Citations

Traditional ice storage has been the historic standard for preserving donor’s hearts. However, this approach provides variability in cooling, increasing risks of freezing injury. To date, no preservation technology has been reported to improve survival after transplantation. The Paragonix SherpaPak Cardiac Transport System (SCTS) is a controlled hypothermic technology clinically used since 2018. Real-world evidence on clinical benefits of SCTS compared to conventional ice cold storage (ICS) was evaluated. Between October 2015 and January 2022, 569 US adults receiving donor hearts preserved and transported either in SCTS (n = 255) or ICS (n = 314) were analyzed from the Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN-Heart) registry. Propensity matching and a subgroup analysis of >240 minutes ischemic time were performed to evaluate comparative outcomes. Overall, the SCTS cohort had significantly lower rates of severe primary graft dysfunction (PGD) ( p = 0.03). When propensity matched, SCTS had improving 1-year survival ( p = 0.10), significantly lower rates of severe PGD ( p = 0.011), and lower overall post-transplant MCS utilization ( p = 0.098). For patients with ischemic times >4 hours, the SCTS cohort had reduced post-transplant MCS utilization ( p = 0.01), reduced incidence of severe PGD ( p = 0.005), and improved 30-day survival ( p = 0.02). A multivariate analysis of independent risk factors revealed that compared to SCTS, use of ice results in a 3.4-fold greater chance of severe PGD ( p = 0.014). Utilization of SCTS is associated with a trend toward increased post-transplant survival and significantly lower severe PGD and MCS utilization. These findings fundamentally challenge the decades-long status quo of transporting donor hearts using ice.

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.

The t:slim X2 insulin pump with Control-IQ technology (Control-IQ) advanced hybrid closed-loop automated insulin delivery system was evaluated in this prospective single-arm trial. Thirty adults with type 2 diabetes using the Control-IQ system showed substantial glycemic improvement with no increase in hypoglycemia. Mean time in range (70–180 mg/dL) improved 15%, representing an increase of 3.6 hours/day, and mean glucose decreased by 22 mg/dL.

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

Introduction Postdural puncture headache (PDPH) can follow unintentional dural puncture during epidural techniques or intentional dural puncture during neuraxial procedures such as a lumbar puncture or spinal anesthesia. Evidence-based guidance on the prevention, diagnosis or management of this condition is, however, currently lacking. This multisociety guidance aims to fill this void and provide practitioners with comprehensive information and patient-centric recommendations to prevent, diagnose and manage patients with PDPH. Methods Based on input from committee members and stakeholders, the committee cochairs developed 10 review questions deemed important for the prevention, diagnosis and management of PDPH. A literature search for each question was performed in MEDLINE (Ovid) on 2 March 2022. The results from each search were imported into separate Covidence projects for deduplication and screening, followed by data extraction. Additional relevant clinical trials, systematic reviews and research studies published through March 2022 were also considered for the development of guidelines and shared with contributors. Each group submitted a structured narrative review along with recommendations graded according to the US Preventative Services Task Force grading of evidence. The interim draft was shared electronically, with each collaborator requested to vote anonymously on each recommendation using two rounds of a modified Delphi approach. Results Based on contemporary evidence and consensus, the multidisciplinary panel generated 50 recommendations to provide guidance regarding risk factors, prevention, diagnosis and management of PDPH, along with their strength and certainty of evidence. After two rounds of voting, we achieved a high level of consensus for all statements and recommendations. Several recommendations had moderate-to-low certainty of evidence. Conclusions These clinical practice guidelines for PDPH provide a framework to improve identification, evaluation and delivery of evidence-based care by physicians performing neuraxial procedures to improve the quality of care and align with patients’ interests. Uncertainty remains regarding best practice for the majority of management approaches for PDPH due to the paucity of evidence. Additionally, opportunities for future research are identified.

Importance Postdural puncture headache (PDPH) can follow unintentional dural puncture during epidural techniques or intentional dural puncture during neuraxial procedures, such as a lumbar puncture or spinal anesthesia. Evidence-based guidance on the prevention, diagnosis, and management of this condition is, however, currently lacking. Objective To fill the practice guidelines void and provide comprehensive information and patient-centric recommendations for preventing, diagnosing, and managing PDPH. Evidence Review With input from committee members and stakeholders of 6 participating professional societies, 10 review questions that were deemed important for the prevention, diagnosis, and management of PDPH were developed. A literature search for each question was performed in MEDLINE on March 2, 2022. Additional relevant clinical trials, systematic reviews, and research studies published through March 2022 were also considered for practice guideline development and shared with collaborator groups. Each group submitted a structured narrative review along with recommendations that were rated according to the US Preventive Services Task Force grading of evidence. Collaborators were asked to vote anonymously on each recommendation using 2 rounds of a modified Delphi approach. Findings After 2 rounds of electronic voting by a 21-member multidisciplinary collaborator team, 47 recommendations were generated to provide guidance on the risk factors for and the prevention, diagnosis, and management of PDPH, along with ratings for the strength and certainty of evidence. A 90% to 100% consensus was obtained for almost all recommendations. Several recommendations were rated as having moderate to low certainty. Opportunities for future research were identified. Conclusions and Relevance Results of this consensus statement suggest that current approaches to the treatment and management of PDPH are not uniform due to the paucity of evidence. The practice guidelines, however, provide a framework for individual clinicians to assess PDPH risk, confirm the diagnosis, and adopt a systematic approach to its management.

AbstractBackgroundReal‐world clinical data on the adverse events related to the use of cryoballoon catheter for pulmonary vein isolation remains limited.ObjectiveTo report and describe the adverse events related to the use of Artic Front cryoballoon catheters (Arctic Front, Arctic Front Advance, and Arctic Front Advance Pro) reported in the Food and Drug Administration's (FDA) Manufacturers and User Defined Experience (MAUDE) database.MethodsWe reviewed all the adverse events reported to the FDA MAUDE database over a 10.7‐year study period from January 01, 2011 to September 31, 2021. All events were independently reviewed by two physicians.ResultsDuring the study period, a total of 320 procedural‐related adverse events reported in the MAUDE database were identified. The most common adverse event was transient or persistent phrenic nerve palsy (PNP), accounting for 48% of all events. This was followed by cardiac perforation (15%), pulmonary vein stenosis (8%), transient ischemic attack or stroke (6%), vascular injury (4%), transient or persistent ST‐elevation myocardial infarction (3%), hemoptysis (2%), pericarditis (2%), and esophageal ulcer or fistula (1%). There were six reported intra‐procedural death events as a result of cardiac perforation.ConclusionThe two most common procedural adverse events associated with cryoballoon ablation were PNP and cardiac perforation. All cases of procedural mortality were due to cardiac perforation.

AbstractNext-generation sequencing (NGS) to identify pathogenic mutations is an integral part of acute myeloid leukemia (AML) therapeutic decision-making. The concordance in identifying pathogenic mutations among different NGS platforms at different diagnostic laboratories has been studied in solid tumors but not in myeloid malignancies to date. To determine this interlaboratory concordance, we collected a total of 194 AML bone marrow or peripheral blood samples from newly diagnosed patients with AML enrolled in the Beat AML Master Trial (BAMT) at 2 academic institutions. We analyzed the diagnostic samples from patients with AML for the detection of pathogenic myeloid mutations in 8 genes (DNMT3A, FLT3, IDH1, IDH2, NPM1, TET2, TP53, and WT1) locally using the Hematologic Neoplasm Mutation Panel (50-gene myeloid indication filter) (site 1) or the GeneTrails Comprehensive Heme Panel (site 2) at the 2 institutions and compared them with the central results from the diagnostic laboratory for the BAMT, Foundation Medicine, Inc. The overall percent agreement was over 95% each in all 8 genes, with almost perfect agreement (κ > 0.906) in all but WT1, which had substantial agreement (κ = 0.848) when controlling for site. The minimal discrepancies were due to reporting variants of unknown significance (VUS) for the WT1 and TP53 genes. These results indicate that the various NGS methods used to analyze samples from patients with AML enrolled in the BAMT show high concordance, a reassuring finding given the wide use of NGS for therapeutic decision-making in AML.

AbstractSynucleinopathies‐related disorders such as Lewy body dementia (LBD) and isolated/idiopathic REM sleep behavior disorder (iRBD) have been associated with neuroinflammation. In this study, we examined whether the human leukocyte antigen (HLA) locus plays a role in iRBD and LBD. In iRBD, HLA‐DRB1*11:01 was the only allele passing FDR correction (OR = 1.57, 95% CI = 1.27–1.93, p = 2.70e‐05). We also discovered associations between iRBD and HLA‐DRB1 70D (OR = 1.26, 95%CI = 1.12–1.41, p = 8.76e‐05), 70Q (OR = 0.81, 95%CI = 0.72–0.91, p = 3.65e‐04) and 71R (OR = 1.21, 95%CI = 1.08–1.35, p = 1.35e‐03). Position 71 (pomnibus = 0.00102) and 70 (pomnibus = 0.00125) were associated with iRBD. Our results suggest that the HLA locus may have different roles across synucleinopathies.