Search Results (919)

Background and Clinical Significance: Wilson’s disease (WD) is an inherited, multisystem disorder of copper metabolism, resulting in pathological copper accumulation in various tissues (predominantly the liver and brain) and leading to secondary organ damage and corresponding clinical manifestations. Sleep disorders are frequent in neurodegenerative disorders, but remain underdiagnosed and poorly characterized in WD. Case presentation: We describe the case of a 51-year-old patient with WD presenting predominantly with neurological symptoms, who underwent routine video-polysomnography (v-PSG). The examination revealed shortened sleep latency, reduced rapid eye movement (REM) sleep latency, and sleep fragmentation—features of sleep architecture frequently observed in narcolepsy. These abnormalities worsened at follow-up despite the introduction of anti-copper treatment and concomitant neurological improvement. However, the patient did not report clinical symptoms of narcolepsy, and none were confirmed by the evaluating sleep specialist. Conclusions: This case highlights that sleep disorders (SDs) are common in patients with WD. Such patients may experience a wide range of SDs, and anti-copper treatment may improve sleep quality in addition to alleviating neurological symptoms. Narcolepsy is a rare but possible manifestation of SDs in WD. Therefore, whenever symptoms suggestive of sleep disturbances occur, WD patients should be referred to a sleep specialist, as accurate diagnosis and targeted treatment may profoundly improve quality of life, daily functioning, and long-term disease management. Full article

Introduction/Aim: As the prevalence of atrial fibrillation (AF) increases with the aging population, the challenge of enhancing the detection rate of AF in embolic stroke of undetermined source (ESUS) has intensified. AF is often detected only after a debilitating or fatal cardioembolic stroke, underscoring the crucial need for early identification to prevent further ischemic stroke (IS). This study aims to assess the efficacy of AF detection in patients with ESUS using a single-lead patch (mobiCARE™; Seers Tech, Inc.) over a period of at least 72 h and up to 5 days, in comparison with standard 24 h Holter monitoring. Design: This multicenter, prospective, consecutive observational trial involves patients aged 18 years and older who have experienced an IS within the past six months. Study outcomes: The primary outcome is the initial detection of AF using either a single-lead wearable patch or 24 h Holter monitoring at both baseline and at a 6-month follow-up among patients diagnosed with ESUS stroke. Secondary outcomes include the first detection of AF among stroke patients with large-artery atherosclerosis or small-vessel occlusion, particularly those whose transthoracic echocardiography reveals a left atrial size of ≥44 mm, an echocardiographic marker of AF. Discussion: Prolonged cardiac monitoring increases the detection rate of paroxysmal AF, but the optimal method should be non-invasive, patient-friendly, and accurate. This new technology may reduce patient burden and socioeconomic impact by facilitating AF detection and preventing cardioembolic stroke, even in patients with non-cardiogenic stroke. Full article

Introduction: Corticosteroid therapy has been demonstrated to improve prognosis and reduce mortality in patients with severe Coronavirus Disease 2019 (COVID-19) infection by attenuating the exaggerated inflammatory response that emerges in the late phase of infection. However, its impact on patients with pre-existing cardiovascular disease, who are at higher risk of complications, has not been specifically studied. The aim of this study is to evaluate the effect of corticosteroid therapy on mortality and long-term COVID-19 symptoms in this high-risk population. Methods: We analyzed the prospective registry HOPE-2. Patients with previous cardiovascular disease were selected, and 18-month all-cause death was defined as the primary endpoint. Long-term COVID-19 symptoms were considered as secondary endpoints. A total of 1188 patients with previous heart disease were included, of which 453 received corticosteroid treatment. Propensity score matching analysis in a 1:1 fashion was performed based on baseline variables that exhibited a p-value < 0.05 in the univariant analysis and outcome variables that defined corticosteroid use, with a final matched population of 796 patients. Results: In patients with pre-existing heart disease, corticosteroid treatment was not associated with differences in 18-month all-cause mortality (p = 0.52). However, a shorter duration of hospitalization (median: 8 days [IQR: 4–14] and 11 days [IQR: 7–18]; p < 0.001) was observed in patients who received corticosteroids. No significant differences in long-term COVID-19 symptoms were observed between the two groups. Conclusions: In patients with pre-existing heart disease, the absence of a clear harmful effect suggests that the positive effects of corticosteroids may be offset by their potential adverse effects which could contribute to the persistence of long COVID symptoms. This finding may reflect a differential response to corticosteroids in this high-risk subgroup, highlighting the need for further studies to clarify the role of this therapy in such patients. Full article

Introduction: A considerable body of evidence shows significant racial inequities in health and health care, affecting access, care and treatment for patients, as well as the wellbeing of employees. Many hospitals and health care organizations have committed to anti-racist change within their systems. Still, there is limited systematic knowledge regarding organizational anti-racist practices, the conditions under which they can be implemented successfully and their effectiveness. This research aims to identify anti-racist practices within health care organizations with a special focus on three areas: (1) increasing workforce diversity, (2) reducing racial health disparities and (3) responding to discriminatory behavior. Moreover, the role of different stakeholders in implementing anti-racist change will be analyzed, as well as the challenges organizations have encountered and strategies they have utilized to implement change. Methods: Primary (n = 11) and secondary qualitative data (n = 26) were used to gain insights from anti-racism diversity experts and health equity officers within organizations across the US in the beginning of 2024. A qualitative content analysis was used to identify anti-racist practices in organizations. Results: Findings reveal a broad range of anti-racist practices in use across these organizations. These practices include (1) collecting patient and staff data, (2) actively normalizing and implementing anti-racist work standards and guidelines, (3) developing organizational policies and tools to address racism, (4) creating accountability procedures for addressing racist behavior and (5) building safe and culturally appropriate spaces for racialized communities. By embedding a structural anti-racist lens across these organizations, stakeholders acknowledge their role in (past) harms and commit to addressing disparities in health care and creating a vision for health equity. Conclusion: The identification of anti-racist practices makes solutions visible to a broader audience and identifies the potential influence and responsibility each stakeholder in health care has to address racism. In order to apply these practices to other health care organizations, there is a need to rigorously evaluate the interventions and analyze their effectiveness. Full article

Background/Objectives: Impella 5.5 provides a higher flow rate than smaller microaxial pumps and has been increasingly adopted for cardiogenic shock (CS). This study aimed to evaluate whether its introduction into our Shock Team program in 2023 improved outcomes compared with a historical cohort supported with other mechanical circulatory support (MCS) devices. Methods: We retrospectively analyzed patients with CS treated with MCS between 2020 and 2024 at a tertiary center. The Impella 5.5 group (n = 17) included patients managed after device implementation, either as stand-alone or sequential therapy. The historical cohort comprised 40 patients treated with ECMO, Impella CP, CentriMag, or IABP prior to 2023. Propensity score matching (age, sex, etiology, lactate, SCAI stage) generated 17 matched pairs. The primary outcome was survival at discharge, 30 days, 3 months, and 6 months. Secondary outcomes included bridging to recovery, heart transplantation (HTx), durable LVAD, and major complications. Results: Impella 5.5 was associated with higher survival at discharge (94.1% vs. 58.8%, p = 0.039), 30 days (94.1% vs. 58.8%, p = 0.039), and 3 months (94.1% vs. 58.8%, p = 0.039). At 6 months, survival remained higher (88.2% vs. 58.8%) but did not reach statistical significance in point analysis (p = 0.118). Bridging occurred more frequently with Impella 5.5 (HTx 64.7% vs. 52.9% (p = 0.464), recovery 17.6% vs. 5.9% (p = 0.292)), while LVAD implantation rates were similar (11.8% vs. 17.6%, p = 1.0). Major bleeding (17.6% vs. 47.1%, p = 0.141), stroke/TIA (5.9% vs. 17.6%, p = 0.601), and the need for renal replacement therapy (5.9% vs. 23.5%, p = 0.335) were numerically lower with Impella 5.5. Conclusions: In this single-center, retrospective analysis, the introduction of Impella 5.5 was associated with higher short-term survival and favorable bridging metrics; estimates are imprecise due to small, heterogeneous samples. These hypothesis-generating findings warrant confirmation in larger, prospective multicenter cohorts Full article

The introduction of functional elements is essential for many industrial components which rely on elements such as bolts, screws, nuts, or clips that are integrated into the workpieces. In the field of cold joining technologies, double-sided self-pierce riveting (DS-SPR) presents itself as a proper alternative to produce the mechanical connection of those elements into sheet panels. For the purpose of this investigation, a tubular rivet with a machined thread to replicate a hollow bolt was joined to a sheet panel. Since this application will be subjected to torsion loads when a nut or other elements are fastened, tubular rivets with different numbers of semi-longitudinal rectangular openings at their ends (0, 2, 4, and 8) were investigated to identify the optimal design that ensures proper performance during its service life. The results show that rivets with four openings achieved a torsional resistance of more than 40 N·m, which is over double that of the original rivet without openings, while maintaining comparable shear strength (~10 kN). A functional hollow bolt with an outer thread was successfully produced, achieving a torque capacity of 35 N·m, equivalent to an M8 solid bolt, but with reduced weight. These findings highlight DS-SPR as a viable technology for manufacturing functional riveted elements that combine the permanent joints between sheets and removable connections with secondary components, offering both structural performance and lightweight advantages. Full article

Resistance to conventional anti-tumor drugs is one of the significant challenges in oncology, responsible for treatment failure and patient death. Introduction of the targeted drugs (e.g., small molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies) in cancer therapy significantly improved overall survival (OS) and progression-free survival (PFS) rates for selected groups of cancer patients and delayed the progression of advanced forms of human malignancies. However, the development of secondary resistance to the targeted drugs remains an unbeatable obstacle to a successful outcome in the long run, thereby making prognosis unfavorable for cancer patients with advanced, recurrent, and metastatic forms of disease. The review focuses on several mechanisms that regulate cancer resistance to conventional chemotherapies. This includes the upregulation of main types of ABC transporters (e.g., ABCB1, ABCC1, and ABCG2), which provides the efflux of chemotherapeutic agents from cancer cells. Additionally, the activation of diverse DNA damage repair (DDR) pathways, epithelial-to-mesenchymal transition (EMT), and the population of cancer stem cells (CSCs) are also discussed in detail, thereby illustrating the diverse molecular mechanisms of cancer sensitivity to chemotherapies. Recently, several TKIs, including those that were initially developed to specifically target FGFR and VEGFR pathways, have also been reported to exhibit “off-target” effects by interacting with ABC transporters and inhibiting their function. This, in turn, illustrates their potency in retaining chemotherapeutic agents within cancer cells and possessing a chemosensitizing function. Of note, FGFR and VEGFR inhibitors may behave as inhibitors or substrates of ABC transporters, depending on the expression of specific pumps and affinity for them, concentrations, and types of co-administered agents, thereby disclosing the complexity of this scenario. Additionally, the aforementioned RTKI can interfere with the other molecular mechanisms regulating tumor sensitivity to conventional chemotherapies, including the regulation of diverse DDR pathways, EMT, and the population of CSCs. Thereby, the aforementioned “off-target” functions of FGFR and VEGFR inhibitors can open novel approaches towards anti-cancer therapies and strategies aimed at counteracting cancer multidrug resistance (MDR), which is important especially as second- or third-line treatments in patients who have progressed on modern chemotherapeutic regimens. Notably, the strategy of using TKIs to potentiate the clinical efficacy of chemotherapies can extend beyond inhibitors of FGFR and VEGFR signaling pathways, thereby providing a rationale for repurposing existing TKIs as an attractive therapeutic approach to overcome cancer chemoresistance. Full article

Background and Objectives: This systematic review and meta-analysis aims to evaluate whether the benefits of sodium–glucose co-transporter-2 (SGLT2) inhibitors on cardiovascular outcomes extend when initiated in patients with acute coronary syndrome (ACS), regardless of diabetic status. Materials and Methods: PubMed, Embase, and the Cochrane Library were searched from 2015 up to July 2025, according to PRISMA 2020 guidelines. Eligible studies were randomized controlled trials (RCTs) and observational studies comparing SGLT2 inhibitors with controls in post-ACS patients. Articles without full-text data for extraction, with unavailable outcome data or evaluating patients with stable coronary artery disease (CAD) were excluded. Primary outcomes were all-cause and cardiovascular (CV) mortality. Secondary outcomes included recurrent myocardial infarction (MI), rehospitalization for ACS, revascularization and stroke. Meta-analysis was conducted using the R statistical software (Version 4.5.1). Subgroup analysis was performed by study design to evaluate outcomes in type 2 diabetes mellitus (T2DM) populations. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2.0 and Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results: A total of 16 studies were included in the meta-analysis, encompassing over 130,000 patients. Initiation of SGLT2 inhibitors after ACS was associated with a significant reduction in the primary outcome of all-cause mortality [hazard ratio (HR) = 0.77; (95% confidence interval (CI): 0.67–0.89)] and CV mortality [HR = 0.83; (95% CI: 0.70–0.99)]. In subgroup analyses, patients with T2DM experienced a significant reduction in all-cause mortality [HR = 0.73, (95% CI: 0.62–0.86)] and recurrent MI [HR = 0.83, (95% CI: 0.69–0.99)]. Conclusions: Initiation of SGLT2 inhibitors after ACS is associated with a significant reduction in all-cause and CV mortality. Subgroup analysis further demonstrated a reduction in all-cause mortality and recurrent myocardial infarction among patients with T2DM, while in patients without diabetes, no significant effects were observed. Although evidence certainty ranged from low to moderate and large RCTs are still ongoing, these findings support the early introduction of SGLT2 inhibitors in eligible patients with T2DM following ACS, pending confirmation by large, prospective clinical trials. Full article

Introduction: Three-dimensional (3D) printing technology has rapidly evolved across various fields of medicine and dentistry, particularly in orthodontics. One key application in orthodontics is the fabrication of dental models. Numerous parameters throughout the dental cast fabrication workflow can influence the accuracy of 3D-printed models. This review aims to evaluate the influence of post-processing procedures, specifically post-curing and post-rinsing, on the dimensional accuracy of 3D-printed dental casts. Materials and Methods: An initial data search was conducted using specific keywords across four databases (PubMed, Scopus, Web of Science, and Google Scholar). A secondary search of references and citations was also performed. This systematic review ultimately identified five studies that met the inclusion criteria (in vitro studies and studies referred to post-processing only of 3D-printed models) for further evaluation and analysis, whereas reviews, opinion studies, and papers in languages other than English were excluded. Based on the QUIN tool, all studies were assessed for their risk of bias. Because of the studies’ heterogeneity, a qualitative descriptive synthesis was conducted. Results: All five included studies were in vitro investigations. One study examined the influence of the post-curing process on dimensional accuracy, while the remaining four explored the impact of post-rinsing procedures on both dimensional accuracy and other surface characteristics of 3D-printed dental casts. Conclusions: According to the findings of the included studies, both post-curing and post-rinsing procedures had statistically significant effects on the dimensional accuracy of 3D-printed dental models. Nevertheless, all five studies concluded that the observed deviations remained within clinically acceptable limits, rendering the casts suitable for diagnostic orthodontic purposes or device fabrication. However, further research is needed to reinforce current findings and to enhance our understanding of the optimal post-processing protocols of additively manufactured dental casts. Full article

Introduction: Ankylosing spondylitis (AS) is a chronic inflammatory disorder that causes progressive ossification and fusion of the spine, particularly in the cervical region. This results in a rigid spinal column that is highly susceptible to unstable fractures, even after low-energy trauma. Cervical fractures in AS are often complex, extending through multiple spinal segments, and are associated with a high risk of neurological compromise. Esophageal injury associated with such fractures is rare but clinically significant, as the anatomical vicinity of the esophagus makes it vulnerable to direct trauma, delayed perforation, or secondary damage from fracture displacement and hardware failure. Aim: The purpose of this review is to present and highlight the clinical relevance of esophageal injury in cervical spine trauma among patients with AS, emphasizing the diagnostic challenges and surgical treatment in order to improve outcomes. Results: Esophageal injuries in the context of AS-related cervical trauma are frequently overlooked due to subtle clinical manifestations such as dysphagia, subcutaneous emphysema, or covert signs of mediastinitis. Plain radiographs are insufficient to identify such complications; advanced imaging modalities are often required for detection. Management is complex and usually demands a multidisciplinary approach, involving both stabilization of the cervical spine and repair of the esophagus. Despite treatment efforts, these patients remain at increased risk for morbidity and mortality, mainly due to infection and sepsis. Conclusions: Esophageal injury in cervical spine trauma associated with AS is an uncommon but life-threatening condition. Early recognition, comprehensive radiologic evaluation, and careful surgical planning are crucial for optimal management. Heightened clinical suspicion and awareness of this rare complication are essential to improve diagnostic accuracy and patient outcomes. Full article

Outdoor learning offers dynamic, real-world educational opportunities that extend beyond traditional classrooms and foster sustainability awareness. This quantitative study endeavors to assess teachers’ competency in facilitating outdoor learning, aiming for a more engaging and impactful introduction. Employing a relational survey design in the form of a multi-survey model, the research engaged 586 teachers representing diverse academic disciplines across public and private elementary and secondary schools. Central to the investigation was the utilization of the “Outdoor Learning Regulation Scale [OLRS]” as the primary data collection instrument. The evaluation of teachers’ aptitude in regulating outdoor learning encompassed various variables, including gender, subject specialization, prior online or in-person training in outdoor learning, use of non-school environments for teaching, childhood environment, and teaching location. To analyze the collected data, a nuanced approach to statistical analysis was undertaken, aiming to provide a clearer and more specific explanation of the data analysis methods employed. The findings of the study unveiled no significant disparities in teachers’ outdoor learning regulation capabilities based on gender, subject specialization, childhood environment, or teaching location. However, discernible differences surfaced in their proficiency in outdoor learning regulation concerning previous online or in-person training in outdoor learning and their utilization of outdoor environments for teaching, thus providing deeper insights into the factors shaping teachers’ efficacy in facilitating outdoor learning experiences. Additionally, the study emphasizes the link between outdoor learning and sustainability education. By equipping teachers with the skills to regulate outdoor learning, this research supports the integration of sustainability into educational practices, promoting students’ ecological awareness and sustainable thinking. These results highlight the importance of professional development and targeted training in outdoor education, with direct implications for strengthening sustainability-oriented teaching practices. Full article

Introduction: Prolonged prone positioning, exceeding 16 h, has been associated with reduced mortality among patients with moderate to severe acute respiratory distress syndrome (ARDS). Extending the duration of prone positioning may provide greater therapeutic benefits. This study aims to assess the clinical outcomes between 16 h and 24 h prone positioning therapy in patients with moderate to severe ARDS. Methods: This prospective randomized clinical trial was conducted in the intensive care unit of a university-affiliated tertiary medical center. Patients were randomly assigned to receive either 16 h or 24 h prone positioning therapy. All participants were managed according to a standardized protocol incorporating low tidal volume and protective lung strategies. Results: Out of 45 patients diagnosed with moderate to severe ARDS requiring mechanical ventilation, 21 were allocated to the 16 h prone positioning group and 24 were assigned to the 24 h group. There were no significant differences in PaO₂/FiO₂ ratios, driving pressure, or serum lactate levels between the two groups. The first session of prone positioning resulted in significantly greater PaO₂/FiO₂ improvement compared to the second session. The 24 h group showed a trend toward requiring fewer prone positioning sessions than the 16 h group. Secondary outcomes did not differ significantly between groups. Conclusions: Both 16 h and 24 h prone positioning therapies improved oxygenation in patients with moderate to severe ARDS. The 24 h prone group showed a trend toward fewer sessions, potentially reducing clinical workload. The first prone session provided greater oxygenation improvement compared to the second session. Full article

Introduction: Pre-pectoral breast reconstruction using implant and acellular dermal matrix (ADM) has become one of the main techniques for immediate reconstruction after mastectomy, with variable approaches and complication rates reported in literature. This study aims to evaluate the early outcomes of this technique, at a single tertiary oncology center. Methods: We performed a retrospective analysis of a prospectively maintained database including women who underwent immediate pre-pectoral reconstruction with implant and ADM following mastectomy between January 2021 and August 2023. The primary outcome was reconstructive failure within 3 months, defined as the need for removal of the implant placed during the index surgery. Secondary outcomes included complications at 3 months and predictive factors for complications. Results: A total of 247 reconstructions were performed in 200 patients, 83.4% following oncological mastectomy and 16.6% after risk-reducing surgery. The median age was 49 (43–56) years; 15.5% of patients were obese and 26.5% were active smokers. Skin-sparing mastectomy was performed in 16.6% and nipple-sparing in 83.4%, with a Wise-pattern incision in 73.3%. Reconstructive failure occurred in 7.7%, with one case (0.4%) of total reconstruction loss. The overall complication rate was 14.6%—skin flap ischemia occurred in 12.6%, primary implant infection in 2.0% and bleeding in 0.8%. The reoperation rate was 8.4%. No predictive factors for complications were identified. Conclusions: In this series, including a high proportion of high-risk patients, immediate pre-pectoral reconstruction with implant and ADM appears safe, with a low rate of early complications. No predictive factors for complications were found, supporting widening its indications. Full article

Introduction: The risk of new or recurrent cancer in inflammatory bowel disease (IBD) patients with a history of cancer treated with immunomodulators (IMMs), including conventional immunosuppressors (ISSs), biologics or small molecules is undefined. The primary aim was to assess the frequency of new or recurrent cancer in IBD patients treated with IMMs after first cancer. The secondary aim was to evaluate risk factors for new/recurrent cancer in the same IBD population. Methods: In a retrospective multicenter study, all IBD patients using any IMM after first (index) cancer were enrolled. Inclusion criteria: Crohn’s disease (CD) or ulcerative colitis (UC), history of any cancer, detailed clinical history, and follow-up after cancer of ≥6 months. Exclusion criteria: IMM use for ≤3 months. Results: In total, 122 IBD patients (84 CD, 38 UC) treated with IMMs after first cancer were enrolled (age 59.5 [26–89] years). Index cancer included (n = [%]) genitourinary tract cancer (18 [14.8]), non-melanotic skin cancer (NMSC) (17 [13.9]), breast cancer (15 [12.3]), thyroid cancer (13 [10.7]), melanoma (14 [11.4]), colorectal cancer (CRC) (11 [9.0]), hematopoietic cancer (9 [7.4]), prostatic cancer (8 [6.6]), neuroendocrine cancer (4 [3.3]), head and neck cancer (3 [2.5]), liver cancer (3 [2.5]), endometrium cancer (2 [1.6]), lung cancer (1 [0.8]) and others (3 [2.5]). ISSs after cancer included (n = [%]) thiopurines (10 [37]), methotrexate (MTX) (14 [51.9]) and others (3 [11.1]) Biologics included (n = [%]) TNF-inhibitors (36 [32.4]), vedolizumab (60 [53.6]), ustekinumab (45 [40.2]), small molecules (9 [7.3]) and others (6 [5.4]). In a median follow-up of 8 [1–45] years after index cancer, 12/122 (9.8%) patients using IMMs after cancer developed new or recurrent cancer. No risk factors for new/recurrent cancer (i.e., age at diagnosis of cancer, smoke, gender, IBD type, IMM use, duration before or after cancer) were identified. Conclusions: In a multicenter study, ISSs or biologics after cancer were not identified as risk factors for new or recurrent cancer in IBD. However, IMMs were used after a long-term interval from index cancer. Full article

The dead-time effect seriously affects the soft-switching performance and operating efficiency of the dual-active-bridge converter, and also causes problems such as reduced duty cycle, distortion of voltage and current waveforms, and narrowed transmission power range. The proposal of the five-degree-of-freedom modulation strategy transforms the working voltage waveforms of the primary and secondary sides as well as the inductor current waveform of the DAB converter from symmetric to asymmetric, while the dead-time issue still persists. Based on the five-degree-of-freedom modulation strategy, this paper analyzes the electrical characteristics of the converter before and after the introduction of dead time, designs switch drive pulses to avoid the dead time, and proposes a dead-time compensation modulation strategy based on five-degree-of-freedom phase shift. The results show that the proposed dead-time compensation control strategy can avoid problems such as voltage and current waveform distortion and reduction in the soft-switching power range caused by dead time, realizing dead-time compensation in the full power range. Experimental measurements show that, for different voltage transmission ratios, the maximum efficiency improvement is approximately 3.8–4% and the current stress is reduced by 2.11% to 3.13% under low-power operating conditions. The maximum efficiency improvement is approximately about 1.4–2.8% and the current stress is reduced by 1.84% to 2.53% under high-power operating conditions. Full article