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.

Background: This study aimed to determine whether trapezium morphology, specifically trapezial inclination, is a risk factor for the failure of primary conservative or minimally invasive treatment for acute traumatic thumb carpometacarpal (CMC) joint dislocations in the relatively early period. We hypothesized that an elevated trapezial inclination would be associated with a higher rate of treatment failure. Methods: We retrospectively reviewed patients treated for acute thumb CMC joint dislocations between 1976 and 2025 with closed reduction and subsequent immobilization or percutaneous pinning. Patients were classified into “failure” (recurrent dislocation or subsequent symptomatic subluxation) or “non-failure” groups. Trapezial inclination, measured on oblique hand radiographs, was compared between the groups using the Mann-Whitney U test. Results: Fourteen patients met the inclusion criteria (7 failure, 7 non-failure). While demographics were not significantly different, the failure group demonstrated a significantly higher mean trapezial inclination (19.1° vs 8.7°; P = .0012). This significant difference persisted in a subgroup analysis that excluded associated Gedda type 3 Bennett fracture ( P = .0318) Conclusions: Elevated trapezial inclination may predict the failure of primary conservative or minimally invasive treatment in the relatively early period for acute thumb CMC joint dislocation. Our findings suggest that patients with this steep trapezium may be poor candidates for conservative or minimally invasive management and should be considered for primary definitive surgery.

BACKGROUND: With pulmonary hypertension (PH), a pulmonary artery wedge pressure (PAWP)>15 mm Hg is used to diagnose left heart dysfunction, but some patients with adjudicated group 1 PH demonstrate PAWP>15 mm Hg. The primary objective of the study was to evaluate group 1 PH with high PAWP>15 mm Hg. METHODS: Patients with adjudicated group 1 PH from PVDOMICS between 2016 and 2019 were separated into high PAWP(>15 mm Hg) or normal PAWP and compared with adjudicated combined pre- and postcapillary (Cpc) PH related to heart failure with preserved ejection fraction (HFpEF). Participants underwent dynamic right heart catheterization and metabolomics. Findings were validated in 3 independent cohorts with adjudicated group 1 PH (validation cohorts 1 and 2 with exercise right heart catheterization and validation cohort 3 with resting right heart catheterization). RESULTS: Of 325 patients with group 1 PH (73% women, mean age 53.0±14.3 years), 15% (n=48) had high PAWP. Group 1 PH+high PAWP demonstrated greater obesity, left ventricular hypertrophy ( P <0.0002), left ventricular strain impairment ( P <0.0001), and decreased left ventricular compliance ( P <0.0001) compared with group 1 PH+normal PAWP, with changes comparable to Cpc-PH HFpEF (n=75). Compared with Cpc-PH HFpEF, left atrial function was better in group 1 PH+high PAWP with lower PAWP V wave, higher left atrial compliance, and left atrial ejection fraction ( P <0.0001 for all). Metabolomics demonstrated little difference between group 1 PH with high versus normal PAWP but large differences between group 1 PH+high PAWP versus Cpc-PH HFpEF (100 metabolites altered at false discovery rate P <0.05). Elevated PAWP was also observed in 18% of group 1 PH in the validation cohort 1 (n=402), with exercise PAWP response intermediately abnormal in group 1 PH+high PAWP relative to Cpc-PH HFpEF and group 1 PH+normal PAWP (interaction P <0.0001). Elevated PAWP was similarly observed in 22% and 19% of group 1 PH in validation cohorts 2 (n=55) and 3 (n=787), respectively. CONCLUSIONS: Approximately 1 in 5 adjudicated patients with group 1 PH has elevation in resting PAWP despite severe pulmonary vascular dysfunction and metabolomics consistent with traditionally defined group 1 PH. Despite resting PAWP elevation, these patients with group 1 PH were metabolomically and biologically distinct from Cpc PH HFpEF, with better left atrial function and diastolic reserve during exercise. These data emphasize the limitations of using resting PAWP alone to separate group 1 PH from HFpEF and call for development of more integrated clinical diagnostic criteria.

Background Patients with atrial fibrillation (AF) often complain of dyspnea, raising the question that symptoms could be related to unrecognized heart failure (HF) with preserved ejection fraction (HFpEF). Methods We used the HFpEF‐age, body mass index and history of AF algorithm to estimate the probability of undiagnosed HFpEF in CABANA (Catheter Ablation vs. Antiarrhythmic Drug Therapy), and its interaction with catheter ablation on quality of life (QOL). Probable HFpEF was defined as patient‐reported dyspnea with HFpEF‐age, body mass index and history of AF probability≥75%. Absence of dyspnea or HFpEF‐age, body mass index and history of AF probability<75% was considered to reflect patients without HFpEF. The effect of randomization to catheter ablation on QOL (Mayo Atrial Fibrillation‐Specific Symptom Inventory questionnaire and EuroQol‐5 Dimension‐3 Level score) was assessed using mixed models. Results Of participants without known HF, 70% (n=1225) had probable HFpEF and the remaining 30% (n=522) did not. Those with probable HFpEF had worse New York Heart Association class, EuroQol‐5 Dimension‐3 Level score, Mayo Atrial Fibrillation‐Specific Symptom Inventory severity, and Mayo Atrial Fibrillation‐Specific Symptom Inventory frequency scores ( P <0.0001 for all), with higher risk of HF hospitalization (hazard ratio [HR], 2.19 [95% CI, 1.11–4.31], P =0.01). Ablation resulted in greater improvement in EuroQol‐5 Dimension‐3 Level and Mayo Atrial Fibrillation‐Specific Symptom Inventory severity/frequency scores in probable HFpEF (interactions P =0.005, P =0.05, and P =0.04 respectively). In probable HFpEF, catheter ablation was associated with lower risk of cardiovascular hospitalization (HR, 0.78 [95% CI, 0.66–0.92], P =0.003, interaction P =0.03) but not HF hospitalization (HR, 0.94 [95% CI, 0.55–1.64], P =0.84). Conclusions Nearly three quarters of CABANA participants had potentially undiagnosed HFpEF, with worse QOL and risk of HF hospitalization. Catheter ablation in probable HFpEF resulted in greater improvement in QOL, but residual QOL impairment and HF risk remained elevated despite ablation. These data reinforce the importance of diligent consideration of HFpEF among patients with symptomatic AF to ensure optimal use of foundational treatments for HF.

Chronic wounds remain a major unmet clinical challenge, often failing to progress to normal healing due to persistent inflammation, impaired angiogenesis, and cellular senescence. Exosomes have recently been investigated as promising acellular therapeutics capable of restoring intercellular communication and promoting tissue regeneration. Among these, the Purified Exosome Product (PEP) represents a next-generation, platelet-derived exosome formulation manufactured under Good Manufacturing Practice (GMP) conditions with high purity, stability, and reproducibility. This review summarizes the current advances in exosome-based chronic wound therapeutics and PEP delivery systems and their translational potentials. Incorporation of PEP into bioengineered carriers such as fibrin sealant, collagen scaffolds, and hyaluronic acid (HA) hydrogels enables localized and sustained exosome release, significantly prolonging therapeutic effects and improving regenerative outcomes. Fibrin-based PEP delivery achieved complete wound closure and functional skin regeneration in animal models, while collagen and HA-based systems showed promising results for injectable and dermatologic applications. Beyond its intrinsic healing effects, PEP may also serve as a nanocarrier for other drugs, offering a future direction in chronic wound management.

Abstract Castleman disease (CD) is a heterogeneous group of lymphoproliferative disorders anatomically classified by distribution (unicentric CD [UCD], oligocentric CD [oligoCD], or multicentric CD [MCD]). Human herpes virus 8–negative MCD is called idiopathic MCD (iMCD), which includes clinical subtypes with varying phenotypes and responses: TAFRO (thrombocytopenia, anasarca, fever, renal dysfunction and/or reticulin fibrosis, and organomegaly), IPL (idiopathic plasmacytic lymphadenopathy), and not otherwise specified. OligoCD has recently emerged as an intermediate form between UCD and MCD, with unclear clinical behavior, and IPL has not been validated in a Western cohort. We retrospectively analyzed 217 patients with CD evaluated at our institution between January 2004 and August 2024. Survival probabilities were compared using log-rank tests. Overall, 57% had UCD, 20% had oligoCD, and 23% had iMCD. Patients with oligoCD and iMCD more frequently exhibited systemic symptoms than those with UCD. Patients with oligoCD and iMCD had significantly shorter event-free survival (EFS) of 8.9 and 2.3 years, respectively, than those with UCD (not reached; P&lt; .001 and P&lt; .02). Among iMCD subtypes, iMCD-IPL demonstrated a longer EFS than iMCD-TAFRO (P = .02), with no deaths during the follow-up periods. The results validate oligoCD and iMCD-IPL as new subtypes in this Western cohort. The survival outcome in oligoCD was intermediate between UCD and iMCD, with only a subset of patients with oligoCD requiring systemic therapy. iMCD-IPL had a favorable survival outcome in this US cohort, similar to what has been reported in non-Western countries. Tailoring treatment strategies to disease subtypes and vigilant monitoring of oligoCD for progression may improve survival outcomes in CD.

Importance Primary mitral regurgitation (MR) is a prevalent valvular lesion. Current American College of Cardiology/American Heart Association guidelines include class I recommendations for intervention for severe primary MR at the onset of symptoms, significant left ventricular (LV) enlargement (end-systolic dimension ≥40 mm), or dysfunction (ejection fraction ≤60%), with a class IIA recommendation for mitral valve repair when performed at an experienced surgical center. Recent data suggest a survival penalty when waiting for class I surgical guideline indications, and novel markers of decompensation are under investigation. Observations Comprehensive assessment of MR severity using echocardiography is critical, and when warranted, cardiac magnetic resonance (CMR) is complementary. Assessment of LV size and function, as well as serial changes in both, is crucial for determining timing of surgery. New-onset atrial fibrillation, left atrial enlargement, pulmonary hypertension, and exercise-induced changes in LV function should also be considered in borderline scenarios. The roles of LV volumes, global longitudinal strain, CMR-derived measures of myocardial dysfunction, and cardiac biomarkers are worthy of further investigation regarding consideration for early surgical intervention. Conclusions and Relevance A more refined approach incorporating assessment of extravalvular cardiac injury, novel imaging markers, and biomarkers is needed to optimize surgical timing in primary MR. Further research is warranted to validate these emerging parameters and refine guidelines to improve patient outcomes.

Abstract Introduction: Patients with multiple myeloma (MM) have an increased risk of infection secondary to hypogammaglobulinemia, due to myeloma itself and anti-myeloma therapies. Prophylactic immunoglobulin (Ig) supplementation has been considered a potential strategy to reduce the risk of infections. A randomized controlled trial (Chapel, Lancet, 1994) demonstrated a reduction in both overall and major infections with the use of Ig. However, its real-world benefit remains unclear and prophylactic Ig is not routinely given as part of standard therapies. Furthermore, little is known regarding the routine use of Ig in the context of modern therapeutic agents such as chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibody therapies. To address this gap, we conducted an updated systematic review and meta-analysis (SRMA) to elucidate the efficacy of prophylactic immunoglobulin in patients with MM. Methods: We performed a SRMA of observational and randomized controlled trials comparing the outcomes in patients with MM who received prophylactic immunoglobulin versus those who did not. A comprehensive search of PubMed, Scopus, and Cochrane CENTRAL databases was conducted up to July 2025, along with a manual review of the reference lists from relevant articles. This review adheres to the recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. R software version 4.5.1 was used for statistical analyses. Results: A total of 18 studies were included in the systematic review. Among them, 11 studies compared patients who received immunoglobulin prophylaxis with those who did not (“Ig” versus “no Ig” groups). The remaining seven studies analyzed the same group of patients, comparing periods when they were receiving Ig (“on-Ig”) with periods when they were not (“off-Ig”). Among 18 studies, 13 studies were included in meta-analysis due to data availability (eight from the former group and five from the latter group). First, we conducted a meta-analysis of 1,234 patients from the eight studies that preceded this analysis, comparing Ig and no-Ig. Three studies included MM patients treated with bispecific antibodies, two focused on those treated with autologous stem cell transplantation (ASCT), and one on those treated with anti-CD38 antibodies. The dose of Ig was 0.4 g/kg every four weeks in most studies, and the timing of initiation of Ig varied across studies. The majority of Ig was delivered through an intravenous route. Most studies defined severe infections as those greater than grade 3 according to the Common Terminology Criteria for Adverse Events, while one study defined them as infections requiring intravenous or oral antibiotic treatment. The incidence of severe infection was significantly lower in patients who received prophylactic Ig compared with those who did not (odds ratio [OR] 0.22; 95% CI 0.08-0.63; p = 0.005). There was no significant difference in the overall infection rate between the two groups (OR 0.97; 95% CI 0.68-1.37; p = 0.85). A subgroup analysis by treatment type (chemotherapy, bispecific antibody, and ASCT) showed no significant differences in the overall infection rate among the subgroups (ASCT: OR 0.97; 95% CI 0.64-1.45; Bispecific antibody: OR 0.74; 95% CI 0.49-1.11). However, a significant reduction in the rate of severe infections was observed in patients treated with bispecific antibodies (OR 0.33; 95% CI 0.13-0.85; p = 0.021). Next, we analyzed 460 patients from the latter five studies comparing on-Ig and off-Ig. The incidence rate ratio (IRR) of overall infection was significantly lower during on-Ig periods compared with off-Ig periods (IRR 0.62; 95% CI 0.43-0.88; p = 0.0082). Conclusions: In patients with MM, prophylactic Ig use was associated with a low incidence of severe infections. Furthermore, the incidence rate ratio of overall infection was lower during periods of Ig prophylaxis compared to periods without Ig. These findings underscore the potential efficacy of a routine Ig prophylaxis in patients with MM to mitigate the risk of infections. Since this meta-analysis does not include studies involving patients treated with CAR-T therapy, further studies are warranted to evaluate the effectiveness of Ig in patients receiving novel therapies such as CAR-T therapy, while also considering the cost and time associated with Ig administration in real-world clinical practice.