sumoylation protects against persistent inclusion formation during hyperosmotic stress, allowing optimal transcriptional function of the Cyc8-Tup1 complex.

A Conserved Deubiquitinating Enzyme Uses Intrinsically Disordered Regions to Scaffold Multiple Protein Interaction Sites.

In the canonical view of protein function, it is generally accepted that the three-dimensional structure of a protein determines its function. However, the past decade has seen a dramatic growth in the identification of proteins with extensive intrinsically disordered regions (IDRs), which are conformationally plastic and do not appear to adopt single three-dimensional structures. One current paradigm for IDR function is that disorder enables IDRs to adopt multiple conformations, expanding the ability of a protein to interact with a wide variety of disparate proteins. The capacity for many interactions is an important feature of proteins that occupy the hubs of protein networks, in particular protein-modifying enzymes that usually have a broad spectrum of substrates. One such protein modification is ubiquitination, where ubiquitin is attached to proteins through ubiquitin ligases (E3s) and removed through deubiquitinating enzymes. Numerous proteomic studies have found that thousands of proteins are dynamically regulated by cycles of ubiquitination and deubiquitination. Thus, how these enzymes target their wide array of substrates is of considerable importance for understanding the function of the cell's diverse ubiquitination networks. Here, we characterize a yeast deubiquitinating enzyme, Ubp10, that possesses IDRs flanking its catalytic protease domain. We show that Ubp10 possesses multiple, distinct binding modules within its IDRs that are necessary and sufficient for directing protein interactions important for Ubp10's known roles in gene silencing and ribosome biogenesis. The human homolog of Ubp10, USP36, also has IDRs flanking its catalytic domain, and these IDRs similarly contain binding modules important for protein interactions. This work highlights the significant protein interaction scaffolding abilities of IDRs in the regulation of dynamic protein ubiquitination.

A conserved deubiquitinating enzyme controls cell growth by regulating RNA polymerase I stability.

Eukaryotic ribosome biogenesis requires hundreds of trans-acting factors and dozens of RNAs. Although most factors required for ribosome biogenesis have been identified, little is known about their regulation. Here, we reveal that the yeast deubiquitinating enzyme Ubp10 is localized to the nucleolus and that ubp10Δ cells have reduced pre-rRNAs, mature rRNAs, and translating ribosomes. Through proteomic analyses, we found that Ubp10 interacts with proteins that function in rRNA production and ribosome biogenesis. In particular, we discovered that the largest subunit of RNA polymerase I (RNAPI) is stabilized via Ubp10-mediated deubiquitination and that this is required in order to achieve optimal levels of ribosomes and cell growth. USP36, the human ortholog of Ubp10, complements the ubp10Δ allele for RNAPI stability, pre-rRNA processing, and cell growth in yeast, suggesting that deubiquitination of RNAPI may be conserved in eukaryotes. Our work implicates Ubp10/USP36 as a key regulator of rRNA production through control of RNAPI stability.