Notes

Piezoelectric Nanogenerator for Very Hypersensitive and also Synchronous Multi-Stimuli Sensing.
Cancer immunotherapies that target the programmed cell death 1 (PD-1)programmed death-ligand 1 (PD-L1) immune checkpoint pathway have ushered in the modern oncology era. Drugs that block PD-1 or PD-L1 facilitate endogenous antitumor immunity and, because of their broad activity spectrum, have been regarded as a common denominator for cancer therapy. Nevertheless, many advanced tumors demonstrate de novo or acquired treatment resistance, and ongoing research efforts are focused on improving patient outcomes. Using anti-PD-1 or anti-PD-L1 treatment against earlier stages of cancer is hypothesized to be one such solution. This Review focuses on the development of neoadjuvant (presurgical) immunotherapy in the era of PD-1 pathway blockade, highlighting particular considerations for biological mechanisms, clinical trial design, and pathologic response assessments. Findings from neoadjuvant immunotherapy studies may reveal pathways, mechanisms, and molecules that can be cotargeted in new treatment combinations to increase anti-PD-1 and anti-PD-L1 efficacy. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.BACKGROUND Cryoneurolysis of peripheral nerves uses localised intense cold to induce a prolonged block over multiple weeks that has the promise of providing potent analgesia outlasting the duration of postoperative pain following surgery, as well as treat other acute and chronic pain states. However, it remains unclear whether persistent functional motor deficits remain following cryoneurolysis of mixed sensorimotor peripheral nerves, greatly limiting clinical application of this modality. To help inform future research, we used a rat peroneal nerve injury model to evaluate if cryoneurolysis results in persistent deficits in motor function. METHODS Male Lewis rats (n=30) had their common peroneal nerves exposed bilaterally at the proximal lateral margin of the knee and subsequently underwent cryoneurolysis on one limb and sham treatment on the contralateral limb. Outcomes were evaluated on days 3, 14, 30, 90 and 180. Erastin concentration The primary end point was motor function, based on ankle dorsiflexion torque. In addition, sensory function was tested based on von Frey's filament sensitivity to the peroneal sensory distribution. A subset of animals was sacrificed following functional testing at each time point, and general tissue morphology, connective tissue deposition, and axon counts were evaluated. RESULTS Motor deficits in treated limbs were observed at 3 and 14 days but had resolved at time points beyond 1 month. Bilateral sensory deficits were also observed at 3 and 14 days, and also resolved within 1 month. Consistent with motor functional deficits, axon counts trended lower in treated nerves compared with contralateral controls at 3 days; however, axon counts were not significantly different at later time points. CONCLUSIONS When applied to a mixed sensorimotor nerve, cryoneurolysis did not result in persistent motor deficits. © American Society of Regional Anesthesia & Pain Medicine 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.INTRODUCTION In 2016, individual training programs in regional anesthesiology and acute pain medicine (RA/APM) became eligible for accreditation by the Accreditation Council for Graduate Medical Education (ACGME), thereby culminating a process that began 15 years earlier. Herein, we review the origins of regional anesthesia training in the USA, the events leading up to accreditation and the current state of the fellowship. METHODS We reviewed pertinent literature on the historical aspects of RA/APM in the USA, related subspecialty training and the formation and current state of RA/APM fellowship training programs. Additionally, a survey was distributed to the directors of the 74 RA/APM fellowships that existed as of 1 January 2017 to gather up-to-date, program-specific information. RESULTS The survey yielded a 76% response rate. Mayo Clinic Rochester and Virginia Mason Medical Center likely had the first structured RA/APM fellowships with formalized curriculums and stated objectives, both starting in 1982. Most programs (86%), including ACGME and non-ACGME fellowships, came into existence after the year 2000. Six responding programs have or previously had RA/APM comingled with another subspecialty. Eight current programs originally offered unofficial or part-time fellowships in RA/APM, with fellows also practicing as attending physicians. DISCUSSION The history of RA/APM training in the USA is a tortuous one. It began with short 'apprenticeships' under the tutelage of the early proponents of regional anesthesia and continues today with 84 official RA/APM programs and a robust fellowship directors' group. RA/APM programs teach skills essential to the practice and improvement of anesthesiology as a specialty. © American Society of Regional Anesthesia & Pain Medicine 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE Troponin and high signal intensity on T2-weighted (HighT2) cardiovascular magnetic resonance imaging (CMRi) are both markers of myocardial injury in hypertrophic cardiomyopathy (HCM). The interplay between exercise and disease development remains uncertain in HCM. We sought to assess the occurrence of postexercise troponin rises and its determinants. METHODS Multicentre project on patients with HCM and mutation carriers without hypertrophy (controls). Participants performed a symptom limited bicycle test with hs-cTnT assessment pre-exercise and 6 hours postexercise. Pre-exercise CMRi was performed in patients with HCM to assess measures of hypertrophy and myocardial injury. Depending on baseline troponin (20% increase, respectively. RESULTS Troponin rises occurred in 18% (23/127) of patients with HCM and 4% (2/53) in mutation carriers (p=0.01). Comparing patients with HCM with and without a postexercise troponin rise, maximum heart rates (157±19 vs 143±23, p=0.004) and maximal wall thickness (20 mm vs 17 mm, p=0.023) were higher in the former, as was the presence of late gadolinium enhancement (85% vs 57%, p=0.02). HighT2 was seen in 65% (13/20) and 19% (15/79), respectively (p less then 0.001). HighT2 was the only independent predictor of troponin rise (adjusted odds ratio 7.9; 95% CI 2.7 to 23.3; p less then 0.001). CONCLUSIONS Postexercise troponin rises were seen in about 20% of patients with HCM, almost five times more frequent than in mutation carriers. HighT2 on CMRi may identify a group of particularly vulnerable patients, supporting the concept that HighT2 reflects an active disease state, prone to additional injury after a short episode of high oxygen demand. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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