Search Results (12,472)

Background/Objectives: Fusarium species are recognized as difficult-to-treat opportunistic pathogens due to extensive antifungal resistance and high mortality rates. Variability in its incidence and outcomes exists across different countries and centers. Large studies on Fusarium species are lacking in Saudi Arabia, with most previous publications being case reports. We describe all cases of invasive fusariosis identified at a tertiary center during a 10-year period and review previous reports in the country. Methods: A retrospective search of hospital records and the microbiology database was conducted to identify cases of invasive fusariosis among patients admitted during 2016–2025 at King Abdulaziz Medical City, Jeddah, Saudi Arabia. Results: Three cases of invasive fusariosis occurring over a 10-year period were identified. All cases occurred in the last three years of the study period. The incidence during those three years was 0.4 cases per 10,000 admissions per year. Clinical manifestations were fungemia in two immunocompetent patients and ulcers progressing to osteomyelitis in an immunocompromised patient. None of the patients progressed to death within 30 days of diagnosis. Conclusions: Data on Fusarium species are scarce in Saudi Arabia. Additional studies are required to better understand differences in invasive fusariosis between countries. Full article

Background: Obstructive sleep apnea (OSA) affects quality of life and increases cardiovascular risk. Nocturnal oxygen therapy (NOT) offers a potential alternative for patients intolerant to CPAP. The objective of this study was to compare NOT and continuous positive airway pressure (CPAP) by evaluating five-year survival in patients with obstructive sleep apnea. Methods: A retrospective cohort study was conducted using propensity score matching (PSM) methodology. A PSM analysis was conducted to reduce selection bias due to differences in baseline characteristics between patients using CPAP and those receiving oxygen therapy. Balance between treated and untreated groups was assessed using standardized mean differences. A PSM was estimated using a logistic regression model, matching patients adherent to CPAP therapy to those treated with NOT. Results: A total of 497 patients with a confirmed diagnosis of OSA were included in the analysis. The mean age was 62.1 years (SD13.6), and 54.3% (270/497) were male. Overall, 42.1% (209/497) of the patients were over 65 years old. Of the total, 303 patients received CPAP therapy and 194 received NOT. After PSM, a matched cohort of 370 patients (185 per group) was obtained. The CPAP-treated group showed a significantly lower residual Apnea–Hypopnea Index compared to the oxygen therapy group (3.9, IQR: 1.8–6.5 vs. 15, IQR:7.5–29.1; p < 0.001), indicating better physiological control of respiratory events. Treatment with CPAP was associated with a significantly lower risk of mortality compared with NOT across analytical approaches, including weighted logistic regression (OR = 0.11; 95% CI 0.02–0.48; p = 0.004) and PSM with bootstrap estimation (ATT = −0.12; 95% CI −0.22 to −0.01; p = 0.030). Conclusions: In this cohort, higher five-year survival was observed among patients with OSA treated with CPAP compared with those receiving supplemental oxygen. These findings indicate a favorable association between CPAP use and long-term outcomes, supporting its role as the preferred first-line therapy in patients with OSA. Full article

Background/Objectives: Reduced-ejection-fraction heart failure (HFrEF) constitutes a challenge due to its high morbidity and mortality. The use of sacubitril/valsartan (angiotensin receptor–neprilysin inhibitors [ARNI]) and SGLT2 inhibitors (SGLT2i) represents a change in management approach with a demonstrated association with positive ventricular remodeling and a reduction in cardiovascular events. We describe the clinical and therapeutic course of patients with HFrEF in a specialized unit, comparing two consecutive periods (2011–2016 vs. 2017–2021), with emphasis on the impact of ARNI and SGLT2i upon clinical parameters and the use of devices. Methods: A retrospective, longitudinal observational study was carried out in 1363 outpatients with HFrEF, with at least two years of follow-up. Clinical characteristics, treatments, the evolution of left ventricular ejection fraction (LVEF), mortality, and the use of devices (implantable cardioverter–defibrillator [ICD], cardiac resynchronization therapy [CRT]) were evaluated. Results: A total of 1363 patients were analyzed, showing a significant therapeutic change in the 2017–2021 group with the incorporation of ARNI (40%) and SGLT2i (25%). This cohort achieved better ventricular recovery, with a significantly higher mean LVEF at one year compared to the 2011–2016 group (44.3% vs. 42.1%; p = 0.004). Regarding devices, ICD implantation rate decreased in the recent period (7.2% vs. 11.1%; p = 0.016), while CRT indication increased. Most importantly, all-cause mortality after two years fell from 9.4% to 5.9% (p = 0.023). Multivariate analysis confirmed that this survival improvement was independently associated with the study period (HR 1.57 for the earlier group) and was linked to the protective effect of contemporary pharmacological treatments. Conclusions: The systematic introduction of ARNI and SGLT2i in the treatment of HFrEF was associated with improved ventricular function, reduced need for device implantation, and lower mortality over the middle term in a real-life clinical setting. Full article

Background: Beyond the direct COVID-19 effects, the pandemic’s broader impact on vulnerable groups, such as patients with systemic sclerosis (SSc), is particularly concerning, especially regarding any resulting increase in overall mortality due to healthcare access disruptions. We aimed to determine excess all-cause mortality in SSc patients before and during the pandemic. Methods: We examined mortality data from Thailand’s Ministry of Public Health database for adults with SSc (ICD-10: M34). According to the WHO methodology, a negative binomial distribution model was used to estimate the expected number of deaths using pre-pandemic data (1 January 2015–31 December 2019). We evaluated actual versus expected deaths during the pandemic (1 January 2020 to 31 December 2022), defining excess mortality as the difference between observed and projected deaths under normal conditions. Results: The total number of all-cause deaths in Thailand was 2,325,384 in the pre-pandemic period and 1,634,121 during the pandemic period. The mortality rate among patients with SSc was 3693 before and 3107 during the pandemic. Of those with SSc, 1785 of the deceased were female, and the observed mortality was significantly lower than expected, with an excess death count of −368 (95% CI: −459 to −277), as well as in males with an excess death count of −123 (95% CI: −198 to −48). However, younger SSc patients (aged 18–29 years) experienced significantly higher excess mortality, with an excess death count of 11 (95% CI: 4–18). Conclusions: During the COVID-19 pandemic, neither sex had significantly higher SSc mortality; however, mortality in younger SSc patients increased significantly compared to pre-pandemic levels, underscoring the need for tailored therapies. Full article

Cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality worldwide, underscoring the urgent need for novel therapeutic alternatives. In recent years, marine ecosystems have garnered increasing attention as a promising source of bioactive compounds with unique structural and pharmacological properties. Marine-derived toxins and venoms, including tetrodotoxin, ω-conotoxins, anthopleurins, palytoxin, brevetoxin, aplysiatoxin, and asterosaponins, exert cardioprotective effects through diverse mechanisms such as modulation of ion channels, inhibition of sympathetic overactivity, antioxidative actions, and enhancement of myocardial contractility. These properties make them potential candidates for addressing various CVD manifestations, including arrhythmia, hypertension, ischemia–reperfusion injury, and heart failure. However, despite their therapeutic promise, the clinical application of these marine compounds remains limited due to poor tissue selectivity, narrow therapeutic indices, proinflammatory activity, and limited metabolic stability. Structural modifications, advanced drug delivery platforms, and in vivo validation studies are crucial for overcoming these challenges. This review highlights the pharmacological actions, molecular targets, and cardiovascular relevance of selected marine toxins and venoms while also addressing key translational barriers. Advances in biotechnology and peptide engineering are enabling the safer and more targeted use of these compounds. Collectively, marine-derived toxins and venoms represent a largely untapped but highly promising frontier in cardiovascular drug discovery. Strategic research focused on elucidating mechanisms, optimizing delivery, and translating clinical applications will be critical to unlocking their full therapeutic potential. Full article

Background: Dynapenia refers to the age-related decline in muscle strength that occurs even when muscle mass is preserved. It has become an important issue in older adults because reduced strength is strongly linked to many negative health outcomes. When dynapenia occurs together with obesity—referred to as dynapenic obesity or dynapenic abdominal obesity—the risks, including mortality, falls, and the development of multiple chronic conditions, appear to increase even further. This umbrella review aimed to bring together and summarize existing systematic reviews and meta-analyses that examined how dynapenia and its obesity-related subtypes are associated with mortality, falls, and multimorbidity among community-dwelling older adults. Methods: Following PRISMA 2020 and JBI guidelines, six major databases and search engines (PubMed, Embase, Cochrane Library, Scopus, CINAHL, and Airiti Library) were searched from their inception to October 2025. Systematic reviews and meta-analyses involving adults aged 60 years and older and reporting quantitative results on the relationships between dynapenia-related conditions and adverse health outcomes were included. The methodological quality of each review was evaluated using AMSTAR 2, and the certainty of evidence was assessed with the GRADE approach. This umbrella review followed the PRIOR framework and was reported according to PRISMA 2020. The protocol for this review was registered in PROSPERO (ID: CRD 42023415232). Results: A total of four systematic reviews and meta-analyses were included, covering more than 73,000 community-dwelling older adults. The pooled data showed that dynapenic obesity significantly increased the risk of all-cause mortality, with hazard ratios ranging from 1.50 (95% CI 1.14–1.96) to 1.73 (95% CI 1.38–2.16). Dynapenic abdominal obesity was also strongly linked to falls, with pooled estimates ranging from HR = 1.82 (95% CI 1.04–3.17) to RR = 6.91 (95% CI 5.42–8.80). For multimorbidity, older adults with dynapenia had 1.38 times higher odds of having two or more chronic diseases than those without dynapenia (OR = 1.38, 95% CI 1.10–1.72). Based on the GRADE evaluation, the certainty of evidence was moderate for mortality and falls and low for multimorbidity. Conclusions: Overall, the findings indicate that dynapenia and its obesity-related forms meaningfully increase the risks of mortality, falls, and multimorbidity among community-dwelling older adults. Importantly, these results position dynapenia not merely as a musculoskeletal condition, but as a clinically relevant marker of aging-related vulnerability. This underscores the need for early screening of muscle strength alongside obesity-related indicators, as well as the development of integrated preventive strategies that combine strength-oriented interventions with obesity management in older populations. Full article

Background: The characteristics and prognosis of HIV-associated Kaposi sarcoma (KS) among people living with HIV (PLWH), and their association with HHV-8 viral load are not well understood in Japan. Methods: We conducted a retrospective study of PLWH diagnosed with KS at Tokyo Medical University from 2000 to 2023. Results: Seventy cases of KS were identified; HHV-8 viral load data were available for twenty-three of these cases. The median age was 43 years (interquartile range [IQR], 11 years). The median HIV viral load at diagnosis was 150,000 copies/mL (IQR, 560,000 copies/mL). The median CD4 count was 76.0/μL (IQR, 157/μL). Lesions other than those of the skin were observed in the gastrointestinal tract (nine cases, 39.1%), oropharynx (three cases, 13.0%), and bronchial/lung (two cases, 8.7%). The median HHV-8 viral load was 0.0 copies/10⁶ WBC (IQR, 1500 copies/10⁶ WBC). Among the nine deceased PLWH, KS inflammatory cytokine syndrome (KICS) was diagnosed in five PLWH. Older age (≥50 years) and a high HHV-8 viral load (>615 copies/10⁶ WBCs) were significantly associated with worse survival. Conclusion: A high HHV-8 viral load may be a risk factor for mortality in PLWH with KS. Notably, all PLWH diagnosed with KICS in this study died, underscoring the poor prognosis associated with this condition. Full article

Objectives: Central airway obstruction (CAO) caused by malignant tumors may necessitate combined and prompt treatment. The aim is to recanalize and stabilize the airways as palliation. We present our multicentric experience managing malignant CAO through the placement of Y-shaped self-expanding covered metallic or silicone trachea-bronchial stents. Methods: This retrospective study includes patients who underwent placement of Y-shaped stents from 2002 to 2024 across six different centers in Italy and Great Britain. We evaluated outcomes related to the feasibility and safety of the procedure, as well as the palliation of dyspnoea on the Modified Borg Scale of Dyspnoea. Results: Eighty patients (56.2% female) with a mean age of 64.8 ± 9.6 years were included in the study. Successful placement was achieved in 76 (95%) cases, with no cases of intraoperative mortality. The mean procedure time was 36.64 ± 15.7 min. The complications noted included: 7 (8.7%) cases of periprocedural clinical complications and 7 (8.7%) patients requiring intensive care unit admittance after the procedure. Fifty patients (78.1%) received cancer treatment following the procedure. The mean dyspnoea score on the Borg scale decreased from 7.78 ± 0.98 to 4.02 ± 2.2 (p < 0.05). Conclusions: The placement of metal or silicone Y-shaped stents is a feasible and safe procedure for the palliative treatment of dyspnoea in patients with malignant stenosis of the trachea and main bronchi. Stabilizing the airway also enables these patients to access cancer treatments. Full article

Background/Objectives: Carbapenem-resistant Klebsiella spp. (CRK) causes healthcare-associated infections with high mortality. This study evaluated the clinical outcomes of ceftazidime–avibactam (CZA) therapy in CRK infections. Methods: Patients hospitalized in a tertiary care hospital in Türkiye between June 2021 and December 2022 with CRK-positive cultures, CZA susceptibility, and ≥72 h of CZA treatment were retrospectively analyzed. Results: Ninety-nine patients (61.6% male; mean age 63.7 ± 17.5 years) were included, 89.9% of whom were treated in the intensive care unit (ICU). Hypertension (29.3%), diabetes (28.3%), and malignancy (26.3%) were the most frequent comorbidities. The main infection types were bloodstream infection (56.6%) and ventilator-associated pneumonia (29.3%). CZA was used as monotherapy in 49.5%, and in combination in 50.5% of cases. The mean treatment duration was 13.2 ± 6.3 days. Clinical improvement occurred at 3.4 ± 1.2 days and microbiological eradication at 4.7 ± 2.1 days. Treatment success was achieved in 76.8% of patients, while 30- and 90-day mortality rates were 48.5% and 72.7%, respectively. Only treatment duration significantly affected clinical outcome (p < 0.001). Conclusions: CZA demonstrates favorable outcomes in CRK infections, with no significant difference between monotherapy and combination therapy. These findings support the use of CZA as an effective treatment option for severe CRK infections in real-world clinical settings and may help guide antimicrobial stewardship strategies in high-risk hospitalized patients. Full article

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and constitute a substantial economic burden. Despite population aging, recent years have witnessed an increasing prevalence of conditions such as heart failure (HF), including among young adults. In this context, coronary artery disease (CAD) has also become an increasingly discussed issue. It has long been recognized that control of risk factors is crucial for prevention. Researchers stress the need to monitor these factors from the earliest stages of life, and detailed analyses indicate an influence of the prenatal period on the development of chronic diseases, including cardiovascular disorders. Transgenerational and intergenerational epigenetic mechanisms are also taken into account. This review aims to systematically evaluate the existing literature and summarize the mechanisms that may link these factors. We consider epigenetic, metabolic, immunological, and inflammatory influences. We describe examples of environmental exposures, such as air pollution, maternal diet, toxins, and infections, and analyze data derived from clinical studies. We discuss gaps in the literature and identify limitations, outlining directions for future research and emphasizing the need for CVD prevention initiated at the earliest stages of life. Full article

Inflammation is strongly related to the development of multiple chronic diseases, such as cardiovascular and autoimmune diseases, and is considered a crucial target for new therapeutic approaches, since it significantly impacts public health, contributes to high mortality rates, and decreases the quality of life. Conventional anti-inflammatory approaches are commonly used, but they present multiple limitations, such as undesirable side effects and low target-specificity. Medicinal plants and their bioactive phytochemical compounds have been studied in recent years and are considered promising alternatives to classical therapies. They are widely recognized for their capacity to modulate inflammatory pathways, regulate inflammatory responses, and consequently reduce inflammation and related symptoms. Although they are considered a good therapeutic alternative, their application in the human body is limited by certain characteristics, such as low solubility, which leads to rapid metabolism and excretion by the organism, significantly reducing bioavailability; for these reasons, the use of medicinal plants remains a biopharmaceutical challenge. Nanotechnology represents a promising tool in this context, since it can improve several characteristics of these compounds. By incorporating plant-derived compounds in nanosystems, considerable advantages, including sustained release, protection from degradation, an increase in the specificity to target tissues, and consequent reduction in toxicity, can be achieved. Thus, nanosystems promote more favorable therapeutic outcomes. This work aims to compile scientific evidence supporting the use of medicinal plants and their bioactive phytochemical compounds, incorporated in nanosystems, in inflammatory disorders. This review enlarges knowledge by integrating both in vitro and in vivo studies involving multiple medicinal plants and bioactive phytochemical compounds, describing their mechanisms of action and the nanosystems employed for drug delivery. In the future, the need for deeper mechanistic studies, the development of targeted and stimuli-responsive systems, and advancement toward clinically translatable, sustainable, and cost-effective plant-based nanotherapies is required. Full article

Background: Childhood cancer is the leading cause of natural death among children in high-income countries, despite treatment improvements. The Spanish Registry of Childhood Tumours (RETI-SEHOP) systematically records all cases treated within the network of SEHOP units. Using RETI-SEHOP data, we evaluated survival trends to assess progress in patient care, both overall and by tumour. Methods: A total of 20,534 childhood cancer cases (0–14 years) were recorded across the period 1999–2021. The 1-, 3-, and 5-year overall survival (OS) were estimated using the Kaplan–Meier method, applying the cohort approach for 1999–2018 and the period approach for 2019–2022. OS by age and sex was analysed in the recent 2009–2018 incidence cohort. Age-adjusted OS time trends were examined using joinpoint Cox models for 1999–2022. Results: For all tumours combined, 5-year OS increased from 75.4% to 84.6% between 1999–2003 and 2019–2022. While positive trends were identified for all haematological malignancies examined, a more varied scenario was evident for solid tumours, as ependymomas improved fastest (1.51 points annually), and sarcomas, except for rhabdomyosarcoma, remained stagnant. Conclusions: Our results reflect a period characterised by a combination of new therapeutic developments, improved diagnostics, and more refined risk stratification, which has ultimately led to a reduction in disease-related mortality. Full article

Background/Objectives: Despite the long-standing history of liver transplantation (LT) in Spain, no multicenter study has reviewed national outcomes for LT in metastatic neuroendocrine tumors (NETs). In the current era of transplant oncology, auditing these results is essential to refine patient selection and improve long-term outcomes. Methods: This retrospective observational study analyzed data from 13 centers, including 91 patients who underwent LT for NET between 1995 and 2024. Patients were stratified into two groups: Milan IN (those meeting the Milan criteria) and Milan OUT (the remainder). Results: Recurrence occurred in 57.1% of cases, and overall mortality was 51.6%. Of the 91 patients, 71 (78.0%) were Milan IN and 20 (22.0%) were Milan OUT. Five-year overall survival was 71.0% in Milan IN and 58.0% in Milan OUT, with a statistically significant difference. The 5-year disease-free survival (DFS) rate was 58.8% in Milan IN and 36.3% in Milan OUT; this difference was not statistically significant. Conclusions: In conclusion, strict adherence to Milan criteria and incorporation of modern prognostic factors are critical to optimize long-term survival in LT for NET. While the overall outcomes in this historical cohort are modest, future improvements are expected through more rigorous selection and the potential use of bridging or downstaging therapies. Full article

Objectives: Thoracic endovascular aortic repair (TEVAR) is rarely indicated on an urgent or emergent basis soon after open surgical repair of type A aortic dissection (TAAD), and systematic data on clinical outcomes are therefore missing. In the present study, we analyze a contemporary case series regarding the outcome after urgent and emergent endovascular treatment of the downstream thoracic aorta, following open surgery for TAAD. Methods: The study was conducted as a retrospective observational analysis. From January 2024 until April 2025, seven patients (four male, aged 56.8 ± 5.6 years) were treated with TEVAR on an urgent or emergent basis within 48 h after open surgical repair of TAAD at our institution. In all seven patients, the initial dissection extended from the ascending to the abdominal aorta. All seven patients had previously received emergent open surgical repair by ascending aortic repair combined with hemiarch replacement (five patients) or total arch replacement, utilizing the frozen elephant trunk (FET) technique (two patients). Results: In four patients, the indication for urgent TEVAR was due to true lumen collapse (TLC) of the downstream aorta with resulting visceral or peripheral malperfusion symptoms. Three patients were treated on an emergent basis, due to rupture of the descending thoracic aorta with a resulting hemorrhage. Technical success of the TEVAR procedure was 100%. Thirty-day mortality was 0% in the TLC cases but 66% in the ruptured cases, where two of three patients died postoperatively due to the consequences of severe hemorrhagic shock. Within the surviving patients, no subsequent aortic events occurred during follow-up. Late mortality was 0%. The follow-up period was 15.7 ± 2.0 months. Conclusions: In our case series, mortality of urgent or emergent TEVAR soon after open surgical repair for TAAD is substantial, especially in patients that were treated due to acute rupture of the descending thoracic aorta and consecutive hemorrhagic shock. On the other hand, true lumen collapse with resulting malperfusion was successfully treated by instant TEVAR application in all patients without late aortic complications by the midterm follow-up. Full article

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is one of the most common extra-articular manifestations of rheumatoid arthritis (RA) and a leading cause of mortality in RA patients. The diverse and nonspecific clinical presentations of RA-ILD make early diagnosis particularly challenging. In recent years, with a deeper understanding of the pathogenesis of RA-ILD and rapid advancements in medical imaging, artificial intelligence (AI) technologies, and biomarker research, notable progress has been achieved in the diagnostic approaches for RA-ILD. This review summarizes the latest research developments in the diagnosis of RA-ILD, with a focus on the clinical practice guidelines released in 2025. It discusses the application of high-resolution computed tomography (HRCT), the potential of AI in assisting HRCT-based diagnosis, and the discovery and validation of biomarkers. Furthermore, the review addresses current diagnostic challenges and explores future directions, providing clinicians and researchers with a cutting-edge perspective on RA-ILD diagnosis. Full article