Citations

Abstract Background Stroke is a leading cause of mortality and disability globally. However, information about stroke burden in the Philippines is limited. We sought to analyze stroke burden in the Philippines from 1990 to 2023. Methods Incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) estimates from the Global Burden of Disease Study 2023 data were used as indicators to analyze the burden of stroke by sex and age. Temporal trends in both crude and age-standardized rates were analyzed using joinpoint regression analysis. Results In 2023, stroke incidence was estimated at 156.2 (95% uncertainty interval [UI]: 140.8–175.4) thousand, prevalence at 1.2 (95% UI: 1.2–1.4) million, mortality at 72.2 (95% UI: 63.2–83.0) thousand, and DALYs at 2.1 (95% UI: 1.8–2.3) million. High systolic blood pressure was the leading contributor to risk-attributable stroke mortality and DALYs. Since 1990, age-standardized rates declined significantly, whereas crude rates increased markedly. Compared with women, men had a higher fatal burden and consistently exhibited a higher age-standardized burden. Although older adults (≥ 55 years) had the highest stroke burden and achieved reductions in stroke incidence and fatal outcomes, both fatal and non-fatal burdens consistently increased among young adults (35–54 years). Conclusion While age-standardized rates have improved, the rising crude burden and shift towards younger adults present significant public health challenges. These trends highlight the pressing need for aggressive and targeted risk factor control, sustained risk monitoring, and strengthened acute and post-stroke care to mitigate the growing health burden of stroke in the Philippines.

Abstract Frailty is highly prevalent in cardiovascular disease and associates with poor clinical outcomes. Several cardiovascular conditions benefit from invasive interventions, but the impact of these procedures in frail patients remains unclear. We thus performed a systematic review and meta-analysis to summarize evidence and quantify the pooled effect of clinical outcomes of invasive cardiovascular interventions among frail vs. non-frail patients. Systematic search of two electronic databases from January 2015 to April 2025 was performed including all randomized controlled trials (RCTs) and prospective cohort studies examining outcomes of invasive cardiovascular interventions stratified by frailty. Outcomes included all-cause mortality, hospitalizations, and other adverse outcomes. Risk ratios (RRs) and their 95% confidence intervals (CI) were assessed using random-effects models. Thirty-one studies (10 RCTs, 21 prospective, 3 retrospective studies) with a total of 27 534 participants were included. Compared with non-frail patients, frail patients after cardiovascular procedures were at higher risks of all-cause mortality (RR 3.14, 95% CI: 2.29-4.30), and hospitalizations (RR 1.88, 95% CI: 1.29-2.73). Frail patients undergoing transcatheter aortic-valve implantation and percutaneous mitral-valve interventions did not have significant increased mortality risks compared with non-frail patients (P > 0.05). Pre-frailty predicted lower mortality risks amongst patients undergoing transcatheter vs. surgical aortic valve replacement (HR 0.78, 95% CI: 0.67-0.92). Frail patients with non-ST elevation myocardial infarction derived similar mortality benefits from an invasive vs. conservative approach (HR 1.13, 95% CI: 0.64-2.01). In conclusion, frailty prognosticates adverse outcomes following invasive cardiovascular interventions and influences treatment efficacy, highlighting its significance in treatment selection

Introduction The treatment of cancer is associated with high risk for toxicity and high cost. Strategies to enhance the value, quality, and safety of cancer care are often managed independently of one another. Oncology stewardship is a potential framework to unify these efforts and enhance outcomes. This landscape survey establishes baseline information on oncology stewardship in the United States. Methods The Hematology/Oncology Pharmacy Association (HOPA) distributed a 38-item survey composed of demographic, institutional, clinical decision-making, support staff, metrics, and technology sections to 675 HOPA members between 9 September 2022 and 9 October 2022. Results Most organizations (78%) have adopted general pharmacy stewardship practices; however, only 31% reported having established a formalized oncology stewardship team. More than 70% of respondents reported implementation of biosimilars, formulary management, and dose rounding as oncology stewardship initiatives in both inpatient and outpatient settings. Frequently cited barriers to oncology stewardship included lack of clinical pharmacist availability (74%), lack of oncology stewardship training (62%), lack of physician/provider buy-in (32%), and lack of cost-saving metrics (33%). Only 6.6% of survey respondents reported their organization had defined “value in oncology.” Lack of a formalized stewardship program was most often cited (77%) as the rationale for not defining value. Conclusions Less than one-third of respondents have established oncology stewardship programs; however, most are providing oncology stewardship practices. This manuscript serves as a call to action for stakeholders to work together to formalize oncology stewardship programs that optimize value, quality, and safety for patients with cancer.

Abstract Outcomes for marginal zone lymphoma (MZL) and follicular lymphoma (FL) remain suboptimal, owing to the limited number of approved agents and the incurable nature of the diseases. BGB-3111-AU-003 was a phase 1/2, open-label, multicenter, single-agent study of the selective Bruton’s tyrosine kinase inhibitor zanubrutinib in 385 patients with B-cell malignancies. Here, we present safety and efficacy outcomes for the 53 enrolled patients with relapsed/refractory MZL (n = 20) and relapsed/refractory FL (n = 33), all of whom were enrolled during the part 2 dose expansion, and therefore received zanubrutinib at the recommended phase 2 dose. Treatment with zanubrutinib was generally well tolerated, with most adverse events being ≤ grade 2. Atrial fibrillation/flutter was not reported. Two patients required dose reduction, and 4 patients discontinued treatment because of adverse events. Response was assessed by an independent review committee for MZL and the investigators for FL, per Lugano 2014 classification for non-Hodgkin lymphoma. In patients with MZL, the overall response rate (ORR) was 80%, and the complete response (CR) rate was 20%. With median follow-up of 33.8 months, median progression-free survival (PFS) was not reached. In patients with FL, the ORR was 36.4%, and the CR rate was 18.2%. After a median follow-up of 33.9 months, median PFS was 10.4 months. In conclusion, the results of this study suggest a favorable benefit–risk profile and support zanubrutinib as a potentially meaningful addition to available therapies for patients with relapsed/refractory MZL and FL. This trial was registered at www.clinicaltrials.gov as #NCT02343120.

Study Design: Literature review. Objectives: Surgical site infection (SSI) following spine surgery leads to significant patient morbidity, mortality, and increased health care costs. The purpose of this article is to identify risk factors and strategies to prevent SSIs following spine surgery, with particular focus on avoiding infections in posterior cervical surgery. Methods: We performed a literature review and synthesis to identify methods that can be used to prevent the development of SSI following spine surgery. Specific pearls for preventing infection in posterior cervical spine surgery are also presented. Results: SSI prevention can be divided into patient and surgeon factors. Preoperative patient factors include smoking cessation, tight glycemic control, weight loss, and nutrition optimization. Surgeon factors include screening and treatment for pathologic microorganisms, skin preparation using chlorhexidine and alcohol, antimicrobial prophylaxis, hand hygiene, meticulous surgical technique, frequent irrigation, intrawound vancomycin powder, meticulous multilayered closure, and use of closed suction drains. Conclusion: Prevention of SSI following spine surgery is multifactorial and begins with careful patient selection, preoperative optimization, and meticulous attention to numerous surgical factors. With careful attention to various patient and surgeon factors, it is possible to significantly reduce SSI rates following spine surgery.

Abstract Background: PARP inhibitor (PARPi) monotherapy has previously demonstrated clinical activity only in patients with a germline BRCA mutation (BRCAmut), while single-agent anti-programmed cell death protein 1 (PD-1) therapy has achieved response rates of only 5–20% in advanced triple negative breast cancer (TNBC). In preclinical studies, PARP inhibition enhanced anti-tumor immunity, increased infiltration of proliferating CD8+ T cells, and synergized with anti-PD-1 agents in BRCA wildtype (wt) tumors. TOPACIO is a fully enrolled, phase I/II trial of niraparib + pembrolizumab (pembro) in advanced TNBC. This combination achieved 28% objective response rate (ORR) and 50% disease control rate (DCR) in evaluable patients. Although activity was highest in patients with BRCAmut (ORR=60%; DCR=80%), durable clinical benefit was also observed in patients without BRCA mutations. In this study, we conducted exploratory biomarker analyses to evaluate their potential correlation with durable clinical benefit (any complete response [CR] or partial response [PR] regardless of duration or stable disease [SD] for ≥16 weeks) beyond BRCA mutations. Method: ORR was assessed by RECIST v1.1. Duration of disease control (DDC) was defined as time from first dose of study treatment to radiologic disease progression or death. Tumor mutational status of homologous recombination repair (HRR) and other DNA damage repair (DDR) pathway genes was determined using an NGS panel. Immunoprofiling was conducted using NanoString IO360 panel complimented with 30 DNA repair spike-ins. Tumor immune micro-environment was characterized using multiplex immuno-fluorescence (CycIF). PD-L1 status was determined using the Agilent/DAKO 22C3 IHC clinical trial assay. Results: Of 46 evaluable patients, 20 achieved durable clinical benefit (any CR/PR or SD≥16 weeks) with niraparib + pembro combination, of which 8 were tumor BRCA wild type (wt), and 1 was BRCA unknown. Of the 9 BRCAwt/unknown patients, 5 had deleterious mutations in HRR/DDR pathway genes, whereas the remaining 4 had no mutations (HRR/DDR wt). Mutations that were associated with response include CHEK1 (CR; DDC=10.3 mos), ATR (CR; DDC=6.4 mos), PALB2 (PR; DDC=3.5 mos), BLM (SD; DDC=8.1 mos), and NBN/RAD51C (SD; DDC=3.7 mos). Of 4 patients that had no identified mutations (HRR/DDR wt), 1 patient had CR; DDC=10.3 mos, and the remaining 3 patients had SD with DDC ranging from ∼4-8 mos. Of note, all 4 HRR/DDR wt patients were also PD-L1-negative. Table:Durable clinical benefit in BRCAwt/unknown patientsHRR/DRR MutationsPD-L1 StatusBest ResponseDDC (Months)CHEK1+CR10.3†ATR+CR6.4PALB2*UnknownPR3.5BLM-SD8.1NBN/RAD51C+SD3.7None-CR10.3†None-SD8.2None-SD4.2None-SD3.9*BRCA status unknown; †Treatment is ongoing. Conclusion: Patients with mutations beyond BRCA achieved durable clinical benefit with niraparib + pembro treatment; five of these patients had DDC >6 mos. Mutations in genes that are associated with the HRR/DDR pathway appear to confer sensitivity to niraparib + anti-PD1. Additional translational analyses, including immunoprofiling and CycIF, will be presented. Funding: TESARO, Inc., Waltham, MA, USA sponsored the study. Citation Format: Vinayak S, Tolaney SM, Schwartzberg L, Mita M, McCann G, Tan AR, Wahner Hendrickson A, Forero A, Anders C, Wulf G, Dillon P, Lynce F, Zarwan C, Erban J, Färkkilä A, Zhou Y, Buerstatte N, Graham JR, Arora S, Dezube B, Telli ML. Durability of clinical benefit with niraparib + pembrolizumab in patients with advanced triple-negative breast cancer beyond BRCA: (TOPACIO/Keynote-162) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD5-02.

Abstract Aims Hypothesis 1 of the Surgical Treatment for Ischemic Heart Failure (STICH) trial enrolled 1212 patients with an LVEF of ≤35% and CAD amenable to coronary artery bypass grafting (CABG). Patients were randomized to CABG and optimal medical therapy (MED) or MED alone. The objective was to assess whether or not patients with diabetes mellitus (DM) enrolled in the STICH trial would have greater benefit from CABG than patients without DM. Methods and results The characteristics and clinical outcomes of patients with and without DM randomized to CABG and MED or MED alone were compared. DM was present in 40%. At baseline, patients with DM had more triple vessel CAD, higher LVEF, and smaller left ventricular volumes. In patients with DM, the primary outcome of all-cause mortality occurred in 39% of patients in the MED group and 39% in the CABG group [hazard ratio (HR) with CABG 0.96, 95% confidence interval (CI) 0.73–1.26]. In patients without DM, the primary outcome occurred in 41% of patients in the MED group and 32% in the CABG group (HR with CABG 0.80, 95% CI 0.63–1.02). While numerically it would appear that the treatment effect of CABG is blunted in patients with DM, there was no significant interaction between DM and treatment group on formal statistical testing. Conclusions Patients with DM enrolled in the STICH trial had more triple vessel disease, smaller hearts, and higher LVEF than those without DM. CABG did not exert greater benefit in patients with DM.

A 15-gene expression signature predicts whether a patient with diffuse large B cell lymphoma will respond to dacetuzumab, a therapeutic antibody.