Search Results (2,217)

In recent years, rapid advancements in glaucoma research have led to the development of more effective treatments of this chronic and irreversible condition. Of these, Kahook Blade Dual (KDB) goniotomy and second-generation trabecular micro-bypass stent (iStent) are two novel biomimetic procedures which have designs inspired by the eye’s natural drainage mechanisms. In this retrospective study, we evaluated the safety and effectiveness of both surgeries by including 176 eyes from 110 patients: 142 eyes in the iStent group and 34 in the KDB group. The primary outcomes of this study were the proportions of patients in each group attaining a 20% reduction in IOP and a post-operative IOP < 19 mmHg. At the last follow-up, a 20% reduction in IOP was achieved by 67% of iStent inject patients and 50% of KDB patients (p = 0.07). The iStent group also showed a higher proportion of patients reaching an IOP of less than 19 mmHg (81% vs. 71% in the KDB group, p = 0.13). The number of medications did not decrease in either group from pre-op to the last follow-up. The KDB group had more failures (29.4% vs. 4.2%) and a significantly higher adverse event rate than the iStent inject group (47.1% vs 12.0%). Full article

Background and Objectives: Ixekizumab is a human monoclonal antibody targeting interleukin-17A, approved for the treatment of moderate-to-severe plaque psoriasis. Given its demonstrated efficacy and safety in clinical trials, this study aimed to evaluate the real-world drug survival of Ixekizumab and identify clinical predictors of treatment discontinuation. Materials and Methods: A retrospective, observational, hospital-based study was conducted in the Department of Dermatology at the Central University Hospital of Asturias (HUCA). Patients with moderate-to-severe plaque psoriasis who initiated treatment with Ixekizumab (Taltz^®) between 8 June 2017 and 10 October 2024, were included. Demographic data, comorbidities, age at disease onset, family history, PASI score, and previous treatments were recorded. Drug survival was assessed using Kaplan–Meier survival curves and the log-rank test. Predictors of discontinuation were analyzed using univariate and multivariate Cox proportional hazards models. Results: A total of 103 patients (55.3% women) were included. Drug survival rates were 85% at one year, 73% at two years, and 61% at four years, with a mean treatment duration of 52.5 months (95% CI: 46.01–58.99). Multivariate analysis showed that patients under the age of 65 had a significantly higher risk of treatment discontinuation (hazard ratio: 1.813; p < 0.05). The most common reason for discontinuation was secondary treatment failure (45.16%). Ixekizumab demonstrated sustained drug survival in a real-world setting, with rates falling within the mid-to-upper range reported in the literature. Older age (>65 years) was associated with greater treatment persistence, highlighting a potential influence of age on long-term therapeutic adherence. Full article

Background: Reducing critically ill patients’ exposure to antibiotics is mandatory. In randomized controlled trials, procalcitonin (PCT)-guided algorithms (i.e., antibiotic therapy [ABT] should be stopped whenever PCT is less than 0.5 µg/L or is below 80% of the peak value) reduced the duration of (ABT) more than compliance with the current guidelines. However, the interest of such stopping rules in daily practice remains debated. Thus, we carried out a real-life study addressing this issue. Results: During the study period, 112 patients with sepsis upon intensive care unit admittance were included. The median age was 66 years (56–79). Half of the patients presented with acute respiratory failure. Pneumonia was diagnosed in 78% of them, and 41% met septic shock criteria. The initial ABT was empirical in most cases, and appropriateness rate to the isolated bacteria reached 71%. A median number of four PCT measurements was achieved in both groups. The compliance rate with the PCT algorithm was 54%. The median duration of ABT was 5 (4–7) days if the PCT algorithm was followed, as compared to 7 (5–10) days otherwise (p < 0.001). This ABT stopping rule allowed a 2-day reduction in the treatment duration as compared with those recommended by the guidelines (p < 0.001). The only independent factor associated with shorter treatment duration was compliance with the PCT algorithm (OR = 0.74, 95% CI [0.62; 0.88]; p < 0.001). Regarding safety, no difference in outcome was found between the two groups. Conclusions: Complying with one PCT-based stopping rule is associated with a significant reduction in the duration of ABT in septic critically ill patients, without apparent impact on patient outcomes. Full article

Clarifying the differential effects of temperature gradient and temperature change rate on the evolution of rock fractures and damage mechanism under thermal shock is of great significance for the development and utilization of deep geothermal resources. In this study, granite samples at different temperatures (20 °C, 150 °C, 300 °C, 450 °C, 600 °C, and 750 °C) were subjected to rapid cooling treatment with liquid nitrogen. After the thermal treatment, a series of tests were conducted on the granite, including wave velocity test, uniaxial compression experiment, computed tomography scanning, and scanning electron microscopy test, to explore the influence of thermal shock on the physical and mechanical parameters as well as the meso-structural damage of granite. The results show that with the increase in heat treatment temperature, the P-wave velocity, compressive strength, and elastic modulus of granite gradually decrease, while the peak strain gradually increases. Additionally, the failure mode of granite gradually transitions from brittle failure to ductile failure. Through CT scanning experiments, the spatial distribution characteristics of the pore–fracture structure of granite under the influence of different temperature gradients and temperature change rates were obtained, which can directly reflect the damage degree of the rock structure. When the heat treatment temperature is 450 °C or lower, the number of thermally induced cracks in the scanned sections of granite is relatively small, and the connectivity of the cracks is poor. When the temperature exceeds 450 °C, the micro-cracks inside the granite develop and expand rapidly, and there is a gradual tendency to form a fracture network, resulting in a more significant effect of fracture initiation and permeability enhancement of the rock. The research results are of great significance for the development and utilization of hot dry rock and the evaluation of thermal reservoir connectivity and can provide useful references for rock engineering involving high-temperature thermal fracturing. Full article

Background and Objectives: Endoscopic sleeve gastroplasty (ESG) is a minimally invasive endoscopic procedure that has demonstrated both safety and effectiveness in the treatment of obesity. By reducing the stomach’s volume without the need for surgical incisions, ESG promotes weight loss and can improve obesity-related comorbidities. However, patient responses to ESG can vary significantly. Materials and Methods: A comprehensive search was performed on PubMed, Embase, and Cochrane for studies with endoscopic sleeve gastroplasty; the main outcomes of interest are BMI, weight loss, and postinterventional complications. The search strategy employed a combination of keywords and Medical Subject Heading (MeSH) terms, including “endoscopic sleeve gastroplasty,” “endoscopy,” and “overweight”. To ensure the thoroughness of the review, additional manual searches of key journals and the reference lists of identified studies were performed. Grey literature, such as dissertations and conference abstracts, meta-analysis, and systematic reviews, was excluded to maintain a focus on peer-reviewed evidence. Duplicate records were identified and removed using Rayyan software to streamline the screening process. The I2 test was employed for heterogeneity assessment, while the risk of bias was evaluated utilizing ROBINS-I. Results: Our literature search resulted in the inclusion of 38 studies. Endoscopic sleeve gastroplasty for weight loss is important since it is more effective than pharmacological treatments and lifestyle changes and presents lower adverse event rates compared to bariatric surgery. Long-term weight loss outcomes varied, with total body weight loss ranging from 16% to 20.9% over a period from 2 to 5 years, while excess weight loss ranged from 13% to 79%. Revisional procedures showed higher failure rates, with up to 34.3% of patients experiencing insufficient weight loss. Most interventions led to clinically significant and sustained weight loss, though variability in outcomes highlights the need for further research to optimize long-term weight management strategies. Conclusions: Endoscopic sleeve gastroplasty (ESG) emerges as a promising minimally invasive option for weight loss, offering significant improvements in both weight reduction and obesity-related comorbidities, such as diabetes, hypertension, and dyslipidemia. Full article

Background/Objectives: This retrospective study aimed to evaluate the survival and marginal bone loss (MBL) of sloped-shoulder implants placed in the posterior mandible, and to explore the influence of both patient- and implant-related factors. Materials and Methods: All patients treated with sloped-shoulder-profile implants (Astra Tech Implant System, Dentsply Sirona, Bensheim, Germany) in the posterior mandible between 2012 and 2023 at two private clinics were included. Implant survival was analyzed with Kaplan–Meier estimates. MBL was measured from prosthesis delivery (baseline radiograph) to the most recent available radiograph. Outcomes were compared across thresholds of 0, 0.5, and 1.5 mm, which were considered radiographic success criteria. According to the 2017 World Workshop, peri-implantitis was not diagnosed solely based on MBL. Associations with potential risk factors (periodontitis, bruxism, and smoking) were explored. The study was approved by a local ethics committee (PI 106/2023); informed consent was waived due to the retrospective design and anonymization of data. Results: A total of 43 patients with 48 implants were included, with a mean follow-up of 40.1 months. The cumulative survival rate was 93.7%, with all failures occurring before 24 months. Mean MBL at the mesial and distal aspects was 0.27 mm and 0.39 mm, respectively. In 82.2% of implants, MBL remained ≤0.5 mm at a mean follow-up of 44.2 months. No statistically significant associations were found between risk factors such as periodontitis, bruxism, or smoking and implant outcomes. Conclusions: Sloped-shoulder implants in the posterior mandible showed high survival and stable marginal bone levels over the medium term. Their design may simplify treatment in oblique ridges, potentially reducing the need for GBR procedures. Full article

Background: Conventional HF treatment in transthyretin cardiac amyloidosis (ATTR-CA) resulting in restrictive cardiomyopathy is debated due to absent trial evidence in this specific sub-population of heart failure (HF) patients. Current European Society of Cardiology guidelines recommend the use of diuretics and mineralocorticoid receptor antagonists (MRAs). However, beta-blockers (BBs) and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) are often discontinued due to hypotension or bradycardia. This study assesses real-world HF treatment patterns and their impact on survival in a multinational ATTR-CA cohort. Methods: A retrospective analysis of 794 ATTR-CA patients examined baseline BB, ACEi/ARB, and MRA prescriptions. The cohort was divided based on guideline publication dates. Results: Patients were predominantly male (73.2%) with a median age of 78 years. Prescription of diuretics (52.8%) and disease-modifying therapy (44.9%), mostly tafamidis, was common. BBs (43.7%) and ACEi/ARBs (41.2%) were prescribed more often in patients with higher NYHA class, elevated NT-proBNP, and more comorbidities. Blood pressure and heart rate were similar regardless of BB or ACEi/ARB use. BB prescription and combination therapy with BB and ACEi/ARB increased over time. Neither BB nor ACEi/ARB use significantly impacted mortality when analyzed in a multivariate Cox proportional hazard regression. Conclusions: Use of BBs and ACEi/ARBs has increased over time, particularly in advanced-stage ATTR-CA patients, and although these therapies appear to be reasonably tolerated, survival was not significantly altered. Full article

Background: Healthcare 5.0 represents a shift toward intelligent, human-centric care systems. Intensive care units generate vast amounts of data that require real-time decisions, but current decision support systems lack comprehensive frameworks for safe integration of artificial intelligence. Objective: We developed and validated the Learn–Predict–Monitor–Detect–Correct (LPMDC) framework as a methodology for systematic artificial intelligence integration across the critical care workflow. The framework improves predictive analytics, continuous patient monitoring, intelligent alerting, and therapeutic decision support while maintaining essential human clinical oversight. Methods: Framework development employed systematic theoretical modeling integrating Healthcare 5.0 principles, comprehensive literature synthesis covering 2020–2024, clinical workflow analysis across 15 international ICU sites, technology assessment of mature and emerging AI applications, and multi-round expert validation by 24 intensive care physicians and medical informaticists. Each LPMDC phase was designed with specific integration requirements, performance metrics, and safety protocols. Results: LPMDC implementation and aggregated evidence from prior studies demonstrated significant clinical improvements: 30% mortality reduction, 18% ICU length-of-stay decrease (7.5 to 6.1 days), 45% clinician cognitive load reduction, and 85% sepsis bundle compliance improvement. Machine learning algorithms achieved an 80% sensitivity for sepsis prediction three hours before clinical onset, with false-positive rates below 15%. Additional applications demonstrated effectiveness in predicting respiratory failure, preventing cardiovascular crises, and automating ventilator management. Digital twins technology enabled personalized treatment simulations, while the integration of the Internet of Medical Things provided comprehensive patient and environmental surveillance. Implementation challenges were systematically addressed through phased deployment strategies, staff training programs, and regulatory compliance frameworks. Conclusions: The Healthcare 5.0-enabled LPMDC framework provides the first comprehensive theoretical foundation for systematic AI integration in critical care while preserving human oversight and clinical safety. The cyclical five-phase architecture enables processing beyond traditional cognitive limits through continuous feedback loops and system optimization. Clinical validation demonstrates measurable improvements in patient outcomes, operational efficiency, and clinician satisfaction. Future developments incorporating quantum computing, federated learning, and explainable AI technologies offer additional advancement opportunities for next-generation critical care systems. Full article

Background: Unicompartmental knee arthroplasty (UKA) represents a well-recognized treatment option for isolated medial compartment osteoarthritis; however, the debate regarding the superiority of fixed-bearing versus mobile-bearing designs continues. We aimed to evaluate the mid- to long-term outcomes of medial UKA comparing mobile- versus fixed-bearing designs within a single institution over an average 10-year follow-up. Methods: This retrospective study included 81 consecutive patients who underwent primary medial UKA (45 fixed-bearing and 36 mobile-bearing) with a minimum five-year follow-up. Clinical outcomes were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and range of motion (ROM). Radiological measurements included hip-knee-ankle axis angle (HKA) and osteoarthritis progression. Implant survivorship was evaluated using Kaplan–Meier analysis, with failure defined as either conversion to total knee arthroplasty (TKA) or polyethylene (PE) exchange. Results: At a mean follow-up of 10.6 years, WOMAC scores, ROM, and radiological outcomes showed no statistically significant differences between the fixed-bearing and mobile-bearing groups. Significantly higher failure rates were observed in the mobile-bearing group, both when considering conversion only (p = 0.041) and when including conversion or PE exchange (p = 0.009). Survival analysis demonstrated 10-year rates of 97.8% for fixed-bearing and 88.9% for mobile-bearing with TKA conversion defined as failure (p = 0.066). Using combined failure criteria of TKA conversion or PE exchange, 10-year survival rates were 97.8% for fixed-bearing and 83.3% for mobile-bearing (p = 0.015). Conclusions: At a mean 10.6-year follow-up, clinical and radiological outcomes were comparable, but fixed-bearing UKA demonstrated superior survivorship. Full article

Chronic rhinosinusitis (CRS) is increasingly recognized as a heterogeneous condition characterized by distinct inflammatory endotypes. In Western populations, CRS is mostly type 2 (T2) eosinophilic. In contrast, Asian cohorts show higher rates of non-T2 endotypes, posing unique challenges and limiting the applicability of Western treatment models. This expert commentary and scoping review explores endotype-driven care in CRS, synthesizes current research on Asian CRS cohorts, and examines existing gaps in our understanding, particularly in non-T2 CRS. Endotype-driven care improves treatment precision and minimizes therapeutic failure. However, most models remain largely Western-centric. Establishing Asia-specific criteria, accessible diagnostics, and therapies for non-T2 disease is essential. Full article

Background and Objectives: This study aimed to evaluate the treatment outcomes of adults with pulmonary drug-susceptible tuberculosis (DS-TB) in Lithuania over 22 years, and to examine associations between treatment outcomes, various risk factors, and temporal trends. Materials and Methods: A retrospective cohort analysis was conducted using data from the National Tuberculosis Information System from 2000 to 2021. A total of 18,697 adult patients with DS-TB were included. Patients were grouped into three time periods: Period I (2000–2007), Period II (2008–2015), and Period III (2016–2021). Treatment outcomes were categorized as successful (treatment completed with recovery) or unsuccessful (patients who encountered treatment failure, died during treatment, or converted to drug-resistant tuberculosis). Associations with individual risk factors, including smoking, alcohol use, comorbidities, and sociodemographic variables, were analyzed. Results: Treatment success rates improved steadily across the study periods: 82.3% in Period I, 84.4% in Period II, and 87.6% in Period III. Mortality rates declined over time but remained substantial: 17.1%, 15.2%, and 12.0% in Periods I, II, and III, respectively. Non-lethal treatment failures decreased slightly (0.6%, 0.4%, and 0.4%). Multivariate analysis identified significant associations between treatment failure and multiple risk factors, including low BMI, male gender, unemployment, homelessness, smoking, alcohol and substance use, and comorbid conditions such as cancer, cardiovascular disease, chronic lung disease, diabetes mellitus, HIV, and renal failure. Conclusions: Treatment outcomes for DS-TB in Lithuania have improved over the past two decades; however, certain modifiable risk factors—such as low BMI, homelessness, substance use, and comorbidities—remain strongly linked to treatment failure. To further improve outcomes, targeted interventions such as nutritional support, housing programs, and integrated addiction services should be prioritized for high-risk groups within national TB control efforts. Full article

Clopidogrel is widely used as an antiplatelet therapy for acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Genetic factors influence variability in clopidogrel response, with non-functional CYP2C19 alleles increasing the risk of major adverse cardiovascular events (MACEs). While CYP2C19 genotype-guided therapy after PCI improves outcomes, MACEs persist at variable rates. Pharmacogenomics (PGx) has primarily focused on genes related to drug metabolism, but therapeutic failure may stem from individual disease predisposition. This study aims to identify novel genetic variants underlying adverse events after PCI despite PGx-guided therapy. A custom sequencing panel was analyzed in 244 ACS-PCI-stent patients and 99 controls without cardiovascular (CV) disease. Association analysis was performed independent of treatment and by prescribed treatment (clopidogrel or prasugrel), complemented by random forest models to predict risk during antiplatelet therapy. No polymorphism reached genomic significance, but in clopidogrel-treated patients, rs2472434 in ABCA1, related to altered lipid metabolism, was strongly associated with secondary CV events (p = 1.7 × 10⁻³). Variants in the clopidogrel pathway, including CYP2C19, ABCB1, and UGT2B7, were also identified and may influence clopidogrel response. Predictive models incorporating these variants effectively discriminated patients with and without events (p = 0.02445). Our findings support combined genotyping of CYP2C19 loss-of-function and ABCB1 C3435T variants to guide antiplatelet therapy and suggest additional targets, such as rs2472434 (ABCA1) and rs7439366 (UGT2B7), to improve risk prediction of adverse CV events. Therefore, the unexplained variability in clopidogrel response may be due to disease pathogenesis itself, highlighting the need for a paradigm shift in PGx studies. Full article

Asthma is a chronic inflammatory disease with a heterogeneous course, often progressing silently from mild symptoms to severe, treatment-refractory disease. Current guidelines recommend biologic therapies after failure of high-dose inhaled corticosteroids and additional controllers, typically in patients with frequent exacerbations. This reactive approach may delay intervention until irreversible airway remodeling has occurred, limiting the potential benefits of biologic therapy. Therefore, severe asthma may be envisioned as the consequence of missed opportunities for early interventions. Early initiation of biologic therapy—guided by biomarkers such as blood eosinophil count and fractional exhaled nitric oxide (FeNO), as well as symptom burden and risk of lung function decline—may prevent progression to severe asthma and improve remission rates. This position paper advocates for a shift from severity-based to risk-based treatment strategies, recommending earlier biomarker assessment, redefinition of escalation criteria, and clinical trials designed to evaluate biologics in symptomatic non-exacerbating patients. By recognizing persistent inflammation and progression risk earlier in the disease course, clinicians may have a critical opportunity to alter the trajectory of asthma, reduce long-term morbidity, and achieve sustained control before irreversible damage occurs. Full article

The development of single-crystal Ni-rich layered cathode materials (SC-NCMs) is regarded as an effective strategy to address the mechanical failure issues commonly associated with polycrystalline counterparts. However, the industrial production of SC-NCM faces challenges such as lengthy processing steps, high manufacturing costs, and inconsistent product quality. In this study, we innovatively propose a metal/organic framework (MOF)-mediated one-step synthesis strategy to achieve controllable structural preparation and in situ Nb⁵⁺ doping in SC-NCM. Using a Ni–Co–Mn-based MOF as both precursor and self-template, we precisely regulated the thermal treatment pathway to guide the nucleation and oriented growth of high-density SC-NCM particles. Simultaneously, Nb⁵⁺ was pre-anchored within the MOF framework, enabling atomic-level homogeneous doping into the transition metal layers during crystal growth. Exceptional electrochemical performance is revealed in the in situ Nb-doped SC-NCM, with an initial discharge capacity reaching 176 mAh/g at a 1C rate and a remarkable capacity retention of 86.36% maintained after 200 cycles. This study paves a versatile and innovative pathway for the design of high-stability, high-energy-density cathode materials via a MOF-mediated synthesis strategy, enabling precise manipulation of both morphology and chemical composition. Full article

Treatment for acute liver failure (ALF) is constrained by shortages of liver transplant donors and immune rejection. Porcine bone marrow mesenchymal stem cells (pBMSCs) demonstrate clinical potential in xenotransplantation due to their abundant availability, low immunogenicity, and strong proliferative activity. This study is the first to investigate the reparative effects and mechanisms of pBMSCs derived from Luopan Mountain pigs in a D-galactosamine (D-GalN)-induced ALF rat model. The results demonstrated that tail-vein transplantation of pBMSCs significantly improved survival rates in ALF rats; reduced serum ALT, AST, and TBIL levels; enhanced hepatic glycogen metabolism; and mitigated histopathological liver damage. Additionally, pBMSC transplantation upregulated serum HGF, IGF-1, and VEGF levels while inhibiting hepatocyte apoptosis. Mechanistic studies indicate that pBMSCs promote liver function recovery and regeneration by activating the PI3K/Akt/mTOR signaling pathway and suppressing its key negative regulator, PTEN, by regulating the expression of key genes involved in inflammation, fibrosis, proliferation, and apoptosis. This study provides crucial experimental evidence for the use of pBMSCs in treating acute liver failure (ALF) and lays the groundwork for its clinical translation in the field of xenotransplantation. Full article