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BACKGROUND/PURPOSE The utility of thrombelastography (TEG) in pediatric trauma remains unknown, and differences in coagulopathy between blunt and penetrating mechanisms are not established. We aimed to compare TEG patterns in pediatric trauma patients with blunt solid organ injuries (BSOI) and penetrating injuries to determine the role of mechanism in coagulopathy. METHODS Highest-level pediatric trauma activations with BSOI or penetrating injuries and admission TEG at two pediatric trauma centers were included. TEG abnormalities were defined by each institution's normative values and compared separately by injury mechanism and evidence of shock (elevated SIPA) using Kruskal-Wallis or Fisher's exact tests. RESULTS Of 118 patients included, 64 had BSOI and 54 had penetrating injuries. There were no significant differences in TEG abnormalities between the BSOI and penetrating injury groups. Patients with shock were more likely to have decreased alpha-angles (30.9% vs. 8.0%, p = 0.01) and decreased maximum amplitude (MA) (44.1% vs. 8.0%, p

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio was significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the Pao2 to Fio2 ratio at 48 h (16.9% [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www.clinicaltrials.gov.

Colorectal liver metastases (CRLM) are the most common cause of disease-specific mortality in patients with colorectal cancer. Hepatic artery infusion (HAI) combined with systemic chemotherapy improves survival for these patients. The safety of colorectal resection at the time of HAI pump placement has not been well established. Patients with CRLM who underwent combined HAI pump placement and colorectal (primary) resection or HAI pump placement alone were evaluated for perioperative outcomes, pump-specific complications, infectious complications, and time to treatment initiation. These outcomes were compared using comparative statistics. Patients who underwent combined HAI pump placement and primary resection (n = 19) vs HAI pump placement alone (n = 13) had similar demographics and rates of combined hepatectomy. Combined HAI pump placement and primary resection group had similar operative time and blood loss (both p = NS), but longer length of stay (6 vs 4 days, p = 0.02) compared to pump placement alone. Overall postoperative complications (21% vs 8%) and pump-specific complications (16% vs 31%) were similar (both p = NS). Infection rates were not different between groups, nor was time to initiation of HAI therapy (19 vs 16 days p = NS), or systemic therapy (34 vs 35 days p = NS). Combining colorectal resection with HAI pump implantation is a safe surgical approach for management of unresectable CRLM. Postoperative complications, specifically infectious complications, were not increased, nor was there a delay to initiation of HAI or systemic chemotherapy. Investigation of long-term oncologic outcomes for HAI pump placement and primary tumor resection in patients with unresectable CRLM is ongoing.

[18F]NaF PET measurements of bone metabolic flux (Ki) are conventionally obtained with 60-min dynamic scans analysed using the Hawkins model. However, long scan times make this method expensive and uncomfortable for subjects. Therefore, we evaluated and compared measurements of Ki with shorter scan times analysed with fixed values of the Hawkins model rate constants. The scans were acquired in a trial in 30 postmenopausal women, half treated with teriparatide (TPT) and half untreated. Sixty-minute PET-CT scans of both hips were acquired at baseline and week 12 after injection with 180 MBq [18F]NaF. Scans were analysed using the Hawkins model by fitting bone time–activity curves at seven volumes of interest (VOIs) with a semi-population arterial input function. The model was re-run with fixed rate-constants for dynamic scan times from 0–12 min increasing in 4-min steps up to 0–60 min. Using the Hawkins model with fixed rate-constants, Ki measurements with statistical power equivalent or superior to conventionally analysed 60-min dynamic scans were obtained with scan times as short as 12 min.

Purpose Mothers often request guidance on when it is safe to resume breastfeeding after surgery. At our institution, this guidance was inconsistent and not well-grounded in current research. This project sought to bring recommendations to patients in line with current evidence about when to recommend resumption of breastfeeding after surgery. Design A local practice guideline was developed based on our systematic review, then staff were educated about the guideline. Methods Transfer to clinical practice was measured by reported practice recommendations. A repeated measures design measured change in provider knowledge, recommendations, and confidence in these recommendations. A follow-up assessment was conducted at 2 years to measure long-term impact. Findings After the educational session, there was a two-fold increase in the number of perianesthesia staff who recommended resumption of breastfeeding as soon as the mother had recovered from anesthesia. Conclusions This evidence-based practice project standardized delivery of breastfeeding recommendations by perioperative staff.

Background Hemorrhage is the leading cause of preventable death in pediatric trauma patients. In adults, goal-directed thrombelastography (TEG) has been shown to reduce mortality when used to guide massive transfusion (MT) resuscitation. There remains a paucity of data on the utility of TEG in directing resuscitation of pediatric trauma patients. We hypothesize that abnormalities on admission TEG will differ in pediatric trauma patients who undergo MT, compared to those who do not. Methods Pediatric patients (≤ 18 years) who were highest level trauma activations at two trauma centers from 2015 to 2018 were analyzed. We included patients who had admission TEGs and excluded those who did not. Patients were stratified into two groups: those who received MT (> 40 cc/kg total blood product within 6 h of admission) and those who did not. We defined TEG abnormalities based on each institution’s normative values and compared TEG abnormalities between the groups. Results Of 117 children included, 39 had MT. MT patients had higher injury severity scores (30 vs. 23, p = 0.0004), lactates levels (7.0 vs. 3.5, p

Thrombelastography (TEG) has emerged as a useful tool to diagnose coagulopathy and guide blood product usage during trauma resuscitations. This study sought to evaluate the correlation between TEG-directed blood product administration in severely injured pediatric trauma patients with blunt solid organ injuries (BSOIs).Patients (≤18 years) with severe BSOIs who presented as highest-level trauma activations at two pediatric trauma centers were included. Thrombelastography results were evaluated to determine indications for blood product administration and rates of TEG-directed resuscitation. Tetrachoric correlations and regression modeling were used to correlate TEG-directed resuscitation with clinical outcomes.Of 64 patients who met the inclusion criteria, 32.8% (21) had elevated R times and 23.4% (15) had shortened α angles. Maximum amplitude was shortened in 29.7% (19), and percent clot lysis 30 minutes after maximum amplitude that is3% was seen in 17.0% (9). Thrombelastography-directed resuscitation of fresh frozen plasma was followed 54.7% of the time compared with 67.2% and 81.2% for platelets and cryoprecipitate, respectively. Thrombelastography-directed resuscitation with platelets (odds ratio, 0.56; 95% confidence interval, 0.33-0.93; p = 0.03) and/or cryoprecipitate (odds ratio, 0.09; 95% confidence interval, 0.01-0.42, p = 0.003) were associated with decreased hospital length of stay and mortality, respectively.Severely injured pediatric trauma patients with BSOIs were often coagulopathic upon presentation to the emergency department. Thrombelastography-directed resuscitation with platelets and/or cryoprecipitate was followed for the majority of patients and was associated with improved outcomes.Therapeutic/Care Management, level III.

Purpose This study aims to assess the efficacy and safety of intranasal (IN) esketamine as maintenance antidepressant therapy in patients who have demonstrated clinical improvement with off-label intravenous (IV) racemic ketamine for treatment-resistant depression (TRD). Methods This is a retrospective case series of 10 consecutive outpatients with TRD who all had a clinically meaningful response when treated with IV racemic ketamine and were then switched to IN esketamine for maintenance therapy. Patient outcomes were assessed with the Montgomery-Asberg Depression Rating Scale, Patient Health Questionnaire 9, and Clinical Global Impression of Improvement scale at each visit. Adverse effects were assessed at each treatment. Findings Results indicated that 9 patients either maintained the benefit or showed greater improvement when transitioned to IN esketamine for antidepressant maintenance therapy. One patient had worsening of depression due to an acute psychosocial stressor but still improved from baseline IV racemic ketamine treatment. Six patients returned to work or pursued employment, and 4 patients with suicidal ideation remitted during IV racemic ketamine treatment and had no recurrence of suicidality with IN esketamine. No serious adverse reactions or tolerability issues were observed. Implications This case series reports the outcomes of 10 severely ill patients with TRD who had a clinically meaningful response to IV racemic ketamine and demonstrated a maintenance of effect or continued improvement when transitioned to IN esketamine. Although this finding needs to be replicated in larger, controlled studies, this report provides promising results for patients who have safely and effectively switched to Food and Drug Administration-approved IN esketamine after receiving acute or maintenance depression treatment with off-label IV racemic ketamine.

Millions of people who survive sepsis each year are rehospitalized and die due to late pulmonary complications. To prevent and treat these complications, biomarkers and molecular mediators must be identified. Persistent immune reprogramming in the form of immunoparalysis and impaired host defense is proposed to mediate late pulmonary complications after sepsis, particularly new pulmonary infections. However, immune reprogramming may also involve enhanced/primed responses to secondary stimuli, although their contribution to long-term sepsis complications remains understudied. We hypothesize that enhanced/primed immune responses in the lungs of sepsis survivors are associated with late pulmonary complications. To this end, we developed a murine sepsis model using cecal ligation and puncture (CLP) followed 3 wk later by administration of intranasal lipopolysaccharide to induce inflammatory lung injury. Mice surviving sepsis exhibit enhanced lung injury with increased alveolar permeability, neutrophil recruitment, and enhanced Ly6Chi monocyte Tnf expression. To determine the mediators of enhanced lung injury, we performed flow cytometry and RNA sequencing of lungs 3 wk after CLP, prior to lipopolysaccharide. Sepsis survivor mice showed expanded Ly6Chi monocytes populations and increased expression of many inflammatory genes. Of these, S100A8/A9 was also elevated in the circulation of human sepsis survivors for months after sepsis, validating our model and identifying S100A8/A9 as a potential biomarker and therapeutic target for long-term pulmonary complications after sepsis. These data provide new insight into the importance of enhanced/primed immune responses in survivors of sepsis and establish a foundation for additional investigation into the mechanisms mediating this response.

Objective: To assess the impact of the temporary cessation of orthodontic services on patients undergoing treatment during the COVID-19 pandemic. Design: Two-phase multicentre service evaluation. Setting: Secondary care orthodontic departments in the South West of England. Materials and Methods: Phase 1 – Patient-Reported Experience Measure questionnaire (PREM). The questionnaire was distributed to patients who had undergone orthodontic treatment during the COVID-19 pandemic once services had resumed. Phase 2 – assessment of treatment outcomes, specifically with the Peer Assessment Rating (PAR) Index. A total of 280 PAR scores were obtained from a cohort of patients treated before and during the pandemic. Results: A total of 711 PREM questionnaires were completed. Participants generally felt relaxed when visiting secondary care settings, orthodontic departments and whilst wearing orthodontic appliances during the pandemic. Nearly 40% of participants were concerned that the pandemic would impact on their treatment, particularly treatment length. Treatment outcomes revealed that patients treated before and during the pandemic experienced percentage PAR score reductions of 83.9% and 80.6%, respectively. Patients receiving treatment during the pandemic experienced longer treatment durations of 126 days. Conclusion: During the pandemic, low levels of anxiety were reported with respect to receiving orthodontic treatment in secondary care settings. Irrespective of the pandemic, a high standard of orthodontic treatment was provided. However, patient concerns regarding treatment length were justified.

This review describes the mechanisms underlying trauma-induced coagulopathy (TIC) and the current strategies to measure and mitigate the negative effects of TIC during the initial stages of trauma resuscitation and care. Trauma patients can manifest both early hypocoagulable and later hypercoagulable phenotypes. These are not fixed states and patient transition between states postinjury. Recent trends in resuscitation, driven by the military experience, have promoted the return to whole blood as the initial resuscitative fluid in the severely injured patient, but goal-directed blood product administration remains critically important to restore coagulation homeostasis and avoid microvascular thrombotic events. As our understanding of TIC improves, we anticipate that whole blood resuscitation will replace empiric ratios for the severely injured patient with uncontrolled cavitary bleeding with a transition to goal-directed resuscitation and de-escalation of blood product administration once mechanical hemostasis is achieved.

BACKGROUND: Severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency (ADA-SCID) is a rare and life-threatening primary immunodeficiency. METHODS: We treated 50 patients with ADA-SCID (30 in the United States and 20 in the United Kingdom) with an investigational gene therapy composed of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a self-inactivating lentiviral vector encoding human ADA. Data from the two U.S. studies (in which fresh and cryopreserved formulations were used) at 24 months of follow-up were analyzed alongside data from the U.K. study (in which a fresh formulation was used) at 36 months of follow-up. RESULTS: Overall survival was 100% in all studies up to 24 and 36 months. Event-free survival (in the absence of reinitiation of enzyme-replacement therapy or rescue allogeneic hematopoietic stem-cell transplantation) was 97% (U.S. studies) and 100% (U.K. study) at 12 months; 97% and 95%, respectively, at 24 months; and 95% (U.K. study) at 36 months. Engraftment of genetically modified HSPCs persisted in 29 of 30 patients in the U.S. studies and in 19 of 20 patients in the U.K. study. Patients had sustained metabolic detoxification and normalization of ADA activity levels. Immune reconstitution was robust, with 90% of the patients in the U.S. studies and 100% of those in the U.K. study discontinuing immunoglobulin-replacement therapy by 24 months and 36 months, respectively. No evidence of monoclonal expansion, leukoproliferative complications, or emergence of replication-competent lentivirus was noted, and no events of autoimmunity or graft-versus-host disease occurred. Most adverse events were of low grade. CONCLUSIONS: Treatment of ADA-SCID with ex vivo lentiviral HSPC gene therapy resulted in high overall and event-free survival with sustained ADA expression, metabolic correction, and functional immune reconstitution. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT01852071, NCT02999984, and NCT01380990.)

With the concern of concussion risk and repetitive head impacts in youth football, organizations have adopted rules that limit contact during practice. However, rule changes are not ubiquitous among organizations and are challenging to monitor and enforce. Ultimately, football practice activities are determined by coaches, but it is unknown whether providing objective data to coaches relating activities to their athletes' head impact exposure (HIE) would alter practice structure or help reduce HIE. This study evaluated the effect of coach awareness of HIE on practice structure over time. Head impact data from three intervention (56 players) and three control (38 players) teams were collected over two youth football seasons. Athletes were instrumented with the Head Impact Telemetry (HIT) System and time-synchronized video was recorded for practices and games. Impact frequencies and head accelerations were compiled into weekly HIE practice and game reports and shared with the head coach of each intervention team. Time per drill, impact rate, and impact magnitude were compared across three time frames (pre-season, mid-season, and late-season) using generalized linear models. Control teams had higher impact rates than intervention teams in all drills across time frames. Among all teams, 95th percentile linear and rotational accelerations were highest during mid-season. Among intervention teams, more time was spent on scrimmage and skill development from pre-season to late-season, with less time spent on tackling. This study suggests that receiving objective data informing HIE in practice may contribute to changes in practice structure and help inform intervention efforts to improve head impact safety in football.

Recent data reported that 21.5% of medical students in the United States of America (USA) are Asian American (AA). With the growing focus on developing medical school wellness programs, authors conducted a systematic, nationwide survey to assess prevalence of depression among AA medical students with a focus on disaggregating the AA population. A survey tool comprised of PHQ-9 and depression history, and questions on social support were emailed to members of the Asian Pacific American Medical Students Association enrolled in a USA medical school during the 2016–2017 academic year. Participants were grouped as East Asian American (EAA), Southeast Asian American (SEAA), and South Asian American (SAA). We evaluated associations between depression and regional ethnicity, depression history, and perceived support. A total of 457 AA medical students were surveyed. SAA medical students were more likely to endorse symptoms of depression than EAA students. Students who identified as female were more likely to endorse symptoms of depression than their male-identifying counterparts. There was no significant relationship between students’ perception of the support they received and their depressive symptoms. Medical school administration should be aware of the unique needs of the heterogeneous population that comprises AA medical students. SAA students and those who identify as female are more likely to endorse symptoms of depression than their AA counterparts. Further research must be done to evaluate the factors that influence the mental health needs of AA medical students.

[18F]NaF PET imaging is a useful tool for measuring regional bone metabolism. However, due to tracer in urine, [18F]NaF PET images of the hip reconstructed using filtered back projection (FBP) frequently show streaking artifacts in slices through the bladder leading to noisy time-activity curves unsuitable for quantification. This study compares differences between quantitative outcomes at the hip derived from images reconstructed using the FBP and ordered-subset expectation maximization (OSEM) methods. Dynamic [18F]NaF PET data at the hip for four postmenopausal women were reconstructed using FBP and nine variations of the OSEM algorithm (all combinations of 1, 5, 15 iterations and 10, 15, 21 subsets). Seven volumes of interest were placed in the hip. Bone metabolism was measured using standardized uptake values, Patlak analysis (Ki-PAT) and Hawkins model Ki-4k. Percentage differences between the standardized uptake values and Ki values from FBP and OSEM images were assessed. OSEM images appeared visually smoother and without the streaking artifacts seen with FBP. However, due to loss of counts, they failed to recover the quantitative values in VOIs close to the bladder, including the femoral head and femoral neck. This was consistent for all quantification methods. Volumes of interest farther from the bladder or larger and receiving greater counts showed good convergence with 5 iterations and 21 subsets. For VOIs close to the bladder, including the femoral neck and femoral head, 15 iterations and 10, 15 or 21 subsets were not enough to obtain OSEM images suitable for measuring bone metabolism and showed no improvement compared to FBP.

Background Intrathecal morphine provides effective analgesia after cesarean birth, yet up to 90% of women who receive it experience excessive itching, an undesirable dose-dependent effect. Pruritis may increase nursing workload, delay breastfeeding, and decrease patient satisfaction. When 0.1 mg spinal morphine is given, pruritis is markedly reduced while analgesia is preserved. Purpose The purpose of this project was to determine possible causes and solutions for pruritus after cesarean birth. Methods Anesthesia providers were educated and encouraged to limit spinal morphine to 0.1 mg as a strategy to prevent pruritus. In a repeated measures design, the rate of treatment-required pruritus and opioid consumption were measured 24 hours after surgery. The project included an evaluation of 30 medical records before and 30 medical records after the project intervention. Results Preintervention rate of treatment-required pruritis was 37%, all received spinal morphine ≥ 1.5 mg. Postintervention rate of treatment-required pruritis was 13% and 57% after spinal morphine 0.1 mg and 0.2 mg, respectively. Opioid consumption was similar between groups. Clinical implications Mother-baby nurses can have an impact on the practice of anesthesia providers by advocating for evidence-based dosing of intrathecal morphine to reduce the incidence of pruritis while maintaining effective analgesia for women after cesarean birth.

Background Improvements in health care innovations have resulted in an enhanced ability to extend patient viability. As a consequence, resources are being increasingly utilized at an unsustainable level. As we implement novel treatments, identifying futility should be a focus. The “death diamond” (DD) is a unique thrombelastography (TEG) tracing that is indicative of failure of the coagulation system, with a mortality rate exceeding 90%. The purpose of this study was to determine if the DD was a consistent marker of poor survival in a multicenter study population. We hypothesize that the DD, while an infrequent occurrence, predicts poor survival and can be used to stratify patients in whom resuscitation efforts are futile. Methods A retrospective multi-institutional study of trauma patients presenting with TEG DDs between 8/2008 and 12/2018 at four American College of Surgeons trauma centers was completed. Demographics, injury mechanisms, TEG results, management, and survival were examined. Results A total of 50 trauma patients presented with DD tracings, with a 94% (n = 47) mortality rate. Twenty-six (52%) patients received a repeat TEG with 10 patients re-demonstrating the DD tracing. There was 100% mortality in patients with serial DD tracings. The median use of total blood products was 18 units (interquartile range 6, 34.25) per patient. Discussion The DD is highly predictive of trauma-associated mortality. This multicenter study highlights that serial DDs may represent a possible biomarker of futility.

Purpose:The time between radiographic identification of a renal tumor and surgery can be concerning for patients and clinicians due to fears of tumor progression while awaiting treatment. This stud...

Liver grafts from pediatric donors represent a small fraction of grafts transplanted into adult recipients, and their use in adults requires special consideration of donor size to prevent perioperative complications. In the past, graft weight or volume ratios have been adopted from the living donor liver transplant literature to guide clinicians; however, these metrics are not regularly available to surgeons accepting deceased donor organs. In this study, we evaluated all pediatric-to-adult liver transplants in the United Network for Organ Sharing Standard Transplant Analysis and Research database from 1987 to 2019, stratified by donor age and donor-recipient height mismatch ratio (HMR; defined as donor height/recipient height). On multivariable regression controlling for cold ischemia time, age, and transplantation era, the use of donors from ages 0 to 4 and 5 to 9 had increased risk of graft failure (hazard ratio [HR], 1.81 [P

Background End stage renal disease (ESRD) is associated with elevated fibrinogen levels and fibrinolysis inhibition. However, there is a paucity of data on how renal transplantation impacts coagulation. we hypothesize that renal transplantation recipients with good functioning grafts will have improved fibrinolytic activity following surgery. Methods Kidney recipients were analyzed pre-operatively and on post-operative day 1(POD1) using three different TEG assays with and without two concentration of tissue-plasminogen activator (t-PA). TEG indices and percent reduction in creatinine from pre-op to POD1 were measured, with >50% defining “good” graft function. Follow up was done at 6, 12, and 24 months. Results Percent lysis(LY30) on POD1 the t-PA TEG was significantly correlated to change creatinine from pre-op to POD-1(p = 0.006). A LY30 ≥ 23% was associated with good early graft function, and lower creatinine at 24-months(p = 0.028) compared to recipients with low POD1 LY30. Conclusions Post-operative tPA-TEG LY30 is associated with favorable early and late outcomes in kidney transplant., Highlights • Thromboelastography (TEG) identifies coagulation changes in renal transplant. • Percent lysis on post-op t-PA TEG significantly correlates with graft function. • Post-op fibrinolysis plays a key role in early and late renal graft function.

Introduction During the anhepatic phase of liver transplantation (LT), fibrinolytic activity increases, since the liver clears tissue plasminogen activator (tPA). We hypothesize that patients who fail to reduce fibrinolytic activity following graft reperfusion will have an increased rate of early allograft dysfunction (EAD). Methods Assessment of fibrinolysis in liver transplant recipients was quantified with thrombelastography (TEG) LY30. Changes in LY30 were assessed after graft reperfusion. The 30-min post-reperfusion LY30 was subtracted from the anhepatic LY30 quantifying fibrinolytic changes (delta-LY30). Results Seventy-three primary LT patients were included in the analysis. Receiver operating characteristic curve (ROC) analysis identified an inflection point of delta-LY30–5.3% as a risk factor for EAD. EAD occurred in 44% of these patients compared to 5% in high delta-LY30 (p = 0.002). Conclusion LT recipients that develop hyperfibrinolysis who fail to reduce fibrinolytic activity 30 min after graft reperfusion had an EAD rate 8-fold higher than patients who had a large reduction in LY30 following reperfusion.

In this study, we describe refinements of an accepted technique made by a single surgeon for trapeziectomy and suture suspension arthroplasty for thumb carpometacarpal (CMC) osteoarthritis after 220 cases over 4 years. Results are derived from 77 patients who underwent treatment using this technique comparing postoperative results with preoperative assessment and had sufficient data for inclusion. The surgical technique is described, including tips and modifications to avoid known possible complications. All patients in this study had advanced Eaton stage III or IV osteoarthritis. Grip strength and key pinch showed statistically significant improvement, and the improvement in palmar pinch approached significance. Pain scores were significantly decreased with over 50% of the patients rating their pain at 0 postoperatively. The overall complication rate was very low, and improvements in technique were made to mitigate future occurrence. This surgical technique for the treatment of thumb CMC arthritis achieved pain relief and recreated ligamentous support of the base of the first metacarpal to resist proximal migration after trapeziectomy, providing an increase in grip strength and key pinch with return of range of motion early in the postoperative period. Refinements on this technique through a large volume single surgeon experience provide technical tips for optimizing outcomes.

BACKGROUND Trauma patients with hyperfibrinolysis and depletion of fibrinolytic inhibitors (DFIs) measured by thrombelastography (TEG) gain clot strength with TXA, but TEG results take nearly an hour. We aimed to develop an assay, plasmin TEG (P-TEG), to more expeditiously stratify risk for massive transfusion (MT), mortality, and hyperfibrinolysis. METHODS Trauma patients (N = 148) were assessed using TEG assays without exogenous additives (rapid/native), with exogenous plasmin (P-TEG) or tissue plasminogen activator (tPA TEG). The plasmin dose used does not effect healthy-control clot lysis 30 minutes after maximum amplitude (LY30) but causes shortened reaction time (R time) relative to native TEG (P-TEG R time < native TEG R time considered P-TEG negative). If P-TEG R time is greater than or equal to native TEG R time, the patient was considered P-TEG positive. Each assay's ability to predict MT, mortality, and (risk for) hyperfibrinolysis was determined. χ and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Results were reported as median ± interquartile range or n (%). RESULTS Plasmin TEG provided results faster than all other assays (4.7 ± 2.5-9.1 minutes), approximately 11-fold faster than rapid-TEG (rTEG) LY30 (54.2 ± 51.1-58.1 minutes; p < 0.001). Plasmin TEG-positive patients had greater than fourfold higher MT rate (30% vs. 7%; p = 0.0015) with an area under the receiver operating characteristic curve of 0.686 (p = 0.028), greater than fourfold higher 24-hour mortality (33.3% vs. 7.8%; p = 0.0177), greater than twofold higher 30-day mortality (35% vs. 16.4%; p = 0.0483), higher rates of DFI (55% vs. 18%; p < 0.001), and a trend toward elevated D-dimer (19.9 vs. 3.3 μg/mL; p = 0.14). Plasmin TEG was associated with hyperfibrinolysis on rTEG LY30 at the 7.6% threshold (p = 0.04) but not the 3% threshold (p = 0.40). Plasmin TEG performed best in relation to DFI, with a positive predictive value of 58% and negative predictive value of 81%. When combined with tPA TEG time to maximum amplitude, P-TEG outperformed rTEG LY30 for predicting MT (area under the receiver operating characteristic curve, 0.811 vs. 0.708). CONCLUSION Within 5 minutes, P-TEG can stratify patients at highest risk for MT, mortality, and risk for hyperfibrinolysis. In composite with tPA TEG time to maximum amplitude, P-TEG outperforms rTEG LY30 for predicting MT and does so four times faster (12.7 vs. 54.1 minutes). The rapid results of P-TEG may be useful for those who practice selective TXA administration to maximize TXA's time-dependent efficacy. LEVEL OF EVIDENCE Diagnostic test, level V.

Weight stigma is defined as the social devaluation of people with overweight or obesity, and its negative effects on the health of adolescents from western countries are well documented, but little is known about the relationships with health behaviors and outcomes in Asian youth. The prevalence of obesity among Chinese adolescents continues to increase, potentially causing negative evaluations of youth with obesity, and potentially reduced quality of life. The health effects of these negative evaluations of Chinese youth with obesity have received little attention. The purpose of this study was to examine relationships between weight stigma, stress, depression, and sleep in Chinese adolescents. We utilized a cross-sectional study conducted in Wuhan, China. Sociodemographic, weight stigma, stress, depression, and sleep data were collected through a self-reported questionnaire. Descriptive statistics, t test, correlations, and mediation analyses were performed. A total of 1626 adolescents between 14 and 19 years of age were included in the analysis. The data showed that adolescents with weight stigma presented significantly higher level of stress and depression, lower global sleep quality, longer sleep latency, and shorter sleep duration than those without weight stigma (p

Introduction Evidence supports the use of plasma-first resuscitation in the treatment of trauma-induced coagulopathy (TIC). While thawed plasma (TP) has logistical benefits, the ability of plasma proteins to attenuate fibrinolysis and correct TIC remain unknown. We hypothesize that TP retains the ability to inhibit tissue plasminogen activator(tPA)-induced fibrinolysis at 28-day storage. Methods Healthy volunteers underwent blood draws followed by 50% dilution of whole blood (WB) with TP at 28-, 21-, 14-, 7-, 5-, and, 0-day storage, normal saline (NS), and WB control. Samples underwent citrated tPA-challenge (75 ng/ml) thromboelastography (TEG). Plasminogen activator inhibitor-1 (PAI-1) and α2 -antiplasmin (α2 -AP) concentrations in thawed or stored plasma were determined. Results In the presence of tPA, 28-day TP inhibited tPA-induced coagulopathy as effectively as WB. 28-day TP had a similar R-time, MA, and fibrinolysis (P > 0·05 for all) compared to WB, while angle was enhanced (P = 0·02) compared to WB. Significant correlations were present between storage time and clot strength (P = 0·04) and storage time and fibrinolysis (P = 0·0029). Active PAI-1 levels in thawed plasma were 1·10 ± 0·54 ng/mL while total PAI-1 levels were 4·79 ± 1·41 ng/mL. There was no difference of α2 -AP levels in FFP (40·45 ± 3·5 μg/mL) compared to plasma thawed for 14 (36·78 ± 5·39 μg/mL, P = 0·65) or 28 days (45·16 ± 5·61 μg/mL, P = 0·51). Discussion Thawed plasma retained the ability to inhibit tPA-induced fibrinolysis over 28-day storage at 1-4°C. α2 -AP levels were maintained in plasma thawed for 28 days and FFP. These in vitro results suggest consideration should be made to increasing the storage life of TP.

In response to the economic shock induced by the COVID-19 pandemic, Congress passed the $2 trillion Coronavirus Aid, Relief, and Economic Security (CARES) Act. Using household data on savings, income and expenses from the Survey of Consumer Finances, we show that cash assistance included in the CARES Act –namely, unemployment insurance benefit expansions and stimulus payments-- are instrumental in allowing almost all families to cover their recurring, non-discretionary expenses in the event of long-term unemployment. In the absence of such substantial government support, we document that nearly half of families who lose their income for six months would not be able to cover their expenses due to low levels of liquid savings and standard UI benefits that typically fall well below full replacement of income. Even though the increased UI payments expire after four months, because these benefits substantially exceed lost earnings for many workers, they have the potential to help households cover expenses well beyond four months by allowing otherwise paycheck-to-paycheck families to save.

Highlights • Patients having COVID-19 pneumonia are at risk of venous thromboembolism. • Prophylaxis versus anticoagulation for severely ill patients is currently debated. • No specific guidelines for the management of severe pulmonary embolism exist. • Endovascular pulmonary embolism therapy may play a critical role in severe COVID-19.

Forthcoming article in: Research and Practice in Thrombosis and Haemostatis., Background The COVID‐19 pandemic has caused a large surge of acute respiratory distress syndrome (ARDS). Prior phase I trials (non COVID‐19) demonstrated improvement in pulmonary function in ARDS patients using fibrinolytic therapy. A follow‐up trial using the widely available tissue‐plasminogen activator (alteplase) is now needed to assess optimal dosing and safety in this critically ill patient population. Objective To describe the design and rationale of a Phase IIa trial to evaluate the safety and efficacy of alteplase treatment for moderate/severe COVID‐19‐induced ARDS. Patients/Methods A rapidly adaptive, pragmatic, open label, randomized, controlled, phase IIa clinical trial will be conducted with three groups: intravenous(IV) alteplase 50mg, IV alteplase 100mg, and control (standard‐of‐care). Inclusion criteria are known/suspected COVID‐19 infection with PaO2/FiO2 ratio4 hours despite maximal mechanical ventilation management. Alteplase will be delivered through an initial bolus of 50mg or 100mg followed by heparin infusion for systemic anticoagulation, with alteplase re‐dosing if there is a >20% PaO2/FiO2 improvement not sustained by 24 hours. Results The primary outcome is improvement in PaO2/FiO2 at 48 hours post‐randomization. Other outcomes include: ventilator‐ and ICU‐free‐days, successful extubation (no reintubation ≤3 days after initial extubation), and mortality. Fifity eligible patients will be enrolled in a rapidly adaptive, modified stepped‐wedge design with four looks at the data. Conclusion Findings will provide timely information on the safety, efficacy and optimal dosing of tPA to treat moderate/severe COVID‐19‐induced ARDS, which can be rapidly adapted to a phase III trial., National Institutes of Health (Grant UL1 RR025780)

Trauma with hemorrhagic shock causes massive tissue plasminogen activator release, plasmin generation, and hyperfibrinolysis. Tranexamic acid (TXA) has recently been used to treat bleeding in trauma by preventing plasmin generation to limit fibrinolysis. Trauma patients also have increased complement activation that correlates with mortality and organ failure, but the source of activation is not clear, and plasmin has recently been shown to efficiently cleave C3 and C5 to their activated fragments. We hypothesized that trauma patients in hemorrhagic shock with hyperfibrinolysis on thromboelastography (TEG) LY30 would have increased complement activation at early time points, as measured by soluble C5b-9 complex, and TXA would prevent this. Plasma samples were obtained from an unrelated, previously performed IRB-approved prospective randomized study of trauma patients. Three groups were studied with n = 5 patients in each group: patients without hyperfibrinolysis (TEG LY30 3%) (who therefore did not get TXA), patients with hyperfibrinolysis (TEG LY30 3%) who did not get TXA, and patients with hyperfibrinolysis who were then treated with TXA. We found that patients who did not receive TXA, regardless of fibrinolytic phenotype, had elevated soluble C5b-9 levels at 6 h relative to emergency department levels. In contrast, all five patients with initial TEG LY30 more than 3% and were then treated with TXA had reduced soluble C5b-9 levels at 6 h relative to emergency department levels. There were no differences in PF1 + 2, Bb, or C4d levels between groups, suggesting that coagulation and complement activation pathways may not be primarily responsible for the observed differences.

Percutaneous gastrostomy (PEG) is a common inpatient procedure. Prior data from National Inpatient Sample (NIS) in 2006 reported a mortality rate of 10.8% and recommended more careful selection of PEG candidates. This study assessed for improvement in the last 10 years in mortality rate and complications for hospitalized patients. A retrospective cohort analysis of all adult inpatients in the NIS from 2006 to 2016 undergoing PEG placement compared demographics and indication for PEG placement per ICD coding. Survey-based means and proportions were compared to 2006, and rates of change in mortality and complication rates were trended from 2006 through 2016 and compared with linear regression. Multivariable survey-adjusted logistic regression was used to determine predictors of mortality and complications in the 2016 sample. A total of 155,550 patients underwent PEG placement in 2016, compared with 174,228 in 2006. Mortality decreased from 10.8 to 6.6% without decreased comorbidities (p

The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented stresses on modern medical systems, overwhelming the resource infrastructure in numerous countries while presenting a unique series of pathophysiologic clinical findings. Thrombotic coagulopathy is common in critically ill patients suffering from COVID-19, with associated high rates of respiratory failure requiring prolonged periods of mechanical ventilation. Here, we report a case series of five patients suffering from profound, medically refractory COVID-19-associated respiratory failure who were treated with fibrinolytic therapy using tissue plasminogen activator (tPA; alteplase). All five patients appeared to have an improved respiratory status following tPA administration: one patient had an initial marked improvement that partially regressed after several hours, one patient had transient improvements that were not sustained, and three patients had sustained clinical improvements following tPA administration. LEVEL OF EVIDENCE: Therapeutic, Level V.

BACKGROUND Offspring (donor) to parent (recipient) transplant is the most common form of living donor liver transplant in the United States. In kidney transplantation, it has been suggested that female recipients of offspring living donor kidney allografts have inferior outcomes. It is unknown whether such a phenomenon also occurs following living donor liver transplantation. METHODS A retrospective analysis was completed of recipients of a living donor liver transplant from January 1998 to January 2018 in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Patients were grouped as having received a living donor liver allograft from either an offspring or a nonoffspring, with exactly 3 HLA matches, as would be expected between an offspring and parent. Graft and patient survival were analyzed using Cox proportional hazards modeling. RESULTS A total of 279 offspring to parent and 241 nonoffspring donor liver transplants were included in the analysis. Female recipients of offspring liver allografts had both inferior 10-year graft (52% versus 72%; P < 0.001) and patient survival (52% versus 81%; P < 0.001) compared with female recipients of nonoffspring allografts. No such difference in outcomes was discovered among male recipients. A stratified analysis of sex of offspring donors to female recipients demonstrated that donor male gender was associated with graft failure (HR = 2.87; P = 0.04) and mortality (hazard ratio = 3.89; P = 0.03). Again, this association was not seen with male recipients. CONCLUSIONS Among female recipients, offspring to parent living donor liver transplantation yields inferior long-term graft and patient survival. Furthermore, among offspring donors, male sex was strongly associated with inferior outcomes. These findings have significant implications for donor selection.

Background Children from low-income families experience accelerated BMI gain and learning loss during summer. Healthy Summer Learners (HSL) addresses accelerated BMI gain and academic learning loss during summer by providing academic- and health-focused programming. This manuscript reports the effects of HSL on underlying obesogenic behaviors (i.e., physical activity, screen time, sleep, diet) that lead to accelerated summer BMI gain, a necessary first step to informing a future randomized controlled trial of HSL. Methods In the summer of 2018 and 2019 using a quasi-experimental study design, 180 children (90 per summer, 7.9 years [SD = 1.0], 94% non-Hispanic Black, 40% male) at two schools (i.e., one per summer) who were struggling academically (25–75% on a standardized reading test) were provided a free, school-based 6-week health- and academic-focused summer program (i.e., HSL, n = 60), a 4- to 6-week academic-focused summer program (i.e., 21st Century Summer Learning program (21C), n = 60), or no summer program (n = 60). Children wore the Fitbit Charge 2™ over a 10-week period during the summers (June–Aug) of 2018–2019. Differences within (within child days attend vs. not attend) and between (differences between groups attend vs. not attend) were evaluated using mixed effects linear regression. Results Regression estimates indicated that, on days attending, HSL children experienced a greater reduction in sedentary minutes (− 58.6 [95% CI = − 92.7, − 24.4]) and a greater increase in moderate-to-vigorous physical activity (MVPA) (36.2 [95% CI = 25.1, 47.3]) and steps (2799.2 [95% CI = 2114.2, 3484.2]) compared to 21C children. However, both HSL and 21C children were more active (i.e., greater MVPA, total steps) and less sedentary (i.e., less sedentary minutes and total screen time) and displayed better sleeping patterns (i.e., earlier and less variability in sleep onset and offset) on days they attended than children in the control. Conclusions HSL produced greater changes in physical activity than 21C. However, attendance at either HSL or 21C leads to more healthy obesogenic behaviors. Based on the behavioral data in this pilot study, a larger trial may be warranted. These results must be considered along with the pending primary outcomes (i.e., academics and BMI z-score) of the HSL pilot to determine if a full-scale trial is warranted. Trial registration NIH-NCT03321071. Registered 25 October 2017

Obese patients with congestive heart failure (CHF) are often denied access to heart transplantation until they obtain significant weight loss to achieve a certain BMI threshold, often less than 35 kg/m2. It is unknown whether the rapid weight loss associated with bariatric surgery leads to improved waitlist placement, and as such improved survival for morbidly obese patients with CHF. A decision analytic Markov state transition model was created to simulate the life of morbidly obese patients with CHF who were deemed ineligible to be waitlisted for heart transplantation unless they achieved a BMI less than 35 kg/m2. Life expectancy following medical weight management (MWM), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) was estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. Markov parameters were extracted from literature review. RYGB improved survival compared with both SG and MWM. RYGB patients had higher rates of transplantation, leading to improved mean long-term survival. Base case patients who underwent RYGB gained 2.1 additional years of life compared with patient’s who underwent SG and 7.4 additional years of life compared with MWM. SG patients gained 5.3 years of life compared with MWM. When strict waitlist criteria were applied, bariatric surgery improved access to heart transplantation and thereby increased long-term survival compared with MWM. Morbidly obese CHF patients who anticipate need for heart transplantation should be encouraged to pursue surgical weight management strategies, necessitating discussion between bariatric surgeons, cardiologists, and cardiac surgeons for appropriate perioperative risk management.

Fast and accurate identifications of pathogenic bacteria along with their associated antibiotic resistance proteins are of paramount importance for patient treatments and public health. While mass spectrometry has become an important, technique for diagnostics of infectious disease, there is a need for mass spectrometry workflows offering this capability. To meet this need, we have augmented the previously published Microorganism Classification and Identification (MiCId) workflow for this capability. To evaluate the performance of the newly augmented MiCId workflow, we have used MS/MS datafiles from samples of 10 antibiotic resistance bacterial strains belonging to three different species: Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The evaluation results show that MiCId’s workflow has a sensitivity value around 85% (with a lower bound at about 72%) and a precision greater than 95% in the identification of antibiotic resistance proteins. Using MS/MS datasets from samples of two bacterial clonal isolates, one being antibiotic-sensitive while the other (obtained from the same patient at different times) being multidrug-resistant, we applied MiCId’s workflow to investigate possible mechanisms of antibiotic resistance in these pathogenic bacteria; the results showed that MiCId’s conclusions are in agreement with the published study. Furthermore, we show that MiCId’s workflow is fast. It pro-vides microorganismal identifications, protein identifications, sample biomass estimates, and antibiotic resistance protein identifications in 6–17 minutes per MS/MS sample using computing resources that are available in most desktop and laptop computers, making it a highly portable workflow. This study demonstrated that MiCId’s workflow is fast, portable, and with high sensitivity and high precision, making it a valuable tool for rapid identifications of bacteria as well as detection of their antibiotic resistance proteins. The new version of MiCId (v.07.01.2021) is freely available for download at https://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads.html.

Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy.

Modern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy—especially in austere or challenging environments—is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.

N-acetylglutamate synthase deficiency (NAGSD, MIM #237310) is an autosomal recessive urea cycle disorder caused either by decreased expression of the NAGS gene or defective NAGS enzyme resulting in decreased production of N-acetylglutamate (NAG), an allosteric activator of carbamylphosphate synthetase 1 (CPS1). NAGSD is the only urea cycle disorder that can be effectively treated with a single drug, N-carbamylglutamate (NCG), a stable NAG analog, which activates CPS1 to restore ureagenesis. We describe three patients with NAGSD due to four novel non-coding sequence variants in the NAGS regulatory regions. All three patients had hyperammonemia that resolved upon treatment with NCG. Sequence variants NM_153006.2:c.427-222G>A and NM_153006.2:c.427-218A>C reside in the 547 bp long first intron of NAGS and define a novel NAGS regulatory element that binds retinoic X receptor α. Sequence variants NC_000017.10:g.42078967A>T (NM_153006.2:c.-3065A>T) and NC_000017.10:g.42078934C>T (NM_153006.2:c.-3098C>T) reside in the NAGS enhancer, within known HNF1 and predicted glucocorticoid receptor binding sites, respectively. Reporter gene assays in HepG2 and HuH-7 cells demonstrated that all four substitutions could result in reduced expression of NAGS. These findings show that analyzing non-coding regions of NAGS and other urea cycle genes can reveal molecular causes of disease and identify novel regulators of ureagenesis. This article is protected by copyright. All rights reserved.

Type II diabetes mellitus (T2DM) is a metabolic disorder that occurs in the body because of decreased insulin activity and/or insulin secretion. The incidence of T2DM has rapidly increased over recent decades. The relation between consumption of different types of red meats and risk of T2DM remains uncertain. This meta-analysis was conducted to quantitatively assess the associations of processed red meat (PRM) and unprocessed red meat (URM) consumption with T2DM. We searched PubMed, Embase, Web of Science and The Cochrane Library for English-language cohort studies published before January 2021. Summary relative risks (RR) with 95% confidence interval (CI) were estimated using fixed effects and random effects. Additionally, dose–response relationships were explored using meta-regression. Fifteen studies (n = 682,963 participants, cases = 50,675) were identified. Compared with the lowest intake group, high consumption of PRM and URM increased T2DM risk by 27% (95% CI 1.15–1.40) and 15% (95% CI 1.08–1.23), respectively. These relationships were consistently strongest for U.S-based studies, though the effects of sex are inconclusive. In conclusion, PRM and URM are both positively associated with T2DM incidence, and these relationships are strongest in the U.S. reduction of red meat consumption should be explored as a target for T2DM prevention initiatives.

The definition of hyperfibrinolysis based on thrombelastogram LY30 measurements should vary with trauma patient characteristics, i.e., as anatomic injury or shock severity increase, the ability to tolerate even mild degrees of fibrinolysis is markedly reduced. This trend is independent of institutional practice patterns. The management of hyperfibrinolysis, particularly with anti-fibrinolytics administration, should be interpreted in the context of injury severity/shock and managed on an individual patient basis.

Introduction High alcohol consumption has been associated with decreased fibrinolysis and enhanced thrombosis risk in cardiovascular disease. In trauma, alcohol has been associated with poor clot formation; however, its effect on fibrinolysis has not been fully investigated. We assessed the association of blood alcohol levels and fibrinolysis in trauma activation patients. Methods We queried our prospective registry of trauma activations from 2014 to 2016. Associations between viscoelastic measurements [rapid thrombelastography (rTEG)] and blood alcohol level (BAL) were determined and adjusted for confounders by a multinomial logistic regression. Lysis phenotypes were defined by the % lysis in 30 min (LY30) as follows: hyperfibrinolysis ≥ 3%, physiologic 0.9–2.9%, and fibrinolysis shutdown 150 mg/dL. BAL had a moderate, but significant inverse correlation with LY30 (Rho = − 0.315, p 150 mg/dL were independently associated with a threefold increase in the odds of shutdown compared to undetectable BAL (OR 3.37, 95% CI 1.04–8.05, p = 0.006). High BAL was also significantly associated with higher odds of shutdown compared to low BAL (OR 2.63, 95% CI 1.15–6.06). Compared to physiologic fibrinolysis, fibrinolysis shutdown was associated with increased mortality (OR 2.87, 95% CI 1.41–5.83) and VFD

Whole blood (WB) has been used for more than a century for far-forward combat resuscitation. Following the Iraq/Afghanistan combat, maritime, and austere environment use of WB for the resuscitation of severely hemorrhaging patients, there has been an increasing use of WB for the civilian urban resuscitation environment population. The impetus for this was not just improved outcomes in far-forward hospitals, which had different populations and different needs than the civilian urban population, but also an application of the lessons suggested by recent 1:1:1 plasma:platelets:packed red cells fixed-ratio studies for patients with massive transfusion needs. Mechanistic, logistic, and standardization concerns have been addressed and are evolving as the WB project advances. A small number of studies have been published on WB in the civilian urban trauma population. In addition, European experience with viscoelastic testing and resuscitation with fibrinogen and prothrombin complex concentrate has provided another viewpoint regarding the choice of resuscitation strategies for severely bleeding trauma patients in urban civilian environments. There are randomized controlled trials in process, which are testing the hypothesis that WB may be beneficial for the civilian urban population. Whether WB will improve mortality significantly is now a matter of intense study, and this commentary reviews the history, mechanistic foundations, and logistical aspects for the use of WB in the civilian trauma population.

Peptide biomarker candidates for the respiratory tract pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus are presented. First, bacterial cultures representing the genetic variability in each of the four species, were analyzed. The peptide biomarker candidates were then experimentally verified to be present in a clinical situation by analyzing true positive clinical samples. The most promising peptide biomarkers were used in a targeted MS mode, demonstrating their use for future clinical implementation., Graphical Abstract Highlights Discovery of peptide biomarker candidates of respiratory tract pathogens S. pneumoniae, H. influenzae, M. catarrhalis and S. aureus as target pathogens. Peptide biomarker candidates were experimentally verified in clinical samples. Targeted MS using promising peptide biomarker candidates shown as proof-of-concept., Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.

Trauma patients present to the emergency department with a spectrum of fibrinolytic activity. This wide variance in fibrinolysis activity is a complex multifactorial process impacted by the degree of hemorrhagic shock and the amount of tissue injury the individual sustains. The fibrinolytic activity of the trauma patient at presentation to the hospital has prognostic and therapeutic implications. Those patients with high fibrinolytic activity (hyperfibrinolysis) are at risk of mortality from hemorrhage, whereas those patients with low fibrinolytic activity (shutdown or hypofibrinolysis) are at an increased risk of delayed mortality from traumatic brain injury or organ failure. These phenotypes of fibrinolysis acutely following injury change with resuscitation, and the majority of trauma patients will transition to a fibrinolytic resistant state several hours after injury. The mechanism for this near-global transition to this acquired fibrinolysis appears to be related to the generation of plasminogen activator inhibitor-1 in the liver. Those patients who do not recover from this fibrinolytic state 24 hours after injury have a poor prognosis. The purpose of this article is to review the different states of fibrinolytic activity following injury and how they change over time following resuscitation and in the intensive care unit.

INTRODUCTION Patients hospitalized with myocardial infarction (MI) are at risk of gastrointestinal bleeding because of the need for antiplatelet agents and/or anticoagulation. The data regarding the safety of endoscopy after MI are limited. This study sought to assess mortality rates of patients hospitalized with acute MI who require esophagogastroduodenoscopy or colonoscopy using the National Inpatient Sample (NIS) database. METHODS A retrospective cohort analysis of all adult inpatients in the NIS from 2016 admitted for ST-elevation infarction myocardial infarction (STEMI), non-STEMI, or type II non-STEMI was conducted. Data were collected including patient demographics and indication for endoscopy per ICD-10 coding. HCUPnet was used to query NIS to obtain all inpatient mortality. The primary methods included adjusted χ for categorical outcomes, adjusted linear regression for continuous outcomes, and adjusted logistic regression for multivariable analysis. RESULTS A total of 1,281,749 patients were admitted for acute coronary syndrome in 2016, and 55,035 of these patients underwent endoscopy In the multivariable regression analysis, those who underwent a GI procedure (odds ratio [OR] 0.80, P value < 0.002) and angiogram (OR 0.48, P value < 0.001) had lower in-hospital mortality, after adjusting for age, Elixhauser index, need for angiogram, sex, race, and hospital type. Endoscopy postcatheterization was not associated with a difference in mortality compared with preangiogram (OR = 0.84, 95% confidence interval 0.60-1.19). DISCUSSION Patients who underwent endoscopy are sicker and have higher mortality rates than those who do not undergo endoscopy, but after adjusting for comorbidities, mortality is actually lower. This suggests that endoscopy is safe and should be performed when clinically indicated despite recent cardiac ischemia.