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BackgroundEleven states have instituted laws allowing recreational cannabis use leading to growing public health concerns surrounding the effects of cannabis intoxication on driving safety. We hypothesized that after the 2016 legalization of cannabis in California, the use among vehicular injury patients would increase and be associated with increased injury severity.MethodsSan Diego County’s five adult trauma center registries in were queried from January 2010 to June 2018 for motor vehicle or motorcycle crash patients with completed toxicology screens. Patients were stratified as toxicology negative (TOX−), positive for only THC (THC+), only blood alcohol >0.08% (ETOH+), THC+ETOH, or THC+ with any combination with methamphetamine or cocaine (M/C). County medical examiner data were reviewed to characterize THC use in those with deaths at the scene of injury.ResultsOf the 11,491 patients identified, there were 61.6% TOX−, 11.7% THC+, 13.7% ETOH+, 5.0% THC+ETOH, and 7.9% M/C. THC+ increased from 7.3% to 14.8% over the study period and peaked at 14.9% post-legalization in 2017. Compared with TOX− patients, THC+ patients were more likely to be male and younger. THC+ patients were also less likely to wear seatbelts (8.5% vs 14.3%, p<0.001) and had increased mean Injury Severity Score (8.4±9.4 vs 9.0±9.9, p<0.001) when compared with TOX− patients. There was no difference in in-hospital mortality between groups. From the medical examiner data of the 777 deaths on scene, 27% were THC+.DiscussionTHC+ toxicology screens in vehicular injury patients peaked after the 2016 legalization of cannabis. Public education on the risks of driving under the influence of cannabis should be a component of injury prevention initiatives.Level of evidenceIII, Prognostic

Both forms of preconditioning greatly reduced infaction areas relative to controls. Store depletion generated Ca(2þ) selective currents with strong inward rectification. Preconditioning almost completely suppressed these currents, an effect that was almost blocked by 5HD a selective mitoKATP channel blocker and by intracellular BAPTA. And as assessed by Fura-2 this influx was also blocked by preconditioning. In contrast, the expression at the protein level of both STIM1 and Orai1 was strongly up-regulated by preconditioning and confocal microscopy revealed a higher density of Orai1 channels at the surface membrane.Our results indicate that while the expression of protein components of SOCS in heart cells (STIM1 and Orai1) are up-regulated by preconditioning, influx of Ca(2þ) through SOCS is severely impaired by preconditioning, probably by a slow Ca(2þ)-dependent inactivation process.

Purpose of Review Obtaining negative margins in breast conservation surgery continues to be a challenge. Re-excisions are difficult for patients and expensive for the health systems. This paper reviews the literature on current strategies and intraoperative clinical trials to reduce positive margin rates. Recent Findings The best available data demonstrate that intraoperative imaging with ultrasound, intraoperative pathologic assessment such as frozen section, and cavity margins have been the most successful intraoperative strategies to reduce positive margins. Emerging technologies such as optical coherence tomography and fluorescent imaging need further study but may be important adjuncts. Summary There are several proven strategies to reduce positive margin rates to < 10%. Surgeons should utilize best available resources within their institutions to produce the best outcomes for their patients.

Background Structural and electrophysiological remodeling characterize heart failure (HF) enhancing arrhythmias. PKD1 (protein kinase D1) is upregulated in HF and mediates pathological hypertrophic signaling, but its role in K+ channel remodeling and arrhythmogenesis in HF is unknown. Methods and Results We performed echocardiography, electrophysiology, and expression analysis in wild‐type and PKD1 cardiomyocyte‐specific knockout (cKO) mice following transverse aortic constriction (TAC). PKD1‐cKO mice exhibited significantly less cardiac hypertrophy post‐TAC and were protected from early decline in cardiac contractile function (3 weeks post‐TAC) but not the progression to HF at 7 weeks post‐TAC. Wild‐type mice exhibited ventricular action potential duration prolongation at 8 weeks post‐TAC, which was attenuated in PKD1‐cKO, consistent with larger K+ currents via the transient outward current, sustained current, inward rectifier K+ current, and rapid delayed rectifier K+ current and increased expression of corresponding K+ channels. Conversely, reduction of slowly inactivating K+ current was independent of PKD1 in HF. Acute PKD inhibition slightly increased transient outward current in TAC and sham wild‐type myocytes but did not alter other K+ currents. Sham PKD1‐cKO versus wild‐type also exhibited larger transient outward current and faster early action potential repolarization. Tachypacing‐induced action potential duration alternans in TAC animals was increased and independent of PKD1, but diastolic arrhythmogenic activities were reduced in PKD1‐cKO. Conclusions Our data indicate an important role for PKD1 in the HF‐related hypertrophic response and K+ channel downregulation. Therefore, PKD1 inhibition may represent a therapeutic strategy to reduce hypertrophy and arrhythmias; however, PKD1 inhibition may not prevent disease progression and reduced contractility in HF.