To compare systemic antifungal prophylaxis for proven/probable invasive fungal disease (IFD) in high-risk haematology populations using randomised controlled trials, with separate mortality, discontinuation, and formulation analyses.

Six databases and conference sources were searched to 2 September 2026. Bayesian random-effects network meta-analysis included RCTs with traceable proven/probable IFD definitions. Mixed-policy, setting, formulation, mortality, and discontinuation analyses were reported separately.

CRD420261490010 (retrospective).

Twenty-one RCTs (42 arms; 6,338 participants; 363 events) informed the primary network. Versus inactive control, voriconazole (OR 0.042, 95% CrI 0.001-0.793) and liposomal amphotericin B (OR 0.335, 95% CrI 0.127-0.819) had credible intervals excluding 1. Posaconazole suspension showed favourable but imprecise estimates. No mortality comparison demonstrated clear benefit (17 RCTs; 582 deaths). Exploratory peri-HSCT analyses suggested fewer IFDs but more discontinuations with itraconazole. In AML/MDS chemotherapy, posaconazole effects were comparator-dependent. Direct evidence did not distinguish delayed-release tablets from suspension.

No regimen was consistently superior across settings and outcomes. Voriconazole and liposomal amphotericin B had the clearest evidence versus inactive control. Posaconazole effects were comparator-dependent; peri-HSCT itraconazole showed fewer IFDs but more discontinuations. No mortality benefit was established. Prophylaxis should be risk-adapted to clinical setting, baseline mould risk, formulation, tolerability, and feasibility.

Cough syncope (CS) is a rare subtype of syncope that remains underrepresented in evidence-based medicine. We aimed to characterize the clinical features of CS, with the aim of improving recognition and optimizing management strategies.

We present five cases of CS alongside a systematic review of its clinical characteristics based on published literature to improve recognition and optimize management. Reports of eligible patients were screened, and demographic, clinical, diagnostic, treatment, and outcome data were analyzed.

This study included 60 patients with a mean age of 56 ± 15 years, 91% of whom were male. The most common underlying triggers were respiratory diseases, including pulmonary infections (35%) and bronchitis (22%). Common comorbidities included hypertension (26%), bronchial asthma (18%), and diabetes mellitus (15%). CS episodes were directly triggered by severe coughing in 93% (26/28) of patients. Episodes occurred at least twice daily in 20% of patients, and limb convulsions accompanied syncope in 22%. Symptoms improved after treatment in 98% of cases. After a median follow-up of 3.75 months (Interquartile Range: 2-12 months), the recurrence rate of syncope was 11%. CS, predominantly triggered by severe coughing, primarily affected middle-aged and older men.

CS predominantly affects middle-aged and older men and is frequently associated with pulmonary infections. Acute pulmonary infections serve as a common underlying trigger for CS, and patients are at risk of recurrent syncope and falls. Disease management should be focused on treating chronic airway disease, particularly chronic obstructive pulmonary disease.

Inflammation plays a crucial role in adverse outcomes of coronary artery disease. NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome activates 2 classical pathways: interleukin-1β (IL-1β)/IL-6/high-sensitivity C-reactive protein (hsCRP) and IL-18/IL-6/hsCRP. However, the predictive value of pathway-related biomarkers, particularly their combinations, remains to be systematically evaluated.

The authors aimed to explore the predictive value of individual and combined biomarkers from 2 pathways for long-term cardiovascular risk in patients with multivessel disease (MVD).

From a prospective, multicenter cohort, 1,058 consecutive patients with MVD were enrolled. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE-4P), a composite of all-cause death, myocardial infarction, revascularization, and stroke.

During a median 2-year follow-up (IQR: 2.0-2.1 years), 130/1,058 (12.3%) MACCE-4P occurred. After multivariable adjustment, higher levels of IL-1β (HR: 1.63; 95% CI: 1.15-2.32), IL-6 (1.72, 1.20-2.46), and hsCRP (1.59, 1.09-2.30) were associated with increased MACCE-4P risk, whereas IL-18 was not. For combined analysis, any 2-biomarker combination from either the IL-1β/IL-6/hsCRP or IL-18/IL-6/hsCRP pathway significantly predicted higher MACCE-4P risk (HR range: 1.84-2.19), with further risk elevation observed for the 3-biomarker combinations (HR: 3.09; 95% CI: 1.80-5.31 for IL-1β pathway; HR: 2.26; 95% CI: 1.24-4.14 for IL-18 pathway). The 4-biomarker combination (IL-1β+IL-6+IL-18+hsCRP) also predicted significantly higher MACCE-4P risk (HR: 2.64; 95% CI: 1.36-5.14). Notably, 3-/4-combined biomarkers demonstrated significant incremental predictive value over single biomarkers.

In patients with MVD, combined assessment of NLRP3-associated inflammatory biomarkers offers significant incremental predictive value beyond individual biomarkers. These findings highlight the importance of integrating multiple inflammatory biomarkers to better identify patients with residual inflammatory risk.

PREPARE was a prospective, multicentre, randomised controlled trial evaluating purified native type 1 collagen extracellular matrix plus polyhexamethylene biguanide (PCMP) with standard of care (SoC) versus SoC alone in patients with hard-to-heal diabetic foot ulcers (DFUs).

Across 25 US sites, patients with type 1 or type 2 diabetes and hard-to-heal DFUs measuring 1-25cm² were enrolled. Patients demonstrating ≥40 percent area reduction (PAR) during four weeks of screening were excluded to restrict the study population to those with hard-to-heal wounds. SoC included sharp debridement, saline cleansing, use of moisture-balancing dressings and offloading. The primary endpoint was complete wound closure within 12 weeks, confirmed two weeks later. Secondary endpoints included time to closure, PAR and adverse events (AEs).

A total of 170 patients were randomised (PCMP+SoC, n=96; SoC alone, n=74). Complete wound closure occurred in 42% of patients receiving PCMP+SoC versus 27% of patients receiving SoC alone (absolute difference 14.6%; 95% confidence interval: 0.15%, 27.9%; p=0.047). Mean PAR was greater with PCMP+SoC than with SoC alone (75.23% versus 58.06%, respectively). No AEs or serious AEs were attributed to PCMP.

In this study, use of PCMP+SoC significantly improved 12-week closure outcomes in patients with hard-to-heal DFUs compared with SoC alone, supporting its use as an adjunctive antimicrobial barrier for these types of wounds.

Underserved populations often have difficulty accessing care for diabetic eye disease, including screening, referral, and treatment. Although barriers to diabetes care management have been well documented, less is understood about barriers specific to rural and underserved populations. In this study, we interviewed health care professionals to identify barriers to and facilitators of screening for diabetic eye disease and specialty care among underserved patients in Alabama.

We conducted 12 semistructured interviews with experts in ophthalmology, diabetes care management, and primary care in Alabama between November 2023 and January 2024. We used the Health Equity Implementation Framework to code interviews and identify key themes related to access barriers and other obstacles to care, as well as opportunities to improve access to screening and treatment.

Factors associated with access barriers for underserved populations include limited services in rural areas, insufficient referrals, cost, transportation, limited patient knowledge about diabetes and eye health, inadequate information provided during clinical encounters, and mistrust of clinicians. Several innovative approaches were identified to improve access to eye care services at the health system level and during clinical encounters.

Experts have suggested groundbreaking ways to improve access to care across several domains, including clinic mobility, teleophthalmology, and improved information dissemination to patients on disease. Further research is needed to establish an evidence base for additional innovations aimed at improving access to diabetic eye care and expanding their scope through quantitative research efforts, both in Alabama and nationwide.

Human epididymis protein 4 (HE4; WFDC2) has emerged as a profibrotic biomarker associated with adverse outcomes across multiple diseases. However, its prognostic value in patients with established coronary artery disease (CAD) remains insufficiently characterized and was addressed in the present study. We prospectively studied 395 patients with angiographically confirmed CAD. Circulating HE4 levels were measured at baseline and analyzed both as log2-transformed values and by using a data-derived cut-off of 8.0 ng/mL, derived from Youden's index. The primary endpoints were major adverse cardiovascular events (MACE) and all-cause mortality during a 10-year follow-up. Multivariable Cox regression models were adjusted for traditional risk factors, including age, body mass index, hypertension, type 2 diabetes mellitus, LDL cholesterol, HDL cholesterol, and the presence of significant coronary artery disease (Model 1), and additionally for renal function, C-reactive protein, fibrinogen, and N-terminal pro-B-type natriuretic peptide (Model 2). Higher HE4 levels, analyzed as a log2-transformed continuous variable, indicated a significantly increased risk of MACE and all-cause mortality across all adjustment models, with HRs of 1.2-1.4 per doubling of HE4. Also, the categorical HE4 cut-off was significantly associated with all endpoints across all adjustment levels, and the addition of HE4 to the fully adjusted baseline model improved overall risk reclassification across all endpoints. In conclusion, HE4 is significantly associated with long-term cardiovascular outcomes and all-cause mortality in patients with established CAD and may provide prognostic information beyond inflammatory and cardiorenal markers.

Vitamin B6 metabolism is implicated in chronic inflammation and insulin resistance, two important factors influencing stroke and type 2 diabetes, respectively. This study aimed to investigate the prospective associations of multiple plasma biomarkers of vitamin B6 homeostasis, i.e. 4-pyridoxic acid (PA), pyridoxal (PL), pyridoxal-5'-phosphate (PLP) and the ratio of PA:[PL+PLP] (PAr), with the risk of stroke in individuals with type 2 diabetes, and evaluate the predictive performance of these markers.

This nested case-control study involved individuals with type 2 diabetes, 967 cases of incident stroke and 967 matched controls without stroke from a prospective Chinese cohort. Plasma levels of PA, PL and PLP were measured using a targeted metabolomics approach. The net reclassification index (NRI) was calculated to assess the predictive performance of PA, PL, PLP and PAr.

Compared with individuals with the lowest quartile of plasma PAr, the odds ratio (OR) and 95% CI was 2.915 (2.072-4.101) for the highest quartile. By contrast, the ORs (95% CIs) of the highest quartile versus the lowest were 0.577 (0.432-0.771) for PL, 0.652 (0.488-0.871) for PLP, and 1.232 (0.897-1.692) for PA, respectively. In addition, adding plasma levels of PAr, PL and PLP offered incremental reclassification ability for incident stroke beyond the conventional risk factors. The greatest reclassification ability improvement was observed for the combination of PAr, PL and PLP (NRI: 0.482, 95% CI: 0.395-0.568).

Plasma levels of PAr, PL and PLP were significantly associated with the risk of incident stroke and provided incremental ability for the risk prediction of stroke in individuals with type 2 diabetes.

Despite optimal low-density lipoprotein cholesterol (LDL-C) management, residual vascular risk remains high in patients with type 2 diabetes (T2D). Remnant cholesterol (RC) is an atherogenic lipid fraction, yet its longitudinal association with diabetic retinopathy (DR) remains insufficiently characterised. We aimed to evaluate whether longitudinal RC measurements independently predict new-onset DR.

We recruited 1,580 Chinese adults with T2D and no DR from a community-based prospective cohort established between 2017 and 2019. Participants were followed annually until 2023. Association between RC and incident DR was evaluated using time-dependent Cox regression models. We specifically examined this association among participants who achieved clinical targets for conventional lipid panel.

We observed 304 incident DR cases during five follow-up visits. Each one-unit increase in natural log-transformed RC was associated with a 26% higher risk of new-onset DR (adjusted hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.08-1.47). Elevated RC (≥0.8 mmol/L) was associated with a 50% increased DR risk (aHR 1.50, 95% CI 1.11-2.03). These associations persisted among participants meeting guideline-recommended targets for triglycerides, LDL-C, and high-density lipoprotein cholesterol. Such associations were more prominent in women and patients with longer duration of T2D (p for interaction <0.05).

Elevated RC is an independent risk factor for new-onset DR and represents an important contributor to residual risk in patients with otherwise optimal lipid profiles. These findings suggest that RC merits consideration for integration into routine metabolic monitoring to improve DR risk stratification, particularly among female patients and those with long-standing diabetes.

Diabetic foot ulcers and venous leg ulcers (VLUs) frequently recur after closure, and because the underlying disease persists, a more meaningful endpoint to consider is durable healing: sustained closure with low recurrence and fewer complications. Mechanistically, topical wound oxygen supports antimicrobial defence, angiogenesis and collagen cross-linking, while cyclical compression reduces oedema and enables timely resolution of inflammation, improving the structural quality of repaired tissue rather than merely closing the wound. Combining both modalities in one device offers a plausible mechanism for the durability observed across diverse wound aetiologies and comorbid populations.

Clinical and mechanistic evidence was synthesised on the durability of healing achieved by intermittent cyclically pressurised topical wound oxygen (CPTWO) therapy in hard-to-heal (chronic) lower extremity wounds.

In a double-blind randomised trial, adjunctive CPTWO therapy doubled the proportion of ulcers closed at 12 months (56% versus 27%) and tripled 12-week closure (41.7% versus 13.5%; adjusted odds ratio: 6.00). In refractory VLUs, an observational comparative study reported 36-month recurrence with CPTWO of 5.9% versus 46.7% without. In a large retrospective cohort study among 3126 previously refractory wounds, 64.8% healed completely with 2.7% recurrence-related retreatment with CPTWO, and a propensity score-matched Veterans Affairs cohort showed 73% fewer amputations and 82% fewer hospitalisations. As most meta-analyses pool mechanistically different oxygen devices, durability-specific evidence rests uniquely on the CPTWO studies.

Randomised, real-world, and mechanistic evidence converge in support of durable healing with reduced recurrence in hard-to-heal lower extremity wounds. Together with its home-based, patient-administered delivery, these findings favour earlier, durability-focused adoption of CPTWO therapy in refractory wounds.