Wallspilegaard7686

46 - 0.56) and early unplanned reoperations (RR 0.82, 95% CI 0.70 - 0.96). CONCLUSIONS Results of this systematic review indicate that laparoscopic surgery for ASBO is safe and feasible. Laparoscopic surgery is not associated with better or worse postoperative outcomes compared with open adhesiolysis. Future research should focus on the correct selection of those patients who are suitable for laparoscopic approach and may benefit from this approach. LEVEL OF EVIDENCE Level IITherapeutic.BACKGROUND Trauma is the leading cause of death for young Americans. Nonspecific histone deacetylase (HDAC) inhibitors, such as valproic acid (VPA), have been shown to improve survival in preclinical models of lethal trauma, hemorrhage and sepsis. The doses needed to achieve a survival benefit are higher than FDA-approved doses, and the nonspecificity raises concerns about unintended adverse effects. The isoform specific HDAC-6 inhibitor, ACY-1083, has been found to be as efficacious as VPA in a rodent model of hemorrhagic shock. We hypothesized that ACY-1083 treatment would improve survival in a swine model of lethal hemorrhage, polytrauma and bacteremia. selleck chemicals llc METHODS Swine were subjected to 45% blood volume hemorrhage, brain injury, femur fracture, rectus crush, splenic and liver lacerations, and colon injury. After 1 hour of shock (mean arterial pressure 30-35 mmHg), animals were randomized to normal saline resuscitation (control) or normal saline+ACY-1083 30mg/kg treatment (n=5/group). After 3 hours (simulating delayed evacuation), packed red blood cells and antibiotics were administered, the colon injury was repaired, and the abdomen was closed. Animals were then monitored for another 4 hours. Survival was assessed using Kaplan-Meier and log-rank test. RESULTS This combination of injuries was lethal. All animals became bacteremic, in addition to the severe hemorrhagic shock. Survival in the control group was 0% and ACY-1083 treatment increased survival to 80% (p=0.019). There was no difference in the brain lesion size between the groups. CONCLUSION A single dose of ACY-1083 markedly improves survival in an otherwise lethal model of polytrauma, hemorrhagic shock and bacteremia. LEVEL OF EVIDENCE Basic science.BACKGROUND The mechanisms of aberrant circulating platelet behavior following injury remain unclear. Platelets retain megakaryocyte immature ribonucleic acid (RNA) splicing and protein synthesis machinery to alter their functions based on physiologic signals. We sought to identify fluctuating platelet-specific RNA transcripts in cell free plasma (CFP) from traumatic brain injury (TBI) patients as proof-of-concept for using RNA sequencing to improve our understanding of post-injury platelet behavior. We hypothesized that we could identify differential expression of activated platelet-specific spliced RNA transcripts from CFP of patients with isolated severe fatal TBI (fTBI) compared to minimally-injured trauma controls (t-controls), filtered by healthy control (h-control) datasets. METHODS High-read depth RNA sequencing was applied to CFP from ten patients with fTBI (abbreviated injury scale [AIS] for head ≥3, AIS for all other categories 1.5 or less then .67 fold ex-vivo non-activated platelet-specific RNA transcripts. RESULTS 42 differentially spliced activated platelet-specific RNA transcripts in 34 genes were altered in CFP from fTBI patients (both upregulated and downregulated). CONCLUSIONS We have discovered differentially-expressed activated platelet-specific spliced RNA transcripts present in CFP from isolated severe fatal TBI patients that are up- or downregulated compared to minimally-injured trauma controls. This proof-of-concept suggests that a pool of immature platelet RNAs undergo splicing events after injury for presumed modulation of platelet protein products involved in platelet function. This validates our exploration of injury-induced platelet RNA transcript modulation as an upstream 'liquid biopsy' to identify novel post-injury platelet biology and treatment targets for aberrant platelet behavior. LEVEL OF EVIDENCE VDiagnostic tests.BACKGROUND Historically, youth violence prevention strategies used deterrence-based programming with limited success. We developed a youth violence prevention program, Dusk to Dawn (D2D), intended to improve youths' recognition of high-risk situations and teach new skills in conflict resolution. The aim of this study was to evaluate the effect of D2D on youths' perceptions of personal risk factors and high-risk situations. METHODS Youth ages 12-18 were referred to D2D by community-based organizations, probation, or youth detention center. Youth completed a self-report survey before and after participating in D2D. RESULTS 108 youth participated in D2D. Pre and posttest results for self-reported personal risk factors and high-risk situations for violence are presented in Table 1. For Personal Risk Factors, a statistically significant increase in the perception that family (p less then .01) and other issues (p less then .05), and a decrease in the perception that school problems ( less then .05) were seen as important personal risk factors. For High Risk Situations, increases in the perception that peer violence and substance use as high-risk situations were seen as significant at the trend level (p less then .10). Of the 60% of participants who answered questions regarding satisfaction with D2D, 83.3% agreed or strongly agreed that D2D helped them to better understand violence and 83.3% would recommend D2D to others. CONCLUSIONS Youth violence prevention programming including an explicit discussion of how violence is learned and the role of family, friends, school and a community in shaping youths' attitudes towards violence can effectively raise awareness of one's own risk factors. Risk factors for youth violence are often preventable or modifiable, making awareness of one's own risk factors a realistic target for youth violence prevention programs. LEVEL OF EVIDENCE Level III Prospective comparative study with only one negative criterion beyond minimal report bias STUDY TYPE Therapeutic/Care Management.PURPOSE Therapeutic drug monitoring is highly recommended for children and adolescents treated with neurotropic/psychotropic drugs. For interpretation of therapeutic drug monitoring results, drug concentrations (C/D) expected in a "normal" population are helpful to identify pharmacokinetic abnormalities or nonadherence. Using dose-related concentration (DRC) factors obtained from pharmacokinetic data, C/D ranges expected under steady state can be easily calculated by multiplication of DRC by the daily dose. DRC factors, however, are defined only for adults so far. Therefore, it was the aim of this study to estimate DRC factors for children and adolescents and compare them with those of adults. METHODS To obtain pharmacokinetic data (apparent total clearance of drugs from plasma after oral administration, elimination half-life, area under the curve, and minimum serum drug concentration) from children and adolescents treated with psychotropic drugs, a systematic review of published literature was performed, ande drugs.PURPOSE Drug use during pregnancy is a critical global challenge, capable of severe impacts on neonatal development. However, the consumption of cannabis and synthetic cannabinoids is on the rise in pregnant women. Obstetric complications with increased risks of miscarriage, fetal growth restriction, and brain development impairment have been associated with perinatal cannabis exposure, but data on synthetic cannabinoid use during pregnancy are limited. METHODS We reviewed studies that investigated the risks associated with cannabis and synthetic cannabinoid use and those that reported the concentrations of cannabinoids and synthetic cannabinoids in maternal (breast milk) and neonatal (placenta, umbilical cord, meconium, and hair) matrices during human pregnancy. A MEDLINE and EMBASE literature search to identify all relevant articles published in English from January 1998 to April 2019 was performed. RESULTS Cannabis use during pregnancy is associated with increased risks of adverse obstetrical outcomes, although neurobehavioral effects are still unclear. Analyses of cannabinoids in meconium are well documented, but further research on other unconventional matrices is needed. Adverse effects due to perinatal synthetic cannabinoid exposure are still unknown, and analytical data are scarce. CONCLUSIONS Awareness of the hazards of drug use during pregnancy should be improved to encourage health care providers to urge pregnant women to abstain from cannabis and, if cannabis-dependent, seek treatment. Moreover, substances used throughout pregnancy should be monitored as a deterrent to cannabis use, and potential cannabis-dependent women should be identified, so as to limit cannabis-fetal exposure during gestation, and provided appropriate treatment.BACKGROUND Dalbavancin, albeit indicated for the treatment of skin structure infections, is used for a much wider range of infections. This drug is characterized by a long half-life (more than 200 hours), a favorable safety profile, and an activity against a wide array of gram-positive organisms, including several strains of Staphylococci and Enterococci. METHODS In this study, we presented 3 cases of critically ill patients treated with dalbavancin. All patients were therapeutically monitored for plasma dalbavancin concentrations; ultrafiltrate dalbavancin concentrations were assessed in a patient undergoing continuous renal-replacement therapy. Dalbavancin concentrations were measured using a validated liquid chromatographic method coupled with mass spectrometry. RESULTS All 3 severely ill patients experiencing necrotizing fasciitis were successfully treated during the acute phase with dalbavancin. Dalbavancin clearance in patient 3 (0.334 L/h) was considerably increased compared with values measured in the other 2 patients (0.054 and 0.075 L/h) and with data reported in the literature (0.04-0.06 L/h). CONCLUSIONS Our case reports presented preliminary evidence that dalbavancin can be considered a therapeutic option for necrotizing fasciitis in intensive care unit patients. The role of hypoalbuminemia during dalbavancin exposure merits further investigation.In this study, the authors report the case of a patient diagnosed with hepatitis C virus who was treated with sofosbuvir-velpatasvir (400/100 mg). As the patient was unable to swallow whole tablets, therapeutic drug monitoring was performed to evaluate the effect of crushing sofosbuvir-velpatasvir tablets on drug absorption and global exposure.OBJECTIVES Patients with immune thrombocytopenia are at risk of both bleeding complications and venous thromboembolism. There is no standard to treating life-threatening pulmonary embolism in this population. This case illustrates the difficulty of treating significant thromboembolism in pediatric patients who have reduced clotting capacity. CASE This case focuses on a 16-year-old pediatric patient with a history of immune thrombocytopenia presenting with mild chest discomfort and dyspnea on exertion. The d-dimer was mildly elevated, and the subsequent computed tomography angiogram revealed bilateral pulmonary embolisms with right ventricular strain. CONCLUSIONS The patient underwent thromboembolectomy by interventional radiology with subsequent administration of intravenous immunoglobulin, high-dose steroids, and enoxaparin therapy. There is no standard of care for patients with life-threatening pulmonary embolism in this population. Several authors suggest medical therapy options, but do not include patients with potential hemodynamic instability.