Journals
2026 EN
Ahmed Faizan · Haider Faseeh · Ali Ramsha
+17 more
ABSTRACT Introduction Current ESC/EACTS guidelines recommend standard‐duration dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI). However, the subsequent transition to either extended DAPT or single antiplatelet therapy (SAPT) remains debated due to limited comparative outcome data. This Bayesian meta‐analysis and meta‐regression evaluate the clinical safety of DAPT versus SAPT, and the impact of potential confounders on all‐cause mortality. Methods Following PRISMA guidelines, a systematic search of PubMed, Embase, Cochrane Library, ScienceDirect, and Scopus was conducted till April 2025 to identify randomized clinical trials (RCTs) and cohort studies. Primary outcomes were all‐cause mortality and bleeding events. Bayesian random‐effects meta‐analysis was performed using the brms package in R with Markov Chain Monte Carlo sampling and weakly informative priors. Bayesian meta‐regression of log‐transformed odds ratios (OR) assessed associations with relevant covariates. Results Fourteen studies (9 RCTs and 5 cohort studies) comprising 56,572 patients were included. Compared with SAPT, DAPT was associated with increased all‐cause mortality (OR 1.25; 95% credible interval [CrI], 1.04–1.51; posterior probability of harm, Pr[OR > 1] = 84%). DAPT also increased the risk of net adverse clinical events [NACE] (OR, 1.29; 95% CrI, 1.08–1.53), minor bleeding (OR, 1.60; 95% CrI, 1.10–2.33), major bleeding (OR, 1.70; 95% CrI, 1.30–2.23), and BARC 2–5 bleeding (OR, 1.78; 95% CrI, 1.40–2.26) with Pr [OR > 1] >90% for all outcomes. No significant differences were observed in cardiac death, cardiovascular mortality, major adverse cardiac and cerebrovascular events (MACCE), myocardial infarction (MI), stent thrombosis, or stroke. Meta‐regression revealed that higher baseline odds of dyslipidemia (−0.89), hypertension (−1.19), prior MI (−0.94), and previous revascularization (−0.30) were associated with greater mortality benefit from DAPT. However, in the DAPT cohort, increased odds of adverse events, including cardiac death (0.41), MACCE (0.55), stroke (0.60), MI (0.29), and NACE (0.98), were significantly associated with higher all‐cause mortality. Conclusion Extended DAPT is associated with a higher all‐cause mortality, bleeding events, and NACE. While DAPT may benefit high‐risk populations, the increased odds of adverse events are significantly associated with mortality, warranting that it be carefully considered and monitored in post‐PCI patients.
Journals
2026 EN
Awashra Ameer · AbuBaha Mohammed · Emara Ahmed
+9 more
ABSTRACT Percutaneous coronary intervention (PCI) in patients with high bleeding risk (HBR) presents a therapeutic challenge, requiring careful balancing of ischemic prevention and bleeding avoidance. The Academic Research Consortium High Bleeding Risk (ARC‐HBR) criteria provide a standardized framework for identifying this population, yet optimal PCI timing, procedural strategies, and antithrombotic regimens remain uncertain. This review synthesizes data from randomized controlled trials, large‐scale registries, and meta‐analyses involving HBR patients undergoing PCI in settings including stable coronary artery disease, acute coronary syndromes (ACS), ST‐elevation myocardial infarction (STEMI), post‐resuscitation states, and malignancy‐related thrombocytopenia. Special emphasis is placed on procedural approaches (radial vs. femoral access), device selection (drug‐coated balloons, polymer‐free drug‐eluting stents), and dual antiplatelet therapy (DAPT) duration. Evidence supports the safety of abbreviated DAPT regimens (1–3 months) when combined with bleeding‐sparing techniques and devices, with the greatest benefit observed in patients with a high ischemic burden (e.g., GRACE score > 140). Early invasive management in ACS has been associated with reduced ischemic endpoints and shorter hospital stays without a significant rise in major bleeding. Conversely, delayed PCI is advisable in the presence of active bleeding, recent thrombolysis, or severe coagulopathy. Persistent limitations include underrepresentation of ARC‐HBR patients in trials and lack of standardized, bleeding risk–tailored timing protocols. PCI in HBR patients can be performed safely and effectively when guided by individualized, evidence‐based strategies for procedural timing and antithrombotic therapy. Future directions include integrating biomarker‐driven DAPT modulation and artificial intelligence‐based decision frameworks to optimize outcomes in this high‐risk group.
Journals
2026 EN
Tariq Humza · Gohar Ali · Ahmad Muhammad Husnain
+4 more
ABSTRACT Methanol toxicity is an emergency that doctors come across all around the globe, requiring immediate treatment or it can cause life‐threatening conditions affecting the central nervous system, causing toxic optic neuropathy and metabolic acidosis. We present a case of an 18‐year‐old boy, who presented in the medicine emergency with sudden bilateral visual loss and vomiting. He did not have any significant past medical history and all of his examinations were normal except bilaterally dilated pupils and the fundus examination showing bilateral optic disc pallor and cup to disc (C/D) ratio 0.5 and his visual acuity was no perception of light (NPL). He was admitted and treated conservatively with high‐dose steroids and ethanol. Later on, a diagnosis of methanol toxicity was made based on toxicology report and imaging studies. His ABGs remained normal throughout and his vision improved to hand movement (HM) over the course of 2 weeks. Methanol toxicity can vary in presentation and could lead to toxic optic neuropathy causing sudden total visual loss. It usually occurs as an outbreak so cases like these should be reported to have a general awareness about it; aiding in early detection, timely management and better public health strategies.
Journals
2026 EN
Zahran Anwar · AbuKhazneh Omar · Bdair Mohammad
+12 more
ABSTRACT Background The glymphatic system is a perivascular cerebrospinal fluid (CSF)–interstitial fluid (ISF) exchange pathway that supports brain homeostasis by clearing metabolic waste and neurotoxic proteins. Across central nervous system diseases, converging evidence indicates that glymphatic dysfunction represents a shared pathophysiological axis linking vascular, astroglial, inflammatory, and sleep‐related disturbances to impaired solute clearance. Results and Conclusion In this review, we synthesize mechanistic and clinical evidence for glymphatic impairment in acute brain injury (ischemic and hemorrhagic stroke, traumatic brain injury) and chronic neurological disorders (Alzheimer's disease, Parkinson's disease, cerebral small vessel disease, multiple sclerosis, idiopathic normal pressure hydrocephalus, idiopathic intracranial hypertension, epilepsy, and headache disorders). Major mechanisms include (i) aquaporin‐4 (AQP4) depolarization/mislocalization at astrocytic endfeet, reducing perivascular water transport; (ii) perivascular space compression or obstruction from cytotoxic/vasogenic edema, blood‐derived products, protein aggregates, or altered extracellular matrix; (iii) loss of arterial pulsatility and vascular stiffening, weakening the driving forces for convective exchange; (iv) blood–brain barrier disruption and neuroinflammation, which remodel perivascular architecture and amplify clearance failure; and (v) sleep and autonomic dysregulation, including altered noradrenergic tone, which suppresses glymphatic activity during periods when clearance is normally maximal. Clinically, glymphatic dysfunction can be probed using diffusion tensor imaging–analysis along the perivascular space (DTI‐ALPS), contrast‐enhanced MRI approaches, and structural surrogates such as enlarged perivascular spaces, with emerging associations to cognition, mood, and disease severity. Finally, we discuss translational strategies aimed at restoring clearance, including sleep/circadian optimization, vascular risk control, anti‐inflammatory approaches, AQP4‐ and TRPV4‐oriented targets, and neuromodulation. Mechanism‐guided, standardized imaging and longitudinal interventional studies are needed to establish glymphatic biomarkers as actionable therapeutic and prognostic tools.
Journals
2026 EN
Yasin Ameer · Irshed Misan · Hofmann Lukas
+3 more
Metal responsive transcription factors are essential for bacterial metal homeostasis, allowing cells to regulate metal uptake, efflux, and detoxification in response to fluctuating metal ion levels. Among these, CueR, a member of the MerR family, is widely found in Gram‐negative bacteria. While E. coli CueR has been extensively studied, revealing that it adopts multiple conformational states to regulate transcription, P. aeruginosa CueR (PACueR) remains less characterized, with no resolved structure despite regulating a broader set of genes. In this study, we applied electron paramagnetic resonance (EPR) spectroscopy combined with DNA spin‐labeling to investigate the conformational states of PACueR bound to two different promoter sequences, copZ2 and mexPQ‐opmE. We examined the effects of PACueR binding and copper addition, capturing the transcription initiation stage that represents an essential step in copper homeostasis regulation of P. aeruginosa . Our results reveal promoter‐specific differences in PACueR DNA interactions, suggesting that while the core transcription initiation mechanism is conserved, variations in promoter affinity and length of dyad symmetry fine‐tune transcription levels in response to copper. These findings highlight the value of EPR spectroscopy in probing metal‐dependent transcription mechanisms and offer new insights into copper regulation in P. aeruginosa , a clinically important pathogen.
Journals
2026 EN
AbdulHafez Hamza A. · Awashra Ameer · Bdir Sosana
+7 more
ABSTRACT Background Tirzepatide, a dual GIP/GLP‐1 receptor agonist, offers a novel cardiometabolic strategy beyond glycemic control with important implications for heart failure care. By producing potent, sustained weight reduction and favourable changes in lipids, blood pressure, systemic inflammation and endothelial biology, tirzepatide targets central pathophysiologic drivers of obesity‐related HFpEF. Methods We conducted this review to synthesise current evidence on the mechanisms, clinical efficacy and therapeutic implications of tirzepatide for heart failure management, with emphasis on obesity‐related HFpEF, cardiorenal effects and safety considerations. Randomised clinical programmes and the SUMMIT outcomes trial have demonstrated symptomatic and functional improvements, reverse cardiac remodelling on imaging, reduced circulating markers of myocardial stress and fewer worsening heart‐failure events versus placebo, alongside signals of renal stabilisation. Results The tolerability profile aligns with the GLP‐1 class, with gastrointestinal events predominating and a low risk of clinically important hypoglycemia; biliary events may be more likely at higher doses, while pancreatitis risk has not been clearly elevated. Data in HFrEF remain limited and caution is advised given prior mixed results with incretin therapies and theoretical concerns about rapid weight loss in advanced systolic failure. Conclusion This review integrates mechanistic insights and contemporary trial evidence to clarify how dual incretin agonism may modify the trajectory of obesity‐driven heart failure, to inform multidisciplinary clinical decision making, and to highlight key unanswered questions and research priorities needed to define tirzepatide's full role in heart failure management.
Journals
2026 EN
Balbaa Elsayed · Gadelmawla Ahmed Farid · Ibrahim Ahmed
+10 more
ABSTRACT Introduction Concerns about diabetic ketoacidosis (DKA) and euglycemic ketoacidosis (eKA) are balanced against possible organ‐protective benefits in the debated perioperative management of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors. This meta‐analysis compared the perioperative clinical and laboratory outcomes associated with perioperative exposure to SGLT2i. Methods Through July 31, 2025, we searched PubMed, Web of Science, Scopus, and CENTRAL for observational studies and randomised controlled trials comparing the outcomes of preoperative use of SGLT2 inhibitors with non‐use in patients undergoing cardiac or non‐cardiac surgery. We pooled data using a random‐effects model and investigated heterogeneity using leave‐one‐out sensitivity analyses. PROSPERO‐ID: CRD420251155809. Results There were 10 studies comprising 246,242 patients. Due to considerable heterogeneity, the primary pooled analysis revealed no significant association between SGLT2 inhibitor use and either eKA (OR 4.86; p = 0.11) or DKA (OR 2.21; p = 0.11). However, a significant increase in the risk of eKA (OR 1.11; p < 0.001) and DKA (OR 5.33; p < 0.001) was observed using leave‐one‐out sensitivity analysis to identify outliers. On the other hand, the usage of SGLT2 inhibitors was associated with a statistically significant decrease in both mortality (OR 0.73; p = 0.006) and acute renal injury (OR 0.68; p < 0.0001). The SGLT2 inhibitor group had significantly lower perioperative pH, base excess, and blood glucose levels. Conclusion The use of perioperative SGLT2 inhibitors poses a clinical paradox between significant renoprotection and survival advantages and a latent risk of ketoacidosis concealed by considerable heterogeneity. While metabolic monitoring is essential, current surgeries requiring more prolonged withholding may need to weigh metabolic risk against the drug's significant benefit in reducing acute kidney injury and mortality.
Journals
2026 EN
Shah Aadil Abass · Azam Siraj · Azam Ameer
+2 more
A sonochemical strategy was employed to synthesize hexagonal CuCrO 2 nanoplates and their graphene oxide (GO) nanocomposites (CuCrO 2 @GO) via ultrasonic‐assisted nucleation and growth, enabling precise interface coupling and efficient visible‐light photocatalysis. Structural analyses, including X‐ray diffraction (XRD), Raman spectroscopy (Raman), and Fourier‐transform infrared spectroscopy (FTIR), along with morphological characterization using scanning electron microscopy (SEM) and energy‐dispersive X‐ray spectroscopy (EDS), confirmed the formation of phase‐pure CuCrO 2 nanoplates uniformly anchored on the GO framework. The incorporation of GO induced bandgap narrowing from 2.92 eV to 2.23 eV, enhancing visible‐light absorption and charge‐carrier separation. Photocatalytic performance was evaluated against methylene blue (MB), rhodamine B (RB), Congo red (azo dye), and safranin dyes under natural sunlight, achieving 91%–96% degradation within 36–50 min at neutral pH using optimized catalyst loading (0.25 g L −1 ). Kinetic analysis revealed high pseudo‐first‐order rate constants ( k = 0.96–0.99 min −1 ), consistent with a nonselective, radical‐driven degradation mechanism. Band‐alignment analysis indicated that the CuCrO 2 –GO Type‐II heterojunction promotes directional charge transfer and suppresses electron–hole recombination. The photocatalyst retained activity over five cycles, confirming stability and reusability. This study demonstrates precision interface design in delafossite–GO heterostructures and establishes an efficient, solar‐driven pathway for broad‐spectrum wastewater remediation, surpassing conventional Cu‐based photocatalysts.
Journals
2026 EN
Weerasekera Akila · Zhou Shuqin · Wang Chao
+11 more
ABSTRACT Accelerated brain aging has been implicated in severe mental illnesses, particularly schizophrenia (SZ) and bipolar disorder (BD). Brain–PAD, derived from structural MRI, offers a promising biomarker of neurobiological aging, but its developmental course, within‐group variability, and regional drivers remain incompletely understood. A three‐dimensional convolutional neural network (3D‐CNN) was trained exclusively on healthy controls (HC; n = 155) and then applied to independent BD ( n = 122) and SZ ( n = 161) groups. Brain–PAD was computed as predicted brain age minus chronological age. Age‐by‐group interactions, within‐group dispersion, and sensitivity analyses (e.g., piecewise regression, inverse probability weighting) were conducted. Gradient‐weighted Class Activation Mapping (Grad–CAM) was used to identify regional contributions to brain age predictions. The 3D‐CNN achieved high accuracy in HC (MAE = 3.05 years, r = 0.96), with reduced accuracy in BD (MAE = 8.86, r = 0.51) and SZ (MAE = 9.01, r = 0.48). Mean Brain–PAD was significantly elevated in BD (+4.2 ± 10.2 years) and SZ (+6.7 ± 8.7 years) relative to HC (+0.7 ± 3.5 years). Age‐by‐group analyses revealed that BD and SZ exhibited elevated Brain–PAD at younger ages, converging toward HC trajectories by midlife, followed by renewed divergence beyond age 40. This pattern was supported by piecewise and spline models showing steeper negative slopes in BD and SZ compared with HC. Variance and quantile regression indicated greater heterogeneity in BD and SZ across the Brain–PAD distribution. Grad–CAM highlighted temporal and frontal regions as central contributors across all groups; in SZ, Brain–PAD correlated positively with whole‐brain ( r = 0.23, p = 0.004), frontal ( r = 0.21, p = 0.009), and temporal ( r = 0.20, p = 0.012) activations, whereas BD showed weaker and more diffuse associations. SZ and BD exhibit elevated Brain–PAD early in adulthood with greater heterogeneity than healthy controls. Frontotemporal regions contribute prominently to brain‐age predictions, reflecting model sensitivity to age‐informative structure. These findings support Brain–PAD as a group‐level marker of apparent brain aging and motivate longitudinal study of midlife divergence.
Journals
2026 EN
Fatih Mohammed Taib · Mahmood Mohammed Khalid · Garib Balkees Taha
+11 more
ABSTRACT Background Oral leukoplakia (OL) represents the most common oral potentially malignant disorder globally, with highly variable reported malignant transformation (MT) rates creating challenges for evidence‐based clinical management. Objective To systematically synthesize evidence on MT prevalence in OL and evaluate potential predictive biomarkers through an umbrella review of systematic reviews and meta‐analyses. Methods Following PRISMA guidelines, we searched PubMed, MEDLINE, Scopus, and Embase databases through July 2025. Twenty‐seven systematic reviews encompassing more than 125,000 patients were included. Meta‐analyses were conducted using random‐effects models, with quality assessed using AMSTAR 2 and GRADE approaches. Results Transformation rates were considerably higher in proliferative verrucous leukoplakia (48%) than in OL (6%). Females exhibited almost twice the MT rate of males (64% vs. 35%), while tongue lesions showed the highest site‐specific risk (39%). The most promising predictive biomarker with a moderate level of evidence quality was DNA aneuploidy. Conclusions Because of its high malignant potential, OL necessitates risk‐based surveillance protocols. While the bulk of other predictors requires further investigation, DNA aneuploidy shows potential for clinical application.