Search Results (6,958)

Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in patients with cancer. The management of special situations—including recurrent venous thromboembolism (VTE), thrombosis at unusual sites, and central venous catheter-associated thrombosis (CVC-AT)—remains particularly challenging because of the limited availability of high-quality evidence. This narrative review synthesizes recommendations from major international and Spanish clinical practice guidelines and expert consensus documents, including those from SEOM, ESMO, ASCO, NCCN, ITAC and SEMI, to provide a structured framework for the management of these complex scenarios. Our analysis identified substantial heterogeneity across guidelines, particularly regarding anticoagulant selection, dosing strategies, and treatment duration. Although some convergence exists in the management of CVC-AT, important discrepancies and evidence gaps persist in areas such as splanchnic vein thrombosis, hepatic impairment, central nervous system involvement, and recurrent VTE despite treatment. In many cases, recommendations are based primarily on expert opinion rather than robust trial data, and several clinical scenarios are addressed by only a limited number of guidelines. These findings underscore the need for more standardized management strategies and prospective clinical studies to better inform decision-making in daily practice. Overall, this review highlights the growing importance of individualized anticoagulant management aimed at balancing thrombotic and bleeding risks in high-risk oncology patients, thereby helping to bridge the gap between expert consensus and evidence-based precision anticoagulation. Full article

Background: Late-onset neonatal sepsis (LONS) remains a major cause of morbidity in preterm neonates admitted to the neonatal intensive care unit (NICU), yet the contribution of vitamin D status to neonatal infectious susceptibility remains uncertain. Objective: To evaluate clinical and demographic variables and serum vitamin D levels assessed at birth in preterm neonates with and without LONS. Methods: A retrospective observational cohort study was conducted in a tertiary NICU in northeastern Mexico between May 2023 and October 2024. Preterm neonates (<37 weeks of gestation) with serum 25(OH)D measured within the first hour of life were included. Vitamin D status was classified as sufficient (≥30 ng/mL), insufficient (20–29 ng/mL), or deficient (<20 ng/mL). LONS was defined as sepsis occurring after 72 h of life. Comparisons between neonates with and without LONS were performed using Fisher’s exact test for categorical variables and Student’s t-test or Mann–Whitney U test for continuous variables, as appropriate. Results: Twenty-nine preterm neonates were included (mean gestational age: 32.0 ± 2.6 weeks; mean birth weight: 1748 ± 545 g). The mean serum 25(OH)D level at birth was 35.5 ± 13.0 ng/mL. LONS occurred in 31% (9/29) of neonates, of which 55% were microbiologically confirmed. No significant differences were observed in vitamin D levels between neonates with and without LONS (35.0 ± 12.0 vs. 35.7 ± 13.7 ng/mL; p = 0.899). Vitamin D deficiency was not associated with LONS (OR 1.13, 95% CI 0.09–14.28). The prevalence of vitamin D deficiency was low (10%) in this cohort. Conclusions: A clear association between serum 25(OH)D levels at birth and the development of LONS could not be demonstrated in this small exploratory cohort. Given the limited sample size and low prevalence of vitamin D deficiency, further multicenter prospective studies are required to better understand the potential relationship between vitamin D status and neonatal infectious outcomes. Full article

Pediatric septic shock remains a major cause of morbidity and mortality in critically ill children and is increasingly recognized as a syndrome of profound immunometabolic dysregulation. This narrative review synthesizes current clinical, translational, and mechanistic evidence on the glutamate–glutamine axis in pediatric septic shock. The review focuses on how glutamine and glutamate metabolism may interact with immune-cell function, mitochondrial substrate handling, redox defense, and intestinal barrier integrity, while distinguishing biological plausibility from validated clinical utility. Current evidence supports the glutamate–glutamine axis as a mechanistically relevant pathway and a source of candidate biomarkers, but pediatric-specific data remain limited and do not yet justify routine biomarker use or glutamine-based intervention in unselected children with septic shock. Future studies should use standardized sampling, reproducible analytical methods, pediatric validation cohorts, and phenotype-guided trial designs before this axis can be translated into clinical decision making. Full article

Background/Objectives: Lupus nephritis (LN) is one of the most severe complications of systemic lupus erythematosus (SLE); it is associated with increased morbidity and mortality, underscoring the need for new diagnostic markers and therapeutic strategies. In this context, the exostosin 1 (EXT1)/exostosin 2 (EXT2) heterodimer has emerged as a novel antigen in membranous nephropathy associated with SLE. This study evaluated EXT1 prevalence in renal biopsies from patients with lupus membranous nephropathy (LMN) and compared clinical, laboratory, and histopathological characteristics on diagnosis and renal outcomes. Methods: This retrospective study included 97 LMN patients whose renal biopsy underwent immunohistochemistry (IHC) for EXT1. EXT1-positive and EXT1-negative groups were compared using descriptive analyses and repeated measures models. Results: EXT1 positivity was observed in 35% of the cohort, and is more frequent in pure LMN (40%) than in cases with a proliferative component (32%). Regarding SLE diagnostic criteria, EXT1-positive patients showed a higher frequency of antiphospholipid antibodies, although data were available for only a subset of patients. This group also exhibited lower serum creatinine levels, but without statistical significance. EXT1-negative patients more frequently received cyclophosphamide as induction therapy (57.6% vs. 34.5%; p = 0.041). No differences in clinical outcomes were observed during follow-up. Conclusions: EXT1 prevalence was consistent with the literature, reinforcing the epidemiological reproducibility of this marker. EXT1-positive and EXT1-negative groups did not differ regarding clinical presentation, disease progression, and renal outcomes, heightening the need for prospective studies to further elucidate the diagnostic and prognostic role of EXT1 in LMN. Full article

Background: Pulmonary fibrosis (PF) is a major global health issue associated with substantial morbidity across all age groups. One of the important etiological factors contributing to PF is drug-induced lung injury, which can result from both direct and indirect damage to the pulmonary parenchyma caused by various pharmacological agents, including chemotherapeutics, antirheumatic drugs, cardiovascular medications, and certain antimicrobial agents. The aim of our study was to assess the structure of antibacterials involved in drug-induced PF (DIPF) and analyze signals of DIPF, calculating the reporting odds ratio (ROR) and proportional reporting ratio (PRR) using spontaneous reports (SRs) extracted from the Russian National Pharmacovigilance database. Methods: A retrospective, descriptive pharmacoepidemiological analysis of SRs from the AIS database for the period 1 April 2019–31 March 2025 was conducted. Results: A total of 130 SRs with data on DIPF associated with antibacterial agents were identified, with patients’ mean age of 59.1 ± 14.46 years. Death was reported in 65 SRs (50%) with a mean age of 53.0 ± 13.66 years. Next, antibacterials were identified as leaders: sulfamethoxazole (used alone or in combination with trimethoprim, 20.7% (n = 50)), azithromycin (18.2%, n = 44), levofloxacin (12.4%, n = 30), doxycycline (11.6%, n = 28), and cefuroxime (10.7%, n = 26). Disproportionality analysis performed with PRR and ROR calculation revealed the strongest association with DIPF for cefuroxime (PRR = 15.11, 95% confidence interval, CI: 10.25–22.27; ROR = 15.31, 95% confidence interval, CI: 10.33–22.68). Conclusions: Cefuroxime was revealed as a drug with an unexpected but robust safety signal for DIPF, warranting heightened clinical awareness and further investigation. The observed associations between antibacterial agents and DIPF should be interpreted with caution, as they may reflect protopathic bias (antibiotics prescribed for early symptoms of unrecognized pulmonary fibrosis) or context-dependent biological effects rather than true pro-fibrotic drug properties. Our findings do not establish causality but rather generate safety signals that warrant validation through prospective studies with detailed clinical phenotyping and mechanistic investigations using human cell lines. Full article

Background/Objectives: Cardiovascular diseases (CVD) remain leading cause of human morbidity and mortality worldwide. With increasing attention to vitamin K intake’s effect on health, comprehensive knowledge of vitamin K dietary sources is important. This study aims to determine the nutritional value of selected fermented food products (cheese, sauerkraut and natto) as a dietary vitamin K sources and to evaluate their lipid quality in the context of cardiovascular health. Methods: Two kinds of cow’s milk cheeses were selected. Regarding sauerkraut and natto, both commercial products and laboratory-produced samples were taken for comparison. Contents of phylloquinone (PK) and menaquinones (MKn) and fatty acids profiles were analyzed. Moreover, the following lipid quality indices were evaluated: Peroxidisability Index (PI); Atherogenicity Index (AI); Thrombogenicity Index (TI); and Hypocholesterolaemic/Hypercholesterolaemic (HH) ratio. Results: Sauerkraut demonstrated the highest phylloquinone content, while the highest content of MK-7 was found in natto. The fatty acid profile of natto was characterized by the highest proportions of linoleic acid (C18:2) and alpha-linolenic acid (C18:3). Natto’s lipid quality indices were the most favorable compared to cheese and sauerkraut. Conclusions: Based on its MK-7 content and lipid quality profile, natto demonstrates the greatest nutritional potential among the analyzed fermented products. These findings are based on compositional analysis and require confirmation through clinical studies investigating the cardiovascular effects of regular consumption of these specific products. Full article

CRC remains a major cause of cancer-related morbidity and mortality worldwide. In recent years, the gut microbiota has gained increasing attention in CRC research. Intestinal microbes are not passive bystanders in tumor development. They may promote persistent inflammation, disrupt epithelial barrier integrity, alter microbial metabolites, and affect host immune and signaling pathways. Emerging evidence also suggests that microbiota-related metabolites and microbial functional alterations may influence host epigenetic regulation, including DNA methylation and chromatin-associated signaling, thereby further shaping colorectal carcinogenesis. Together, these changes can create a microenvironment that favors tumor initiation and progression. Several bacterial species, including Fusobacterium nucleatum, Parvimonas micra, and Peptostreptococcus anaerobius, have been repeatedly associated with CRC. In contrast, beneficial commensal microbes and their metabolites, especially short-chain fatty acids, may help maintain intestinal homeostasis and limit tumor-promoting processes. Because the gut microbiota is strongly shaped by diet, lifestyle, and environmental exposure, regional differences are also relevant. This is particularly important in Sichuan, China, where distinctive dietary habits and environmental features may influence microbial patterns associated with CRC risk and disease behavior. This review summarizes the main mechanisms linking the gut microbiota to CRC, examines the regional context of Sichuan, China, and discusses current and emerging clinical strategies. These include dietary intervention, probiotics, fecal microbiota transplantation, and microbiome-informed approaches to prevention, diagnosis, and treatment. Full article

Background: Stroke is the most common neurological disorder in adults and a leading cause of mortality and disability. Intracerebral hemorrhage (ICH), although less frequent than ischemic stroke, is associated with higher morbidity and mortality and often requires ICU admission. Predicting mortality remains challenging due to disease heterogeneity. Objectives: This study evaluated the prognostic value of the modified Nutrition Risk in Critically Ill (mNUTRIC) and Controlling Nutritional Status (CONUT) scores, along with conventional severity scores (GCS, APACHE II, SOFA), in ICU patients with ICH. Methods: This retrospective cohort study included 347 ICU patients with ICH admitted between January 2019 and June 2025. Patients were stratified by survival status and nutritional and conventional severity scores were analyzed. Subgroup analysis was performed in patients with GCS ≤ 12 and APACHE II ≥ 17 (n = 96). Multivariate logistic regression and receiver operating characteristic (ROC) analyses assessed predictive performance. Results: ICU mortality was 24.2%. Deceased patients had lower GCS and higher APACHE II, SOFA, mNUTRIC, and CONUT scores (p < 0.001). Subgroup analysis showed higher mortality in patients with elevated mNUTRIC and CONUT scores (p = 0.038 and p = 0.005). Multivariate analysis identified GCS (OR = 0.675, p < 0.001) and CONUT (OR = 1.174, p = 0.040) as independent predictors; mNUTRIC was not significant. ROC analysis demonstrated good discrimination (AUC 0.818 for mNUTRIC and 0.81 for CONUT), with mNUTRIC being more specific and CONUT more sensitive. Optimal cut-off values were >3 for mNUTRIC and >4 for CONUT. Conclusions: Both mNUTRIC and CONUT scores are associated with mortality in ICU patients with ICH, with CONUT showing independent prognostic value. Their combined use may aid clinical decision-making. Full article

Recent paradigms in traumatic brain injury have transitioned from focal-lesion models to an emphasis on diffuse axonal injury and white matter disruption as the primary drivers of cognitive morbidity. This selective review frames information processing speed as the functional signature of this connectivity loss. While processing speed is often theorized as a “cognitive bottleneck” that constrains higher-order functions, we identify critical methodological and conceptual pitfalls in the existing literature. Specifically, we argue that current research is frequently confounded by: (1) measurement impurity, where tasks like the SDMT and TMT-B recruit executive and mnemonic variance; (2) circularity, where speed measures are used to predict time-dependent outcomes; and (3) the neglect of speed–accuracy trade-offs, which may mask volitional cautiousness as neurobiological incapacity. To resolve these challenges, we offer evidence-based recommendations for the clinical setting, including the integration of construct-pure chronometric measures and dual-scoring protocols. We conclude that because white matter integrity functions as a rate-limiting substrate, processing speed must be prioritized as a primary target in early neurorehabilitation. By isolating processing speed from focal-driven deficits, clinicians can more accurately map the path from microstructural disruption to functional recovery. Recognizing this infrastructure is essential to understanding the full scope of cognitive consequences. Full article

Background: Pediatric tuberculosis (TB) remains a major global health concern, accounting for a substantial proportion of TB-related morbidity and mortality worldwide. Treatment in children is particularly challenging due to age-specific pharmacokinetics, difficulties in drug administration, poor palatability, and reliance on caregivers for adherence. Objectives: This narrative review aims to evaluate the advantages and limitations of fixed-dose combinations (FDCs) in the treatment of pediatric TB, with a focus on adherence, pharmacological considerations, clinical outcomes, and implementation challenges. Methods: A narrative review of the literature was conducted, including clinical studies, pharmacokinetic analyses, programmatic data, and international guidelines related to the use of FDCs in pediatric TB management. Results: Evidence indicates that pediatric FDCs significantly improve treatment adherence by reducing pill burden and simplifying dosing regimens. They also decrease the risk of medication errors and inadvertent monotherapy, thereby contributing to the prevention of drug resistance. The availability of dispersible, child-friendly formulations has enhanced acceptability and ease of administration. However, limitations persist, including reduced flexibility in dose individualization, challenges in identifying the causative agent in adverse drug reactions, and variable access across settings. Pharmacokinetic concerns, particularly regarding rifampicin exposure, have been addressed in newer WHO-recommended formulations. Conclusions: FDCs represent a critical advancement in pediatric TB management and are strongly supported by international guidelines. Further research is needed to optimize formulations, ensure equitable access, and evaluate long-term clinical outcomes in diverse pediatric populations. Full article

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy in which radiotherapy plays a uniquely central role compared with other gastrointestinal cancers. Definitive chemoradiotherapy (dCRT) is widely used as a curative treatment; however, a substantial proportion of patients develop residual or recurrent disease, creating a complex clinical scenario that requires tailored salvage strategies. Salvage esophagectomy offers the potential for long-term survival but remains technically demanding and is associated with significant morbidity because of radiation-induced tissue damage. Less invasive local therapies, such as endoscopic submucosal dissection and photodynamic therapy, may provide effective treatment in selected patients, although their indications are limited by tumor characteristics and post-radiation fibrosis. In addition, immune checkpoint inhibitors have demonstrated promising efficacy in advanced ESCC and may represent a potential therapeutic option in the salvage setting. For patients who are not candidates for curative treatment, palliative esophageal stenting remains an important option for symptom relief, although prior radiotherapy may increase the risk of treatment-related complications. Given the diversity of available treatment modalities and their associated risks, a multidisciplinary and individualized treatment approach is essential. Further prospective studies are warranted to optimize treatment algorithms and improve outcomes in patients with ESCC after dCRT. Full article

Tuberculosis remains one of the leading infectious causes of morbidity and mortality worldwide, disproportionately affecting women of reproductive age, particularly in low- and middle-income countries. Tuberculosis during pregnancy represents a major clinical challenge, as physiological and immunological changes associated with pregnancy may obscure symptoms, delay diagnosis, and contribute to adverse maternal and perinatal outcomes. This narrative review provides an updated and clinically oriented overview of tuberculosis during pregnancy, with particular emphasis on diagnostic challenges, imaging strategies, microbiological testing, maternal–fetal complications, and therapeutic management. Key topics include symptom-based screening, tuberculin skin test and interferon gamma release assays, as well as molecular diagnostic methods such as GeneXpert Mycobacterium tuberculosis/Rifampicin (MTB/RIF) and Xpert MTB/RIF Ultra, chest radiography, computed tomography, and emerging biomarkers. We also discuss the impact of tuberculosis on pregnancy outcomes, including prematurity, low birth weight, maternal morbidity, and neonatal complications, as well as the particular challenges posed by human immunodeficiency virus HIV coinfection and multidrug-resistant tuberculosis. Current treatment strategies, preventive approaches, postpartum care, neonatal management, and Bacille Calmette–Guérin vaccination are reviewed in light of contemporary evidence and international recommendations. Finally, we highlight practical diagnostic algorithms, current evidence gaps, and priorities for future research aimed at improving maternal and neonatal outcomes in both high- and low-resource settings. Full article

Background and Clinical Significance: Extramammary Paget disease (EMPD) is a rare cutaneous adenocarcinoma that frequently involves apocrine-rich regions and may extend beyond clinically apparent margins through adnexal structures. Surgical excision remains the standard of care; however, management can be challenging in elderly patients and in anatomically sensitive areas such as the scrotum, where morbidity and functional impairment are significant concerns. Despite increasing use of radiation-based therapies, optimal superficial radiation therapy (SRT) parameters, particularly with respect to depth of penetration, remain poorly standardized. Case Presentation: An 88-year-old male with a history of melanoma, non-melanoma skin cancer, and remote prostate cancer presented with biopsy-proven EMPD involving the scrotum and perineum. Imaging demonstrated no evidence of underlying or metastatic malignancy. Given lesion size (9 × 4 cm), anatomic location, and patient preference to avoid surgery, SRT was selected. The patient underwent treatment with 70 kV energy, delivering a total dose of 5440 cGy in 17 fractions (320 cGy per fraction) administered twice weekly. Energy selection was guided by the known propensity of EMPD for adnexal extension, with the aim of improving treatment coverage of potential subclinical disease. Conclusions: This case highlights the importance of incorporating tumor depth and adnexal involvement into treatment planning for EMPD. Depth-guided SRT may represent a viable non-surgical management strategy in carefully selected patients, particularly when surgical morbidity is a concern. These findings support a more individualized, mechanism-based approach to optimizing radiation therapy in cutaneous malignancies. Full article

This translational synthesis highlights the potential role of obesity-induced low-grade chronic inflammation in modulating clinical outcomes among patients with spondyloarthritis (SpA). Obesity transforms adipose tissue into a pro-inflammatory endocrine organ, where hypertrophic adipocytes release adipokines such as leptin alongside cytokines including TNF-α and IL-6, potentially contributing to macrophage polarization toward an M1 phenotype and activating NF-κB signaling pathways. This systemic immunometabolic priming may lower activation thresholds at the enthesis—the primary pathological site in SpA—potentially amplifying IL-23/IL-17 axis activity via Th17 bias, innate-like lymphocyte responses, and stromal–immune crosstalk under mechanical stress. Clinically, patients with SpA and obesity have been reported to demonstrate heightened disease activity (BASDAI, ASDAS), impaired function (BASFI), accelerated radiographic progression (syndesmophytes, enthesophytes), and diminished biologic response rates, potentially attributable to pharmacokinetic alterations (e.g., subtherapeutic TNF inhibitor levels) and pharmacodynamic resistance. Multisystem comorbidities, including non-alcoholic fatty liver disease, cardiovascular events, metabolic syndrome, sleep disturbances, and depression, further exacerbate morbidity and diminish quality of life. Therapeutic implications emphasize obesity as a modifiable disease modifier. Weight loss interventions, including hypocaloric diets, anti-inflammatory regimens (e.g., Mediterranean diet), multicomponent exercise, GLP-1 receptor agonists, and bariatric surgery, have been associated with reductions in inflammatory biomarkers, improved remission rates (MDA, DAPSA), and prolonged drug survival by restoring adipokine balance and disrupting mechano-inflammatory loops. Future randomized controlled trials should prioritize long-term evaluations of integrated multidisciplinary strategies that combine metabolic optimization with immunomodulatory therapies, addressing adherence challenges through psychological support and patient-tailored protocols, while elucidating dose–response relationships for GLP-1RAs and exercise in diverse SpA subtypes to establish precision management paradigms that mitigate cardiometabolic burden and improve holistic outcomes. Full article

Background: Metabolic and bariatric surgery is an established therapeutic option for severe obesity and obesity-related medical problems. Although minimally invasive techniques and enhanced recovery pathways have reduced postoperative morbidity, infectious complications remain clinically relevant because they may lead to readmission, reoperation, prolonged antimicrobial therapy, and mortality. Methods: We conducted a narrative review of the literature on infectious complications after metabolic and bariatric surgery. Evidence was synthesized across five clinically relevant domains: host-related pathophysiology, microbial epidemiology, preoperative optimization, antimicrobial prophylaxis and pharmacokinetic considerations, and diagnosis and management of postoperative infectious complications. Results: Patients with obesity present specific infection-related vulnerabilities, including chronic low-grade inflammation, altered immune responses, impaired tissue oxygenation, obesity-related medical problems, and procedure-specific risks. Contemporary prevention relies on multidisciplinary preoperative optimization, appropriate skin antisepsis, weight-based antimicrobial prophylaxis, intraoperative redosing when indicated, and adherence to enhanced recovery principles. Anastomotic leaks and intra-abdominal abscesses represent the most severe organ/space infections and require early recognition, source control, antimicrobial therapy, nutritional support, and coordinated surgical, radiological, and endoscopic management. Conclusions: Infectious complications after metabolic and bariatric surgery result from the interaction between host physiology, microbial factors, pharmacological considerations, and surgical technique. A structured approach integrating prevention, early diagnosis, and multidisciplinary management may improve outcomes. Further bariatric-specific studies are needed to strengthen the evidence base for several preventive and therapeutic strategies. Full article