Biomedicines最新文献

Asthma is a chronic inflammatory disease with the main anti-inflammatory drugs for better disease control being steroids or corticosteroids. The use of steroids in asthma patients, in particular in uncontrolled asthma patients, is associated with an increased risk of osteoporosis and fragility fractures. A single oral corticosteroid course increases the risk of osteoporosis and the continual use of inhaled corticosteroids is correlated over time to an increased risk for both bone conditions. With the use of new, available biologic therapies for asthma, perhaps even anticipating the times of their use in therapeutic management, in the current guidelines and with targeted strategies of prevention it may be possible to improve asthma management, preventing some comorbidities, such as osteoporosis.

Background: Congenital mesoblastic nephroma represents 3-10% of all pediatric renal tumors. With the advancement of ultrasound diagnostics and magnetic resonance imaging, the diagnosis of this renal neoplasm is increasingly being established prenatally and at birth. It usually presents as a benign tumor, but it can severely affect pregnancy outcomes, contributing to perinatal morbidity and mortality. Lissencephaly belongs to a rare category of neurodevelopmental disorders marked by the absence of a substantial reduction in the typical folds and grooves in the cerebral cortex. The prognosis for patients with lissencephaly is extremely poor, carrying with it a high mortality rate.

Case presentation: We present a case of congenital mesoblastic nephroma (CMN) diagnosed with polyhydramnios at 28 weeks of gestation, which led to preterm delivery at 29 weeks and a fatal outcome for the newborn. Histopathological examination confirmed the diagnosis of CMN along with fetal pachygyria/lissencephaly. The aim of this study is to point out the characteristics and unique correlation between CMN and lissencephaly, and to illustrate the histopathological features of CMN and lissencephaly through an educational example derived from our presented index case. To the best to our knowledge, the association of CMN with lissencephaly has not been described in the literature so far.

Conclusions: Outlining the prenatal progression of CMN and the outcome of pregnancies involving fetal CMN and lissencephaly, this case underscores the importance of comprehensive ultrasound examinations, including central nervous system evaluation, to identify potential coexisting anomalies and refine prenatal diagnostic practices.

Purpose: The current study aimed to investigate the clinical comorbidities and urodynamic characteristics of a large cohort of women with dysfunctional voiding (DV) validated on a videourodynamic study (VUDS). Methods: Women who presented with VUDS-confirmed DV from 1998 to 2022 were retrospectively analyzed. Data on clinical symptoms, VUDS findings, and medical comorbidities including medical illness and previous surgical history were recorded and examined. Patients with DV were subgrouped according to age, presence of medical comorbidity, and different urodynamic parameters. The urodynamic parameters and treatment outcomes among the different subgroups were examined. Results: In total, 216 women were retrospectively analyzed. Among them, 188 (88.3%) presented with storage symptoms and 130 (61.0%) with voiding symptoms. Regarding outcomes, 48 (22.2%) patients had successful treatment outcomes; 76 (35.2%), improved outcomes; and 92 (42.6%), failed outcomes. Then, 150 (69.0%) patients presented with urodynamic DO. Patients with terminal DO experienced a significantly higher incidence of hypertension (56.8%), diabetes mellitus (37.9%), and latent central nervous system diseases (38.9%) than those with non-DO or phasic DO. Patients with phasic DO had a significantly higher detrusor pressure (Pdet) and bladder outlet obstruction index than those with non-DO and terminal DO. Patients with hypertension or those with a Pdet ≥ 35 cmH₂O had high rates of successful treatment outcomes. Conclusions: DV is significantly associated with older age and a higher incidence of central nervous system diseases, hypertension, and diabetes mellitus in women. Patients with phasic DO had a high Pdet and BOO, and patients with hypertension or those with Pdet ≥35 cm H₂O who received urethral sphincter treatment had a better treatment outcome.

Background/objectives: Differential diagnosis of sudden cardiac death (SCD) remains challenging, particularly in cases lacking evident structural abnormalities. Cardiac markers have been proposed as useful tools for this differentiation in forensic contexts. However, key issues include the influence of postmortem interval (PMI) on marker stability and the limitations of traditional approaches that focus on pericardial fluid, which requires invasive sampling compared to peripheral blood. This study aimed to evaluate the potential of cardiac markers in peripheral blood for diagnosing SCD, addressing methodological concerns related to PMI, hemolysis, and sample handling.

Methods: This study analyzed 5 cardiac markers (creatine kinase-MB [CK-MB], myoglobin, troponin I [TnI], BNP, and D-dimer) in peripheral blood samples from 42 autopsied cadavers, divided into an SCD group and a control group. Marker levels were quantified using immunofluorescence, with cases meticulously selected to exclude confounding factors such as chronic diseases, pulmonary thromboembolism, and drowning. The study also accounted for potential degradation due to PMI, and evaluated the accuracy of point-of-care testing (POCT) in forensic samples.

Results: The study identified statistically significant differences in myoglobin and TnI levels between the SCD group and the control group, though myoglobin's diagnostic reliability remains limited due to its lack of specificity for myocardial injury. TnI emerged as a more robust marker for SCD. Contrary to prior concerns, PMI showed no significant correlation with marker levels in samples handled without freeze-thaw cycles. Issues related to hemolysis were addressed, and no significant effects were observed from resuscitation maneuvers.

Conclusions: This study supports the potential use of cardiac markers, particularly TnI, in peripheral blood for postmortem SCD diagnosis, emphasizing the importance of rapid and systematic analysis to minimize hemolysis-related variability. While further validation is needed to confirm these findings, this approach offers a less invasive, economical, and practical method for forensic investigations.

Background: Ezetimibe is used to treat cardiovascular disease as it blocks the sterol transporter Niemann-Pick C1-Like 1 (NPC1CL1) protein. However, recent evidence indicates that Ezetimibe inhibits several cancers indirectly by reducing circulating cholesterol or via specific signalling pathways.

Methods and results: Our in silico studies indicate that Ezetimibe binds to the Tp53 binding domain in Mdm2, forming a more thermodynamically stable complex than nutlin3a. Furthermore, a docking study of the newly developed inhibitors-RG7388 and RG7112-was conducted. This further showed lower binding energies of -6.337 kcal/mol and -6.222 kcal/mol, respectively, when compared to the -7.919 kcal/mol exhibited by Ezetimibe. We show that Ezetimibe inhibits the growth of several cancer cell lines at concentrations that are not toxic to a normal cell line.

Conclusions: Thus, Ezetimibe is probably active against cancers that overexpress Mdm2. Moreover, inhibitors of RBBP6 may be combined with Ezetimibe for effective anticancer activity. Due to poor oral bioavailability, Ezetimibe must be administered parenterally for cancer treatment.

Subclavian artery pseudoaneurysms are rare but potentially life-threatening vascular injuries frequently associated with trauma such as clavicle fractures. In this paper we describe the case of a 49-year-old male who developed a post-traumatic pseudoaneurysm of the subclavian artery after a bicycle accident. The diagnosis was delayed due to non-specific symptoms and an initially missed aneurysm on computed tomography imaging. Persistent pain, swelling, and erythema in the subclavian region prompted further detailed diagnostics, which ultimately revealed the pseudoaneurysm. The patient was successfully treated with endovascular stent-graft implantation. We screened the PubMed database to identify similar cases managed exclusively through endovascular intervention. Reports of iatrogenic pseudoaneurysms and those treated with open surgery were excluded. Variables such as time to diagnosis, clinical presentation, features of pseudoaneurysms, and complications were analyzed to highlight the role of endovascular techniques as a minimally invasive and effective treatment option. These cases pose both a diagnostic and a therapeutic challenge, as early recognition of symptoms is crucial to prevent serious complications including thrombosis, neurological deficits, and even limb loss.

Background/objectives: Lumbar spinal stenosis (LSS) is a degenerative condition characterized by the narrowing of the spinal canal, resulting in chronic pain and impaired mobility. However, the molecular mechanisms underlying LSS remain unclear. In this study, we performed RNA sequencing (RNA-seq) to investigate differential gene expression in a rat LSS model and identify the key genes and pathways involved in its pathogenesis.

Methods: We used bioinformatics analysis to identify significant alterations in gene expression between the LSS-induced and sham groups.

Results: Pearson's correlation analysis demonstrated strongly consistent intragroup expression (r > 0.9), with distinct gene expression between the LSS and sham groups. A total of 113 differentially expressed genes (DEGs) were identified, including upregulated genes such as Slc47a1 and Prg4 and downregulated genes such as Higd1c and Mln. Functional enrichment analysis revealed that these DEGs included those involved in key biological processes, including synaptic plasticity, extracellular matrix organization, and hormonal regulation. Gene ontology analysis highlighted critical molecular functions such as mRNA binding and integrin binding, as well as cellular components such as contractile fibers and the extracellular matrix, which were significantly affected by LSS.

Conclusions: Our findings provide novel insights into the molecular mechanisms underlying LSS and offer potential avenues for the development of targeted therapies aimed at mitigating disease progression and improving patient outcomes.

In the original publication [...].

Background and Aims: Inflammatory bowel disease (IBD) requires effective treatment options. Upadacitinib, a Janus kinase 1 (JAK1) inhibitor, has shown effectiveness in trials for Crohn's disease (CD) and ulcerative colitis (UC). This study evaluates its real-world effectiveness and safety. Methods: We conducted a multicenter retrospective cohort study in tertiary care centers, involving patients treated with upadacitinib from January 2023 to September 2024. The study included adult patients aged 18 years or older, diagnosed with UC or CD, who received at least 8 weeks of upadacitinib therapy. Treatment outcomes were evaluated using established clinical, endoscopic, imaging, histological, and laboratory parameters. Results: A total of 236 IBD patients received upadacitinib treatment. In 80 UC patients at 8 weeks, 64.0% achieved steroid-free remission, 57.6% clinical remission, and 81.8% response. Endoscopic remission was 35.8% (p = 0.039), with 63.3% response and 35.8% mucosal healing. Histological remission reached 29.2% (p = 0.009). For 156 CD patients at 12 weeks, 76.8% achieved steroid-free remission (p < 0.001), 77.8% clinical remission (p < 0.001), and 81.0% response. Mean CDAI decreased from 214.9 to 117.5 (p < 0.001). Endoscopic remission was 19.4%, with 48.9% response and 4.9% mucosal healing. Radiological remission was 9.1% with 85.7% response. Intestinal ultrasound showed 5.7% remission and 56.7% response. Conclusions: Upadacitinib demonstrates significant real-world effectiveness and safety in IBD, particularly in biologic-resistant cases, as evidenced by high rates of steroid-free remission and clinical response. These outcomes are likely due to its targeted JAK1 inhibition, which effectively reduces inflammation and promotes mucosal healing. Future research should focus on long-term safety, comparative effectiveness with other biologics, and its application in diverse patient populations. These findings support the integration of upadacitinib into IBD management strategies.

Background: Cerebral venous sinus thrombosis (CVT) is a rare cause of stroke, constituting 0.5-3% of all strokes with an extremely varied spectrum of presentation, predisposing factors, neuroimaging findings, and eventual outcomes. A high index of suspicion is needed because timely diagnosis can significantly alter the natural course of the disease, reduce acute complications, and improve long-term outcomes. Due to its myriad causative factors, protean presentation, and association with several systemic diseases, CVT is encountered not only by neurologists but also by emergency care practitioners, internists, hematologists, obstetricians, and pediatricians.

Discussion: Anticoagulation remains the mainstay of treatment for CVT. Heparin and warfarin previously had been the anticoagulation of choice. Recently there has been an increased interest in utilizing direct-acting oral anticoagulants in the treatment of CVT given comparable safety and efficacy with ease of utilization. However recent clinical guidelines given by multiple societies including the American Stroke guidelines and European guidelines do not include these agents so far in their treatment recommendations. Ongoing multicentric clinical trials are currently reviewing the role of these agents in both short-term as well as long-term. Our review of the literature supports the safety and reinforces the efficacy of DOAC in the treatment of CVT. Additionally, patient satisfaction has been shown to be better with the use of DOAC. In conclusion, DOAC continues to have a valid role in the management of CVT.