Search Results (24,103)

In gastrointestinal stromal tumors (GISTs), identifying prototypical mutations in the KIT/PDGFRA oncogenes, or in rare alternate genes, is essential for prognostication and predicting response to tyrosine kinase inhibitors. Conversely, wild-type GISTs (WT-GIST), which lack known mutations, have limited treatment options. Data on the mutational landscape of GISTs and their impact on disease progression are very limited in Kuwait. Using a targeted next-generation sequencing panel, we investigated the spectrum and frequency of KIT, PDGFRA, and RAS-pathway-related mutations in 95 out of 200 GISTs diagnosed at Kuwait Cancer Center from 2005 to 2023 and assessed their correlation with clinicopathological parameters. Among the 200 tumors (median age 55 years; 15–91), 54% originated in the stomach, 33% in the small bowel, 7% in the colorectum, 1.5% in the peritoneum, and 4.5% had an unknown primary site. Of the 95 molecularly profiled cases, 88% had a mutation: KIT (61%), PDGFRA (25%), NF1 (2%), and one NTRK1 rearrangement. Ten WT-GISTs were identified (stomach = 6, small bowel = 2, and colorectum = 2). WT-GISTs tended to be smaller (median 4.0 cm; 0.5–8.0) (p = 0.018), with mitosis ≤5/5 mm², and were of lower risk (p = 0.019). KIT mutations were an adverse indicator of disease progression (p = 0.049), while wild-type status did not significantly impact progression (p = 0.934). The genetic landscape in this cohort mirrors that of global studies, but regional collaborations are needed to correlate outcomes with genetic variants. Full article

Intorduction: Most studies on the progression of childhood-onset multiple sclerosis (MS) involve relatively short follow-up periods, focusing primarily on neurological outcomes and disability progression. The influence of these and other factors on the health-related quality of life is not known. To gain a comprehensive understanding of early-onset MS, it is crucial to evaluate the effects of treatment and the disease on quality of life. Method: This pilot project aimed to evaluate the feasibility of using an online survey tool for long-term follow-up data collection from patients with childhood-onset MS. An anonymized, monocentric, prospective survey was conducted on a convenience cohort of patients treated at a certified centre for neuromuscular diseases in childhood between 2007 and 2019. Results: A total of 27 patients completed the survey. There were no mandatory items, therefore some patients chose not to answer all the questions in the questionnaire. Patients exhibited promising educational achievements, low neurological disease burden, and high resilience. However, anxiety, depression, and pain significantly impacted their perceived health status. Conclusion:This single-centre study has yielded new insights into childhood-onset MS. To enable more accurate comparisons across different centres and countries, it is essential to establish a minimum data set and questionnaire subset for patients with paediatric-onset MS transitioning into adulthood. Full article

Background and Objectives: Rectal cancer is considered cured if no recurrence is found during the 5-year follow-up period after treatment. After this period, patients often believe that the cancer is completely eradicated. However, in modern society, where lifespans have become longer, it is important to recognize that metastatic cancer may occur long after the initial treatment has concluded. This highlights the necessity of continued vigilance and the long-term follow-up of cancer survivors. Case report: We present a case of metastatic cancer of the coccyx in an 87-year-old female patient. This patient had undergone successful surgery and treatment for rectal cancer 10 years prior. She was considered cured after the standard 5-year follow-up period as she showed no signs of recurrence. The patient presented with simple coccygeal pain as the main complaint, without any other accompanying symptoms such as weight loss, fever, or changes in bowel habits, typically associated with cancer recurrence. During the clinical evaluation, irregularities in the bone cortex were detected while performing a nerve block using ultrasound. Given these findings, further diagnostic evaluations were performed. Advanced imaging techniques including MRI and CT scans led to a diagnosis of coccygeal metastasis. Conclusions: While the 5-year mark post-treatment is a significant milestone for rectal cancer patients, it does not guarantee the absolute eradication of the disease. Long-term monitoring and a thorough evaluation of new symptoms are essential for the early detection and management of late metastatic recurrences. This approach ensures that patients receive timely and appropriate care, potentially improving outcomes and quality of life. Full article

Low-dose-rate (LDR) brachytherapy with I-125 seeds is one of the most common primary tumor treatments for low-risk and low-intermediate-risk prostate cancer. This report aimed to present an analysis of single-institution long-term results. We analyzed the treatment outcomes of 119 patients with low- and intermediate-risk prostate cancer treated with LDR brachytherapy at our institution between 2014 and 2020. The analysis focused on biochemical recurrence rates (BRFS), overall survival (OS), cumulative local recurrence rate (CLRR), and the incidence of acute and late toxicities. Patient-reported quality of life measures were also evaluated to provide a holistic view on the treatment’s impact. The median follow-up period was 46 months. CLRR was 3.3% (4/119), five-year BRFS was 87%, and the five-year OS rate was 95%. Dysuria was the most common acute urinary toxicity, reported in 26.0% of patients as grade 1 and 13.4% as grade 2. As a late side effect, 12.6% of patients experienced mild dysuria. Sexual dysfunction persisted in 6.7% of patients as grade 1, 7.5% as grade 2, and 10.0% as grade 3. LDR brachytherapy in patients with prostate cancer is an effective treatment, with favorable clinical outcomes and manageable toxicity. The low CLRR and high OS rates, as well as low incidence of severe side effects, support the continued use of LDR brachytherapy as a primary treatment modality for localized prostate cancer. Full article

Thrombotic microangiopathy (TMA) encompasses a range of disorders characterized by blood clotting in small blood vessels, leading to organ damage. It can manifest as various syndromes, including thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), and others, each with distinct causes and pathophysiology. Thrombo-inflammation plays a significant role in TMA pathogenesis: inflammatory mediators induce endothelial injury and activation of platelet and coagulation cascade, contributing to microvascular thrombosis. Primary TMA, such as TTP, is primarily caused by deficient ADAMTS13 metalloproteinase activity, either due to antibody-mediated inhibition or intrinsic enzyme synthesis defects. In cancer patients, a significant reduction in ADAMTS13 levels and a corresponding increase in VWF levels is observed. Chemotherapy further decreased ADAMTS13 levels and increased VWF levels, leading to an elevated VWF/ADAMTS13 ratio and increased thrombotic risk. Drug-induced TMA (DITMA) can result from immune-mediated or non-immune-mediated mechanisms. Severe cases of COVID-19 may lead to a convergence of syndromes, including disseminated intravascular coagulation (DIC), systemic inflammatory response syndrome (SIRS), and TMA. Treatment of TMA involves identifying the underlying cause, implementing therapies to inhibit complement activation, and providing supportive care to manage complications. Plasmapheresis may be beneficial in conditions like TTP. Prompt diagnosis and treatment are crucial to prevent serious complications and improve outcomes. Full article

Background: This study aimed to examine whether individuals with chronic tinnitus report more positive experiences following internet-based cognitive behavioral therapy (CBT). Methods: A mixed-methods design was used, nested in clinical trials evaluating internet interventions for tinnitus. Participants (n = 164) completed online questionnaires (both structured and open-ended) providing demographic information as well as health variables (e.g., tinnitus distress, anxiety, depression, insomnia). An open-ended question listing positive effects or outcomes related to having tinnitus was also included. Responses to the open-ended questions were analyzed using qualitative content analysis. Results: Of the 164 eligible participants, 32.3% (n = 53) provided at least 1 positive experience both at pre- and post-intervention, with 9.1% (n = 19) providing positive experiences only at pre-intervention, 49 (29.9%) providing positive experiences only at post-intervention, and 28.7% (n = 47) of the participants did not provide any positive experiences on either measurement occasion. Significantly more positive experiences were reported following the intervention in the overall sample (p < 0.0001, paired sample t-test). In addition, participants who reported positive experiences in both pre- and post-intervention also reported more positive experiences following intervention (p = 0.008, paired sample t-test). Conclusions: Internet-based CBT can help individuals with tinnitus to think more positively by changing unhelpful thought patterns. Open-ended questions can supplement structured questionnaires to measure treatment outcomes. Full article

In vitro fertilization (IVF) is an established option for the management of infertility in patients with endometriosis, though there remains ongoing debate around the extent to which endometriosis may compromise IVF treatment success, in which fertilization and preimplantation embryo development occur outside the pelvis. Whether endometriosis impacts oocyte and embryo quality and/or endometrial receptivity remains central to this debate. Here, we review the current literature relating to the impact of endometriosis on IVF outcomes and management strategies to consider when performing IVF treatment. Full article

Coxsackievirus group B (CVB), a member of the Picornaviridae family and enterovirus genus, poses risks during pregnancy due to its potential to cause severe fetal and neonatal infections. Transmission primarily occurs through fecal–oral routes, with infections peaking mostly in warmer months. Vertical transmission to the fetus can lead to conditions such as myocarditis, encephalitis, and systemic neonatal disease, presenting clinically as severe myocardial syndromes and neurological deficits. Diagnostic challenges include detecting asymptomatic maternal infections and conducting in utero assessments using advanced techniques like RT-PCR from amniotic fluid samples. Morbidity and mortality associated with congenital CVB infections are notable, linked to preterm delivery, fetal growth restriction, and potential long-term health impacts such as type 1 diabetes mellitus and structural cardiac anomalies. Current treatments are limited to supportive care, with emerging therapies showing promise but requiring further study for efficacy in utero. Preventive measures focus on infection control and hygiene to mitigate transmission risks, which are crucial especially during pregnancy. Future research should aim to fill knowledge gaps in epidemiology, improve diagnostic capabilities, and develop targeted interventions to enhance maternal and fetal outcomes. Full article

Introduction: The main goal of radiotherapy (RT) is to deliver a precise dose to the target while sparing the surrounding normal tissue and minimizing side effects. Appropriate patient immobilization is crucial, especially for head and neck cancer (HNC) and Brain Cancer (BC). Conventional closed-face masks (CFMs), while effective in minimizing head motion, can cause significant discomfort, anxiety, and claustrophobia. Open-face masks (OFMs) have been developed to increase patient comfort while providing precise immobilization. Methods: Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) extension for scoping reviews and the Arskey and O’Malley framework, an electronic search of EMBASE, PubMed, SCOPUS, and Web of Science was conducted to identify original studies reporting the use and description of OFMs in clinical practice up to April 2024. The inclusion criteria were English-language articles focusing on OFMs for HNC and BC patients undergoing RT. Results: Of 618 titles, 19 articles fulfilled the selection criteria. Most studies were comparative (n = 13) or observational (n = 6). The articles were categorized by treatment site, resulting in three groups: BC (n = 14, 68.4%), HNC (n = 4, 21.4%), and mixed (n = 2, 10.5%), which includes both BC and HNC. Of note, 82.4% (n = 16) of the included studies were published from 2020 onwards, emphasizing the recent adoption of OFM in clinical practice. Conclusions: The reviewed studies show that OFMs, in combination with SGRT, offer significant advantages in terms of patient comfort and positioning accuracy in HNC and BC treatments. Reproducibility in the sub-millimeter and sub-degree range can be achieved, which supports the use of OFMs in clinical practice. Future research should explore innovative combinations of immobilization and monitoring to further improve RT outcomes and ensure precise treatment while increasing patient comfort. Full article

Immunotherapy has revolutionized the treatment paradigm for hepatocellular carcinoma (HCC). However, its efficacy varies significantly with each patient’s genetic composition and the complex interactions with their microbiome, both of which are pivotal in shaping anti-tumor immunity. The emergence of microbial neoantigens, a novel class of tumor vaccines, heralds a transformative shift in HCC therapy. This review explores the untapped potential of microbial neoantigens as innovative tumor vaccines, poised to redefine current HCC treatment modalities. For instance, neoantigens derived from the microbiome have demonstrated the capacity to enhance anti-tumor immunity in colorectal cancer, suggesting similar applications in HCC. By harnessing these unique neoantigens, we propose a framework for a personalized immunotherapeutic response, aiming to deliver a more precise and potent treatment strategy for HCC. Leveraging these neoantigens could significantly advance personalized medicine, potentially revolutionizing patient outcomes in HCC therapy. Full article

Osteochondral defect is a complex tissue loss disease caused by arthritis, high-energy trauma, and many other reasons. Due to the unique structural characteristics of osteochondral tissue, the repair process is sophisticated and involves the regeneration of both hyaline cartilage and subchondral bone. However, the current clinical treatments often fall short of achieving the desired outcomes. Tissue engineering bioscaffolds, especially those created via three-dimensional (3D) printing, offer promising solutions for osteochondral defects due to their precisely controllable 3D structures. The microstructure of 3D-printed bioscaffolds provides an excellent physical environment for cell adhesion and proliferation, as well as nutrient transport. Traditional 3D-printed bioscaffolds offer mere physical stimulation, while drug-loaded 3D bioscaffolds accelerate the tissue repair process by synergistically combining drug therapy with physical stimulation. In this review, the physiological characteristics of osteochondral tissue and current treatments of osteochondral defect were reviewed. Subsequently, the latest progress in drug-loaded bioscaffolds was discussed and highlighted in terms of classification, characteristics, and applications. The perspectives of scaffold design, drug control release, and biosafety were also discussed. We hope this article will serve as a valuable reference for the design and development of osteochondral regenerative bioscaffolds and pave the way for the use of drug-loaded bioscaffolds in clinical therapy. Full article

HER2-positive breast cancer is a significant cause of mortality. Overcoming trastuzumab resistance requires a deeper understanding of its molecular mechanisms to develop effective therapies. This study investigates the role of plasminogen activator inhibitor-1 (PAI1) in migration and drug resistance in trastuzumab-resistant HER2-positive breast cancer. Trastuzumab resistance poses a significant challenge in clinical management due to its association with aggressive disease behaviour and limited treatment options. This study focuses on PAI1, a key player in the TGF-β signalling pathway, which is implicated in cancer progression and metastasis. Trastuzumab-resistant cell lines (SKBR3 and HCC1954) demonstrated markedly elevated PAI1 expression levels, up to 40-fold compared to parental lines. This elevation was accompanied by increased expression of migration markers such as Col4a1, Fibronectin, ICAM1, Timp2, and Vimentin. Through overexpression and silencing experiments, we observed that modulating PAI1 levels significantly impacts cell morphology, transitioning cells from an epithelial to mesenchymal phenotype. Importantly, combining trastuzumab with aleplasinin, a PAI1 inhibitor, synergistically reduced PAI1 expression in both parental and resistant cell lines. This suggests a potential therapeutic strategy to overcome trastuzumab resistance. These findings emphasise PAI1 as a critical mediator of migration and therapeutic response in HER2-positive breast cancer, offering insights into novel treatment approaches targeting PAI1 to improve clinical outcomes in drug resistance. Full article

The treatment of patients with metastatic colorectal cancer (mCRC) is complex and is impacted by the location of the primary tumor (LPT). Our study aims to emphasize the importance of LPT as a prognostic and predictive marker as well as to examine the significance of HER2 overexpression in patients with mCRC, particularly in relation to the response to Epidermal Growth Factor Receptor Antibody treatment (anti-EGFR therapy). In this study, 181 patients with Kirsten RAS (KRAS) wild-type mCRC who received anti-EGFR therapy were included. Among them, 101 had left colon cancer (LCC) and 80 had right colon cancer (RCC). Results demonstrated that patients with KRAS wild-type LCC had better median overall survival (OS) (43 vs. 33 months, p = 0.005) and progression-free survival (PFS) (6 vs. 3 months, p < 0.001) compared to those with RCC. Multivariate analysis identified mucinous adenocarcinoma (p < 0.001), RCC location (p = 0.022), perineural invasion (p = 0.034), and tumors at the resection margin (p = 0.001) as independent predictors of OS, while mucinous adenocarcinoma (p = 0.001) and RCC location (p = 0.004) independently correlated with significantly shorter PFS. In addition, human epidermal growth factor receptor 2 (HER2) positive expression was significantly associated with worse PFS compared to HER2 negative results (p < 0.001). In conclusion, LPT is an important marker for predicting outcomes in the treatment of wild-type mCRC using anti-EGFR therapy, since patients with RCC have a statistically significantly shorter PFS and OS. Further investigation is needed to understand the role of HER2 overexpression in wild-type mCRC, as these patients also exhibit shorter survival. Full article

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059–0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (n = 36). We established an association of MUC5AC expression with treatment response and outcomes. Full article

Sex-related differences in psychopharmacology present unique challenges in both clinical and research settings. Recognition of sex differences in psychopharmacological treatment has increased in recent years, but a significant research gap regarding variations between men and women still exists. Biological factors, including hormonal fluctuations, genetic factors, and brain structure differences, contribute significantly to differential drug responses. Moreover, social determinants can influence the differential burden of psychiatric disorders between the sexes and may impact treatment plans. Incorporating sex as a key variable in personalized treatment programs and plans holds the potential to optimize efficacy and minimize adverse effects in psychopharmacology. Sex-related challenges in psychopharmacology necessitate a nuanced approach to treatment. Further research is needed to fully understand these differences and to develop guidelines for personalized medication management. By addressing these challenges, clinicians can improve treatment outcomes and enhance the quality of life of patients with psychiatric disorders. Full article