Search Results (15,649)

Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and solid tumors. Moreover, given the burden of chronic infectious diseases, the mortality and morbidity of infections in immunocompromised individuals, and the development of multidrug-resistant pathogens, including bacteria, fungi, and mycobacteria, a need for novel and personalized therapeutics in this field is emerging. To this end, the development of CAR cells for the management of chronic infections has been reported. In this literature review, we summarize the ongoing clinical and pre-clinical data about CAR cell products in the field of infectious diseases. Currently, clinical studies on CAR immunotherapy for infections mainly concern human immunodeficiency virus infection treatment, and data regarding other infections largely originate from preclinical in vitro and in vivo models. In the era of personalized medicine, effective and safe therapies for the management of chronic infections and infectious complications in immunocompromised patients are crucial. Full article

Background/Objectives: Adult Spinal Deformity (ASD) is a pathologic malalignment of the spine that can lead to significant reductions in quality of life, functional limitations, and increased morbidity. While poor mental health is commonly observed among patients undergoing ASD surgery, its impact on surgical outcomes remains poorly understood. We conducted a systematic review and meta-analysis to examine the association between preoperative mental health and outcomes following surgical correction for ASD. Methods: A comprehensive search of MEDLINE, Embase, Web of Science, and Scopus was performed from inception to April 2025 to identify studies investigating the relationship between preoperative mental health and postoperative health-related quality of life outcomes or complications. Data was pooled using a restricted maximum likelihood (REML) random-effects model. Heterogeneity was assessed using Cochran’s Q statistic, and between-study variance was reported as τ². Study quality was assessed with the Newcastle–Ottawa Scale, and risk of bias was evaluated using the ROBINS-I tool. Results: Twenty-four studies comprising a total of 248,427 patients met inclusion criteria. In pooled analyses, patients with poor preoperative mental health showed comparable improvements in health-related quality of life measures after surgery (standardized mean difference [SMD] −0.04, 95% CI −0.30 to 0.22; I² = 91.5%, τ² = 0.42) and in pain scores (SMD −0.15, 95% CI −0.42 to 0.11; I² = 71.8%, τ² = 0.09). However, patients with poor mental health had significantly higher odds of postoperative complications (odds ratio [OR] 1.44, 95% CI 1.23 to 1.67; I² = 97.4%, τ² = 0.08). These patients also demonstrated worse preoperative disease severity (SMD –0.94, 95% CI −1.41 to −0.47; I² = 95.5%, τ² = 1.64) and worse postoperative disease severity (SMD –0.34, 95% CI −0.44 to −0.25; I² = 48.9%, τ² = 0.03). Conclusions: While patients with poor preoperative mental health have a greater disease severity both before and after ASD surgery, they appear to experience comparable benefits from surgical intervention compared to those without. Recognizing and managing mental health may be useful in preoperative management of ASD patients. Further prospective studies to further elucidate these associations are necessary. Full article

Monitoring water quality is crucial for achieving clean water and sanitation goals, particularly in remote areas. The project “Morbidity vs. Water Quality for Human Consumption in Tonosí: A Pilot Study” aimed to enhance water quality assessments in Panama using advanced analytical techniques to assess volatile organic compounds, heavy metals, and microbiological pathogens. To support this, the Technical Unit for Water Quality (UTECH) was established, featuring a novel mobile laboratory with cutting-edge technology for accurate testing, minimal chemical reagent use, reduced waste generation, and equipped with a solar-powered battery system. The aim of this paper is to explore the design, deployment, and impact of the UTECH. Furthermore, this study presents results from three sampling points in Tonosí, where several parameters exceeded regulatory limits, demonstrating the capabilities of the UTECH and highlighting the need for ongoing monitoring and intervention. The study also assesses the environmental, social, and economic impacts of the UTECH in alignment with the Sustainable Development Goals and national initiatives. Finally, a SWOT analysis illustrates the UTECH’s potential to improve water quality assessments in Panama while identifying areas for sustainable growth. The study showcases the successful integration of advanced mobile laboratory technologies into water quality monitoring, contributing to sustainable development in Panama and offering a replicable model for similar initiatives in other regions. Full article

Background: Peripheral nerve injuries, especially involving the facial nerve, present unique reconstructive challenges due to their complex functional demands and limited regenerative potential. While autografts remain the gold standard, their drawbacks—such as donor-site morbidity and limited availability—have driven interest in processed nerve allografts. Acellular grafts, in particular, offer promising off-the-shelf alternatives without the need for immunosuppression. Methods: We conducted a narrative review of the literature (1990–2023), identifying 55 peer-reviewed studies via PubMed, Embase, and Cochrane Library. The studies included clinical and preclinical work on motor nerve regeneration using processed nerve allografts, with particular attention to outcomes in facial nerve repair. Two independent reviewers conducted abstract screening, full-text review, and data extraction. Results: Processed nerve allografts show encouraging motor recovery in gaps under 50 mm, with recovery rates of up to 85% reported. Outcomes decrease significantly in longer gaps (>50–60 mm) and in complex cases, including facial nerve repairs, where evidence remains sparse and largely extrapolated from broader motor nerve data. Registry data (e.g., RANGER) support their use but are limited by heterogeneity and lack of randomization. Conclusions: Processed nerve allografts represent a viable alternative to autografts in selected cases—especially short to mid-length motor nerve defects. However, their role in facial nerve reconstruction remains insufficiently studied. Further trials are needed to address specific anatomical and functional challenges in this subgroup and to clarify long-gap efficacy. Full article

Gastrointestinal (GI) cancers represent a significant global health burden, with high morbidity and mortality often linked to late-stage detection and metastatic disease. The progression of these malignancies is critically driven by angiogenesis, the formation of new blood vessels, and the surrounding dynamic tumor microenvironment (TME), a complex ecosystem comprising various cell types and non-cellular components. This comprehensive review, based on a systematic search of the PubMed database, synthesizes the existing literature to define the intertwined roles of angiogenesis and the TME in GI tumorigenesis. The TME’s influence creates conditions favorable for tumor growth, invasion, and metastasis, but sometimes induces resistance to current therapies. Available therapeutic strategies for inhibiting angiogenesis involve antibodies and oral tyrosine kinase inhibitors, while immune modulation within the tumor microenvironment is mainly achieved through checkpoint inhibitor antibodies and chemotherapy. Creative emerging strategies encompassing cellular therapies, bispecific antibodies, and new targets such as CD40, DLL4, and Ang2, amongst others, are focused on inhibiting proangiogenic pathways more profoundly, reversing resistance to prior drugs, and modulating the TME to enhance therapeutic efficacy. A deeper understanding of the complex interactions between components of the TME is crucial for addressing the unmet need for novel and effective therapeutic interventions against aggressive GI cancers. Full article

Tuberculosis (TB) is an ancient and re-emerging granulomatous infectious disease that continues to challenge public health. Early diagnosis and prompt effective treatment are crucial for preventing disease progression and reducing both morbidity and mortality. These steps play a vital role in infection control and in lowering death rates at both individual and population levels. Although diagnostic methods have improved sufficiently in recent decades, TB can still present with ambiguous laboratory and imaging features. This ambiguity can lead to diagnostic pitfalls and potentially disastrous outcomes due to delayed diagnosis. In this article, we present a case of TB that was difficult to diagnose. The disease had invaded the mediastinum, right atrium, right coronary artery, and inferior vena cava (IVC), resulting in Budd–Chiari syndrome. This rare presentation created clinical, laboratory, and radiological confusion, resulting in a diagnostic dilemma that ultimately led to open cardiac surgery. The patient initially presented with progressive shortness of breath on exertion and fatigue, which suggested possible heart disease. This suspicion was reinforced by computed tomography (CT) imaging, which showed infiltrative mass lesions predominantly in the right side of the heart, invading the right coronary artery and IVC, with imaging features mimicking angiosarcoma. Although laboratory findings revealed an exudative effusion with lymphocyte predominance and elevated adenosine deaminase (ADA), the Gram stain was negative for bacteria, and an acid-fast bacilli (AFB) smear was also negative. These findings contributed to diagnostic uncertainty and delayed the confirmation of TB. Open surgery with excisional biopsy and histopathological analysis ultimately confirmed TB. We conclude that TB should not be ruled out solely based on negative Mycobacterium bacteria in pericardial effusion or AFB smear. TB can mimic aggressive tumors such as angiosarcoma or lymphoma with invasion of the surrounding tissues and blood vessels. Awareness of the clinical presentation, imaging findings, and potential diagnostic pitfalls of TB is essential, especially in endemic regions. Full article

Childhood pneumonia remains a key cause of global morbidity and mortality, highlighting the need for accurate and efficient diagnostic tools. Ensemble methods have proven to be among the most successful approaches for identifying childhood pneumonia from chest X-ray images. However, deploying large, complex convolutional neural network models in resource-constrained environments presents challenges due to their high computational demands. Therefore, we propose a novel ensemble-based knowledge distillation method for identifying childhood pneumonia from X-ray images, which utilizes an ensemble of classification models to distill the knowledge to a more efficient student model. Experiments conducted on a chest X-ray dataset show that the distilled student model achieves comparable (statistically not significantly different) predictive performance to that of the Stochastic Gradient with Warm Restarts ensemble method (F1-score on average 0.95 vs. 0.96, respectively), while significantly reducing inference time and decreasing FLOPs by a factor of 6.5. Based on the obtained results, the proposed method highlights the potential of knowledge distillation to enhance the efficiency of complex methods, making them more suitable for utilization in environments with limited computational resources. Full article

Background: Diaper dermatitis (DD) frequently occurs following pediatric gastrointestinal surgery and may lead to severe morbidity despite preventive measures. This study aims to evaluate the effectiveness of potato-derived protease enzyme inhibitor cream (PPEIC) in preventing DD after gastrointestinal surgery in children. Methods: In this double-blinded, single-center RCT, 30 patients under three years of age undergoing gastrointestinal surgery were randomized 1:1 to prevention using PPEIC or Panthenol cream (PC). The creams were applied after each diaper change for four weeks postoperatively. At two and four weeks, two observers evaluated photographs of the perianal region for the presence and severity of DD. The primary outcome was the severity of DD four weeks after surgery. Results: From November 2020 to March 2023, 30 patients were included. Two patients withdrew directly after randomization, resulting in 13 PPEIC and 15 PC patients. In total, nineteen patients (73.1%) developed DD—eight (66.7%) in the PPEIC group and 11 (78.6%) in the PC group (p = 0.665)—of whom twelve (63.2%) suffered severe DD. All DD cases developed within the first two weeks, resulting in half of the patients discontinuing the preventive cream before the four-week endpoint. Conclusions: This study highlights the significant issue of DD after gastrointestinal surgery, which affects 73.1% of diapered children despite prevention with PPEIC or PC. Although the study was unable to identify a superior preventive method, it offers valuable insights and goals for future research. Full article

Cancer and infectious diseases are major causes of global morbidity and mortality stressing the need to find novel drugs with promising dual anticancer and antimicrobial efficacy. Gold complexes have been studied for the past years due to their anticancer properties, with a few of them displaying antimicrobial properties, which support their pharmacological interest. Within this scope, we investigated six gold bisdithiolate complexes [Au (bdt)₂]⁻ (1), [Au (dcbdt)₂]⁻ (2), [Au (3-cbdt)₂]⁻ (3), [Au (4-cbdt)₂]⁻ (4), [Au (pdt)₂]⁻ (5) and [Au (dcdmp)₂]⁻ (6), and) against the ovarian cancer cell lines A2780 and A2780cisR, the Gram-positive bacteria Staphylococcus aureus Newman, the Gram-negative bacteria Escherichia coli ATCC25922 and Burkholderia contaminans IST408, and the pathogenic yeasts Candida glabrata CBS138 and Candida albicans SC5134. Complexes 2 and 6, with ligands containing aromatic pyrazine or phenyl rings, substituted with two cyanonitrile groups, showed after 24 h of incubation high anticancer activities against A2780 ovarian cancer cells (IC₅₀~5 µM), being also able to overcome cisplatin resistance in A2780cisR cells. Both complexes induced the formation of ROS, activated caspase-3/7, and induced necrosis (LDH release) in a dose-dependent way, in a greater extent in the case of 6. Among the bacterial and fungal strains tested, only complex 6 presented antimicrobial activity against S. aureus Newman, indicating that this complex is a potential novel anticancer and antibacterial agent. These results delve into the structure-activity relationship of the complexes, considering molecular alterations such as replacing a phenyl group for a pyrazine group, and the inclusion of one or two cyanonitrile appendage groups, and their effects on biological activity. Overall, both complexes were found to be promising leads for the development of future anticancer drugs against low sensitive or cisplatin resistant tumors. Full article

Obstructive sleep apnea (OSA) is a sleep-related respiratory disorder characterized by partial or complete obstruction of the upper airway, typically resulting in a decrease in arterial oxygen saturation and repeated awakenings from sleep. It is the most common sleep-related respiratory disorder, affecting 9% to 38% of adults. OSA is associated with loss of tone, improper contraction of the tongue, and pharyngeal dilator muscles of the upper airway during sleep. The gold-standard treatment for moderate-to-severe OSA is continuous positive airway pressure (CPAP). However, many patients have poor long-term compliance with CPAP. Stimulation of the upper airway with electrical activation of the hypoglossal nerve has emerged as a promising treatment for patients with moderate-to-severe OSA who have failed CPAP therapy. Objectives: The present paper aims to review the literature regarding neurostimulation for the treatment of OSA. Conclusions: Hypoglossal nerve stimulation (HNS) has shown favorable success and low morbidity in the management of moderate-to-severe OSA. Full article

Background/Objectives: Trochanteric femoral fractures pose significant surgical challenges, particularly in elderly patients. Intramedullary nailing (IMN) and plate fixation (PF) are the primary operative strategies, yet their comparative efficacy and safety remain debated. This meta-analysis synthesizes randomized controlled trials (RCTs) to evaluate clinical, functional, perioperative, and biomechanical outcomes of IMN versus PF specifically in trochanteric fractures. Methods: A systematic search of six databases was conducted up to 20 May 2024, to identify RCTs comparing IMN and PF in adult patients with trochanteric femoral fractures. Data extraction followed PRISMA guidelines, and outcomes were pooled using random-effects models. Subgroup analyses examined the influence of fracture stability, implant type, and patient age. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Results: Fourteen RCTs (n = 4603 patients) were included. No significant differences were found in reoperation rates, union time, implant cut-out, or mortality. IMN was associated with significantly reduced operative time (MD = −5.18 min), fluoroscopy time (MD = −32.92 s), and perioperative blood loss (MD = −111.68 mL). It also had a lower risk of deep infection. Functional outcomes and anatomical results were comparable. Subgroup analyses revealed fracture stability and nail type significantly modified operative time, and compression screws were associated with higher reoperation rates than IMN. Conclusions: For trochanteric femoral fractures, IMN and PF yield comparable results for most clinical outcomes, with IMN offering some advantages in surgical efficiency and perioperative morbidity, though functional outcomes were comparable. Implant selection and fracture stability influence outcomes, supporting individualized surgical decision making. Full article

Cardiorenal syndrome (CRS) is a term used to describe the combined dysfunction of the heart and kidneys. This complex disorder is widely acknowledged to be challenging in both its diagnosis and management, and this is the case particularly in the elderly population, due to multi-morbidity, polypharmacy, and age-related physiological changes. Given advancements in medicine and more prolonged cumulative exposure to risk factors in the elderly population, it is likely that the prevalence of chronic kidney disease (CKD) and heart failure (HF) will continue to rise going forward. Hence, understanding the mechanisms involved in the development of CRS is paramount. There are five different CRS types—they are categorised depending on the primary organ involved the acuity of disease. The pathophysiological process behind CRS is complex, involving the interplay of many processes including hemodynamic changes, neurohormonal activation, inflammation, oxidative stress, and endothelial dysfunction and vascular stiffness. The numerous diagnostic and management challenges associated with CRS are significantly further exacerbated in an elderly population. Biomarkers used to aid the diagnosis of CRS, such as serum creatinine and brain natriuretic peptide (BNP), can be challenging to interpret in the elderly population due to age-related renal senescence and multiple comorbidities. Polypharmacy can contribute to the development of CRS and therefore, before initiating treatment, coordinating a patient-centred, multi-speciality, holistic review to assess potential risks versus benefits of prescribed treatments is crucial. The overall prognosis of CRS in the elderly remains poor. Treatments are primarily directed at addressing the sequelae of the underlying aetiology, which often involves the removal of fluid through diuretics or ultrafiltration. Careful considerations when managing elderly patients with CRS is essential due to the high prevalence of frailty and functional decline. As such, in these patients, early discussions around advance care planning should be prioritised. Full article

Penile cancer is a rare malignancy, with approximately 2100 cases diagnosed annually in the United States. The 5-year overall survival rate varies significantly depending on the node involvement status, at 79% in node-negative disease versus 51% for patients with inguinal metastasis. Inguinal lymph nodes are involved in micrometastatic disease in up to one out of four patients. Early inguinal lymph node dissection (ILND) has been shown to provide a survival advantage, which is why many patients undergo inguinal lymph node dissection for diagnostic and therapeutic purposes. Unfortunately, ILND is associated with high morbidity rates, which have led to potential overtreatment and decreased quality of life in the penile cancer population. Several advancements have been made to mitigate these challenges, such as dynamic sentinel node dissection, modifications to the technique or surgical templates, the introduction of minimally invasive procedures, and changes to the postoperative pathway. This manuscript examines the evolution in managing the inguinal lymph nodes in penile cancer, its associated complications, and effective strategies for their prevention and management. Full article

Background: Childhood cancer is considered one of the main causes of mortality and morbidity worldwide. There is strong evidence of the oral toxic effects of oncologic treatments, but their incidence is difficult to determine. The novel therapeutic strategies in Pediatric Oncology have led to increased survival in this population, resulting in an increased incidence of long-term effects, which diminish the patient’s quality of life. Methods: The search for articles started on 5 November 2024 and ended on 5 December 2024. Following the PRISMA Statement, a total of 1266 articles were obtained, from which 13 were selected for review. All articles were considered to be of high quality. The antineoplastic treatments used in them were chemotherapy, radiotherapy, surgery and immune therapy. Results: Most articles were cohorts and case controls. Only one case report was obtained. The results revealed that the most prevalent sequelae in the pediatric population after antineoplastic treatment were enamel alterations, microdontia, dental caries, periodontal disease, gingivitis, hyposalivation, alteration of the oral microbiome, alteration of mandibular bone density and malocclusion. The lesions are different depending on the therapy used. Conclusions: Oncologic treatments in children with cancer cause multiple oral sequelae such as microdontia, dental caries, enamel alterations, salivary gland alterations, mucositis and root resorption. It cannot be concluded which therapy has the most detrimental effect as each has a different mechanism of action in the oral cavity. Full article

Staphylococcus aureus is a Gram-positive bacterium that causes significant human morbidity and mortality. The capacity of S. aureus to cause disease is primarily attributed to an array of virulence factors produced by this pathogen that collectively overcome immune defenses and promote survival in a variety of host tissues. These include an arsenal of different cytotoxins that compromise plasma membrane integrity, with the specificity of each dependent upon the host organism and cell type. S. aureus encounters a variety of peripheral blood cell types during infection that play important roles in maintaining homeostasis and defending against microbial invasion, namely erythrocytes, thrombocytes, and leukocytes. S. aureus targets each of these cell types with specific cytotoxins to successfully establish disease. This review summarizes our current understanding of the susceptibility of different human peripheral blood cell types to each of these cytotoxins. Full article