Systemic allergic reaction to galcanezumab (emgality): a case report.

BACKGROUND: A previously unreported systemic reaction to Galcanezumab (Emgality) is described. Galcanezumab is a humanized monoclonal antibody designed to bind to calcitonin gene-related peptide, a neuropeptide associated with neurogenic inflammation during migraine attacks. Although clinical trials showed that Galcanezumab had few adverse reactions (injection site related erythema, pruritus, and swelling), no systemic drug reactions have been noted. CASE REPORT: A 50-year-old female with chronic migraine, mast cell disorder, Hashimoto's disease, positive antinuclear antibody and positive anti-cyclic citrullinated peptide antibody not on immune modulators received the initial dose of galcanezumab 240 mg after failing multiple migraine treatments. The following day, she developed injection site reaction, malar erythema and flu-like symptoms. Symptoms progressed the second day after injection, and she developed swelling in her lips and throat. Intravenous steroid and antihistamines improved airway symptoms, and the remaining symptoms improved after a course of oral steroids. CONCLUSIONS: Delayed system allergic reaction to Galcanezumab requiring emergency intervention may occur. A history of autoimmune disorder may be a predisposing factor.

Spontaneous coronary artery dissection and its association with takotsubo syndrome: Novel insights from a tertiary center registry.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a relatively rare cause of acute coronary syndrome historically thought to primarily affect young, healthy women. The lack of multicenter collaborative research efforts has made it challenging to identify the precise etiology and pathological mechanisms underlying SCAD. However, there are many similarities in the patient demographics, clinical presentations, and predisposing stressors between SCAD and takotsubo syndrome (TTS). OBJECTIVES: The aim of this observational study was to examine the coronary and left ventriculographic features of patients with angiographically confirmed SCAD and determine the prevalence of concomitant TTS. METHODS: In this observational study, patients with angiographically confirmed SCAD were identified from the Massachusetts General Hospital SCAD registry. The coronary angiograms with simultaneous left ventriculograms (LVG) were carefully analyzed by an independent and blinded angiographic core laboratory. RESULTS: From our analysis of patients with SCAD who also underwent a LVG at time of coronary angiography, we identified a high prevalence of SCAD and concomitant TTS. CONCLUSIONS: Therefore, we present TTS as a plausible mechanistic etiology for SCAD in some patients. In light of this finding as well as the many similarities between SCAD and TTS, clinicians should be vigilant about the potential concomitant presence of these two entities. Additional future investigations further exploring the clinical implications of the association between SCAD and TTS are warranted.

Competing risk analysis in a large cardiovascular clinical trial: An APEX substudy.

Competing risk methods are time-to-event analyses that account for fatal and/or nonfatal events that may potentially alter or prevent a subject from experiencing the primary endpoint. Competing risk methods may provide a more accurate and less biased estimate of the incidence of an outcome but are rarely applied in cardiology trials. APEX investigated the efficacy of extended-duration betrixaban versus standard-duration enoxaparin to prevent a composite of symptomatic deep-vein thrombosis (proximal or distal), nonfatal pulmonary embolism, or venous thromboembolism (VTE)-related death in acute medically ill patients (n = 7513). The aim of the current analysis was to determine the efficacy of betrixaban vs standard-duration enoxaparin accounting for non-VTE-related deaths using the Fine and Gray method for competing risks. The proportion of non-VTE-related death was similar in both the betrixaban (133, 3.6%) and enoxaparin (136, 3.7%) arms, P = .85. Both the traditional Kaplan-Meier method and the Fine and Gray method accounting for non-VTE-related death as a competing risk showed equal reduction of VTE events when comparing betrixaban to enoxaparin (HR/SHR = 0.65, 95% 0.42-0.99, P = 0.046). Due to the similar proportion of non-VTE-related deaths in both treatment arms and the use of a univariate model, the Fine and Gray method provided identical results to the traditional Cox model. Using the Fine and Gray method in addition to the traditional Cox proportional hazards method can indicate whether the presence of a competing risk, which is dependent of the outcome, altered the risk estimate.

Dextrose Prolotherapy for the Treatment of Chronic Shoulder Pain in Patients With Joint Hypermobility: A Case Series.

Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are common causes of chronic musculoskeletal pain. Current practices rely on analgesics, physical therapy, bracing, and assistive devices. Dextrose prolotherapy (DPT) is a regenerative injection modality used to treat chronic painful musculoskeletal conditions through stimulation of tissue proliferation. The effectiveness of DPT for the treatment of chronic shoulder pain in patients with hEDS/HSD has not been established in the literature. Three patients with hEDS or HSD presented with refractory shoulder pain due to microinstability. Patients were treated with 20% DPT injected in the glenohumeral joint and surrounding structures as indicated. Outcomes assessed were pain and clinical improvement in joint stability at 2- to 7-week follow-up intervals. All patients reported subjective improvement in their shoulder pain and function. Disabilities of the Arm, Shoulder and Hand (DASH) scores after DPT decreased from initial assessment in all patients. Patients reported a cumulative improvement in pain and joint stability with each injection. Regenerative treatment with DPT may help restore structural integrity of affected joints and serve as an adjunctive therapy for the management of chronic shoulder pain due to microinstability in patients with hEDS/HSD.

Surgical Preparation by Urology Trainees in 2021: The Interplay of Video and Print Resources.

INTRODUCTION: We investigate urology trainee preparation for surgical procedures by querying type and degree of video sources used and combination with traditional print materials for preparation of surgical procedures. METHODS: An Institutional Review Board-approved 13-question REDCap® survey was distributed to 145 American College of Graduate Medical Education-accredited urology residency programs. Social media were also used to recruit participants. Results were collected anonymously and analyzed using Excel®. RESULTS: A total of 108 residents completed the survey. The majority (87%) reported using videos for surgical preparation including, YouTube (93%), American Urological Association (AUA) Core Curriculum videos (84%) and institutional or attending-specific videos (46%). Video selection was based on quality (81%), length (58%) and the site of video creation (37%). Video preparation was reported predominantly for minimally invasive surgery (95%), subspecialty procedures (81%) and open procedures (75%). The most common print sources reported include Hinman's Atlas of Urologic Surgery (90%), Campbell-Walsh-Wein Urology (75%) and the AUA Core Curriculum (70%). When asked to rank their overall top 3 sources, 25% of residents reported YouTube as their primary source and 58% included it in their top 3. Only 24% of residents reported being aware of the AUA YouTube channel, while 77% were aware of the video section of the AUA Core Curriculum. CONCLUSIONS: Urology residents use video resources to prepare for surgical cases, with a heavy reliance on YouTube. AUA-curated video sources should be highlighted in the resident curriculum as the quality and educational content of YouTube videos are variable.

Blindfolding Improves Communication in Inexperienced Residents Undergoing ACLS Training.

BACKGROUND: Closed-loop communication (CLC) is associated with decreased medical errors and improved time-to-task completion during resuscitations. Depriving team leaders of sight during training may accelerate the acquisition of favorable communication skills; however, its effect on the frequency of CLC is unclear, especially with trainees. OBJECTIVE: We assessed the effect of depriving interns of sight during advanced cardiovascular life support (ACLS) on verbal communication patterns and resuscitation confidence. METHODS: All interns undergoing ACLS training in June 2019 at a single center were eligible. Interns were randomized to blindfolded training (BT) or standard training (ST). BT team leaders were blindfolded during practice sessions and permitted to use sight during testing. Testing scenarios were video- and audio-recorded. Recordings were assessed for teams' performance and communication patterns. Participants were surveyed for confidence with resuscitation skills before and after ACLS training. RESULTS: All 87 eligible interns participated in the study (100% participation). Eighty-five of 87 (98%) interns were included for analysis; 46 were randomized to BT and 39 to ST. Interns in the BT group were significantly more likely to exhibit CLC (mean: BT 20.3, ST 16.6; P = .003), directed communication (mean: BT 4.3, ST 1.5; P < .001), and follower-initiated communication (mean: BT 12.8, ST 10.2; P = .028). There was no significant difference in clinical performance measures or self-reported confidence with resuscitation between BT and ST groups. CONCLUSIONS: Blindfolding trainees results in greater instances of CLC, directed communication, and follower-initiated communication during ACLS training.

Efficacy of a student-led community contact tracing program partnered with an academic medical center during the coronavirus disease 2019 pandemic.

PURPOSE: Contact tracing has proven successful at controlling coronavirus 2019 (COVID-19) globally, and the Center for Health Security has recommended that the United States add 100,000 contact tracers to the current workforce. METHODS: To address gaps in local contact tracing, health professional students partnered with their academic institution to conduct contact tracing for all COVID-19 cases diagnosed onsite, which included identifying and reaching their contacts, educating participants, and providing social resources to support effective quarantine and isolation. RESULTS: From March 24 to May 28, 536 laboratory-confirmed COVID-19 cases were contacted and reported an average of 2.6 contacts. Contacts were informed of their exposure, asked to quarantine, and monitored for the onset of symptoms. Callers reached 94% of cases and 84% of contacts. Seventy-four percent of cases reported at least one contact. Household members had higher rates of reporting symptoms (odds ratio, 1.65; 95% confidence interval, 1.19-2.28). The average test turnaround time decreased from 21.8 days for the first patients of this program to 2.3 days on the eleventh week. CONCLUSIONS: This provides evidence for the untapped potential of community contact tracing to respond to regional needs, confront barriers to effective quarantine, and mitigate the spread of COVID-19.

Andexanet alfa for the reversal of anticoagulant activity in patients treated with direct and indirect factor Xa inhibitors.

INTRODUCTION: Andexanet alfa is a recombinant factor Xa decoy molecule that inhibits direct and indirect factor Xa inhibitors to allow the normal coagulation process to resume. Its development arises in a space where novel oral anticoagulants are receiving expanded indications yet their use is limited by the lack of an effective reversal agent. Areas covered: This article reviews the biochemical properties, mechanism of action and the preclinical and clinical trials on andexanet alfa. It additionally aims to provide expert commentary and future perspectives on the efficacy, safety and challenges facing andexanet alfa as a universal antidote for direct and indirect factor Xa inhibitors. Expert commentary: Andexanet alfa shows promise to become a highly effective, novel antidote for factor Xa anticoagulation. Its biochemical profile and mechanism of action are immediately more attractive than other drugs on the market and under development due to its inert nature within the normal coagulation cascade, with minimal intrinsic procoagulant or anticoagulant properties. The anticoagulant antidote space will continue to develop as more specific and universal options become available for reversal of the effect of DOACs. Preliminary results of a pivotal phase 3b/4 trial demonstrate a favorable efficacy and safety profile in patients with acute hemorrhage.

Relation of Left Ventricular Mass and Infarct Size in Anterior Wall ST-Segment Elevation Acute Myocardial Infarction (from the EMBRACE STEMI Clinical Trial).

Biomarker measures of infarct size and myocardial salvage index (MSI) are important surrogate measures of clinical outcomes after a myocardial infarction. However, there is variability in infarct size unaccounted for by conventional adjustment factors. This post hoc analysis of Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events (EMBRACE) ST-Segment Elevation Myocardial Infarction (STEMI) trial evaluates the association between left ventricular (LV) mass and infarct size as assessed by areas under the curve for creatine kinase-MB (CK-MB) and troponin I release over the first 72 hours (CK-MB area under the curve [AUC] and troponin I [TnI] AUC) and the MSI. Patients with first anterior STEMI, occluded left anterior descending artery, and available LV mass measurement in EMBRACE STEMI trial were included (n = 100) (ClinicalTrials.govNCT01572909). MSI, end-diastolic LV mass on day 4 cardiac magnetic resonance, and CK-MB and troponin I concentrations were evaluated by a core laboratory. After saturated multivariate analysis, dominance analysis was performed to estimate the contribution of each independent variable to the predicted variance of each outcome. In multivariate models that included age, gender, body surface area, lesion location, smoking, and ischemia time, LV mass remained independently associated with biomarker measures of infarct size (CK-MB AUC p = 0.02, TnI AUC p = 0.03) and MSI (p = 0.003). Dominance analysis demonstrated that LV mass accounted for 58%, 47%, and 60% of the predicted variances for CK-MB AUC, TnI AUC, and MSI, respectively. In conclusion, LV mass accounts for approximately half of the predicted variance in biomarker measures of infarct size. It should be considered as an adjustment variable in studies evaluating infarct size.

Dietary vitamin C supplementation reduces noise-induced hearing loss in guinea pigs.

Vitamin C (ascorbate) is a water-soluble, low molecular weight antioxidant that works in conjunction with glutathione and other cellular antioxidants, and is effective against a variety of reactive oxygen species, including superoxide and hydroxyl radicals that have been implicated in the etiology of noise-induced hearing loss (NIHL). Whereas most animals can manufacture their own vitamin C, humans and a few other mammals such as guinea pigs lack the terminal enzyme for vitamin C synthesis and must obtain it from dietary sources. To determine if susceptibility to NIHL could be influenced by manipulating dietary levels of vitamin C, albino guinea pigs were raised for 35 days on a diet with normal, supplemented or deficient levels of ascorbate, then exposed to 4 kHz octave band noise at 114 dB SPL for 6 h to induce permanent threshold shifts (PTS) of the scalp-recorded auditory brainstem response. Animals that received the highest levels of dietary ascorbate developed significantly less PTS for click stimuli and 4, 8, 12, and 16 kHz tones than animals on normal and deficient diets. Outer hair cell loss was minimal in all groups after noise exposure, but permanent damage to stereocilia were observed in noise-exposed ears. The results support the hypothesis that dietary factors influence individual susceptibility to hearing loss, and suggest that high levels of vitamin C may be beneficial in reducing susceptibility to NIHL.