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Summary Background The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. Methods In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , NCT04351152 , and is completed. Findings Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41–137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79–89) participants in the lenzilumab group and in 190 (78%; 72–83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02–2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. Interpretation Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown. Funding Humanigen.

Introduction An ED visit for opioid overdose may be a person's only contact with the medical and behavioral health care systems and is an important opportunity to reduce risk of subsequent overdose and death. While ED initiatives to engage people with opioid use disorder (OUD) are being increasingly implemented, there are significant gaps in the receipt of services at the time of the ED encounter. Methods This is a retrospective cohort study of an outreach pilot project providing real-time telehealth delivered buprenorphine initiation and referral to community harm reduction and addiction treatment services via a follow up telephone call to patients after an ED visit for an opioid overdose. Results From January 2020 to April 2021 there were 606 patients with an ED visit for an opioid overdose eligible for a callback. Of the 606 eligible patients, 254/645 (42%) patients could be contacted and accepted service and/or treatment referrals. Fifteen patients were connected same-day to a buprenorphine prescriber for a telehealth encounter and, of connected patients, nine received a buprenorphine prescription. Conclusion A post-ED follow up telephone call protocol is an opportunity to improve treatment engagement and access to buprenorphine for patients at high risk for opioid overdose and death.

Background Nearly 300 medications contain pharmacogenomic information in their labeling approved by the U.S. Food and Drug Administration. As this number continues to grow, community pharmacists will be called on to use available pharmacogenomic data at the point of dispensing. Objective This qualitative study aimed to describe how pharmacists envision the integration of pharmacogenomic data into the current workflows of community pharmacy practice. Methods Community pharmacists from a regional supermarket chain pharmacy in the greater Pittsburgh area were interviewed using a semistructured interview guide. Participating pharmacists were presented with 3 clinical scenarios, followed by questions, to gain insight into how they envisioned the integration of pharmacogenomic data into community pharmacy workflow. The interview transcriptions were transcribed and coded. The content was analyzed to deduce the final themes. Supporting quotes were selected to illustrate each theme. Results Ten community pharmacists from 3 different pharmacy locations participated in the study. A thematic analysis produced 6 themes: (1) integrating pharmacogenomic data into the dispensing software, (2) receiving an alert for pharmacogenomic information within the dispensing software, (3) accessing pharmacogenomic clinical guidelines to guide drug–decision-making, (4) contacting the prescriber by adding a task to the call queue, (5) placing a mandatory counseling alert on medications that were adjusted using pharmacogenomic data, and (6) counseling the patient on the first refill of a medication that was adjusted using pharmacogenomic data. Conclusion This study describes how pharmacists envisioned the integration of pharmacogenomic data into community pharmacy workflow. The participants sought the integration of pharmacogenomic data into existing dispensing software, alerts for actionable prescribing changes using patient-specific pharmacogenomic data when available, and access to clinical decision support. In addition, the participants preferred to engage prescribers and receive alerts to counsel patients at prescription pick-up. These findings are key to integrating pharmacogenomic data into community pharmacy practice.

Women experiencing incarceration (WEI) in the United States are disproportionately impacted by HIV, yet HIV pre-exposure prophylaxis (PrEP) is underutilized by women in the United States. In order to inform an intervention to promote PrEP initiation during incarceration and facilitate linkage to PrEP care following release from incarceration, we conducted individual, semistructured qualitative interviews with WEI (N = 21) and key stakeholders (N = 14). While WEI had little or no previous knowledge about PrEP, they viewed it as something that would benefit women involved in the criminal justice system. Participants stated that HIV-related stigma and underestimation of HIV risk might serve as barriers to PrEP initiation during incarceration. Participants reported that competing priorities, difficulty scheduling an appointment, and lack of motivation could interfere with linkage to PrEP care in the community. Further, cost, substance use, and difficulty remembering to take the medication were cited most commonly as likely barriers to adherence.

Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a glomerular disease defined by non-organized glomerular deposits of heavy and light chain–restricted immunoglobulin and is rarely reported in children. We characterized a series of nine pediatric patients from two academic centers with biopsy-proven PGNMID and additionally describe two patients with monotypic IgG in the setting of IgM deposition. Each patient presented with hematuria and/or proteinuria; however, only five had elevated serum creatinine. Prodromal or concurrent infection was identified in six patients, low C3 in five, and alternate complement pathway gene variants in two. No monoclonal serum proteins were identified in five tested patients. Seven patients had monotypic deposits composed of IgG3-λ, two showed IgG3-κ, and one each IgG1 and IgG3 with lambda dominance in the setting of IgM deposition. The glomerular pattern was predominantly mesangial proliferative or membranoproliferative glomerulonephritis (MPGN). Treatment and outcomes were variable; four patients have recent PGNMID diagnoses and therefore minimal follow up, one had relatively stable kidney function for over a decade, and six experienced kidney failure, with four receiving transplants. Recurrent deposits of the same isotype were identified in five of six transplanted kidneys, corresponding to three of four transplanted patients. One of these patients developed PGNMID recurrences in three separate kidney allografts over a 20-year disease course. Our study emphasizes the need for upfront IgG subclass investigation in pediatric mesangial or MPGN with IgG deposition and monotypic or biased light-chain staining. Furthermore, this pediatric experience suggests expanded pathogenic considerations in PGNMID.

In 2009, the International Society for Heart and Lung Transplantation recognized the importance and challenges surrounding generic drug immunosuppression. As experience with generics has expanded and comfort has increased, substantial issues have arisen since that time with other aspects of immunomodulation that have not been addressed, such as access to medicines, alternative immunosuppression formulations, additional generics, implications on therapeutic drug monitoring, and implications for special populations such as pediatrics and older adults. The aim of this consensus document is to address critically each of these concerns, expand on the challenges and barriers, and provide therapeutic considerations for practitioners who manage patients who need to undergo or have undergone cardiothoracic transplantation.

Background Gastrointestinal bleeding (GIB) is common in left ventricular assist device (LVAD) patients. Serotonin release from platelets promotes platelet aggregation, and selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) therapy inhibits the transporter responsible for re-uptake. Methods We reviewed the records of LVAD (HeartMateII™, Abbott Medical, Lake Bluff, IL, USA and Heartware™, Medtronic, Minneapolis, MN, USA) patients at the Medical University of South Carolina and Johns Hopkins Hospital between January 2009 and January 2016. After exclusions, 248 patients were included for analysis. After univariate analysis, logistic regression multivariate analysis was performed to adjust for any demographic, cardiovascular, and laboratory data variables found to be associated with GI bleeding post-LVAD. Results Gastrointestinal bleeding occurred in 85 patients (35%) with 55% of GIBs due to arteriovenous malformations (AVMs). Of the total cohort, 105 patients received an SSRI or SNRI during LVAD support. Forty-four (44) SSRI/SNRI (41.9%) and 41 non-SSRI/SNRI (28.7%) patients had a GIB (RR 1.46, p = 0.03). Twenty-six (26) (24.8%) of the SSRI/SNRI patients had a GIB due to AVMs versus 21 (14.7%) of the non-SSRI/SNRI patients (RR 1.69, p = 0.05). In fully-adjusted multivariate regression analysis, SSRI/SNRI therapy was independently associated with GIB (OR 1.78, p = 0.045). For GIB, the number needed to harm (NNH) was 7.6. Conclusion In conclusion, SSRI/SNRI therapy is independently associated with an increased risk of GIB in LVAD patients.

ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence. (C) 2021 International Society for Heart and Lung Transplantation. All rights reserved.

BackgroundIntravenous erythromycin prior to endoscopy for upper gastrointestinal bleeding (GIB) improves outcomes but requires immediate preparation delaying administration in emergency cases. Azithromycin is readily available and does not require prolonged preparation. The aim of the study was to assess the effect of azithromycin in improving the quality of endoscopic visualization in upper GIB compared to erythromycin.MethodsPatients admitted with upper GIB who received erythromycin or azithromycin before urgent endoscopy were included. Primary outcome of the quality of visualization was assessed by two gastroenterologists, blinded to the choice of infusion, using a scoring system ranging from 0 to 8, with a maximum of 2 points assigned to the fundus, body, antrum and bulb.ResultsSixty-six patients were included; 25 received azithromycin and 41 received erythromycin. Mean total visualization score was significantly higher with azithromycin compared to that with erythromycin (6.8±1.4 vs. 5.5±2.2, respectively; P=0.01) and remained significant after adjusting for confounders (Diff: 0.01, 1.88; P=0.05). Secondary outcomes analyses showed a shorter LOS when given azithromycin compared to erythromycin [6 (3 to 9) vs. 8 (7 to 16) days, respectively, 95% CI: 1.03, 3.89; P=0.04]. Time between initiating the infusion and endoscopy was longer with azithromycin (Diff: 40.64 min; 95% CI: 7.23, 74.05; P=0.02). Need for second look endoscopy, procedure time, blood transfusion requirements and procedure-related complications did not differ between the groups.ConclusionsAzithromycin infusion before endoscopy for upper GIB was associated with better visualization than that of erythromycin. Randomized trials are needed to validate these findings.

Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end organ failure, as compared to only 20.9% of deaths in the reduced intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD were associated with worse OS. In addition, a diagnosis of therapy related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.

Although the concept of nephrotoxicity has been recognized for more than 80 years, interest in nephrotoxins has intensified dramatically over the past two decades. Much of this attention has rightfully been focused on pharmaceutical agents and iatrogenic harm; however, it is important for providers to recognize that nephrotoxins can be found in naturally occurring substances as well. Although nephrotoxins exist in a myriad of forms, the means by which they induce injury can be organized into a few categories. For most of these agents, regardless of the mechanism, the final common pathway is acute kidney injury (AKI). Unfortunately, therapeutic options are limited and no treatments currently exist to reverse nephrotoxic AKI once it occurs. As a result, current strategies focus on increased awareness, nephrotoxin avoidance, early injury detection, and mitigation of disease severity. The goal of this review is to summarize our current understanding of nephrotoxic mechanisms and the epidemiology of nephrotoxic AKI. Additionally, avoidance and preventative strategies are discussed, screening approaches are suggested, and chronic monitoring recommendations are made.

This study examined feasibility, acceptability, and preliminary efficacy of an mHealth facilitated health coaching antiretroviral therapy (ART) adherence intervention. Persons living with HIV (n = 53) were randomized to an in-person adherence session and 12 months of app access and health coaching via the app (Fitbit Plus) versus single adherence session (SOC). At baseline and 1, 3, 6, and 12 months, we measured ART adherence, substance use, and depressive symptoms. We also conducted individual qualitative interviews. The intervention was found to be largely feasible and highly acceptable, with the health coach spending an average of 2.4 min per month with a participant and 76.5% of Fitbit Plus participants using the app regularly at 12 months. While most comparisons were not significant, the pattern of results was consistent with better adherence in the Fitbit Plus compared to SOC condition. Substance use was significantly associated with poorer ART adherence while depressive symptoms were not.ClinicalTrials.gov Identifier: NCT02676128; Registered: 2/8/2016.En este estudio se examinó la viabilidad, aceptabilidad y la eficacia preliminar de una intervención de cumplimiento de la terapia antirretroviral (ART, por sus siglas en inglés) proporcionada por mHealth. Los pacientes con VIH (n = 53) fueron seleccionados al azar para participar en una sesión de cumplimiento presencial y para tener acceso a la aplicación y recibir asesoría médica a través de la aplicación (Fitbit Plus) durante 12 meses contra una sola sesión de cumplimiento (SOC, por sus siglas en inglés). Al comenzar y al mes 1, 3, 6 y 12, evaluamos el cumplimiento con la ART, el uso de sustancias y los síntomas de depresión; también realizamos entrevistas cualitativas individuales. Se encontró que la intervención es bastante viable y muy aceptable, con un promedio de 2.4 minutos de interacción entre el asesor médico y el participante y un 76.5% de uso de la aplicación por parte de los participantes de Fitbit Plus a los 12 meses. Si bien la mayoría de las comparaciones no fueron significativas, el patrón en los resultados fue consistente con un mayor cumplimiento en Fitbit Plus comparado con la condición SOC. El uso de sustancias se asoció significativamente con un cumplimiento de la ART más deficiente mientras que los síntomas depresivos no.

The relative efficacy of bridging with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) in left ventricular assist device (LVAD) patients has not been established. We performed a retrospective, longitudinal cohort study to evaluate safety and efficacy of bridging strategies including all adult LVAD patients implanted at the Medical University of South Carolina from August 2014 to July 2017. In addition to LMWH and UFH exposure, we recorded any time period a patient did not receive a bridging agent for a subtherapeutic international normalized ratio (INR) value as a control group; these events were defined as nonbridging (NB) events. Multivariable Cox regression survival models were utilized for analysis. There were 563 episodes evaluated in 50 patients. Compared with NB events, UFH (adjusted hazard ratio [aHR], 3.75; 95% CI, 1.45-9.73; p = 0.007) and LMWH (aHR, 2.25; 95% CI, 1.03-4.94; p = 0.043) were both associated with an increased risk of bleeding. Compared with NB events, LMWH was not associated with a decreased risk of clotting events (aHR, 1.56; 95% CI, 0.28-8.73; p = 0.616). In the 381 NB events, a nonsignificant signal was noted toward increased risk of thrombotic events in those with an INR ≤ 1.5 (aHR, 2.99; 95% CI, 0.57-15.8; p = 0.2). Among all 563 episodes, those with a baseline INR ≥ 2.0 demonstrated an increased risk of bleeding events (aHR, 2.35; 95% CI, 1.18-5.69; p = 0.016). Our data suggest that the efficacy of LMWH bridging in LVAD patients warrants further investigation.

IntroductionDual antiplatelet therapy (DAPT), primarily the combination of aspirin with a P2Y12 inhibitor, in patients undergoing intravascular stent or flow diverter placement remains the primary strategy to reduce device-related thromboembolic complications. However, selection, timing, and dosing of DAPT is critical and can be challenging given the existing significant inter- and intraindividual response variations to P2Y12 inhibitors.MethodsAssessment of indexed, peer-reviewed literature from 2000 to 2020 in interventional cardiology and neuroendovascular therapeutics with critical, peer-reviewed appraisal and extraction of evidence and strategies to utilize DAPT in cardio- and neurovascular patients with endoluminal devices.ResultsBoth geno- and phenotyping for DAPT are rapidly and conveniently available as point-of-care testing at a favorable cost-benefit ratio. Furthermore, systematic inclusion of a quantifying clinical risk score combined with an operator-linked, technical risk assessment for potential adverse events allows a more precise and individualized approach to new P2Y12 inhibitor therapy.ConclusionsThe latest evidence, primarily obtained from cardiovascular intervention trials, supports that combining patient pharmacogenetics with drug response monitoring, as part of an individually tailored, precision medicine approach, is both predictive and cost-effective in achieving and maintaining individual target platelet inhibition levels. Indirect evidence supports that this gain in optimizing drug responses translates to reducing main adverse events and overall treatment costs in patients undergoing DAPT after intracranial stent or flow diverting treatment.

Background/objectives: There is evidence that vitamin D (VD) supplementation may help in the management of atopic dermatitis (AD). The aim of this study was to assess the influence of VD supplementation on the severity of AD.Methods: Pre–post interventional study with prospective data collection in patients younger than 14 years. The severity of AD was determined through SCORAD (SCORing Atopic Dermatitis) and classified as mild (SCORAD < 25), moderate (≥25 and

Ubiquinol is a fundamental component of cellular metabolism. Low ubiquinol levels have been associated with mortality. This was a substudy of a randomized trial in patients undergoing coronary artery bypass grafting. We drew blood before and after surgery. Ubiquinol or placebo was added to peripheral blood mononuclear cells for oxygen consumption (OCR) measurements. In vivo ubiquinol levels were lower postsurgery compared to presurgery (0.16 μmol/L [quartiles: 0.02-0.39], P = .01), although the difference disappeared when adjusting for hemoglobin levels ( P = .30). There was no difference in presurgical basal (1.0 mL/min/mg [95% confidence interval [CI]: −0.9 to 2.2], P = .08) and maximal (0.5 mL/min/mg [95% CI: −4.3 to 7.3], P = .56) OCR in cells receiving ubiquinol or placebo. There was a difference in postsurgical basal (1.1 mL/min/mg [95% CI: 0.9-1.6], P < .001) and maximal (4.2 mL/min/mg [95% CI: 0.3-7.0], P = .01) OCR between the groups. We found no association between ubiquinol and OCR levels (all P > .05).

This study aims to describe infectious complications in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) patients with sustained return of spontaneous circulation (ROSC) and to compare differences in antimicrobial treatment and outcomes between the two groups. This was a retrospective, single-center, observational study. Adult patients (≥ 18 years) with OHCA or IHCA who had sustained ROSC between December 2007 to March 2015 were included. Blood, urine, sputum, and other fluid cultures, as well as radiologic imaging, were obtained at the discretion of the treating clinical teams. 275 IHCA and 318 OHCA patients were included in the analysis. We found evidence of infection in 181 IHCA and 168 OHCA patients. Significant differences were found between the IHCA and OHCA group in terms of initial rhythm, duration of arrest (10 min vs. 20, p =

Heart and lung procurements are multiphased processes often accompanied by an array of complex logistics. Approaches to donor evaluation and management, organ procurement, and organ preservation vary among individual procurement teams. Because early graft failure remains a major cause of mortality in contemporary thoracic organ transplant recipients, we sought to establish some standardization in the procurement process. This paper, in this vein, represents an international consensus statement on donor heart and lung procurement and is designed to serve as a guide for physicians, surgeons, and other providers who manage donors to best optimize the clinical status for the procurement of both heart and lungs for transplantation. Donation after brain death (DBD) and donation after circulatory determination death (referred to as donation after circulatory death [DCD] for the remainder of the paper) for both heart and lung transplantation will be discussed in this paper. Although the data available on DCD heart donation are limited, information regarding the surgical technique for procurement is included within this consensus statement. Furthermore, this paper will focus on adult DBD and DCD heart and lung procurement. Currently, no certification, which is either recognized and/or endorsed by the transplant community at large, exists for the training of a cardiothoracic procurement surgeon. Nevertheless, establishing a training curriculum and credentialing requirements are beyond the scope of this paper.

The advent of therapies for successful treatment of hepatitis C virus has allowed the heart and lung transplant community to re-explore the use of hepatitis C virus-positive donors for organ transplantation, with a benefit for many terminally ill patients. The consensus statements provided herein represent the current state of knowledge and expertise in this area, which we expect will continue to rapidly evolve over the next few years.

Over the past decade, the nephrology and critical care communities have adopted a consensus approach to diagnosing acute kidney injury (AKI) and, as a result, we have seen transformative changes in our understanding of pediatric AKI epidemiology. The data regarding outcomes among neonates and children who develop AKI have become far more robust and AKI has been clearly linked with an increased need for mechanical ventilation, longer inpatient stays, and higher mortality. Though AKI was historically thought to be self-limited, we now know that renal recovery is far from universal, particularly when AKI is severe; the absence of recovery from AKI also carries longitudinal prognostic implications. AKI survivors, especially those without full recovery, are at risk for chronic renal sequelae including proteinuria, hypertension, and chronic kidney disease. This review comprehensively describes AKI-related outcomes across the entire pediatric age spectrum, using the most rigorous studies to identify the independent effects of AKI events.

Though acute kidney injury (AKI) is often multifactorial, investigators are now emphasizing the specific contribution of nephrotoxins. This study examines the epidemiology of nephrotoxin exposure and nephrotoxin-associated AKI among children undergoing congenital heart surgery (CHS). This is a retrospective cohort study of children admitted following CHS between June 1, 2014, and September 30, 2014. Nephrotoxins were defined according to the Nephrotoxic Injury Negated by Just-in-time-Action (NINJA) collaborative; high nephrotoxin exposure was defined as receipt of ≥ 3 nephrotoxins concurrently. AKI was diagnosed according to KDIGO creatinine criteria. Severe AKI was defined as KDIGO stage ≥ 2. Poisson models were used to compute adjusted relative risk (aRR) of high nephrotoxin exposure for AKI. One hundred fifty-four children (median age 20.4 months, IQR 2.3–59.5) were included. One hundred thirty-one (85.1%) received at least one nephrotoxin; 32 (20.8%) received ≥ 3 nephrotoxins. The most commonly administered medications were ketorolac (n = 74, 48.1%), aspirin (n = 62, 40.3%), ibuprofen (n = 51, 33.1%), vancomycin (n = 39, 25.3%), piperacillin/tazobactam (n = 35, 22.7%), and enalapril (n = 14, 9.1%). AKI occurred more commonly in those exposed to ≥ 3 nephrotoxins (62.5 vs. 50.8%); this was not statistically significant after adjusting for confounders (aRR = 1.2, 95% CI 0.9–1.7). Severe AKI was similar between those with and without high nephrotoxin exposure (21.9 vs. 19.7%, p = 0.78). Nephrotoxin use is common following pediatric CHS. While we found no association between high nephrotoxin exposure and AKI, this may be related to the multifactorial nature of AKI in this population. For many common nephrotoxins, less injurious agents exist and nephrotoxin exposure may represent a modifiable risk factor for AKI.

Objectives Assess if amount of heat generated by postcardiac arrest patients to reach target temperature (Ttarget) during targeted temperature management is associated with outcomes by serving as a proxy for thermoregulatory ability, and whether it modifies the relationship between time to Ttarget and outcomes. Design Retrospective cohort study. Setting Urban tertiary-care hospital. Patients Successfully resuscitated targeted temperature management-treated adult postarrest patients between 2008 and 2015 with serial temperature data and Ttarget less than or equal to 34°C. Interventions None. Measurements and main results Time to Ttarget was defined as time from targeted temperature management initiation to first recorded patient temperature less than or equal to 34°C. Patient heat generation ("heat units") was calculated as inverse of average water temperature × hours between initiation and Ttarget × 100. Primary outcome was neurologic status measured by Cerebral Performance Category score; secondary outcome was survival, both at hospital discharge. Univariate analyses were performed using Wilcoxon rank-sum tests; multivariate analyses used logistic regression. Of 203 patients included, those with Cerebral Performance Category score 3-5 generated less heat before reaching Ttarget (median, 8.1 heat units [interquartile range, 3.6-21.6 heat units] vs median, 20.0 heat units [interquartile range, 9.0-33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.3 hr [interquartile range, 1.5-4.0 hr] vs median, 3.6 hr [interquartile range, 2.0-5.0 hr]; p = 0.01) than patients with Cerebral Performance Category score 1-2. Nonsurvivors generated less heat than survivors (median, 8.1 heat units [interquartile range, 3.6-20.8 heat units] vs median, 19.0 heat units [interquartile range, 6.5-33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.2 hr [interquartile range, 1.5-3.8 hr] vs median, 3.6 hr [interquartile range, 2.0-5.0 hr]; p = 0.01). Controlling for average water temperature between initiation and Ttarget, the relationship between outcomes and time to Ttarget was no longer significant. Controlling for location, witnessed arrest, age, initial rhythm, and neuromuscular blockade use, increased heat generation was associated with better neurologic (adjusted odds ratio, 1.01 [95% CI, 1.00-1.03]; p = 0.039) and survival (adjusted odds ratio, 1.01 [95% CI, 1.00-1.03]; p = 0.045) outcomes. Conclusions Increased heat generation during targeted temperature management initiation is associated with better outcomes at hospital discharge and may affect the relationship between time to Ttarget and outcomes.

Background Collaborative drug therapy management is a formal partnership between a pharmacist and physician to allow the pharmacist to manage a patient’s drug therapy. Literature supports collaborative disease therapy management can improve patient outcomes, improve medication adherence, enhance medication safety, and positively influence healthcare expenditures. Chemotherapy induced nausea or vomiting is considered one of the most distressing and feared adverse events among patients receiving chemotherapy. Chemotherapy induced nausea or vomiting can impact a patient’s quality of life and may affect compliance with the treatment plan. Purpose The objective of this pilot study was to determine the pharmacy impact of implementing a chemotherapy induced nausea or vomiting collaborative disease therapy management protocol in the outpatient oncology clinics at a National Cancer Institute (NCI)-designated cancer center associated with an academic medical center. The primary endpoint was to determine the number and type of chemotherapy induced nausea or vomiting clinical interventions made by the oncology pharmacists. Secondary endpoints included comparing patient’s Multinational Association for Supportive Care in Cancer scores and revenue of pharmacists’ services. Methods The credentialed oncology pharmacists were consulted by an oncologist to manage chemotherapy induced nausea or vomiting. Patients were included in the chemotherapy induced nausea or vomiting collaborative disease therapy management if they were seen in an outpatient oncology clinic from October 2016 to January 2017 and had a referral from a qualified provider to help manage chemotherapy induced nausea or vomiting. Patients admitted to the hospital at the time of consult were excluded from the study. The pharmacists interviewed patients and provided recommendations. The pharmacists followed up with the patient via a telephone call or during the next scheduled clinic visit to assess their symptoms. Results The chemotherapy induced nausea or vomiting collaborative disease therapy management pilot study was implemented in October 2016. From October 2016 to January 2017, there were 45 consults for the management of chemotherapy induced nausea or vomiting. The pharmacists made 188 clinical interventions, which included addition of new medications (37%), patient education (34%), deletion of medications (10%), changing a dose/duration/frequency (8%), and other interventions (11%). Multinational Association for Supportive Care in Cancer symptom scores were available for 5 patients, in which all showed improvements from baseline with the pharmacists’ clinical interventions. Conclusions The implementation of our chemotherapy induced nausea or vomiting collaborative disease therapy management pilot study has shown favorable results after a 4-month evaluation period. The pharmacists have made a substantial number of clinical interventions and provided patient education to patients undergoing chemotherapy.

PURPOSE: Alcohol-use disorders (AUDs) have been associated with increased sepsis-related mortality. As patients with AUDs are often thiamine deficient, we investigated practice patterns relating to thiamine administration in patients with AUDs presenting with septic shock and explored the association between receipt of thiamine and mortality.MATERIALS: We performed a retrospective cohort study of patients presenting with septic shock between 2008 and 2014 at a single tertiary care center. We identified patients with an AUD diagnosis, orders for microbial cultures and use of antibiotics, vasopressor dependency, and lactate levels≥4mmol/L. We excluded those who received thiamine later than 48h of sepsis onset.RESULTS: We included 53 patients. Thirty-four (64%) patients received thiamine. Five patients (15%) received their first thiamine dose in the emergency department. The median time to thiamine administration was 9 (quartiles: 4, 18) hours. The first thiamine dose was most often given parenterally (68%) and for 100mg (88%). In those receiving thiamine, 15/34 (44%) died, compared to 15/19 (79%) of those not receiving thiamine, p=0.02.CONCLUSIONS: A considerable proportion of patients with AUDs admitted for septic shock do not receive thiamine. Thiamine administration in this patient population was associated with decreased mortality.

Objective The aim of this study was to compare flow rates over time and the deviations from the target flow rate of a magnetic resonance imaging contrast agent achieved by an automated injector versus manual injection. Materials and Methods In this laboratory study, the magnetic resonance contrast agent gadobutrol was repeatedly injected by an injector and by 10 experienced technologists. Six scenarios with 2 different target flow rates (1 and 5 mL/s), 2 different contrast volumes (10 and 20 mL), and 2 different intravenous (IV) catheters (22 gauge and 20 gauge) were tested. The flow rates over time were recorded. The target variable was the average absolute deviation and average absolute percentage deviation from the target flow rate. Results The flow rates over time achieved by an injector were almost identical. Slight deviations from the target flow rate occurred during ramp-up and ramp-down only. Those of manual injection showed high variability over the whole course of the injection. In the 1 mL/s scenarios, the injector deviated from the target flow rate by 0.06 mL/s or less (≤6%) and in the 5 mL/s scenarios by 1.02 mL/s or less (

OBJECTIVES Geographic clustering of bystander cardiopulmonary resuscitation (CPR) is associated with demographic and socioeconomic features of the community where out-of-hospital cardiac arrest (OHCA) occurred, although this association remains largely untested in rural areas. With a significant rural component and relative racial homogeneity, Kent County, Michigan, provides a unique setting to externally validate or identify new community features associated with bystander CPR. Using a large, countywide data set, we tested for geographic clustering of bystander CPR and its associations with community socioeconomic features. METHODS Secondary analysis of adult OHCA subjects (2010-2015) in the Cardiac Arrest Registry to Enhance Survival (CARES) data set for Kent County, Michigan. After linking geocoded OHCA cases to U.S. census data, we used Moran's I-test to assess for spatial autocorrelation of population-weighted cardiac arrest rate by census block group. Getis-Ord Gi statistic assessed for spatial clustering of bystander CPR and mixed-effects hierarchical logistic regression estimated adjusted associations between community features and bystander CPR. RESULTS Of 1,592 subjects, 1,465 met inclusion criteria. Geospatial analysis revealed significant clustering of OHCA in more populated/urban areas. Conversely, bystander CPR was less likely in these areas (99% confidence) and more likely in suburban and rural areas (99% confidence). Adjusting for clinical, demographic, and socioeconomic covariates, bystander CPR was associated with public location (odds ratio [OR] = 1.19; 95% confidence interval [CI] = 1.03-1.39), initially shockable rhythms (OR = 1.48; 95% CI = 1.12-1.96), and those in urban neighborhoods (OR = 0.54; 95% CI = 0.38-0.77). CONCLUSIONS Out-of-hospital cardiac arrest and bystander CPR are geographically clustered in Kent County, Michigan, but bystander CPR is inversely associated with urban designation. These results offer new insight into bystander CPR patterns in mixed urban and rural regions and afford the opportunity for targeted community CPR education in areas of low bystander CPR prevalence.

INTRODUCTION: Mitochondrial injury post-cardiac arrest has been described in pre-clinical settings but the extent to which this injury occurs in humans remains largely unknown. We hypothesized that increased levels of mitochondrial biomarkers would be associated with mortality and neurological morbidity in post-cardiac arrest subjects.METHODS: We performed a prospective multicenter study of post-cardiac arrest subjects. Inclusion criteria were comatose adults who suffered an out-of-hospital cardiac arrest. Mitochondrial biomarkers were measured at 0, 12, 24, 36 and 48h after return of spontaneous circulation as well as in healthy controls.RESULTS: Out of 111 subjects enrolled, 102 had evaluable samples at 0h. Cardiac arrest subjects had higher baseline cytochrome c levels compared to controls (2.18ng/mL [0.74, 7.74] vs. 0.16ng/mL [0.03, 0.91], pCONCLUSIONS: Cytochrome c was increased in post- cardiac arrest subjects compared to controls, and in post-cardiac arrest non-survivors compared to survivors. Nuclear DNA and cell free DNA was increased in plasma of post-cardiac arrest subjects. There were no differences in mitochondrial DNA, nuclear DNA, or cell free DNA between survivors and non-survivors. Mitochondrial injury markers showed mixed results in the post-cardiac arrest period. Future research needs to investigate these differences.

Morinda citrifolia L. (noni) has been indicated to treat a variety of disorders; however, important aspects surrounding the consumption of products derived from noni still require clarification. We investigated the immune-related effects produced by the consumption of noni fruit juice by C57BL/6 mice. In the intestine, IL-4 and IL-10 levels were reduced following consumption of the fruit juice at a 1:100 dilution. However, when the highest concentrations were administered, IFN-γ, TNF-α and IL-12 levels increased in this organ. Similarly, IFN-γ, TNF-α, IL-12, IL-4, IL-23 and IL-10 levels increased in the liver. In the kidney, IL-12 production decreased following consumption of the juice at a 1:100 dilution. In the intestine, only a mild edema was observed followed by the consumption of noni fruit juice at the highest concentrations. Overall, noni fruit juice consumption did not cause any significant disturbances in liver or kidney outside of immune modulation.

Morinda citrifoliaL. (noni) has been shown to treat different disorders. However, data concerning its role in the treatment of intestinal inflammation still require clarification. In the current study, we investigated the effects of noni fruit juice (NFJ) in the treatment of C57BL/6 mice, which were continuously exposed to dextran sulfate sodium (DSS) for 9 consecutive days. NFJ consumption had no impact on the reduction of the clinical signs of the disease or on weight loss. Nonetheless, when a dilution of 1 : 10 was used, the intestinal architecture of the mice was preserved, accompanied by a reduction in the inflammatory infiltrate. Regardless of the concentration of NFJ, a decrease in both the activity of myeloperoxidase and the key inflammatory cytokines, TNF-αand IFN-γ, was also observed in the intestine. Furthermore, when NFJ was diluted 1 : 10 and 1 : 100, a reduction in the production of nitric oxide and IL-17 was detected in gut homogenates. Overall, the treatment with NFJ was effective in different aspects associated with disease progression and worsening. These results may point to noni fruit as an important source of anti-inflammatory molecules with a great potential to inhibit the progression of inflammatory diseases, such as inflammatory bowel disease.

Purpose Aspirin (ASA) therapy is recommended in left ventricular assist device (LVAD) patients to prevent thromboembolic complications. Up to 30% of LVAD patients may demonstrate ASA resistance, which has been related to thrombotic complications. However, it is unknown whether individual patients exhibit temporal alterations in ASA sensitivity during LVAD support. This project evaluated changes in ASA platelet inhibition over the first 6 months of LVAD support. We hypothesized that ASA platelet inhibition would wane after the initial post-implant period. Methods Patients who underwent placement of Heartware or Heartmate III LVAD at our institution and had serial ASA platelet sensitivity assays were included for analysis. ASA responsiveness was determined by VerifyNow assay with results expressed in aspirin reactivity units (ARU). ASA platelet resistance was defined by ARU greater than 550. ASA responsiveness was assessed post-implant after 5 days, 3 months, and 6 months. Results Out of 28 patients included for analysis only 7% were ASA-resistant at baseline. However, 32% of patients were ASA-resistant at 3 months and 28% at 6 months. (Figure 1). ASA-resistance was significantly more prevalent at 3-months (OR 6.1, p=0.03) with a trend toward increased prevalence at 6 months (OR 4.1, p=0.1) compared to early post-implant. ASA dose was increased in 4% and 14.3% of ASA-resistant patients at 3 and 6 months, respectively. Conclusion ASA responsiveness not only varies between patients, but can significantly change within individual LVAD patients over time. Over the first 3 months, the odds of ASA-resistance increased 6-fold and remained relatively constant at 6 months despite aspirin dose adjustment. Serial assessment of ASA responsiveness may help better identify LVAD patients at risk for thrombotic or bleeding complications. Further study is required into the both the clinical implications and the mechanism of waning aspirin sensitivity in LVAD patients.

Background We studied longitudinal levels of angiotensin-II type 1 receptor antibody (AT1R-Ab) and their effects on adverse events (death, treated rejection and cardiac allograft vasculopathy) in patients who were bridged to heart transplant using a continuous flow left ventricular assist device (LVAD). Methods and Results Sera of 77 patients bridged to heart transplant (from 2009 to 2017) were tested for AT1R-Ab and CRP before and after LVAD. Elevated AT1R-Ab was defined as >10.0 U/mL. The median follow-up after transplant was 3.6 years (interquartile range, 2.2–5.6 years). After LVAD, AT1R-Ab levels increased from baseline and remained elevated until transplant. Freedom from adverse events at 5 years was lower in those with elevated AT1R-Ab levels at time of transplant. In an adjusted, multivariable Cox analysis, an AT1R-Ab level of >10 U/mL was associated with developing the primary end point (adjusted hazard ratio 3.4, 95% confidence interval 1.2–9.2, P = .017). Although C-reactive protein levels were high before and after LVAD placement, C-reactive protein did not correlate with AT1R-Ab. Conclusions In LVAD patients bridged to heart transplant, an increased AT1R-Ab level at time of transplant was associated with poor outcomes after heart transplant. Post-LVAD AT1R-Ab elevations were not correlated with serum markers of systemic inflammation. Larger studies are needed to examine the pathologic role of AT1R-Ab in heart transplant.

Pharmacogenomics (PGx), studying the relationship between drug response and genetic makeup of an individual, is accelerating advances in precision medicine. The FDA includes PGx information in the labeling of approved drugs to better inform on their safety and effectiveness. We herein present a summary of PGx information found in 261 prescription drug labeling documents by querying the publicly available FDALabel database. A total of 362 drug–biomarker pairs (DBPs) were identified. We profiled DBPs using frequency of the biomarkers and their therapeutic classes. Four categories of applications (indication, safety, dosing and information) were discussed according to information in labeling. This analysis facilitates better understanding, utilization and translation of PGx information in drug labeling among researchers, healthcare professionals and the public.

Objective The aim of this study was to compare Conventional fractionated radiotherapy (CFRT) and Hypofractionated radiotherapy (HFRT) in terms of treatment outcomes, such as in 5-year loco-regional recurrence free survival, disease free survival, overall survival, and distant metastatic free survival rates as well as toxicity. Materials and methods We retrospectively analyzed the data obtained from 462 breast cancer patients who received complete adjuvant radiotherapy treatment between January 2012 and December 2014. One hundred twenty eight patients received CFRT 2 Gy daily fractions at a total dose of 48-60 Gy (group 1), while 334 patients received HFRT 2.65-2.67 Gy daily for 15-19 fractions at a total dose of 39.7-47.8 Gy 9 (grup 2). Treatment outcome such as 5-year loco-regional recurrence free survival, disease free survival, overall survival, and distant metastatic free survival rates as well as toxicity were measured and compared between two groups. Results Median follow-up was 65.7 months (ranging from 45.1 to 95.2 months). Five-year loco-regional recurrence free survival rate was 96.1% in both CFRT and HFRT groups (p=0.993). Five-year disease-free survival rate of CFRT group was higher (68.8%), but this difference was not significant (HFRT =63.5%) (p=0.396). These were complied with 5-year overall survival rate (71.9% and 64.7%, p=0.385). Five-year distant metastatic free survival rate was 85.9% in CFRT group and 79.6% in HFRT group (p=0.169). No difference was observed between two groups in terms of toxicities, including changes in chest wall appearance, skin fibrosis, brachial plexopathy, arm edema, pulmonary fibrosis, and cardiovascular events. Conclusion The treatment outcomes of hypofractionated radiotherapy in the postmastectomy breast cancer patients is comparable to the outcomes of conventional treatment at the Chonburi Cancer Hospital as previously reported from other studies, and HFRT can be implemented in resource-limited settings.

Objective: To investigate the anti-hyperglycemic effects of Plathymenia reticulata hydroalcoholic extract and related changes in body weight, lipid profile and the pancreas. Methods: Diabetes was induced in 75 adult male Wistar rats via oral gavage of 65mg/Kg of streptozotocin. Rats were allocated to one of 8 groups, as follows: diabetic and control rats treated with water, diabetic and control rats treated with 100mg/kg or 200mg/kg of plant extract, and diabetic and control rats treated with glyburide. Treatment consisted of oral gavage for 30 days. Blood glucose levels and body weight were measured weekly. Animals were sacrificed and lipid profile and pancreatic tissue samples analyzed. Statistical analysis consisted of ANOVA, post-hoc Tukey-Kramer, paired Student's t and χ2 tests; the level of significance was set at 5%. Results: Extract gavage at 100mg/kg led to a decrease in blood glucose levels in diabetic rats in the second, third (198.71±65.27 versus 428.00±15.25) and fourth weeks (253.29±47.37 versus 443.22±42.72), body weight loss (13.22±5.70 versus 109.60±9.95) and lower cholesterol levels (58.75±3.13 versus 80.11±4.01) in control rats. Extract gavage at 200mg/Kg led to a decrease in glucose levels on the fourth week in diabetic rats, body weight loss in the second, third and fourth weeks in control rats, and lower cholesterol levels in diabetic and control rats. Islet hyperplasia (p=0.005) and pancreatic duct dilation (p=0.047) were observed in diabetic and control rats. Conclusion: Plathymenia extract reduced blood glucose levels in diabetic rats, and body weight in control rats, and promoted pancreatic islet hyperplasia in diabetic and control rats. RESUMO Objetivo: Avaliar o efeito anti-hiperglicêmico do extrato hidroalcoólico de Plathymenia reticulata, alterações no peso, lipídeos e efeito sobre o pâncreas. Métodos: O diabetes foi induzido pela administração de estreptozotocina 65mg/kg, em 75 ratos Wistar adultos machos, divididos em 8 grupos diferentes: ratos diabéticos e controle + água, ratos diabéticos e controle + 100mg/kg ou 200mg/kg de extrato, ratos diabéticos e controle + gliburida. O tratamento foi realizado por gavagem (oral) por 30 dias. Níveis de glicose e peso foram verificados semanalmente. Os animais foram sacrificados, e amostras de lipídeos e do pâncreas foram analisadas. A análise estatística incluiu ANOVA, post-hoc Tukey-Kramer, teste t de Student pareado e teste do χ2, com nível de significância de 5%. Resultados: O extrato 100mg/kg promoveu redução nos níveis de glicose sanguínea em ratos diabéticos na segunda, terceira (198,71±65,27 versus 428,00±15,25) e quarta semanas (253,29±47,37 versus 443,22±42,72), perda de peso (13,22±5,70 versus 109,60±9,95) e diminuição do colesterol (58,75±3,13 versus 80,11±4,01) em ratos controle. Com extrato de 200mg/kg, houve redução dos níveis de glicose na quarta semana, nos ratos diabéticos; de peso na segunda, terceira e quarta semanas, nos ratos controle; e de colesterol nos animais diabéticos e controle. Ocorreram hiperplasia de ilhotas (p=0,005) e dilatação dos ductos pancreáticos (p=0,047) em ratos diabéticos e controles. Conclusão: O extrato de Plathymenia reduziu os níveis de glicose em ratos diabéticos e de peso em ratos controle, além de ter promovido hiperplasia de ilhotas pancreáticas em diabéticos e controles.

ObjectivePatients with psychogenic non-epileptic seizures (PNES) may present with convulsive events that are not accompanied by epileptiform brain activity. Video-electroencephalography (EEG) monitoring is the gold standard for diagnosis, yet not all patients experience convulsive episodes during video-EEG sessions. Hence, we aimed to construct a predictive model in order to detect PNES from serum hormone levels, detached from an evaluation of patients’ convulsive episodes.MethodsFifteen female patients with PNES and 60 healthy female controls participated in the study, providing blood samples for hormone analysis. A binomial logistic regression model and the leave-one-out cross-validation were employed.ResultsWe found that levels of neuropeptide Y and adrenocorticotropic hormone were the optimal combination of predictors, with over 90% accuracy (area under the curve=0.980).ConclusionsThe ability to diagnose PNES irrespective of convulsive events would represent an important step considering its feasibility and affordability in daily clinical practice. Objective Patients with psychogenic non-epileptic seizures (PNES) may present with convulsive events that are not accompanied by epileptiform brain activity. Video-electroencephalography (EEG) monitoring is the gold standard for diagnosis, yet not all patients experience convulsive episodes during video-EEG sessions. Hence, we aimed to construct a predictive model in order to detect PNES from serum hormone levels, detached from an evaluation of patients' convulsive episodes.Methods Fifteen female patients with PNES and 60 healthy female controls participated in the study, providing blood samples for hormone analysis. A binomial logistic regression model and the leave-one-out cross-validation were employed.Results We found that levels of neuropeptide Y and adrenocorticotropic hormone were the optimal combination of predictors, with over 90% accuracy (area under the curve=0.980).Conclusions The ability to diagnose PNES irrespective of convulsive events would represent an important step considering its feasibility and affordability in daily clinical practice.

(1) Glycoproteins account for ~80% of proteins located at the cell surface and in the extracellular matrix. A growing body of evidence indicates that &alpha, L-fucose protein modifications contribute to breast cancer progression and metastatic disease. (2) Using a combination of techniques, including matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) based in cell and on tissue imaging and glycan sequencing using exoglycosidase analysis coupled to hydrophilic interaction ultra-high performance liquid chromatography (HILIC UPLC), we establish that a core-fucosylated tetra-antennary glycan containing a single N-acetyllactosamine (F(6)A4G4Lac1) is associated with poor clinical outcomes in breast cancer, including lymph node metastasis, recurrent disease, and reduced survival. (3) This study is the first to identify a single N-glycan, F(6)A4G4Lac1, as having a correlation with poor clinical outcomes in breast cancer.

Continuous-flow left ventricular assist device (LVAD) placement has become a standard of care in advanced heart failure treatment. Bleeding is the most frequently reported adverse event after LVAD implantation and may be increased by antithrombotic agents used for prevention of pump thrombosis. This retrospective cohort included 85 adult patients implanted with a Heartmate II LVAD. Major bleeding was defined as occurring >7 days after implant and included intracranial hemorrhage, events requiring 2 units of packed red blood cells within a 24-h period, and death from bleeding. Primary outcome was intensity of anticoagulation between patients with or without at least one incidence of nonsurgical major bleeding. Major bleeding occurred in 35 (41%) patients with 0.48 events per patient year and a median (IQR) time to first bleed of 134.5 (39.3, 368.5) days. The median (IQR) INR at time of bleed was 1.7 (1.4, 2.5). Median INR during follow-up did not differ between groups and patients with major bleeding were not more likely to have a supra-therapeutic INR. Patients who bled were more likely to have received LVAD for destination therapy, to have lower weight, worse renal function, and lower hemoglobin at baseline. Duration of LVAD support and survival were similar between groups with no difference in occurrence of thrombosis. Incidence of nonsurgical major bleeding was not significantly associated with degree of anticoagulation. Certain baseline characteristics may be more important than anticoagulation intensity to identify patients at risk for bleeding after LVAD implant. Modification of anticoagulation alone is not a sufficient management strategy and early intervention may be required to mitigate bleeding impact.

Background: Intravenous erythromycin prior to endoscopy for upper gastrointestinal bleeding (GIB) improves outcomes but requires immediate preparation delaying administration in emergency cases. Azithromycin is readily available and does not require prolonged preparation. The aim of the study was to assess the effect of azithromycin in improving the quality of endoscopic visualization in upper GIB compared to erythromycin. Methods: Patients admitted with upper GIB who received erythromycin or azithromycin before urgent endoscopy were included. Primary outcome of the quality of visualization was assessed by two gastroenterologists, blinded to the choice of infusion, using a scoring system ranging from 0 to 8, with a maximum of 2 points assigned to the fundus, body, antrum and bulb. Results: Sixty-six patients were included; 25 received azithromycin and 41 received erythromycin. Mean total visualization score was significantly higher with azithromycin compared to that with erythromycin (6.8 ± 1.4 vs 5.5 ± 2.2, respectively; P=0.01) and remained significant after adjusting for confounders (Diff: 0.01, 1.88; P=0.05). Secondary outcomes analyses showed a shorter LOS when given azithromycin compared to erythromycin {6 (3-9) vs 8 (7-16) days, respectively, CI: 1.03, 3.89; P = 0.04}. Time between initiating the infusion and endoscopy was longer with azithromycin (Diff = 40.64 min; 95% CI: 7.23, 74.05; P=0.02). Need for second look endoscopy, procedure time, blood transfusion requirements and procedure-related complications did not differ between the groups. Conclusions: Azithromycin infusion before endoscopy for upper GIB was associated with better visualization than that of erythromycin. Randomized trials are needed to validate these findings. Funding: None. Declaration of Interest: All authors report no conflict of interest in relation to this study. Ethical Approval: The study protocol was approved by the Institutional Review Board of Virginia Commonwealth University.

Purpose Guidelines suggest optional use of Cytomegalovirus (CMV) T Cell immunity monitoring (TCell) to guide primary prophylaxis duration or need for secondary prophylaxis after infection. This may help balance the negative implications of CMV (rejection, coronary artery vasculopathy) against those of valganciclovir (expense, leukopenia/neutropenia). We present one year of experience to evaluate the potential utility of this test. Methods CMV TCell was implemented at our center to assess immunity at end of primary prophylaxis (R+ serostatus) and need for secondary prophylaxis after treatment of CMV. Heart transplant recipients with CMV TCell September 2019 to 2020 were retrospectively reviewed. Primary prophylaxis tests were excluded if R- serostatus or within 6 months of rATG. Tests at time of CMV detection prior to treatment were also excluded. Results Table 1 describes requirements for implementation. 24 patients had CMV TCell during study period; 1 never processed. Patients were excluded for: R- serostatus (6), rATG (1), and at time of CMV detection (2). 14 patients were included for analysis; 5 CMV R+ to guide primary prophylaxis discontinuation, 8 for secondary prophylaxis after infection treatment, 1 early for neutropenia. The early test for neutropenia was inconclusive after G-CSF administration. Immunity was noted at first test in 2/5 (40%) of the primary prophylaxis and 4/8 (50%) of the secondary group. Of non-immune in primary prophylaxis group, 2 had inconclusive tests concurrent to non-CMV infection and other in setting of neutropenia. After repeat tests, 9/14 (64%) patients were noted to have immunity. Of those with immunity, 5/9 (55%) had recurrence of low level viremia; 2 treated at detection, 3 self-cleared without treatment. Conclusion Early review of our data suggests CMV TCell may serve a role to identify patients who would benefit from secondary prophylaxis after treatment of CMV infection. Additional data over future years will help better define optimal utilization of this test.

Background:Health care providers nationwide are routinely trained in Advanced Cardiac Life Support (ACLS), an American Heart Association program that teaches cardiac arrest management. Recent changes in the ACLS approach have de-emphasized routine pulse checks in an effort to promote uninterrupted chest compressions. We hypothesized that this new ACLS algorithm may lead to uncertainty regarding the appropriate action following detection of a pulse during a cardiac arrest.Methods:We conducted an observational study in which a Web-based survey was sent to ACLS-trained medical providers at 4 major urban tertiary care centers in the United States. The survey consisted of 5 multiple-choice, scenario-based ACLS questions, including our question of interest. Adult staff members with a valid ACLS certification were included.Results:A total of 347 surveys were analyzed. The response rate was 28.1%. The majority (53.6%) of responders were between 18 and 32 years old, and 59.9% were female. The majority (54.2%) of responders incorrectly stated that they would continue CPR and possibly administer additional therapies when a team member detects a pulse immediately following defibrillation. Secondarily, only 51.9% of respondents correctly chose to perform a rhythm check following 2 minutes of CPR. The other 3 survey questions were correctly answered an average of 89.1% of the time.Conclusion:Confusion exists regarding whether or not CPR and cardiac medications should be continued in the presence of a pulse. Education may be warranted to emphasize avoiding compressions and medications when a palpable pulse is detected.

Objective: To evaluate the pH value of children's antibacterial soaps and syndets used in children's baths and verify whether there is information regarding pH on the product label. Methods: Quantitative, cross-sectional, analytical observational study that included ninety soap samples, both in bar and liquid presentations, as follows: 67 children's soap (group 1), 17 antibacterial soaps (group 2), and 6 syndets (group 3). Each sample had its pH measured after 1% dilution. In addition to descriptive statistics, the Pearson–Yates chi-squared test and Student's t-tests were applied, considering the minimal significance level of 5%. The Wilcoxon–Mann–Whitney test, Fisher's exact test, and the Kruskal–Wallis test were used for inferential statistics. Results: The pH levels varied considerably between liquid and bar presentations, with lower levels (4.4–7.9) found for the liquids (p

In-hospital cardiac arrest (IHCA) strikes over 200,000 people in the United States annually. Targeted temperature management (TTM) is considered beneficial in other settings, but there is no prospective data for IHCA. Recent work on TTM and IHCA found an association between TTM and worse outcome. However, the authors used intubation as a marker for coma to determine eligibility for TTM. The validity of this approach is unexplored.Retrospective, single center study of adult patients with IHCA occurring in an intensive care unit, intubated prior to or during the event, or immediately after ROSC. We evaluated the percentage of patients documented as comatose after arrest, defined as Glasgow Comas Score (GCS)8 for the primary analysis. We also evaluated the difference in hospital survival in patients with GCS8 versus ≥8. Two sensitivity analyses using different methods for defining coma using post-ROSC GCS were conducted.29/102 (28%) intubated patients had a post-ROSC GCS≥8, and 22 (22%) were documented as following commands. Survival in patients with GCS≥8 vs.8 was 62% (18/29) vs. 37% (27/73) in unadjusted analysis (p=0.02). The adjusted odds ratio for survival to hospital discharge was 3.81 (95%CI: 1.37-10.61, p=0.01). Results were similar in both sensitivity analyses.Intubation prior to or during IHCA was not a valid marker of coma after ROSC. Post-ROSC mental status was associated with hospital survival, and thus could be an important confounder when conducting observational studies on the association of TTM with outcomes in this patient population.

A missense point mutation in nerve growth factor (NGFR100W) is associated with hereditary sensory autonomic neuropathy V (HSAN V), originally discovered in a Swedish family. These patients develop severe loss of perception to deep pain but with apparently normal cognitive functions. To better understand the disease mechanism, we have generated the first NGFR100Wknockin mouse model of HSAN V. Mice homozygous for the NGFR100Wmutation (NGFfln/fln) showed significant structural deficits in intra-epidermal nerve fibers (IENFs) at birth. These mice had a total loss of pain perception at ∼2 months of age and they often failed to survive to full adulthood. Heterozygous mice (NGF+/fln) developed a progressive degeneration of small sensory fibers both behaviorally and functionally: they showed a progressive loss of IENFs starting at the age of 9 months accompanied with progressive loss of perception to painful stimuli such as noxious temperature. Quantitative analysis of lumbar 4/5 dorsal root ganglia (DRG) revealed a significant reduction in small size neurons positive for calcitonin gene-related peptide, while analysis of sciatic nerve fibers revealed the mutant NGF+/flnmice had no reduction in myelinated nerve fibers. Significantly, the amount of NGF secreted from fibroblasts were reduced in heterozygous and homozygous mice compared to their wild-type littermates. Interestingly, NGF+/flnshowed no apparent structural alteration in the brain: neither the anterior cingulate cortex nor the medial septum including NGF-dependent basal forebrain cholinergic neurons. Accordingly, these animals did not develop appreciable deficits in tests for central nervous system function. Our study provides novel insights into the selective impact of NGFR100Wmutation on the development and function of the peripheral sensory system.