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1.
J Immunother Cancer ; 12(7)2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39032941

ABSTRACT

BACKGROUND: Limited data exist for management strategies targeting immunotherapy-related enteritis (irEnteritis). Systemic corticosteroids are commonly used but often are limited by adverse events. Enteric corticosteroids such as budesonide offer an attractive alternative; however, the ileocolonic release of enteric-coated budesonide has limited utility for diffuse enteritis. Open-capsule budesonide (OCB) is a novel therapeutic approach that offers drug delivery throughout the small bowel. We report outcomes in patients treated with OCB for confirmed or suspected irEnteritis. METHODS: This retrospective cohort included all individuals treated with OCB for irEnteritis at Memorial Sloan Kettering from July 2018 to August 2023. Primary outcomes included clinical response, clinical remission, and corticosteroid-free remission following OCB. Secondary outcomes were OCB-related adverse events and efficacy by gastrointestinal toxicity location. RESULTS: 19 patients (53% female) with irEnteritis were treated with OCB. All patients presented with diarrhea; 15 (79%) reported anorexia with median 6 kg weight loss. 17 patients (89%) underwent esophagogastroduodenoscopy with biopsies revealing enteritis in all; 8 (42%) had concomitant colitis. 15 (79%) patients were treated previously with systemic corticosteroids: 8 (53%) were corticosteroid-dependent while 7 (47%) demonstrated non-response. 18 patients (95%) achieved clinical response, 15 (79%) attained clinical remission, and 11 (58%) had corticosteroid-free remission. Response to OCB was rapid with improvement noted after a median 4 days. 14 (74%) patients restored their pre-irEnteritis weight by OCB cessation. One mild, self-resolving adverse event was reported. CONCLUSIONS: OCB is a safe and effective therapy for irEnteritis. OCB avoids systemic immunosuppression and successfully achieves clinical response and remission even in patients previously nonresponsive to systemic corticosteroids. Future studies are needed to optimize indications and duration.


Subject(s)
Budesonide , Enteritis , Immune Checkpoint Inhibitors , Humans , Female , Budesonide/therapeutic use , Budesonide/pharmacology , Enteritis/drug therapy , Male , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Middle Aged , Retrospective Studies , Aged , Adult
2.
J Nucl Med ; 65(5): 722-727, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38514081

ABSTRACT

Anti-programmed death 1 (PD-1) inhibitors are the standard of care for advanced gastroesophageal cancer. Although recommendations and approval by regulatory agencies are often based on programmed death ligand 1 (PD-L1) expression, pathologic assessments of PD-L1 status have several limitations. Single-site biopsies do not adequately capture disease heterogeneity within individual tumor lesions or among several lesions within the same patient, the PD-L1 combined positive score is a dynamic biomarker subject to evolution throughout a patient's disease course, and repeated biopsies are invasive and not always feasible. Methods: This was a prospective pilot study of the PD-L1-targeting radiotracer, 18F-BMS-986229, with PET imaging (PD-L1 PET) in patients with gastroesophageal cancer. Patients were administered the 18F-BMS-986229 radiotracer intravenously at a dose of 370 MBq over 1-2 min and underwent whole-body PET/CT imaging 60 min later. The primary objective of this study was to evaluate the safety and feasibility of 18F-BMS-986229. The trial is registered with ClinicalTrials.gov (NCT04161781). Results: Between February 3, 2020, and February 2, 2022, 10 patients with gastroesophageal adenocarcinoma underwent PD-L1 PET. There were no adverse events associated with the 18F-BMS-986229 tracer, and imaging did not result in treatment delays; the primary endpoint was achieved. Radiographic evaluation of PD-L1 expression was concordant with pathologic assessment in 88% of biopsied lesions, and 18F-BMS-986229 uptake on PET imaging correlated with pathologic evaluation by the combined positive score (Spearman rank correlation coefficient, 0.64). Seventy-one percent of patients with 18F-BMS-986229 accumulation on PET imaging also had lesions without 18F-BMS-986229 uptake, highlighting the intrapatient heterogeneity of PD-L1 expression. Patients treated with frontline programmed death 1 inhibitors who had 18F-BMS-986229 accumulation in any lesions on PET imaging had longer progression-free survival than patients without tracer accumulation in any lesions (median progression-free survival, 28.4 vs. 9.9 mo), though the small sample size prevents any definitive conclusions. Conclusion: PD-L1 PET imaging was safe, feasible, and concordant with pathologic evaluation and offers a potential noninvasive tool to assess PD-L1 expression.


Subject(s)
B7-H1 Antigen , Esophageal Neoplasms , Positron Emission Tomography Computed Tomography , Stomach Neoplasms , Humans , B7-H1 Antigen/metabolism , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/metabolism , Male , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/metabolism , Female , Middle Aged , Aged , Pilot Projects , Fluorine Radioisotopes , Prospective Studies , Adult
3.
J Adv Periodontol Implant Dent ; 15(2): 93-99, 2023.
Article in English | MEDLINE | ID: mdl-38357330

ABSTRACT

Background: Replacing missing teeth with dental implants has become the best treatment option; therefore, clinicians need to understand the predictability of the treatment. Surface treatment of implants is one of the methods to improve osseointegration, thus improving the quality of treatment. Increasing esthetic awareness among patients has led to the popularity of immediate provisionalization of dental implants. This study investigated the effect of surface treatment on implant stability when loaded with immediate non-functional temporary prostheses and compared the superiority of one surface treatment over the other in terms of osseointegration by evaluating implant stability quotient (ISQ). Methods: Twenty implants with different surface treatments were placed, i.e., resorbable blast media (RBM) surface and alumina blasted/acid-etched (AB/AE) surfaces. All the implants were non-functionally loaded, and ISQ was measured immediately after implant placement and 6 and 12 weeks after non-functional loading. Crestal bone levels, mPI, mSBI, and peri-implant probing depths were compared for both groups at 1, 3, and 6 months. Results: At 12 weeks, all the implants showed desirable ISQ, indicating successful osseointegration. The increase in ISQ at 12 weeks was significantly higher for RBM implants compared to baseline, indicating a more predictable course of osseointegration. Crestal bone levels recorded at 1, 3, and 6 months did not significantly differ between the groups. All other parameters showed comparable values for both groups at all intervals. Conclusion: Replacing missing teeth with dental implants with immediate non-functional restorations is a predictable treatment option.

4.
Braz. j. oral sci ; 8(4): 201-205, Oct.-Dec. 2009. ilus, tab
Article in English | LILACS, BBO - Dentistry | ID: lil-578034

ABSTRACT

Aim: Prevention of periodontal disease progression is the primary goal of periodontal therapy. When conventional therapy is found inadequate to attain periodontal health in chronic periodontitis, local antimicrobial agents have been used as adjunct to scaling and root planing, producing encouragingresults. Hence, a study was undertaken to evaluate clinically, the newly released sustained drugs, PerioColTMCG(Chlorhexidine - CHX- chip) with Periodontal Plus ABTM (Tetracycline fibers). Methods: Patients wereallocated in 3 experimental treatment groups, Group A- SRP + CHX Chip, Group B- SRP + Tetracycline fibers, and Group C- SRP alone (control group). Forty-five sites in 14 patients (9 females and 5 males) with chronic periodontitis (5-8mm probing depth), were evaluated clinically for probing depth (PD) and relative attachment level (RAL). Results: All the treatment groups were found to be efficacious in the treatment of periodontal disease as demonstrated by improvement in PD and RAL. Conclusion: Combination of SRP + CHX chip (Group A) resulted in added benefits compared to the other two treatment groups.


Subject(s)
Humans , Male , Female , Young Adult , Middle Aged , Anti-Infective Agents, Local , Anti-Bacterial Agents/pharmacology , Chlorhexidine/pharmacology , Chronic Periodontitis/drug therapy , Tetracycline/pharmacology , Periodontal Pocket/drug therapy , Combined Modality Therapy , Chlorhexidine/therapeutic use , India , Time Factors , Tetracycline/therapeutic use
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