Showing papers by "Atlantic Health System published in 2021"

Symptomatic Acute Myocarditis in 7 Adolescents After Pfizer-BioNTech COVID-19 Vaccination.

Abstract: Trials of coronavirus disease 2019 (COVID-19) vaccination included limited numbers of children, so they may not have detected rare but important adverse events in this population. We report 7 cases of acute myocarditis or myopericarditis in healthy male adolescents who presented with chest pain all within 4 days after the second dose of Pfizer-BioNTech COVID-19 vaccination. Five patients had fever around the time of presentation. Acute COVID-19 was ruled out in all 7 cases on the basis of negative severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction test results of specimens obtained by using nasopharyngeal swabs. None of the patients met criteria for multisystem inflammatory syndrome in children. Six of the 7 patients had negative severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody assay results, suggesting no previous infection. All patients had an elevated troponin. Cardiac MRI revealed late gadolinium enhancement characteristic of myocarditis. All 7 patients resolved their symptoms rapidly. Three patients were treated with nonsteroidal antiinflammatory drugs only, and 4 received intravenous immunoglobulin and corticosteroids. In this report, we provide a summary of each adolescent's clinical course and evaluation. No causal relationship between vaccine administration and myocarditis has been established. Continued monitoring and reporting to the US Food and Drug Administration Vaccine Adverse Event Reporting System is strongly recommended.

Lifileucel, a Tumor-Infiltrating Lymphocyte Therapy, in Metastatic Melanoma.

Abstract: PURPOSEEffective treatment options are limited for patients with advanced (metastatic or unresectable) melanoma who progress after immune checkpoint inhibitors and targeted therapies. Adoptive cell...

Clinical practice guidelines by the infectious diseases society of America (IDSA), American academy of neurology (AAN), and american college of rheumatology (acr): 2020 guidelines for the prevention, diagnosis and treatment of lyme disease

Abstract: This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis, and Treatment of Lyme Disease.

Abstract: This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Motixafortide and Pembrolizumab Combined to Nanoliposomal Irinotecan, Fluorouracil, and Folinic Acid in Metastatic Pancreatic Cancer: The COMBAT/KEYNOTE-202 Trial

Abstract: Purpose: Pancreatic ductal adenocarcinoma (PDAC) is largely unresponsive to checkpoint inhibitors. Blockade of the CXCR4/CXCL12 axis increases intratumoral trafficking of activated T cells while restraining immunosuppressive elements. This study evaluates dual blockade of CXCR4 and PD1 with chemotherapy in PDAC. Experimental Design: Multicenter, single arm, phase II study to evaluate the safety and efficacy of motixafortide and pembrolizumab combined to chemotherapy in patients with de novo metastatic PDAC and disease progression on front-line gemcitabine-based therapy (NCT02826486). Subjects received a priming phase of motixafortide daily on days 1-5, followed by repeated cycles of motixafortide twice a week, pembrolizumab every 3 weeks, nanoliposomal irinotecan, fluorouracil and leucovorin every 2 weeks (NAPOLI-1 regimen). The primary objective was objective response rate (ORR). Secondary objectives included overall survival (OS), progression-free survival (PFS), disease control rate, safety and tolerability. Results: A total of 43 patients were enrolled. The objective response rate according to RECISTv1.1 was 21.1% with confirmed ORR of 13.2%. The disease control rate was 63.2% with median duration of clinical benefit of 5.7 months. In the intention to treat population, median PFS was 3.8 months and median OS was 6.6 months. The triple combination was safe and well tolerated with toxicity comparable to the NAPOLI-1 regimen. Notably, the incidence of grade 3 or higher neutropenia and infection were 7%, lower than expected for this chemotherapy regimen. Conclusion: Triple combination of motixafortide, pembrolizumab and chemotherapy was safe, well tolerated and showed signs of efficacy in a population with poor prognosis and aggressive disease.

Natural History of Very Early Onset Inflammatory Bowel Disease in North America: A Retrospective Cohort Study.

Abstract: Background The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. Methods We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years. Results The study population included 269 children (105 [39%] Crohn's disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9-5.2). Most (94%) Crohn's disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn's disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis. Conclusions Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%-15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.

Clinical Responses of Oncolytic Coxsackievirus A21 (V937) in Patients With Unresectable Melanoma.

Abstract: PURPOSEWe evaluated the activity of intratumoral Coxsackievirus A21 (V937) in 57 patients with unresectable stage IIIC or IV melanoma.PATIENTS AND METHODSIn this multicenter, open-label, phase II s...

Assessment of Arsenic Trioxide and All-trans Retinoic Acid for the Treatment of Pediatric Acute Promyelocytic Leukemia: A Report From the Children's Oncology Group AAML1331 Trial.

Abstract: Importance All-trans retinoic acid (ATRA) and arsenic trioxide therapy without the use of maintenance therapy has been found to be beneficial for the treatment of adults with standard-risk acute promyelocytic leukemia (APL). However, it is unclear whether similar regimens are safe and beneficial for the treatment of high-risk APL or pediatric patients with standard-risk APL. Objective To assess whether treatment with an ATRA and arsenic trioxide-based regimen is safe and allows for the elimination or substantial reduction of chemotherapy use among pediatric patients with standard-risk or high-risk APL, respectively. Design, Setting, and Participants The Children's Oncology Group AAML1331 study is a nonrandomized, noninferiority trial that examined survival outcomes among 154 pediatric patients with APL compared with a historical control group of patients with APL from the AAML0631 study. Patients aged 1 to 21 years were enrolled at 85 pediatric oncology centers (members of the Children's Oncology Group) in Australia, Canada, and the US from June 29, 2015, to May 7, 2019, with follow-up until October 31, 2020. All patients had newly diagnosed APL and were stratified into standard-risk APL (white blood cell count <10 000/μL) and high-risk APL (white blood cell count ≥10 000/μL) cohorts. Interventions All patients received ATRA and arsenic trioxide continuously during induction therapy and intermittently during 4 consolidation cycles. Patients with high-risk APL received 4 doses of idarubicin during induction therapy only. The duration of therapy was approximately 9 months, and no maintenance therapy was administered. Main Outcomes and Measures Event-free survival (EFS) at 2 years after diagnosis. Results Among 154 patients (median age, 14.4 years [range, 1.1-21.7 years]; 81 male participants [52.6%]) included in the analysis, 98 patients (63.6%) had standard-risk APL, and 56 patients (36.4%) had high-risk APL. The median follow-up duration was 24.7 months (range, 0-49.5 months) for patients with standard-risk APL and 22.8 months (range, 0-47.7 months) for patients with high-risk APL. Patients with standard-risk APL had a 2-year EFS rate of 98.0% and an overall survival rate of 99.0%; adverse events included 1 early death during induction therapy and 1 relapse. Patients with high-risk APL had a 2-year EFS rate of 96.4% and an overall survival rate of 100%; adverse events included 2 relapses and 0 deaths. These outcomes met predefined noninferiority criteria (noninferiority margin of 10% among those with standard-risk APL and 14.5% among those with high-risk APL). Conclusions and Relevance In this nonrandomized, noninferiority trial, pediatric patients with standard-risk APL who received treatment with a chemotherapy-free ATRA and arsenic trioxide regimen experienced positive outcomes. Patients with high-risk APL also had positive outcomes when treated with a novel ATRA and arsenic trioxide-based regimen that included 4 doses of idarubicin during induction therapy only and no maintenance therapy. The 2-year EFS estimates were noninferior to the historical comparator group, and advantages of the regimen included shorter treatment duration, lower exposure to anthracycline and intrathecal chemotherapy, and fewer days hospitalized. Trial Registration ClinicalTrials.gov Identifier: NCT02339740.

Lower rates of readmission following integration of family-based treatment in a higher level of care.

Abstract: There has been a growing effort to incorporate the evidence-based practices of family-based treatment (FBT) into higher levels of care, such as day-treatment programs. This study tracked the effect...

How to screen for vasa previa.

Abstract: We discuss practical points and useful tips which are helpful in evaluating patients for vasa previa. This article is protected by copyright. All rights reserved.

Specificity and Diagnostic Utility of Cerebrospinal Fluid CXCL13 in Lyme Neuroborreliosis.

Abstract: Background Demonstration of intrathecal production of Borrelia-specific antibodies (ITAb) is considered the most specific diagnostic marker of Lyme neuroborreliosis (LNB). Limitations include delayed detectability in early infection and continued presence long after successful treatment. Markers of active inflammation-increased cerebrospinal fluid (CSF) leukocytes, protein, and CXCL13-provide nonspecific markers of active infection. To assess the utility of CSF CXCL13, we measured its concentration in 132 patients with a broad spectrum of neuroinflammatory disorders, including LNB. Methods CSF CXCL13 was measured by immunoassay. Spearman rank correlation test was performed to explore its relationship to conventional markers of neuroinflammation and Borrelia-specific ITAb production. Results In non-LNB neuroinflammatory disorders, CSF CXCL13 elevation correlated with CSF immunoglobulin G (IgG) synthesis and leukocyte count. In LNB, CXCL13 concentration was far greater than expected from overall CSF IgG synthesis, and correlated with Borrelia-specific ITAb synthesis. Median CSF CXCL13 concentration in ITAb-positive LNB patients was > 500 times greater than in any other group. Conclusions Intrathecal CXCL13 and IgG production are closely interrelated. CXCL13 is disproportionately increased in "definite LNB," defined as having demonstrable Borrelia-specific ITAb, but not "probable LNB," without ITAb. This disproportionate increase may help identify patients with very early infection or those with active vs treated LNB, or may help to differentiate ITAb-defined active LNB from other neuroinflammatory disorders. However, its reported specificity is closely related to the diagnostic requirement for ITAb. It may add little specificity to the demonstration of a pleocytosis or increased overall or specific IgG production in the CSF.

Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy.

Abstract: 9505Background: Immune checkpoint inhibitors (ICI) have become standard of care for treatment of metastatic melanoma. Most patients with advanced melanoma progress on ICI and treatment options are ...

Leptomeningeal Disease in Glioblastoma: Endgame or Opportunity?

Abstract: Glioblastoma is an aggressive cancer with a notoriously poor prognosis. Recent advances in treatment have increased overall survival, though this may be accompanied by an increased incidence of leptomeningeal disease (LMD). LMD carries a particularly severe prognosis and remains a late stage manifestation of glioblastoma without satisfactory treatment. The objective of this review is to survey the literature on treatment of LMD in glioblastoma and to more fully characterize the current therapeutic strategies. The authors performed a systematic review following PRISMA criteria on PubMed and OVID databases. Articles that included adult patients with LMD from glioblastoma were retrieved and reviewed. LMD in glioblastoma patients is increasing in incidence, with reports of up to 21%. The overall survival without treatment is alarmingly brief, with patients surviving between 1.6–3.8 months. All studies showed that treatment does improve overall survival significantly, increasing to 11.7 months in one study. However, no one adjuvant or surgical therapy has been shown to improve survival in LMD significantly over another. Direct treatment methods include chemotherapy (standard, anti-angiogenic, intrathecal, immunotherapy), and radiation. Hydrocephalus is a complication in LMD that can be treated with ventriculoperitoneal shunt placement, however treating hydrocephalus and delivering intrathecal chemotherapy is a challenge. Though evidence remains lacking and there is no consensus, treatments show a trend towards improving survival and should be considered on a case-by-case basis. Further studies are necessary in the pursuit of a standard of care.

Myocarditis in COVID-19 presenting with cardiogenic shock: a case series.

Abstract: Background SARS-CoV2, also known as COVID-19, is a specific strain of coronavirus that is responsible for an ongoing global pandemic. COVID-19 primarily targets the respiratory system via droplet transmission, causing symptoms similar to influenza, including fever, cough, and shortness of breath. It is now known to impact other organ systems, causing significant cardiovascular and gastrointestinal illness, among others. Case summary We describe two cases of COVID-19 induced myocarditis presenting with cardiogenic shock. These cases highlight the importance of understanding the lethal cardiac complications of COVID-19 infection, as well as its presentation, diagnosis, pathophysiology, and potential treatment options. These two cases involve patients without underlying cardiovascular disease risk factors who experienced prolonged symptoms of COVID-19 infection. Both patients presented with cardiogenic shock more than one week after symptom onset and diagnosis. These cases demonstrate the late presentation of myocarditis and cardiogenic shock, treated with corticosteroids and inotropes, with subsequent recovery of cardiac function. Discussion The cases highlight the importance of recognizing late presentation viral myocarditis secondary to COVID-19 infection, even in patients without underlying cardiac disease.

Transcriptome analysis of collagen VI-related muscular dystrophy muscle biopsies

Abstract: Objective To define the transcriptomic changes responsible for the histologic alterations in skeletal muscle and their progression in collagen VI-related muscular dystrophy (COL6-RD). Methods COL6-RD patient muscle biopsies were stratified into three groups based on the overall level of pathologic severity considering degrees of fibrosis, muscle fiber atrophy, and fatty replacement of muscle tissue. Using microarray and RNA-Seq, we then performed global gene expression profiling on the same muscle biopsies and compared their transcriptome with age- and sex-matched controls. Results COL6-RD muscle biopsy transcriptomes as a group revealed prominent upregulation of muscle extracellular matrix component genes and the downregulation of skeletal muscle and mitochondrion-specific genes. Upregulation of the TGFβ pathway was the most conspicuous change across all biopsies and was fully evident even in the mildest/earliest histological group. There was no difference in the overall transcriptional signature between the different histologic groups but polyserial analysis identified relative changes along with COL6-RD histological severity. Interpretation Overall, our study establishes the prominent dysregulation of extracellular matrix genes, TGFβ signaling, and its downstream cellular pathways at the transcriptomic level in COL6-RD muscle.

Suppression of Bile Acid Synthesis in a Preterm Infant Receiving Prolonged Parenteral Nutrition

Abstract: Bile acid metabolism is altered in neonates on parenteral nutrition (PN), predisposing them to parenteral nutrition-associated liver disease. Cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in the bile acid synthesis pathway, is repressed by fibroblast growth factor 19 (FGF19) and phytosterols (PS). We describe a case of a preterm infant who developed necrotizing enterocolitis (NEC) and received exclusive PN for over 2 months. Our objective was to serially assess CYP7A1 activity and plasma FGF19 and PS concentrations in this infant case compared to five healthy preterm infants. We found that CYP7A1 activity increased during the first 2 weeks of life in control infants but was undetectable in the infant case. FGF19 concentrations were high at birth in all infants and subsequently declined and did not differ between the case and control infants. As expected, PS concentrations were elevated in the infant case and continued to increase despite lipid minimization. In conclusion, CYP7A1 activity was gradually upregulated in healthy preterm infants but remained suppressed in the infant requiring prolonged PN. Preterm infants also had elevated FGF19 concentrations at birth, which decreased with advancing postnatal age.

First-time in-human study of VMD-928, an oral allosteric TrkA selective inhibitor targeting TrkA protein overexpression, in patients with solid tumors or lymphoma.

Abstract: 3081Background: Tropomyosin receptor kinase A (TrkA) is a protein encoded by the NTRK1 gene. Upregulation of TrkA signal transduction pathways, which can be caused by either NTRK1 gene fusions or i...

Sports-Related Traumatic Brain Injury and Concussion

Abstract: Sports-related concussions (SRC) continue to be a major area of concern in athletes who participate in collision and contact sports. There is growing recognition that concussion from sport is a public health priority, with many states and sport-governing bodies changing rules in an attempt to prevent and/or reduce the incidence of concussion from sport-related impact.

A urinary catheter valve is non-inferior to continuous bladder drainage with respect to post-operative UTIs: a randomized controlled trial

Abstract: Urinary tract infections (UTIs) are common with indwelling catheter use. Our primary aim was to compare UTI rates in women sent home after surgery with continuous bladder drainage versus a urinary catheter valve. This was a non-inferiority prospective randomized controlled study between June 2016 to June 2019. Women who were being discharged home with a Foley catheter following urogynecologic surgery due to urinary retention were randomized to a continuous urinary drainage bag or a urinary catheter valve. The primary outcome of this study was post-operative UTI rates within 30 days of surgery. The secondary outcome was patient satisfaction, as determined by a Foley satisfaction questionnaire. Out of 97 women, 51 were randomized to continuous drainage and 46 to the urinary catheter valve. Comparing UTI rates, the urinary catheter valve (32.6%) was non-inferior to the continuous urinary drainage bag (33.3%). The upper bound of the 95% CI was less than the predetermined non-inferiority margin (difference 0.7%, 95% CI: −0.195, 0.180), and therefore non-inferiority criteria were met. Patients were more satisfied with the urinary catheter valve than with the continuous drainage bag (p ≤ 0.001). Use of this urinary catheter valve increased patient satisfaction without affecting the post-operative UTI rate. This easy and inexpensive device could help patients have a better catheter experience and should be considered in women being discharged home with a urinary catheter.

Periurethral Lidocaine Does Not Decrease Pain After Urodynamic Testing in Women: A Double-Blinded Randomized Control Trial.

Abstract: Objective Urodynamic testing of women is a common procedure to evaluate lower urinary tract symptoms but may cause discomfort. The objective of our study was to determine the effect of externally applied periurethral 2% lidocaine gel on pain scores after complex urodynamic testing in women. Methods This prospective, double-blinded, placebo-controlled randomized trial compared 2% lidocaine gel to water-based lubricant applied to the periurethral area before urodynamic testing in women. Discomfort was measured using a visual analog pain scale (VAS) ranging from 0 to 100. The primary outcome was the difference in VAS from baseline to 4 to 6 hours after urodynamic testing. Secondary outcomes included: VAS difference from baseline to immediately postprocedure and 24 hours after urodynamic testing; VAS scores: at baseline, immediately postprocedure, after 4-6 hours, and after 24 hours; urodynamic testing results; and any adverse events. Sixty-four women per group were needed to provide a power of 80% to detect a 10-mm difference on a 100-point VAS. Results From January 2018 to March 2019, 134 subjects were randomized, 6 subjects were excluded, which resulted in 64 subjects in both the water-based lubricant group and 2% lidocaine gel group. There was no difference in baseline demographics. There was no significant difference in the change in VAS from baseline to 4 to 6 hours after UDT (0, 0 P = 0.88). No difference in secondary outcomes was noted. Conclusions Topically applied 2% lidocaine gel does not decrease pain compared with water-based lubricant. For most women, complex urodynamic testing is not associated with any significant pain. Clinical trial registration www.ClinicalTrials.gov,-NCT03390790, "Lidocaine for Pain After Urodynamic Testing".

Imaging strategies for safety surveillance after renal artery denervation

Abstract: Renal denervation has emerged as a safe and effective therapy to lower blood pressure in hypertensive patients. In addition to the main renal arteries, branch vessels are also denervated in more contemporary studies. Accurate and reliable imaging in renal denervation patients is critical for long-term safety surveillance due to the small risk of renal artery stenosis that may occur after the procedure. This review summarizes three common non-invasive imaging modalities: Doppler ultrasound (DUS), computed tomography angiography (CTA), and magnetic resonance angiography (MRA). DUS is the most widely used owing to cost considerations, ease of use, and the fact that it is less invasive, avoids ionizing radiation exposure, and requires no contrast media use. Renal angiography is used to determine if renal artery stenosis is present when non-invasive imaging suggests renal artery stenosis. We compiled data from prior renal denervation studies as well as the more recent SPYRAL-HTN OFF MED Study and show that DUS demonstrates both high sensitivity and specificity for detecting renal stenosis de novo and in longitudinal assessment of renal artery patency after interventions. In the context of clinical trials DUS has been shown, together with the use of the baseline angiogram, to be effective in identifying stenosis in branch and accessory arteries and merits consideration as the main screening imaging modality to detect clinically significant renal artery stenosis after renal denervation and this is consistent with guidelines from the recent European Consensus Statement on Renal Denervation.