Search Results (120)

Background/Objectives: Posterior inferior cerebellar artery (PICA) aneurysms are one of the most difficult cerebrovascular lesions to treat and account for 0.5–3% of all intracranial aneurysms. They have deep anatomical locations, broad-neck configurations, high perforator density, and a close association with the brainstem, which creates considerable technical challenges for either microsurgical or endovascular treatment. Despite its acceptance as the standard of care for most posterior circulation aneurysms, PICA aneurysms are often associated with flow diversion using a coil or flow diversion due to incomplete occlusions, parent vessel compromise and high rate of recurrence. This case aims to describe the utility of microsurgical clipping as a durable and definitive option demonstrating the value of tailored surgical planning, preservation of anatomy and ancillary technologies for protecting a genuine outcome in ruptured PICA aneurysms. Methods: A 66-year-old male was evaluated for an acute subarachnoid hemorrhage from a ruptured and broad-necked fusiform left PICA aneurysm at the vertebra–PICA junction. Endovascular therapy was not an option due to morphology and the center of the recurrence; therefore, a microsurgical approach was essential. A far-lateral craniotomy with a partial C1 laminectomy was carried out for proximal vascular control, with careful dissection of the perforating arteries and precise clip application for the complete exclusion of the aneurysm whilst preserving distal PICA flow. Results: Post-operative imaging demonstrated the complete obliteration of the aneurysm with unchanged cerebrovascular flow dynamics. The patient had progressive neurological recovery with no new cranial nerve deficits or ischemic complications. Long-term follow-up demonstrated stable aneurysm exclusion and full functional independence emphasizing the sustainability of microsurgical intervention in challenging PICA aneurysms. Conclusions: This case intends to highlight the current and evolving role of microsurgical practice for treating posterior circulation aneurysms, particularly at a time when endovascular alternatives are limited by anatomy and hemodynamics. Advances in artificial intelligence cerebral aneurysm rupture prediction, high-resolution vessel wall imaging, robotic-assisted microsurgery and new generation flow-modifying implants have the potential to revolutionize treatment paradigms by embedding precision medicine principles into aneurysm management. While the discipline of cerebrovascular surgery is expanding, it can be combined together with microsurgery, endovascular technologies and computational knowledge to ensure individualized, durable, and minimally invasive treatment options for high-risk PICA aneurysms. Full article

Spinal muscular atrophy (SMA) is a severe autosomal recessive neuromuscular disorder and a leading genetic cause of infant mortality. Advances in disease-modifying therapies have significantly improved outcomes when treatment is initiated early, underscoring the importance of timely diagnosis. With the growing availability of prenatal genetic screening and high-resolution molecular diagnostics, opportunities for early detection, and potentially in utero intervention, are rapidly expanding. This narrative review synthesizes current evidence on the prenatal management of SMA, focusing on diagnostic strategies, the clinical application of fetal genetic testing, and the emerging potential of fetal therapy. We explore both invasive and non-invasive diagnostic approaches and evaluate experimental prenatal treatment modalities, while critically addressing the associated ethical, regulatory, and economic considerations. As the field progresses, integrating in utero strategies into clinical care may reshape perinatal medicine and offer transformative potential for genetic neurodegenerative disorders diagnosed before birth. The convergence of early diagnosis, fetal intervention, and personalized genetic counseling will be central to optimizing care pathways and outcomes in the era of precision medicine. Although significant challenges remain, the translation of fetal therapy into routine clinical practice is approaching feasibility. Future clinical trials, anchored in definitive prenatal diagnosis, will be essential, with benefits potentially outweighing the inherent procedural risks. Full article

Background: Ankylosing Spondylitis (AS) is a rare autoinflammatory disorder affecting 0.1–1.4% of the population, with increasing recognition over the past 20 years. Although the specific causes of AS remain unclear, the presence of the HLA-B27 gene is associated with increased risk, though only 1–5% of carriers develop the disease. Despite extensive research, no definitive lab tests exist, and many patients are diagnosed years after symptom onset. Methods: In the present study, in order to investigate the disease’s genetic background in correlation with autoimmune diseases, a metanalysis has been performed following PRISMA guidelines using Scopus and PubMed publications towards extracting single-nucleotide polymorphisms (SNPs) of high importance for the disease. Moreover, the polymorphisms have been annotated and analyzed using information from several databases, including PubMed, LitVar2, ClinVar, and Gene Ontology. Results: From 1940 screened titles and abstracts, 57,909 studies were selected, with 539 meeting the inclusion criteria. The genetic background of AS is described through 794 genetic variants, of which 76 SNPs are directly associated with AS (Classes A and B), predominantly located in intronic regions. ERAP1 and IL23R emerged as key genes implicated in AS, while chromosomes 1, 2, and 5 accumulated the most associated SNPs. Functional enrichment revealed strong associations with immune regulation and interleukin signaling pathways, particularly IL6 and IL10 signaling. IL-6 promotes inflammation in AS, while IL-10 tries to suppress it, acting as an anti-inflammatory cytokine. Of the 78 AS-related SNPs, 16 were unique to AS, while 66 were common to autoimmune diseases, especially rheumatoid arthritis (RA) and psoriasis (PsO), suggesting genetic overlap between these diseases. Conclusions: This study creates a comprehensive genetic map of AS-associated SNPs, highlighting key pathways and genetic overlap with autoimmune diseases. These findings contribute to understanding disease mechanisms and could guide therapeutic interventions, advancing precision medicine in AS management. Full article

Background/Objectives: For people with haemophilia, health-related quality of life mainly depends on the arthropathy caused by repeated joint bleeding. Prophylaxis is the standard of care in patients with severe bleeding phenotypes, but globally, none of the measures used to assess patients’ outcomes consider their desires and life expectations. We propose the concept of the “patient-centred management of well-controlled haemophilia” to define individual responses to prophylaxis. The aims of this work are (1) to achieve agreement about the definition of the “patient-centred management of well-controlled haemophilia” by a steering committee of experts, and (2) to share a series of statements that should define the “patient-centred management of well-controlled haemophilia” with other haemophilia clinicians looking for a consensus in this scenario. Methods: An eight-expert group was established to define the concept of the “patient-centred management of well-controlled haemophilia”. Seven major aspects were identified, and a final version of 42 statements was established and distributed to a 75-expert panel for consensus gathering using the Delphi methodology. Results: Forty-eight experts participated in the first round (participation rate: 64%); two sentences from domain 3 were split, leading to a total of 44 statements across the seven domains. Consensus was achieved in 92.85% of cases. Five items and three statements advanced to the second round. Eleven statements were reconsidered in the second round (response rate: 100%). The questionnaire presented high internal consistency. Conclusions: New treatments offer promising solutions for patients, but there is a paucity of models to measure global outcomes. Patient-centred medicine requires multidimensional assessment, and the “patient-centred management of well-controlled haemophilia” concept is intended to enable this. Full article

Objective: This study aims to review the existing literature on the efficacy and safety of unconventional treatments among pancreatic cancer patients, including the use of natural products, dietary supplements, probiotics, whole medical systems, and body-based therapies. Methods: An electronic, systematic, and comprehensive literature review was conducted searching for studies up to November 2024 following the PRISMA 2020 guidelines. Randomized controlled trials and prospective and retrospective studies assessing the efficacy and safety of unconventional treatments for pancreatic cancer were considered eligible. Data on overall survival, quality of life, and treatment tolerability were extracted. Results: A total of 21 studies, providing data from 3095 patients, met the inclusion criteria. Various types of unconventional treatments are used in pancreatic cancer patients, including Chinese herbal medicine (CHM), mistletoe extract (ME), curcumin, and electroacupuncture. Among these, the use of CHM and curcumin concomitant with standard therapy was associated with survival and quality-of-life benefits. Electroacupuncture reduced pancreatic cancer pain intensity in a cost-effective manner. The data on ME are mixed and of insufficient quality for drawing definitive conclusions. Conclusions: Some unconventional treatments showed potential benefits in improving overall survival and quality of life in pancreatic cancer patients within an integrative oncology setting. Further high-quality studies are needed to provide robust, rigorous, and ethical evidence to support their integration into future guidelines, ensuring a holistic approach to cancer treatment. Full article

Low health literacy is a known contributing factor to poorer patient outcomes. Health information is often presented through materials written at high reading levels and thus may be an ineffective education tool for patients of diverse socioeconomic backgrounds, age ranges, and education levels. Graphic medicine (i.e., healthcare concepts presented through illustrations, such as comics or cartoons) may be a more equitable and efficacious format for many patients. The purpose of this review was to describe the efficacy and use of graphic medicine interventions regarding health outcomes, behavior changes, and engagement with health services. Nine databases were searched for studies that were randomized controlled trials in the English language, published before 4 December 2023. The searches identified 34 research articles that met the inclusion/exclusion criteria. This review revealed four key takeaways: (1) graphic medicine interventions are used globally; (2) graphic medicine interventions may be efficacious for a wide variety of health topics; (3) graphic medicine can be equitably delivered in many formats; and (4) graphic medicine can be applied broadly across the lifespan. The findings suggest that graphic medicine enhances patient engagement, empowers individuals with knowledge, and ultimately contributes to improved health outcomes across various populations; however, more effectiveness trials are needed. Additionally, an expanded definition of graphic medicine is presented. Full article

The production of advanced therapy medicinal products (ATMP) is a long and highly technical process, resulting in a high cost per dose, which reduces the number of eligible patients. There is a critical need for a closed and sample-free monitoring system to perform the numerous quality controls required. Current monitoring methods are not optimal, mainly because they require the system to be opened up for sampling and result in material losses. White light spectroscopy has emerged as a technique for sample-free control compatible with closed systems. We have recently proposed its use to monitor cultures of CEM-C1 cell lines. In this paper, we apply this method to T-cells isolated from healthy donor blood samples. The main differences between cell lines and human primary T-cells lie in the slightly different shape of their absorption spectra and in the dynamics of cell expansion. T-cells do not multiply exponentially, resulting in a non-constant generation time. Cell expansion is described by a power-law model, which allows for the definition of instantaneous generation times. A correlation between the linear asymptotic behavior of these generation times and the initial cell concentration leads to the hypothesis that this could be an early predictive marker of the final culture concentration. To the best of our knowledge, this is the first time that such concepts have been proposed. Full article

Upper gastrointestinal (GI) malignancies, including esophageal, gastroesophageal junction (GEJ), and gastric adenocarcinomas, remain a major global health concern, with poor overall survival and high recurrence rate despite aggressive treatment. Patients with very early tumors (cT1a) can benefit from endoscopic therapy. However, patients with locally advanced disease require multimodal therapies that may combine surgery, radiation, and systemic therapies. This review provides a comprehensive overview of recent advancements in the treatment of locally advanced upper GI adenocarcinomas. Surgical resection remains the cornerstone of curative treatment, with perioperative chemotherapy emerging as the standard of care. While preoperative chemoradiation has demonstrated some benefits in esophageal and GEJ cancers, recent data suggest a more limited role for radiation going forward. Immunotherapy has shown some promise in both the adjuvant and perioperative settings but has yet to establish definitive survival benefit. The integration of HER2-targeted therapies into treatment regimens for HER2-positive locally advanced gastroesophageal cancers has not yielded significant improvements, underscoring the need for more effective strategies. Ongoing research focuses on better predictive biomarkers, personalized treatment approaches, and potential organ preservation strategies for patients achieving a clinical complete response. Continued advancements in treatment modalities and precision medicine are critical to improving survival for patients with locally advanced upper GI adenocarcinomas. Full article

Advanced heart failure (AHF) represents the terminal stage of heart failure (HF), characterized by persistent symptoms and functional limitations despite optimal guideline-directed medical therapy (GDMT). This review explores the clinical definition, pathophysiology, and therapeutic approaches for AHF. Characterized by severe symptoms, New York Heart Association (NYHA) class III-IV, significant cardiac dysfunction, and frequent hospitalizations, AHF presents substantial challenges in prognosis and management. Pathophysiological mechanisms include neurohormonal activation, ventricular remodeling, and systemic inflammation, leading to reduced cardiac output and organ dysfunction. Therapeutic strategies for AHF involve a multidisciplinary approach, including pharmacological treatments, device-based interventions like ventricular assisted devices, and advanced options such as heart transplantation. Despite progress, AHF management faces limitations, including disparities in access to care and the need for personalized approaches. Novel therapies, artificial intelligence, and remote monitoring technologies offer future opportunities to improve outcomes. Palliative care, which focuses on symptom relief and quality of life, remains crucial for patients ineligible for invasive interventions. Early identification and timely intervention are pivotal for enhancing survival and functional outcomes in this vulnerable population. This review underscores the necessity of integrating innovative technologies, personalized medicine, and robust palliative strategies into AHF management to address its high morbidity and mortality. Full article

In neonates, estimation of the glomerular filtration rate is problematic, and assessment of renal impairment is challenging. Serum creatinine is a widely used marker, and urine output is an important vital parameter monitored in intensive care settings, particularly in unwell neonates. However, the rapid changes after birth with adaptation to the extrauterine environment is a unique situation in which absolute serum creatinine is not a reliable indicator of renal function. A rise in serum creatinine from the previous value during the neonatal period can be a result of worsening renal function in neonates but is dependent on many other factors. In addition, urine output can be difficult to measure in sick neonates during their intensive care stay. Despite a high prevalence of acute kidney injury (AKI) in preterm and/or unwell infants, the current definitions are not straightforward and do not take postnatal adaptation processes into account. The management of AKI is challenging in very young and small patients because the assessment of fluid status as well as balancing nutritional needs with fluid restriction can be problematic. The Australian Neonatal Medicines Formulary provides advice on drug dosing in the face of reduced renal function in neonates. Predictors (or long-term outcome, or recovery) after AKI diagnosis are still poorly described. Therefore, the diagnosis of neonatal AKI needs to be documented and transferred to the paediatrician responsible for the follow-up of the child. This educational review aims to give a perspective on neonatal kidney function and AKI, the relation of fluid balance and creatinine, the management of neonatal AKI and the consequences for drug dosing and long-term outcomes. Full article

Background. Despite dentistry’s alarmingly high energy use, plastic waste, and travel emissions, research on Romanian dental students’ sustainability awareness is absent. This study aimed to assess their knowledge of the environmental impact of dental materials and practices, hypothesizing that early exposure to sustainability education would benefit preclinical students most. Materials and Methods. A cross-sectional survey using a form questionnaire with 15 items was conducted on 1800 dental students at Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, for one week in March 2022. The questionnaire, consisting of socio-demographics, students’ perspectives on sustainability in dentistry, and personal sustainability, was analyzed using SPSS 26. Data analysis included the Shapiro–Wilk test for normality, Fisher’s exact test for categorical variables, the Mann–Whitney U test for non-parametric quantitative comparisons, and Z-tests with Bonferroni correction for contingency tables. Results. A response rate of 26.06% was achieved, with 469 participants. The majority (51.1%), particularly males (66.1%), perceived sustainability as promoting durability. The most common definition of sustainability (33.8%) was related to environmental protection, with significantly higher agreement among female students (39.4%) (p = 0.001). While 49.3% of participants identified single-use plastics in patient care as having the greatest environmental impact in dental practices, 39.2% of female students, primarily from clinical study years (50%), ranked patient paperwork and records as the most significant factor (p = 0.031). The highest-carbon-footprint dental procedures were considered to be amalgam and composite fillings (50.7%), with clinical year students indicating this as the most relevant issue (62.8% vs. 47.7%) (p = 0.011). Students aged 25–30 were more actively engaged in sustainability initiatives compared to the younger group (p = 0.005), while all students over 30 identified scaling and polishing as the most impactful procedure (p < 0.001). A majority of students supported future university sustainability initiatives (62.7%) and an elective course on sustainability in dentistry (65%). Female students showed significantly greater interest than male students in both initiatives (66.3% vs. 52.7%, p = 0.003 and 70.8% vs. 49.6%, p < 0.001, respectively). Conclusions. Greater awareness of sustainability was found in preclinical-year dental students and among female students, with knowledge gaps in clinical-year students, particularly regarding the environmental impact of dental practices and materials. Introducing sustainability courses could better prepare future dentists for sustainable practices in dentistry. Research collaborations and curriculum reforms to further promote sustainability would also be beneficial. Full article

Atopic dermatitis is prevalent in humans (hAD) and dogs (cAD) and profoundly impacts the patients’ quality of life. The increasing number of new drugs in development for atopic dermatitis indicates both the need and potential for precision medicine to generate an optimised benefit–risk therapeutic plan. Cannabidiol (CBD), known for its potential anti-inflammatory and antipruritic properties, shows promise in hAD and cAD management, prompting the exploration of cannabinoids (CBs) and CBD as therapeutic tools. In fact, encouraging results on the benefits of using CBD in cAD have been published, along with safety evaluations that reveal that CBD is generally well tolerated in dogs. However, limited placebo-controlled trials and dosage variations in dogs pose barriers that hinder definitive conclusions. Challenges in product stability, inconsistent formulations, and legal ambiguities highlight the need for standardised CBD-based products for both research and commercial uses. The complex legal landscape further complicates accessibility and regulation. Despite these challenges, CBD is emerging as a potential avenue for cAD management, urging further high-quality research, standardised formulations, and legal clarity. This brief review provides valuable insights into the therapeutic potential of CBs and CBD in cAD, compared to hAD, emphasising the importance of rigorous research and unambiguous regulation for successful integration into veterinary dermatology. Full article

Background/Objectives: Kissing aneurysms, a rare and intriguing cerebrovascular anomaly, challenge even the most advanced neurosurgical techniques. These lesions, characterized by two intimately apposed aneurysms with shared arterial walls, often masquerade as single, irregular aneurysms. This report documents a case of ruptured kissing aneurysms in the M1 segment of the right middle cerebral artery (MCA), complicated by ischemic stroke and pulmonary thromboembolism (PTE)—a convergence of severe complications rarely encountered. The case underscores the importance of precise diagnostics, innovative surgical strategies, and multidisciplinary care. Methods: A 55-year-old female presented with subarachnoid hemorrhage, confirmed by advanced imaging to arise from ruptured kissing aneurysms in the M1 segment of the right MCA. Surgical intervention via a right frontotemporal craniotomy and microsurgical clipping achieved definitive aneurysmal exclusion. Postoperatively, the patient experienced ischemic stroke and PTE, necessitating dynamic adjustments in anticoagulation therapy, intensive care, and rehabilitation protocols. Results: The dual aneurysms were successfully clipped, as confirmed by intraoperative and postoperative imaging. Despite developing significant complications, including left-sided motor deficits and PTE, a carefully orchestrated treatment strategy enabled the patient’s full recovery, with marked neurological and systemic improvement by her three-month follow-up. This favorable outcome highlights the resilience of a multidisciplinary approach in navigating such high-risk scenarios. Conclusions: This case showcases the formidable challenges of managing kissing aneurysms, particularly when compounded by stroke and PTE. It emphasizes the transformative role of cutting-edge imaging and surgical techniques in achieving successful outcomes. By illustrating how precision medicine and collaborative care can overcome rare and complex cases, this report contributes valuable insights to the evolving field of cerebrovascular surgery and postoperative management. Full article

Regenerative medicine and tissue engineering aim to restore or replace impaired organs and tissues using cell transplantation supported by scaffolds. Recently scientists are focusing on developing new biomaterials that optimize cellular attachment, migration, proliferation, and differentiation. Nanoparticles, such as graphene oxide (GO), have emerged as versatile materials due to their high surface-to-volume ratio and unique chemical properties, such as electrical conductivity and flexibility. However, GO faces challenges such as cytotoxicity at high concentrations, a negative surface charge, and potential inflammatory responses; for these reasons, variations in synthesis have been studied. A GO derivative, Graphene Oxide-Polyethylenimine (GO-PEI), shows controlled porosity and structural definition, potentially offering better support for cell growth. Human amniotic fluid stem cells (hAFSCs) are a promising candidate for regenerative medicine due to their ability to differentiate into mesodermic and ectodermic lineages, their non-immunogenic nature, and ease of isolation. This study investigates the effects of GO and GO-PEI on hAFSCs, focusing on the effects on adhesion, proliferation, and metabolic features. Results indicate that GO-PEI restores cell proliferation and mitochondrial activity to control levels, with respect to GO that appeared less biocompatible. Both materials also influence the miRNA cargo of hAFSC-derived microvesicles, potentially influencing also cell-to-cell communication. Full article

The COVID-19 outbreak caused saturations of hospitals, highlighting the importance of early patient triage to optimize resource prioritization. Herein, our objective was to test if high definition metabolomics, combined with ML, can improve prognostication and triage performance over standard clinical parameters using COVID infection as an example. Using high resolution mass spectrometry, we obtained metabolomics profiles of patients and combined them with clinical parameters to design machine learning (ML) algorithms predicting severity (herein determined as the need for mechanical ventilation during patient care). A total of 64 PCR-positive COVID patients at the Poitiers CHU were recruited. Clinical and metabolomics investigations were conducted 8 days after the onset of symptoms. We show that standard clinical parameters could predict severity with good performance (AUC of the ROC curve: 0.85), using SpO2, first respiratory rate, Horowitz quotient and age as the most important variables. However, the performance of the prediction was substantially improved by the use of metabolomics (AUC = 0.92). Our small-scale study demonstrates that metabolomics can improve the performance of diagnosis and prognosis algorithms, and thus be a key player in the future discovery of new biological signals. This technique is easily deployable in the clinic, and combined with machine learning, it can help design the mathematical models needed to advance towards personalized medicine. Full article