Atlantic Health System

About: Atlantic Health System is a healthcare organization based out in Morristown, New Jersey, United States. It is known for research contribution in the topics: Health care & Medicine. The organization has 277 authors who have published 299 publications receiving 6594 citations.

799 Durable responses and immune activation with intratumoral electroporation of pIL-12 plus pembrolizumab in actively progressing anti-PD-1 refractory advanced melanoma: KEYNOTE 695 interim data

Abstract: Background Electroporated plasmid IL-12 (TAVO or tavokinogene telseplasmid) is a novel pro-inflammatory intratumoral therapy with substantial single agent activity in melanoma, which has been shown to synergize with anti-PD-1 antibodies in patients predicted as non-responders to anti-PD-1.1 2 Interim data from patients with stage III/IV melanoma actively progressing on anti-PD-1 antibody are presented herein. Methods Patients with confirmed disease progression by RECIST v1.1 after at least 12 weeks of treatment on pembrolizumab or nivolumab (or combination checkpoint blockade) and within 12 weeks of last dose (with no intervening therapies) were enrolled. There was no limit on the number of prior lines of therapy. At least one accessible lesion was electroporated with plasmid IL-12 (pIL-12-EP) on days 1, 5 and 8 every 6 weeks and pembrolizumab was administered every 3 weeks. Tumor response in treated and untreated lesions was assessed by RECIST v1.1 every 12 weeks. Endpoints include ORR, safety, PFS, OS, and DOR. Results The first 56 patients treated of 100 planned were included in this interim analysis. Of these, 84% had Stage IV disease, 30% had M1c or M1d disease, and 27% had prior exposure to ipilimumab. In 54 efficacy evaluable patients the investigator-assessed ORR was 30% (3 CR/13 PR), 5 patients had 100% reduction of target lesions. All responses have been confirmed, only two responding patient progressed while on study, 2 patients completed the study with ongoing responses (figures 1 and 2). In patients with M1c/M1d disease, the ORR was 35.2% (n=6/17). Tumor reduction was observed in untreated lesions in 12 of 12 patients who had unaccessible lesions or accessible untreated lesions. The median overall survival (mOS) and duration of response (mDOR) has not been reached, with a median follow-up time of 13 months. Grade 3 treatment-related adverse events (TRAEs) were seen in 5.4% of patients, and there were no grade 4/5 TRAEs. The rate of grade 3 treatment-emergent (TEAEs) regardless of cause was 23.2%. The median time for pIL-12-EP treatment was 10 minutes (range 2,46). Consistent with prior studies of single-agent pIL-12-EP, tumor IHC, and transcriptomic assessments revealed hallmarks of antigen-specific antitumor immunity in this study. Additional analyses including microbiome, TCR clonality, and peripheral blood biomarker assays will be presented. Conclusions In this rigorously defined PD-1 antibody refractory patient population, the addition of pIL-12-EP to PD-1 antibody therapy induced deep, durable, systemic response in local treated and distant visceral metastatic untreated lesions with nominal systemic toxicity. Trial Registration Trial Registration: NCT#03132675 Ethics Approval The study was approved by a central IRB and/or local institutional IRBs/Ethics Committees as required for each participating institution. Consent Written informed consent was obtained from the patients participating within the trial, the current abstract does not contain sensitive or identifiable information requiring an additional consent from patients. References Algazi A, Bhatia S, Agarwala S, et al. Intratumoral delivery of tavokinogene telseplasmid yields systemic immune responses in metastatic melanoma patients. Annals of Oncology 2019;31:532–540. Algazi A, Twitty C, Tsai K, et al. Phase II trial for IL-12 plasmid transfection and PD-1 blockade in immunologically quiescent melanoma. Clinical Cancer Research 2020;26:2827-2837.

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.

The female continence mechanism measured by high resolution manometry: Urethral bulking versus midurethral sling.

Abstract: Author(s): Wasenda, Erika J; Kirby, Anna C; Lukacz, Emily S; Nager, Charles W | Abstract: AIMS:Traditional technology to characterize urethral pressure changes during dynamic conditions is limited by slow response times or artifact-inducing withdrawal maneuvers. The 8F high-resolution manometry (HRM) catheter (ManoScan™ ESO, Covidien) has advantages of fast response times and the ability to measure urethral pressures along the urethral length without withdrawal. Our objective was to determine static and dynamic maximum urethral closure pressures (MUCPs) and resting functional urethral length (FUL) in women using HRM before and after transurethral bulking and compare results to other women who underwent midurethral sling (MUS). METHODS:We recorded rest, cough, and strain MUCPs and FUL in 24 women before and after transurethral bulking with polydimethylsiloxane (Macroplastique®) using the HRM catheter and compared these changes to HRM values from 26 women who had the same measures before and after MUS. RESULTS:At rest, MUCPs increased minimally after both urethral bulking and MUS (3 vs 0.4 cm H2 O respectively, P = 0.4). Under dynamic conditions there were statistically insignificant small increases in MUCP and these increases were markedly less than after MUS (cough: 1.5 vs 63.8 cm H2 O, P l 0.001 and strain: 11.5 vs 57.7 cm H2 O, P l 0.001). FUL increased by 0.5 cm after transurethral bulking (P = 0.003), and decreased by 0.25 cm after MUS placement (P = 0.012). CONCLUSIONS:The mechanism of continence after urethral bulking differs from MUS. While MUS increases dynamic MUCP, bulking may rely on increasing the length of the continence zone.

Indwelling Versus Immediate Removal of Transurethral Catheter After Robotic Sacrocolpopexy: A Randomized Clinical Trial.

Abstract: INTRODUCTION AND HYPOTHESIS This study evaluates the necessity and effect of an indwelling transurethral catheter in the early postoperative period following a robotic-assisted laparoscopic sacrocolpopexy. METHODS This was a randomized clinical trial of patients who underwent a robotic sacrocolpopexy for pelvic organ prolapse. Patients were randomized to have their transurethral catheter removed 6 hours postoperative (intervention group) or the morning following surgery (control group). Our primary outcome was to compare the number of patients diagnosed with postoperative incomplete bladder empyting in each group. A sample size of 36 patients per group was needed to detect a 25% difference between the 2 groups. Anticipating a 20% patient withdrawal rate, we estimated that we would need a total of 88 participants. Outcome variable was analyzed using χ test, Fisher exact test, Mann-Whitney U test, 2-proportions test, and 2-sample t test. RESULTS From December 2015 through May 2017, 88 women were randomized and analyzed: 44 in the intervention group and 44 in the control group. Women in the intervention group were more likely to be diagnosed with incomplete bladder emptying, 14 (31%) of 44, compared with the control group, 2 (4.5%) of 44, P <0.001. Rate of urinary tract infections within the 30-day postoperative period was also increased in the intervention group, 4 (9%) of 44, compared with 0 in the control group. Postoperative complications were similar between groups. CONCLUSIONS In women undergoing a robotic sacrocolpopexy, early transurethral catheter removal (6 hours postoperative) is associated with an increased rate of incomplete bladder emptying, recatheterization, and urinary tract infections.