Medicine and Health Sciences Commons^™

Acute Pulmonary Injury In Hematology Patients Supported With Pathogen-Reduced And Conventional Platelet Components, Allison P Wheeler, Ronald Jackups, Et Al.

2020-Current year OA Pubs

Patients treated with antineoplastic therapy often develop thrombocytopenia requiring platelet transfusion, which has potential to exacerbate pulmonary injury. This study tested the hypothesis that amotosalen-UVA pathogen-reduced platelet components (PRPCs) do not potentiate pulmonary dysfunction compared with conventional platelet components (CPCs). A prospective, multicenter, open-label, sequential cohort study evaluated the incidence of treatment-emergent assisted mechanical ventilation initiated for pulmonary dysfunction (TEAMV-PD). The first cohort received CPC. After the CPC cohort, each site enrolled a second cohort transfused with PRPC. Other outcomes included clinically significant pulmonary adverse events (CSPAE) and the incidence of treatment-emergent acute respiratory distress syndrome (TEARDS) diagnosed by blinded …

Stay On Track: A Pilot Randomized Control Trial On The Feasibility Of A Diet And Exercise Intervention In Patients With Breast Cancer Receiving Radiotherapy, Gopika Senthilkumar, Aronne M Schottstaedt, Lindsay L Peterson, Lauren N Pedersen, Christopher R Chitambar, Alexis Vistocky, Anjishnu Banerjee, John M Longo, Tracy Kelly, Adam Currey, Melinda R Stolley, Carmen Bergom

2020-Current year OA Pubs

PURPOSE: Among patients with breast cancer undergoing radiotherapy, posttreatment cardiovascular disease and worsened quality of life (QoL) are leading causes of morbidity and mortality. To overcome these negative radiotherapy effects, this prospective, randomized clinical trial pilots a 12-week Stay on Track exercise and diet intervention for overweight patients with nonmetastatic breast cancer undergoing whole-breast radiotherapy.

EXPERIMENTAL DESIGN: The intervention group (n = 22) participated in three personal exercise and dietary counseling sessions, and received three text reminders/week to adhere to recommendations. The control group (n = 22) was administered a diet/exercise information binder. All patients received a Fitbit, and at …

Sleep And Circadian Biomarkers Of Postoperative Delirium (Sleep-Pod): Protocol For A Prospective And Observational Cohort Study, Elizabeth Sugg, Elizabeth Gleeson, Sarah N Baker, Peng Li, Chenlu Gao, Ariel Mueller, Hao Deng, Shiqian Shen, Esteban Franco-Garcia, Richa Saxena, Erik S Musiek, Oluwaseun Akeju, Zhongcong Xie, Kun Hu, Lei Gao

2020-Current year OA Pubs

INTRODUCTION: Surgical patients over 70 experience postoperative delirium (POD) complications in up to 50% of procedures. Sleep/circadian disruption has emerged as a potential risk factor for POD in epidemiological studies. This protocol presents a single-site, prospective observational study designed to examine the relationship between sleep/circadian regulation and POD and how this association could be moderated or mediated by Alzheimer's disease (AD) pathology and genetic risk for AD.

METHODS AND ANALYSIS: Study staff members will screen for eligible patients (age ≥70) seeking joint replacement or spinal surgery at Massachusetts General Hospital (MGH). At the inclusion visit, patients will be asked a …

Streamlined Identification Of Clinically And Functionally Relevant Genetic Regulators Of Lower-Tract Urogenital Development, Meade Haller, Yan Yin, Gabe Haller, Tian Li, Qiufang Li, Laura E Lamb, Liang Ma

2020-Current year OA Pubs

Congenital anomalies of the lower genitourinary (LGU) tract are frequently comorbid due to genetically linked developmental pathways, and are among the most common yet most socially stigmatized congenital phenotypes. Genes involved in sexual differentiation are prime candidates for developmental anomalies of multiple LGU organs, but insufficient prospective screening tools have prevented the rapid identification of causative genes. Androgen signaling is among the most influential modulators of LGU development. The present study uses SpDamID technology in vivo to generate a comprehensive map of the pathways actively regulated by the androgen receptor (AR) in the genitalia in the presence of the p300 …

Feasibility Of Interleukin-6 Receptor Blockade In Cardiac Antibody-Mediated Rejection, April A Pottebaum, Spenser E. January, Chang Liu, Steven Lavine, Joel D. Schilling, Kory J. Lavine

2020-Current year OA Pubs

BACKGROUND: Antibody-mediated rejection (AMR) remains a significant cause of heart transplant mortality with few effective therapies.

METHODS: This study aimed to describe initial experience of using interleukin-6 receptor blockade with tocilizumab in the treatment of acute cardiac AMR at Barnes-Jewish Hospital/Washington University Transplant Center from July 2017 to May 2021 (n = 7). Clinical, echocardiographic, and serum alloantibody data were analyzed before and after treatment.

RESULTS: All participants demonstrated marked improvement in functional status. Echocardiographic data following 4-6 mo of tocilizumab revealed significant improvements in biventricular systolic function for all participants. Consistent reductions in donor-specific HLA or angiotensin type I …

Disease Characteristics, Treatments, And Outcomes Of Patients With Pulmonary Arterial Hypertension Treated With Selexipag In Real-World Settings From The Sphere Registry (Selexipag: The Users Drug Registry), Vallerie Mclaughlin, Harrison W Farber, Kristin B Highland, Anna R Hemnes, Murali M Chakinala, Kelly M Chin, Michelle Han, Michelle Cho, Tobore Tobore, Mohammad Rahman, Nick H Kim

2020-Current year OA Pubs

BACKGROUND: Selexipag is an oral prostacyclin receptor agonist, indicated for pulmonary arterial hypertension to delay disease progression and reduce the risk of pulmonary arterial hypertension-related hospitalization. SelexiPag: tHe usErs dRug rEgistry (NCT03278002) was a US-based, prospective, real-world registry of selexipag-treated patients.

METHODS: Adults with pulmonary hypertension (enrolled 2016-2020) prescribed selexipag were followed for ≤18 months, with data collected at routine clinic visits. Patients were defined as newly or previously initiated if they had started selexipag ≤60 days or >60 days, respectively, before enrollment.

RESULTS: The registry included 829 patients (430 newly initiated, 399 previously initiated; 759 with pulmonary arterial hypertension), …

Adverse Outcomes And An Immunosuppressed Endotype In Septic Patients With Reduced Ifn-Γ Elispot, Evan L. Barrios, Drew E. Del Toro, Alexandra Dram, Sandra Meszaros, Sydney Miles, Andrew H. Walton, Anne M. Drewry, Isaiah R. Turnbull, Richard S Hotchkiss, Et Al.

2020-Current year OA Pubs

BACKGROUNDSepsis remains a major clinical challenge for which successful treatment requires greater precision in identifying patients at increased risk of adverse outcomes requiring different therapeutic approaches. Predicting clinical outcomes and immunological endotyping of septic patients generally relies on using blood protein or mRNA biomarkers, or static cell phenotyping. Here, we sought to determine whether functional immune responsiveness would yield improved precision.METHODSAn ex vivo whole-blood enzyme-linked immunosorbent spot (ELISpot) assay for cellular production of interferon γ (IFN-γ) was evaluated in 107 septic and 68 nonseptic patients from 5 academic health centers using blood samples collected on days 1, 4, and 7 …

Low Rna Disruption During Neoadjuvant Chemotherapy Predicts Pathologic Complete Response Absence In Patients With Breast Cancer, Marina Elena Cazzaniga, Foluso Ademuyiwa, Et Al.

2020-Current year OA Pubs

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in …

Biopsychosocial Factors Associated With Pain And Pain-Related Outcomes In Adults And Children With Sickle Cell Disease: A Multivariable Analysis Of The Grndad Multicenter Registry, Martha O Kenney, Sana Saif Ur Rehman, Et Al.

2020-Current year OA Pubs

Pain is the primary symptomatic manifestation of sickle cell disease (SCD), an inherited hemoglobinopathy. The characteristics that influence pain experiences and outcomes in SCD are not fully understood. The primary objective of this study was to use multivariable modeling to examine associations of biopsychosocial variables with a disease-specific measure of pain interference known as pain impact. We conducted a secondary analysis of data from the Global Research Network for Data and Discovery national SCD registry. A total of 657 children and adults with SCD were included in the analysis. This sample was 60% female with a median age of 34 …

Primary Results Of The Saval Randomized Trial Of A Paclitaxel-Eluting Nitinol Stent Versus Percutaneous Transluminal Angioplasty In Infrapopliteal Arteries, Hans Van Overhagen, Patrick J Geraghty, Et Al.

2020-Current year OA Pubs

BACKGROUND: Effective and durable options for infrapopliteal artery revascularization for patients with chronic limb-threatening ischemia (CLTI) are limited.

METHODS: The SAVAL trial is a prospective, multicenter, randomized trial of patients with CLTI and infrapopliteal artery lesions with total lesion length ⩽ 140 mm, stenosis ⩾ 70%, and Rutherford category 4-5 assigned 2:1 to treatment with the SAVAL self-expandable paclitaxel drug-eluting stent (DES) or percutaneous transluminal angioplasty (PTA) with an uncoated balloon. The primary effectiveness endpoint was primary vessel patency (i.e., core lab-adjudicated duplex ultrasound-based flow at 12 months in the absence of clinically driven target lesion revascularization or surgical bypass …

Enlarged Perivascular Spaces In Infancy And Autism Diagnosis, Cerebrospinal Fluid Volume, And Later Sleep Problems, Dea Garic, Robert C Mckinstry, Kelly N Botteron, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Perivascular spaces (PVS) and cerebrospinal fluid (CSF) are essential components of the glymphatic system, regulating brain homeostasis and clearing neural waste throughout the lifespan. Enlarged PVS have been implicated in neurological disorders and sleep problems in adults, and excessive CSF volume has been reported in infants who develop autism. Enlarged PVS have not been sufficiently studied longitudinally in infancy or in relation to autism outcomes or CSF volume.

OBJECTIVE: To examine whether enlarged PVS are more prevalent in infants who develop autism compared with controls and whether they are associated with trajectories of extra-axial CSF volume (EA-CSF) and sleep …

Stratification Of Risk For Emergent Intracranial Abnormalities In Children With Headaches: A Pediatric Emergency Care Applied Research Network (Pecarn) Study Protocol, Daniel S Tsze, Kimberly S Quayle, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA …

A Multi-Institutional Phase 2 Trial Of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy For Borderline Resectable And Locally Advanced Pancreatic Cancer, Parag Jitendra Parikh, Hyun Kim, Lauren E Henke, Alex T Price, Et Al.

2020-Current year OA Pubs

PURPOSE: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC).

METHODS AND MATERIALS: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to …

Humoral Immune Response To Covid-19 Mrna Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Ofatumumab, Amit Bar-Or, Rany Aburashed, Angel R Chinea, Barry A Hendin, Elisabeth Lucassen, Xiangyi Meng, James Stankiewicz, Mark J Tullman, Anne H Cross

2020-Current year OA Pubs

BACKGROUND: There are limited data available regarding the impact of ofatumumab, an anti-CD20 B-cell-depleting monoclonal antibody for relapsing multiple sclerosis (RMS), on vaccination response. The study objective was to assess humoral immune response (HIR) to non-live coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccination in patients with RMS treated with ofatumumab.

METHODS: This was an open-label, single-arm, multicenter, prospective pilot study of patients with RMS aged 18-55 years who received 2 or 3 doses of a COVID-19 mRNA vaccine after ≥1 month of subcutaneous ofatumumab (20 mg/month) treatment. The primary endpoint was the proportion of patients achieving HIR, as defined …

A Blood Biomarker Test For Brain Amyloid Impacts The Clinical Evaluation Of Cognitive Impairment, Mark Monane, B Joy Snider, Et Al.

2020-Current year OA Pubs

OBJECTIVE: The objective of this study was to examine clinicians' patient selection and result interpretation of a clinically validated mass spectrometry test measuring amyloid beta and ApoE blood biomarkers combined with patient age (PrecivityAD® blood test) in symptomatic patients evaluated for Alzheimer's disease (AD) or other causes of cognitive decline.

METHODS: The Quality Improvement and Clinical Utility PrecivityAD Clinician Survey (QUIP I, ClinicalTrials.gov Identifier: NCT05477056) was a prospective, single-arm cohort study among 366 patients evaluated by neurologists and other cognitive specialists. Participants underwent blood biomarker testing and received an amyloid probability score (APS), indicating the likelihood of a positive result …

Prospective Ptctc Trial Of Myeloablative Haplo-Bmt With Posttransplant Cyclophosphamide For Pediatric Acute Leukemias, Juan C Fierro-Pineda, Andrew Cluster, Et Al.

2020-Current year OA Pubs

Promising results have been reported for adult patients with high-risk hematologic malignancies undergoing haploidentical bone marrow transplant (haploBMT) with posttransplant cyclophosphamide (PTCy). To our knowledge, we report results from the first multicenter trial for pediatric and young adult patients with high-risk acute leukemias and myelodysplastic syndrome (MDS) in the Pediatric Transplantation and Cellular Therapy Consortium. Nine centers performed transplants in 32 patients having acute leukemias or MDS, with myeloablative conditioning (MAC), haploBMT with PTCy, mycophenolate mofetil, and tacrolimus. The median patient age was 12 years. Diagnoses included AML (15), ALL (11), mixed-lineage leukemia (1), and MDS (5). Transplant-related mortality (TRM) …

Proteogenomic Insights Suggest Druggable Pathways In Endometrial Carcinoma, Yongchao Dou, Rita Jui-Hsien Lu, Yige Wu, Matthew A Wyczalkowski, David Mutch, Li Ding, Et Al.

2020-Current year OA Pubs

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render …

Medication And Road Test Performance Among Cognitively Healthy Older Adults, David B Carr, Kebede Beyene, Jason Doherty, Samantha A Murphy, Ann M Johnson, Hailee Domash, Noah Riley, Alexis Walker, Ashwin Sabapathy, John C Morris, Ganesh M Babulal

2020-Current year OA Pubs

IMPORTANCE: Older adults are increasingly prescribed medications that have adverse effects. Prior studies have found a higher risk of motor vehicle crashes to be associated with certain medication use.

OBJECTIVE: To determine whether specific medication classes were associated with performance decline as assessed by a standardized road test in a community sample of cognitively healthy older adults, to evaluate additional associations of poor road test performance with comorbid medical conditions and demographic characteristics, and to test the hypothesis that specific medication classes (ie, antidepressants, benzodiazepines, sedatives or hypnotics, anticholinergics, antihistamines, and nonsteroidal anti-inflammatory drugs or acetaminophen) would be associated with …

Development And Replication Of Objective Measurements Of Social Visual Engagement To Aid In Early Diagnosis And Assessment Of Autism, Warren Jones, Cheryl Klaiman, Shana Richardson, Meena Lambha, Morganne Reid, Taralee Hamner, Chloe Beacham, Peter Lewis, Jose Paredes, Laura Edwards, Natasha Marrus, John N Constantino, Sarah Shultz, Ami Klin

2020-Current year OA Pubs

IMPORTANCE: Autism spectrum disorder is a common and early-emerging neurodevelopmental condition. While 80% of parents report having had concerns for their child's development before age 2 years, many children are not diagnosed until ages 4 to 5 years or later.

OBJECTIVE: To develop an objective performance-based tool to aid in early diagnosis and assessment of autism in children younger than 3 years.

DESIGN, SETTING, AND PARTICIPANTS: In 2 prospective, consecutively enrolled, broad-spectrum, double-blind studies, we developed an objective eye-tracking-based index test for children aged 16 to 30 months, compared its performance with best-practice reference standard diagnosis of autism (discovery study), …

Lower Levels Of Th1 And Th2 Cytokines In Cerebrospinal Fluid (Csf) At The Time Of Initial Csf Shunt Placement In Children Are Associated With Subsequent Shunt Revision Surgeries, Tamara D Simon, Sabrina Sedano, Yael Rosenberg-Hasson, Ramon Durazo-Arvizu, Kathryn B Whitlock, Paul Hodor, Jason S Hauptman, David D Limbrick, Patrick Mcdonald, Jeffrey G Ojemann, Holden T Maecker, Cerebrospinal Fluid Microbiota In Shunts Climb Study Group

2020-Current year OA Pubs

OBJECTIVE: We compare cytokine profiles at the time of initial CSF shunt placement between children who required no subsequent shunt revision surgeries and children requiring repeated CSF shunt revision surgeries for CSF shunt failure. We also describe the cytokine profiles across surgical episodes for children who undergo multiple subsequent revision surgeries.

METHODS: This pilot study was nested within an ongoing prospective multicenter study collecting CSF samples and clinical data at the time of CSF shunt surgeries since August 2014. We selected cases where CSF was available for children who underwent an initial CSF shunt placement and had no subsequent shunt …

Safety And Efficacy Of Riluzole In Acute Spinal Cord Injury Study (Riscis): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial, Michael G Fehlings, Wilson Z Ray, Et Al.

2020-Current year OA Pubs

Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.

Feasibility Of The Audio-Visual Assisted Therapeutic Ambience In Radiotherapy (Avatar) System For Anesthesia Avoidance In Pediatric Patients: A Multicenter Trial, Paulina M Gutkin, Stephanie M Perkins, Et Al.

2020-Current year OA Pubs

PURPOSE: The Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) system was the first published radiation therapy (RT)-compatible system to reduce the need for pediatric anesthesia through video-based distraction. We evaluated the feasibility of AVATAR implementation and effects on anesthesia use, quality of life, and anxiety in a multicenter pediatric trial.

METHODS AND MATERIALS: Pediatric patients 3 to 10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled. Children able to undergo at least 1 fraction of RT using AVATAR without anesthesia were considered successful (S). Patients requiring anesthesia for their entire treatment course were nonsuccessful (NS). …

Evaluation Of Plasma Biomarkers To Predict Major Adverse Kidney Events In Hospitalized Patients With Covid-19, Steven Menez, Madhurima Kaushal, Sanjay Jain, Et Al.

2020-Current year OA Pubs

RATIONALE & OBJECTIVE: Patients hospitalized with COVID-19 are at increased risk for major adverse kidney events (MAKE). We sought to identify plasma biomarkers predictive of MAKE in patients hospitalized with COVID-19.

STUDY DESIGN: Prospective cohort study.

SETTING & PARTICIPANTS: A total of 576 patients hospitalized with COVID-19 between March 2020 and January 2021 across 3 academic medical centers.

EXPOSURE: Twenty-six plasma biomarkers of injury, inflammation, and repair from first available blood samples collected during hospitalization.

OUTCOME: MAKE, defined as KDIGO stage 3 acute kidney injury (AKI), dialysis-requiring AKI, or mortality up to 60 days.

ANALYTICAL APPROACH: Cox proportional hazards regression …

Intensive Care Unit Sinks Are Persistently Colonized With Multidrug Resistant Bacteria And Mobilizable, Resistance-Conferring Plasmids, Luke Diorio-Toth, Meghan A. Wallace, Christopher W. Farnsworth, Bin Wang, Danish Gul, Jennie H. Kwon, Saadia Andleeb, Carey-Ann D. Burnham, Gautam Dantas

2020-Current year OA Pubs

Contamination of hospital sinks with microbial pathogens presents a serious potential threat to patients, but our understanding of sink colonization dynamics is largely based on infection outbreaks. Here, we investigate the colonization patterns of multidrug-resistant organisms (MDROs) in intensive care unit sinks and water from two hospitals in the USA and Pakistan collected over 27 months of prospective sampling. Using culture-based methods, we recovered 822 bacterial isolates representing 104 unique species and genomospecies. Genomic analyses revealed long-term colonization by

Prospective Role Of Cefiderocol In The Management Of Carbapenem-Resistant Acinetobacter Baumannii Infections: Review Of The Evidence, Marin Kollef, Herve Dupont, David E Greenberg, Pierluigi Viale, Roger Echols, Yoshinori Yamano, David P Nicolau

2020-Current year OA Pubs

Carbapenem-resistant Acinetobacter baumannii (CRAB) has been classified by the World Health Organization as being in the critical category of pathogens requiring urgent new antibiotic treatment options. Cefiderocol, the first approved siderophore cephalosporin, was designed for the treatment of carbapenem-resistant Gram-negative pathogens, particularly the non-fermenting species A. baumannii and Pseudomonas aeruginosa. Cefiderocol is mostly stable against hydrolysis by serine β-lactamases and metallo-β-lactamases, which are leading causes of carbapenem resistance. This review collates the available evidence on the in vitro activity, pharmacokinetics/pharmacodynamics, and efficacy and safety of cefiderocol, and outlines its current role in the management of CRAB infections. In vitro surveillance …

Androgen Deprivation And Radiotherapy With Or Without Docetaxel For Localized High-Risk Prostate Cancer: Long-Term Follow-Up From The Randomized Nrg Oncology Rtog 0521 Trial, Oliver Sartor, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

BACKGROUND: Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer.

OBJECTIVE: To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT.

DESIGN, SETTING, AND PARTICIPANTS: High-risk localized prostate cancer patients (>50% of patients had Gleason 9-10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. …

Gel Stent Versus Trabeculectomy: The Randomized, Multicenter, Gold-Standard Pathway Study (Gps) Of Effectiveness And Safety At 12 Months, Arsham Sheybani, Vanessa Vera, Davinder S Grover, Steven D Vold, Frank Cotter, Sahar Bedrood, Gagan Sawhney, Scott D Piette, Susan Simonyi, Xuemin Gu, Mini Balaram, Mark J Gallardo

2020-Current year OA Pubs

PURPOSE: To compare effectiveness and safety of the gel stent to trabeculectomy in open-angle glaucoma (OAG).

DESIGN: Prospective, randomized, multicenter, noninferiority study.

METHODS: Patients with OAG and intraocular pressure (IOP) 15 to 44 mm Hg on topical IOP-lowering medication were randomized 2:1 to gel stent implantation or trabeculectomy. Primary end point (surgical success): percentage of patients at month 12 achieving ≥20% IOP reduction from baseline without medication increase, clinical hypotony, vision loss to counting fingers, or secondary surgical intervention (SSI) in a noninferiority test with 24% margins. Secondary end points (month 12) included mean IOP and medication count, postoperative intervention …

Long-Term Endothelial Safety Profile With Istent Inject In Patients With Open-Angle Glaucoma, Iqbal Ike K Ahmed, Arsham Sheybani, Ticiana De Francesco, Jonathan H Lass, Beth Ann Benetz, Thomas W Samuelson, Dale Usner, L Jay Katz

2020-Current year OA Pubs

PURPOSE: To report 5-year postoperative safety data of iStent inject, including overall stability, endothelial cell density (ECD), and endothelial cell loss (ECL) in patients with mild-to-moderate primary open-angle glaucoma (POAG).

DESIGN: 5-year follow-up safety study of the prospective, randomized, single-masked, concurrently controlled, multicenter iStent inject pivotal trial.

METHODS: In this 5-year follow-up safety study of the 2-year iStent inject pivotal randomized controlled trial, patients receiving iStent inject placement and phacoemulsification or phacoemulsification alone were studied for the incidence of clinically relevant complications associated with iStent inject placement and stability. Corneal endothelial endpoints were mean change in ECD from screening and …

Utility Of Targeted Gene Sequencing To Differentiate Myeloid Malignancies From Other Cytopenic Conditions, Amy E Dezern, Robert S Fulton, Matthew J Walter, Et Al.

2020-Current year OA Pubs

The National Heart, Lung, and Blood Institute-funded National MDS Natural History Study (NCT02775383) is a prospective cohort study enrolling patients with cytopenia with suspected myelodysplastic syndromes (MDS) to evaluate factors associated with disease. Here, we sequenced 53 genes in bone marrow samples harvested from 1298 patients diagnosed with myeloid malignancy, including MDS and non-MDS myeloid malignancy or alternative marrow conditions with cytopenia based on concordance between independent histopathologic reviews (local, centralized, and tertiary to adjudicate disagreements when needed). We developed a novel 2-stage diagnostic classifier based on mutational profiles in 18 of 53 sequenced genes that were sufficient to best …

Metabolic Signatures Of Cardiac Dysfunction, Multimorbidity, And Post-Transcatheter Aortic Valve Implantation Death, Andrew S Perry, Nishath Quader, Alan Zajarias, Et Al.

2020-Current year OA Pubs

Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort …