Diseases (Basel, Switzerland)最新文献

Background: Youth suicide remains a significant public health concern in Japan, driven by multifaceted factors such as academic pressures, social isolation, bullying, and family dysfunction. Recent societal changes, including the rise of internet addiction and subcultural influences from anime, manga, and gaming, have further shaped the psychological landscape of Japanese youth. The COVID-19 pandemic has exacerbated these challenges, intensifying feelings of loneliness and anxiety about the future.

Methods: This study explores the impact of these factors on youth suicide risk through a systematic review of existing literature and statistical data, focusing on trends from 2000 to 2024.

Results: In 2023, 513 school-aged youth in Japan died by suicide, marking persistently high rates. High school students accounted for the majority of cases, followed by middle and elementary school students. Key risk factors include intense academic expectations, cyberbullying, and internet addiction, which are often compounded by cultural stigmas surrounding mental health. Subcultures offer both solace and potential alienation, influencing youth emotions in complex ways. The COVID-19 pandemic has also worsened mental health issues and heightened suicide risks among this vulnerable group.

Conclusions: The findings highlight the urgent need for comprehensive mental health support systems tailored to Japanese cultural contexts. Recommendations include enhancing access to school-based counseling, promoting family-based interventions, and implementing policies to regulate harmful online content. Additionally, efforts must address cultural attitudes that stigmatize mental health care. Collaborative societal and policy-level interventions are crucial for mitigating youth suicide and fostering a supportive environment for young people in Japan.

Background/objectives: Breast cancer (BC) is a heterogeneous disease with multifactorial origins, including environmental, genetic, and immunological factors. Inflammatory cytokines, such as alpha 1 antitrypsin (α1-AT), are increased in BC and affect physiological and pathological conditions. This study aimed to evaluate the serum levels of α1-AT and perform a computational analysis of SERPINA1 in BC, as well as their association with molecular subtypes and clinical features.

Methods: For the experimental analysis, we evaluated 255 women with BC and 53 healthy women (HW) in a cross-sectional study. Molecular subtypes were identified by immunohistochemistry and TNM was used for clinical staging. Soluble levels of α1-AT were quantified by ELISA. Computational analysis of SERPINA1 expression was performed using GEPIA and cBioPortal.

Results: α1-AT was increased in BC women versus HW (75.8 ng/mL vs. 532.2 ng/mL). Luminal A had higher concentration (547.5 ng/mL) than Triple Negative (TN) (484.1 ng/mL), but the levels were not associated with clinical stage. The computational analysis showed that SERPINA1 is overexpressed in BC with differential expression among subtypes; its overexpression is associated with a better prognosis, longer disease-free survival, and overall survival.

Conclusions: α1-AT levels are increased in women with BC women compared to HW. The Luminal A subtype shows higher soluble protein levels than the TN one. Furthermore, SERPINA1 mRNA overexpression in BC is linked to a protective effect.

Background: Iron deficiency (ID) often coexists with heart failure (HF), and its prevalence increases with the severity of HF. Intravenous ferric carboxymaltose (FCM) has been associated with improvements in clinical outcomes, functional capacity, and quality of life (QoL) in patients with HF and ID. However, while earlier studies showed favorable results, more recent studies have failed to demonstrate significant improvements in outcomes for patients with heart failure with reduced ejection fraction (HFrEF) and ID. This meta-analysis seeks to provide updated insights into the effectiveness and safety of FCM compared to placebo/standard of care (SoC) among patients with HFrEF and ID/iron deficiency anemia (IDA). Methods: We performed a systematic review and meta-analysis of the literature from inception to December 2023, utilizing databases such as MEDLINE (via PubMed), Google Scholar, the Cochrane Library, ClinicalTrials.gov, and the ScienceDirect portal. A statistical analysis was carried out using RevMan 5.4 with a random-effects model. Dichotomous outcomes were reported as odds ratios (OR), while continuous outcomes were presented as the weighted mean difference (WMD) with corresponding 95% confidence intervals (CI), and heterogeneity was assessed using the I² test. Results: The final analysis included data from six randomized controlled trials (RCTs), comprising 5132 patients. Our findings indicate a significant reduction in total HF hospitalizations among patients with HFrEF and ID/IDA treated with FCM compared to those receiving the placebo or SoC, with an OR of 0.59 (95% CI: 0.40 to 0.88, p < 0.010). However, no statistically significant difference was observed in the total number of deaths between the FCM and placebo/SoC groups (OR: 0.85; 95% CI: 0.70 to 1.03, p = 0.09), non-HF hospitalizations (OR: 0.71; 95% CI: 0.41 to 1.25, p = 0.24), or the composite outcome of cardiovascular hospitalizations and cardiovascular deaths (OR: 0.65; 95% CI: 0.40 to 1.04, p = 0.07). Regarding functional capacity, as assessed by the change in 6-min walk test (6MWT) distance, no significant improvement was found, with a weighted mean difference (WMD) of 14.03 (95% CI: -10.94 to 38.99, p = 0.27). QoL, measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) score, also did not show significant enhancement, with a WMD of 3.85 (95% CI: -0.55 to 8.24, p = 0.09). Furthermore, the safety analysis revealed no significant difference in the incidence of serious adverse events between the FCM and placebo/SoC groups, with an OR of 0.73 (95% CI: 0.49 to 1.10, p = 0.13). Conclusions: In patients with HFrEF and IDA, treatment with intravenous FCM significantly lowers the risk of total HF hospitalizations but does not appear to affect functional capacity, QoL, or mortality.

Background: Monitoring of measurable residual disease (MRD) requires highly sensitive flow cytometry protocols to provide an accurate prediction of shorter progression-free survival. High assay sensitivity generally requires rapid processing to avoid cell loss from small bone marrow sample volumes, but this requirement conflicts with the need in most clinical cytometry laboratories for long processing and acquisition times, especially when multiple MRD studies coincide on the same day.

Methods: The proposed protocol was applied to 226 human bone marrow and 45 peripheral blood samples submitted for the study of MRD or the detection of rare cells. Samples were processed within 24 h of extraction and acquired with an eight-color flow cytometer.

Results: The FACSLyse-Bulk protocol allows for the labelling of millions of cells in under 90 min in small sample volumes without affecting the FSC/SSC pattern or antigen expression, and it also allows antigens to be fixed to the membrane, thus avoiding the capping phenomenon.

Conclusions: The proposed protocol would allow clinical flow cytometry laboratories to perform MRD studies in house and easily achieve a limit of detection and limit of quantification <0.001%, thus avoiding the need to outsource analysis to specialized cytometry laboratories.

Background: Coronavirus Disease 2019 (COVID-19), triggered by SARS-CoV-2, has represented a global pandemic associated with an elevated rate of mortality, mainly among older individuals. The extensive pulmonary involvement by the viral infection might have precipitated pre-existing chronic conditions in this vulnerable population, including heart failure (HF). Materials and Methods: The aim of this retrospective, observational study was to assess the impact of COVID-19 in patients with a prior diagnosis of HF referred to the Emergency Department of the Agostino Gemelli University Hospital between March 2020 and January 2023. A total of 886 HF patients (444 men and 442 women, mean age of 80 ± 10 years) were identified. Patients were matched in a 1:1 ratio by gender, age, number of comorbidities (excluding HF), and vaccination status, using a propensity score matching (PSM) procedure. We compared the outcomes of 189 patients with a concomitant diagnosis of HF with those of 189 matched controls without HF. Results: Among patients with HF, there was a significantly higher prevalence of valvular disease (p = 0.004), atrial fibrillation (p = 0.003), use of anticoagulants (p = 0.001), chronic obstructive pulmonary diseases (p = 0.03), and chronic kidney disease (p = 0.001). In contrast, hypertension was more prevalent among controls than HF patients (p = 0.04). In addition, controls exhibited higher lymphocytes counts and a higher PaO₂/FiO₂ ratio compared to HF patients. During hospitalization, patients with HF were more frequently treated with high-flow nasal cannulas (p = 0.01), required more frequent admission to an intensive care unit (ICU) (p = 0.04), and showed a significantly higher mortality rate (p 0.0001) than controls. Conclusions: HF is an independent risk factor for ICU admission and death in COVID-19 patients.

Background: The term "fetal programming" refers to the effects of endogenous and exogenous corticosteroids, whether received from the mother or the fetus, on brain development and the hypothalamic-pituitary-adrenal axis reset. The authors of this narrative review examine the WHO's guidelines for prenatal corticosteroids in pregnant women who are at high risk of premature delivery. These guidelines are regarded as the best available for preventing late-life problems resulting from preterm.

Methods: In order to find full-text publications published in peer-reviewed journals between 1990 and 2023 that were written in English, the authors searched PubMed, Scopus, Cochrane Library, and Web of Science.

Results: The authors highlight the possible adverse long-term effects of prenatal corticosteroid medication on human brain development and function. This pharmacological feature is therapeutically significant because there is less evidence in the scientific literature regarding the potential role that the timing, mode, and dosage of exogenous steroid treatment may have in neurological illnesses down the road.

Conclusions: The authors expect that these studies will shed light on the relationship between specially designed prenatal corticosteroid therapy and the molecular mechanisms underlying the prenatal programming of neurodevelopment in childhood and adulthood.

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by mutations in the TSC1 and TSC2 genes, leading to the dysregulation of the mammalian target of rapamycin (mTOR) pathway. This dysregulation results in the development of benign tumors across multiple organ systems and poses significant neurodevelopmental challenges. The clinical manifestations of TSC vary widely and include subependymal giant cell astrocytomas (SEGAs), renal angiomyolipomas (AMLs), facial angiofibromas (FAs), and neuropsychiatric conditions such as autism spectrum disorder (ASD). mTOR inhibitors, notably everolimus, have become central to TSC management, with documented efficacy in reducing the sizes of SEGAs and AMLs and showing promise in addressing additional TSC-related symptoms.

Case presentation: We report the case of an 11-year-old male diagnosed with TSC, presenting with hallmark features including hypopigmented macules, early-onset infantile spasms, SEGA, and AMLs. Initial interventions included adrenocorticotropic hormone (ACTH) therapy and sodium valproate for seizure management and a minimally invasive keyhole craniotomy for SEGA reduction. At age 12, oral everolimus therapy was introduced to address both SEGA recurrence risk and ASD-related social deficits. Over the course of 24 weeks, a reduction in the size and erythema of the patient's FAs was observed, alongside improvements in social engagement, suggesting potential added benefits of systemic mTOR inhibition beyond tumor control.

Results: Treatment with everolimus over a 24-month period led to significant reductions in both FA and AML size, as well as measurable improvements in ASD-associated behaviors. Therapeutic drug monitoring maintained serum levels within the effective range, minimizing adverse effects and underscoring the tolerability and feasibility of long-term everolimus administration.

Conclusions: This case underscores the efficacy of oral everolimus in reducing FA size in a pediatric TSC patient, with broader therapeutic benefits that support the potential of mTOR inhibition as a multi-targeted strategy for TSC management. Further studies are needed to explore the full range of applications and long-term impact of mTOR inhibitors in TSC care.

Osteocalcin (OCN), a protein predominantly produced by osteoblasts in bone, has emerged as a significant factor in bone metabolism and reproductive function. This article reviews the latest research on the role of OCN beyond its traditional functions in bone mineralisation, particularly its influence on testicular steroidogenesis and male fertility. The structure and modifications of OCN are elaborated upon, highlighting its uncarboxylated form (ucOCN), which is becoming increasingly recognised for its bioactive properties. The impact of OCN on bone quantity, quality and strength is summarised, emphasising its role as a regulator of bone metabolism. Furthermore, the influence of ucOCN on testicular steroidogenesis and the involvement of GPRC6A, a G protein-coupled receptor, in mediating these effects are also explored. Evidence suggests that ucOCN regulates testosterone synthesis and spermatogenesis, which indirectly have the potential to influence bone metabolism integrity. In conclusion, OCN, particularly in its uncarboxylated form, plays a crucial role in bone metabolism and male fertility by regulating testicular steroidogenesis, with GPRC6A mediating these effects, thereby linking bone health and reproductive functions.

Background: Obstructive jaundice is a common health challenge in daily clinical practice caused by a heterogeneous group of benign and malignant conditions in or around extrahepatic bile ducts. This study aimed to investigate the causes of obstructive jaundice, analyze the age and sex distribution, and report the locations of obstruction.

Methods: This was a retrospective study of electronic records of patients diagnosed with obstructive jaundice in the Hadhramout region in Yemen.

Results: This study analyzed the data of 303 patients (mean age: 57 ± 17.99 years; range: 18-95 years); 60.40% (n = 183) were female, and 39.60% (n = 120) were male. The highest prevalence was found in middle-aged adults (n = 112, 36.96%), followed by the old (n = 101, 33.33%). Common bile duct (CBD) stones were the most common cause of obstructive jaundice (n = 175, 57.8%), followed by CBD stricture (n = 58, 19.1%), carcinoma of the head of the pancreas (n = 35, 11.6%), cholangiocarcinoma (n = 21, 6.9%), and external compression of the CBD (n = 2, 0.7%). CBD stones, cholangiocarcinoma, and ampulla of Vater masses were more prevalent in females (30.9%, 3.8%, and 2.2%, respectively) than in males (25.8%, 2.9%, and 1.7%, respectively). In contrast, CBD stricture and carcinoma of the pancreas were more frequent in males, occurring in 12.1% and 7.1% of male patients, respectively, compared to 7.9% and 4.9% in female patients. The primary obstruction site was the CBD (n = 254, 83.8%), followed by the head of the pancreas (n = 30, 9.9%), and the ampulla of Vater (n = 13, 4.3%).

Conclusions: Obstructive jaundice predominantly affects middle-aged adults followed by the old-aged patients predominantly in females. The most common cause of obstructive jaundice was CBD stones, followed by CBD stricture, while carcinoma of the head of the pancreas was the most common malignant cause, followed by cholangiocarcinoma. Distal CBD is the most common anatomical location of obstructive jaundice.

Background: Acetaminophen is generally considered safe when used according to the recommended guidelines. Consumption in excessive doses can lead to severe liver damage and, in critical cases, may even result in death. To reduce the effects of acetaminophen overdose, N-acetylcysteine (NAC) has been established as the preferred intervention to prevent liver damage.

Objectives: The purpose of this updated systematic review and meta-analysis is to evaluate the potential benefits of a two-bag N-acetylcysteine (NAC) dosing regimen compared to the traditional three-bag protocol in the treatment of acetaminophen-induced liver toxicity.

Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The research team utilized the PubMed and Cochrane databases to perform a thorough and comprehensive search of the relevant literature from the inception of these databases up until January 2024.

Results: Nine studies were included. The overall use of two-bag NAC was associated with lower anaphylactic reactions and gastrointestinal symptoms compared to the three-bag method. The rate of liver toxicity resolution was the same between the two treatment groups.

Conclusions: The two-bag NAC regimen can be considered a safe and effective method for managing acetaminophen toxicity.