Treatment Interventions Research Articles

Machine learning identifies the role of SMAD6 in the prognosis and drug susceptibility in bladder cancer.

Bladder cancer (BCa) is among the most prevalent malignant tumors affecting the urinary system. Due to its highly recurrent nature, standard treatments such as surgery often fail to significantly improve patient prognosis. Our research aims to predict prognosis and identify precise therapeutic targets for novel treatment interventions. We collected and screened genes related to the TGF-β signaling pathway and performed unsupervised clustering analysis on TCGA-BLCA samples based on these genes. Our analysis revealed two novel subtypes of bladder cancer with completely different biological characteristics, including immune microenvironment, drug sensitivity, and more. Using machine learning classifiers, we identified SMAD6 as a hub gene contributing to these differences and further investigated the role of SMAD6 in bladder cancer in the single-cell transcriptome data. Additionally, we analyzed the relationship between SMAD6 and immune checkpoint genes. Finally, we performed a series of in vitro assays to verify the function of SMAD6 in bladder cancer cell lines. We have revealed two novel subtypes of bladder cancer, among which C1 exhibits a worse prognosis, lower drug sensitivity, a more complex tumor microenvironment, and a 'colder' immune microenvironment compared to C2. We identified SMAD6 as a key gene responsible for the differences and further explored its impact on the molecular characteristics of bladder cancer. Through in vitro experiments, we found that SMAD6 promoted the prognosis of BCa patients by inhibiting the proliferation and migration of BCa cells. Our study reveals two novel subtypes of BCa and identifies SMAD6 as a highly promising therapeutic target.

Endovascular treatments of acute pulmonary embolism in the post-fibrinolytic era: an up-to-date review.

Pulmonary embolism (PE) is a significant contributor to global cardiovascular-related mortality that mainly depends on the severity of the event. The treatment approach for intermediate and high-risk PE remains a topic of debate due to the fine balance between hemodynamic deterioration and bleeding risk. The initial treatment choice for intermediate-risk PE with hemodynamic deterioration and high-risk PE is historically systemic thrombolysis, but this approach is not always effective and carries a notable risk of severe bleeding. For such patients, various interventional treatments have been introduced to clinical practice, including catheter-directed lysis (CDL), ultrasound-assisted CDL, pharmacomechanical CDL, and aspiration thrombectomy. However, the optimal treatment approach remains uncertain. Encouraging outcomes have been presented assessing the novel endovascular treatments, in terms of reducing right ventricular dysfunction and improving hemodynamic stability, opening the possibility of using these devices to prevent hemodynamic instability in less severe cases. However, ongoing randomized trials that assess the efficacy and the association with mortality, especially for aspiration devices, have not yet published their final results. This article aims to offer a comprehensive update of the available catheter-directed therapies for PE, with a focus on novel mechanical thrombectomy techniques, assessing their safety and efficacy, after comparison to the conventional treatment. CRITICAL RELEVANCE STATEMENT: This is a comprehensive review of the indications of use, techniques, and clinical outcomes of the most novel endovascular devices for the treatment of pulmonary embolism. KEY POINTS: Mechanical thrombectomy is an effective tool for patients with PE. Aspiration devices prevent hemodynamic deterioration. Catheter directed therapy reduces bleeding complications.

Effect of Akkermansia muciniphila on pancreatic islet β-cell function in rats with prediabetes mellitus induced by a high-fat diet.

Prediabetes is an important stage in the development of diabetes. It is necessary to find a safe, effective and sustainable way to delay and reverse the progression of prediabetes. Akkermansia muciniphila (A. muciniphila) is one of the key bacteria associated with glucose metabolism. Recent studies mainly focus on the effect of A. muciniphila on obesity and insulin resistance, but there is no research on the effect of A. muciniphila on pancreatic β-cell function and its mechanism in prediabetes. In this study, we investigated the effects of A. muciniphila on β-cell function, apoptosis and differentiation, as well as its effects on the gut microbiome, intestinal barrier, metaflammation and the expression of Toll-like receptors (TLRs) in a high-fat diet (HFD)-induced prediabetic rat model. The effect of A. muciniphila was compared with dietary intervention. The results showed both A. muciniphila treatment and dietary intervention can reduce metaflammation by repairing the intestinal barrier in rats with prediabetes induced by an HFD and improve β-cell secretory function, apoptosis and differentiation through signaling pathways mediated by TLR2 and TLR4. Additionally, A. muciniphila can further elevate β-cell secretion, attenuate apoptosis and improve differentiation and the TLR signaling pathway on the basis of diet.

The Holocaust Experience and Its Role in the Association Between Meaning in Life, Depressive Symptoms and Life Satisfaction.

Holocaust survivors often reveal long-term depressive symptoms, while demonstrating life satisfaction. The present study examined the role of meaning in life (MIL) of Holocaust survivors in this context. Survivors (n = 44) and comparisons (n = 51) provided background information and completed MIL, depressive symptoms, and life satisfaction scales. MIL was associated with lower depressive symptoms and higher life satisfaction. Moreover, the MIL-depressive symptoms/life satisfaction links were stronger among Holocaust survivors. Results provide insight for tailoring treatment interventions for older adults who have been exposed to prolonged traumatic experiences or genocide, that focus on MIL, to enhance mental health.

Contingency management as a maintenance intervention in the long-term treatment of substance use disorders.

Contingency management as a maintenance intervention in the long-term treatment of substance use disorders.

Bipolar disorder staging and the impact it has on its management: an update.

The longitudinal course of bipolar disorder (BD) is associated with an active process of neuroprogression, characterized by structural brain alterations and progressive functional impairment. In the last decades, a growing need of a standardized staging model for BD arose, with the aim of a more appropriate definition of stage-specific clinical manifestations and the identification of more customized therapeutic tools. The authors review the literature on clinical aspects, neurobiological correlates and treatment issues related to BD progression. Thereafter, they address the definition, constructs, and evolution of the staging concept, focusing on the clinical applications of BD staging models available in literature. Although several staging models for BD have been proposed to date, their application in clinical practice is still relatively scant. This may have a detrimental impact on the clinical and therapeutic management of BD, in terms of early and proper diagnosis as well as tailored treatment interventions according to the different stages of illness. Future research efforts should tend to the integration of recent insights on neuroimaging and epigenetic markers, toward a standardized and multidimensional staging model.

CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis

BackgroundChaperonin Containing TCP1 Subunit 6 A (CCT6A) is a prominent protein involved in the folding and stabilization of newly synthesized proteins. However, its roles and underlying mechanisms in lung adenocarcinoma (LUAD), one of the most aggressive cancers, remain elusive.MethodsOur study utilized in vitro cell phenotype experiments to assess CCT6A’s impact on the proliferation and invasion capabilities of LUAD cell lines. To delve into CCT6A’s intrinsic mechanisms affecting glycolysis and proliferation in lung adenocarcinoma, we employed transcriptomic sequencing and liquid chromatography-mass spectrometry analysis. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (CHIP) assays were also conducted to substantiate the mechanism.ResultsCCT6A was found to be significantly overexpressed in LUAD and associated with a poorer prognosis. The silencing of CCT6A inhibited the proliferation and migration of LUAD cells and elevated apoptosis rates. Mechanistically, CCT6A interacted with STAT1 protein, forming a complex that enhances the stability of STAT1 by protecting it from ubiquitin-mediated degradation. This, in turn, facilitated the transcription of hexokinase 2 (HK2), a critical enzyme in aerobic glycolysis, thereby stimulating LUAD’s aerobic glycolysis and progression.ConclusionOur findings reveal that the CCT6A/STAT1/HK2 axis orchestrated a reprogramming of glucose metabolism and thus promoted LUAD progression. These insights position CCT6A as a promising candidate for therapeutic intervention in LUAD treatment.

Risk factors for preeclampsia in patients with chronic kidney disease primarily focused on stage 1 CKD. Are referred and registered patients alike?

Limited research exists on identifying risk factors for preeclampsia (PE) in the chronic kidney disease (CKD) population, especially across different patient sources. This study aimed to address this gap by analyzing clinical data from CKD pregnant women admitted to Peking University Third Hospital from January 2012 to December 2022. Logistic regression analysis identified independent risk factors for PE in the CKD population and assessed variations among patients from different sources. Additionally, a predictive model for PE was established using data from the registered group. The study included 524 CKD patients. Hypertension, proteinuria, fibrinogen >4 g/L, serum albumin ≤30 g/L, and uric acid >260 μmol/L were independent risk factors for PE in the overall CKD population. Subgroup analysis revealed that hypertension, serum albumin ≤30 g/L, and uric acid >260 μmol/L were independent risk factors in the referred group, while hypertension, uric acid >260 μmol/L, and fibrinogen >4 g/L were independent risk factors in the registered group. The prediction model based on registered group risk factors showed good predictive efficiency, with the area under the curve of 0.774 in the training set and 0.714 in the validation set. In conclusion, this study revealed that hypertension and elevated uric acid are independent risk factors for PE in CKD patients regardless of patient source, while serum albumin and fibrinogen levels are associated with PE risk in specific patient subgroups. Our predictive model enables clinicians to quickly identify the risk of PE in CKD patients, and early intervention treatment to improve pregnancy outcomes.

Treatment Case Studies in the Consolidation and Adhesion of Cellulose Nitrate

ABSTRACT Cellulose nitrate artifacts from the collections of the Queen’s University Master of Art Conservation Program and Glanmore National Historic Site were examined and treated by graduate students in the Master of Art Conservation Program at Queen’s. Each object was in a varied state of degradation with unique condition problems. Under the supervision of the artifacts conservation professor, graduate students identified the materials constituting their objects and tested various treatment methods for consolidation and structural repair. Paraloid® B-67 in n-butanol and Aquazol® resins in isopropanol and distilled water were found to be effective in different roles, depending on the object and its state of degradation. This paper will discuss the factors that influenced decision-making for each object, with the aim of expanding interventive treatment strategies for cellulose nitrate objects.

Early Non-Surgical Treatment For Microtia Types 1 and 2.

Esthetic concerns and psychosocial distress often accompany auricular deformities and malformations in both children and their parents. Approximately 30% of newborns are affected by auricular anomalies, with 15% to 20% resulting in permanent defects. While surgical intervention is typically considered the gold standard for malformations, a non-surgical approach, such as splinting, molding, or other non-invasive techniques, can effectively address deformations if promptly administered by a specialist. Microtia, classified into 4 types, presents challenges ranging from fundamental structural anomalies in types 1 and 2 to severe defects in type 3 and complete absence of the external ear in type 4 (anotia). This study introduces a novel non-invasive treatment modality for microtia types 1 and 2. The cohort consisted of 5 newborns treated for microtia types 1 or 2 between 2022 and 2023. Utilizing the EarWell system, treatment was initiated before 3 weeks of age (mean age: 2 weeks), with an average treatment duration of 6.6 weeks, supplemented by molding treatment as needed. Minor adverse effects, such as simple dermatitis, were observed in 2 patients. All parents expressed high satisfaction with the esthetic outcomes, with 60% reporting extreme satisfaction. The prompt initiation of the treatment protocol for microtia types 1 and 2 led to outstanding and timely outcomes in infants, enhancing the quality of life for both parents and their children. Early intervention for subsequent treatment may improve the condition and, in certain cases, serve as a satisfactory alternative for parents hesitant about further surgical intervention for their children.

Analysis of interventional treatment options of the common femoral artery - a retrospective single center experience.

Background: Due to the rapid development of treatment techniques of peripheral arterial disease (PAD) treatment is nowadays predominantly interventional. An exception are lesions of the common femoral artery (CFA), which should be treated surgically according to vascular guidelines. However, recent evidence has shown that endovascular techniques, e.g. stenting, have comparable clinical outcomes while causing fewer complications. The aim of the present analysis was to evaluate the therapeutic success of endovascular therapy of CFA lesions in a single center, all - comers registry. Patients and methods: All patients who were treated for a CFA lesion at the Department of Internal Medicine I of the University Hospital Jena in the period from 01/2017 to 12/2020 were included. Treatment success was determined by evaluating the ankle-brachial-index (ABI) pre- and post-interventional as well as after follow-up (FU), measuring walking distance (WD) and by target revascularization rate (TLR) and primary patency rate (PPR). Results: The analysis included 109 patients with a mean age of 73.4 years, with 67% (73) of those being men. 72 patients received interventional treatment, whereas 33 were treated surgically and 4 conservatively. Resting ABI in the overall cohort showed an increase from 0.5 to 0.7 post intervention (p=<0.05; mean FU-time: 6.5 months). In the interventional cohort ABI increases from 0.6 to 0.8 (p=<0.05; mean FU-time: 5,8 months) at FU and from 0.3 to 0.6 (p=<0.05; mean FU-time: 8,8 month) in the surgically treated group. The WD improved in the whole collective from 116.5 meter (m) to 152.5 m (p=<0.05). The TLR showed no significant difference with 8.1% after interventional treatment and 6.1% after vascular surgery in the present analysis (p=0.72) as well as PPR with 89.8% after EVT and 90.9% after surgical approach (p=0.87). The intra-/postinterventional complication rate was 5.5% in the intervention group, compared to postoperative complication rate of 15.2% in the surgically treated group. Conclusions: The present analysis demonstrates that even in a real-world, all-comers collective, interventional therapy for CFA lesions was safe and equally effective as the surgically treated patient cohort. Continuing to generate registry data is important to eventually initiate a paradigm shift.

Analysis of lumbar spine loading during walking in patients with chronic low back pain and healthy controls: An OpenSim-Based study

Low back pain (LBP) is one of the most prevalent and disabling disease worldwide. However, the specific biomechanical changes due to LBP are still controversial. The purpose of this study was to estimate the lumbar and lower limb kinematics, lumbar moments and loads, muscle forces and activation during walking in healthy adults and LBP. A total of 18 healthy controls and 19 patients with chronic LBP were tested for walking at a comfortable speed. The kinematic and dynamic data of the subjects were collected by 3D motion capture system and force plates respectively, and then the motion simulation was performed by OpenSim. The OpenSim musculoskeletal model was used to calculate lumbar, hip, knee and ankle joint angle variations, lumbar moments and loads, muscle forces and activation of eight major lumbar muscles. In our results, significant lower lumbar axial rotation angle, lumbar flexion/extension and axial rotation moments, as well as the muscle forces of the four muscles and muscle activation of two muscles were found in patients with LBP than those of the healthy controls (p &amp;lt; 0.05). This study may help providing theoretical support for the evaluation and rehabilitation treatment intervention of patients with LBP.

Pulmonary Embolism in Pregnancy: A Review for Clinical Practitioners

Diagnostic and therapeutic decision-making in pregnancy with suspected pulmonary embolism (PE) is challenging. European and other international professional societies have proposed various recommendations that are ambiguous, probably due to the unavailability of randomized controlled trials. In the following sections, we discuss the supporting diagnostic steps and treatments. We suggest a standardized diagnostic work-up in pregnant patients presenting with symptoms of PE to make evidence-based diagnostic and therapeutic decisions. We strongly recommend that clinical decisions on treatment in pregnant patients with intermediate- or high-risk pulmonary embolism should include a multidisciplinary team approach involving emergency physicians, pulmonologists, angiologist, cardiologists, thoracic and/or cardiovascular surgeons, radiologists, and obstetricians to choose a tailored management option including an interventional treatment. It is important to be aware of the differences among guidelines and to assess each case individually, considering the specific views of the different specialties. This review summarizes key concepts of the diagnostics and acute management of pregnant women with suspected PE that are supportive for the clinician on duty.

Modified sports interventions for children and adolescents with disabilities: A scoping review.

To establish the scope of the literature on modified sports interventions for children and adolescents with disabilities. For this scoping review, articles were screened and the characteristics of studies were extracted. The modified sports interventions were described in terms of their structure, using the items of the Template for Intervention Description and Replication. Components of intervention treatment were described by using the language of the Rehabilitation Treatment Specification System. Results were analysed and validated by a group of professionals, using the Public and Patient Involvement strategy. Twelve studies were eligible for inclusion, investigating interventions for children with autism spectrum disorder, cerebral palsy, and other conditions. Most studies presented a moderate level of evidence. Active ingredients were repeated sports-related motor training and introduction to the sport through a 'learning by action' mechanism. The intervention target was gross motor skills performance, and intervention aims (indirect outcomes) were physical activity participation and different body functions. The inclusion of stakeholders in this review helped to validate our findings about the characteristics and structure of modified sports interventions, to identify research gaps, and to provide a step process for clinical implementation. Future investigations are warranted of the effectiveness of modified sports investigations with better quality studies, including participation outcomes and studies with non-ambulant children.

Transarterial Embolisation of Abdominal Aortic Type II Endoleaks Accessed via the Deep Circumflex Iliac Artery: A Case Series and Literature Review.

We report our technique and experience treating 3 patients with native abdominal aortic aneurysm (AAA) sac expansion following EVAR, who were managed with transarterial embolisation via the deep circumflex iliac artery (DCIA). In this case series, we demonstrate that transarterial embolisation via the DCIA is a feasible and safe treatment option. The DCIA should be routinely interrogated with angiography as not only a cause of possible Type II endoleak, but also to identify a potential access route to the abdominal aortic sac for interventional treatment.

Long-term clinical outcomes in patients with CIS treated with interferon beta-1b: results from the 15-year follow up of the BENEFIT trial.

Multiple sclerosis (MS) treatment intervention with immunomodulating therapy at early disease stage improves short term clinical outcomes. The objective of this study is to describe the long-term outcomes and healthcare utilization of patients with clinically isolated syndrome (CIS) included in the Betaferon®/Betaseron® in Newly Emerging MS for Initial Treatment (BENEFIT) randomized, parallel group trial. In BENEFIT patients were assigned to "early" IFNB-1b treatment or placebo ("delayed" treatment). After 2years or conversion to clinically definite multiple sclerosis (CDMS), all patients were offered IFNB-1b and were reassessed 15years later. Of 468 patients, 261 (55.8%) were enrolled into BENEFIT 15 (161 [55.1%] from the early, 100 [56.8%] from the delayed treatment arm). In the full BENEFIT analysis set, risk of conversion to CDMS remained lower in the early treatment group ( - 30.5%; hazard ratio 0.695 [95% CI, 0.547-0.883]; p = 0.0029) with a 15.7% lower risk of relapse than in the delayed treatment group (p = 0.1008). Overall, 25 patients (9.6%; 9.9% early, 9.0% delayed) converted to secondary progressive multiple sclerosis. Disability remained low and stable with no significant difference between groups in Expanded Disability Status Scale score or MRI metrics. Paced Auditory Serial Addition Task-3 scores were better in the early treatment group (p = 0.0036 for treatment effect over 15years). 66.3% of patients were still employed at Year 15 versus 74.7% at baseline. In conclusion, results 15years from initial randomization support long-term benefits of early treatment with IFNB-1b.

Does IPSS-R down-staging before transplantation improve the prognosis of patients with Myelodysplastic Neoplasms?

In MDS patients higher IPSS-R at transplant is associated with worse transplant outcome. Thus, it may seem beneficial to improve IPSS-R by therapeutic intervention prior to transplantation in order to “down-stage” the disease risk. However, there is no evidence to date to support this approach. A retrospective analysis of the EBMT transplant registry was performed to investigate the role of therapeutic interventions prior to transplantation with regard to changes in IPSS-R and transplant outcomes. A total of 1482 MDS patients with sufficient data to calculate IPSS-R at diagnosis and at time of transplantation were selected and analysed for transplant outcome in a multivariable Cox model including IPSS-R at diagnosis, treatment intervention, change in IPSS-R before transplant and several patient and transplant variables.Transplant outcome was unaffected by IPSS-R change in untreated patients and moderately superior in chemotherapy-treated patients with improved IPSS-R at transplant. Improved IPSS-R after hypomethylating agents (HMA) or other therapies showed no beneficial effect. However, when IPSS-R progressed after chemotherapy, (HMA) or other therapies, transplant outcome was worse than without any prior treatment. Similar results were found when reduction or increase in bone marrow (BM) blasts between diagnosis and transplantation was considered. The results show a limited benefit of IPSS-R down staging or reduction of BM blasts after chemotherapy and no benefit for HMA or other treatments and thus question the role of prior therapy in MDS patients scheduled for transplantation. The model-based survival estimates should help inform decision making for both doctors and patients.

A Sole Case of the FGF23 Gene Mutation c.202A&gt;G (p.Thr68Ala) Associated with Multiple Severe Vascular Aneurysms and a Hyperphosphatemic Variant of Tumoral Calcinosis—A Case Report

Tumoral calcinosis is an extremely rare genetic disease caused by mutations in three genes, GALNT3, FGF23, and KL, which disrupt phosphorus metabolism. The hallmark of this condition is the formation of tumors in the soft tissues around the joints. Other phenotypic features of tumoral calcinosis are dental involvement and brain and vascular calcifications. The clinical case reported herein presents for the first time to the scientific community the c.202A&gt;G (p.Thr68Ala) mutation of the FGF23 gene, associated with a hyperphosphatemic variant of tumoral calcinosis and multiple severe vascular aneurysms. A female patient underwent multiple surgeries for tumor formations in her soft tissues that first appeared at the age of 12 months. On this occurrence, the patient was found to have hyperphosphatemia, low phosphate clearance, increased tubular reabsorption with normal levels of total and ionized calcium, vitamin D3, and parathyroid hormone, and no effect of treatment with sevelamer hydrochloride and a low-phosphate diet. At the age of 39, the patient underwent imaging studies due to edema and a pulsating formation in the neck area, which revealed multiple vascular aneurysms with thrombosis, for which she received operative and interventional treatment. In this connection, and because of the established phosphorus metabolism disturbance, a genetic disease was suspected. The sequence analysis and deletion/duplication testing of the 358 genes performed on this occasion revealed that the woman was homozygous for a variant of the c.202A&gt;G (p.Thr68Ala) mutation of the FGF23 gene. The established mutation is not present in population databases. The presented clinical case is the first and only one in the world to demonstrate the role of this type of FGF23 gene mutation in the development of a hyperphosphatemic variant of tumoral calcinosis characterized by aggressive formation of multiple vascular aneurysms.

Personalized Approaches to Cardiovascular Disease: Insights into FDA-Approved Interventions and Clinical Pharmacogenetics.

Cardiovascular diseases place a considerable burden on global health systems, contributing to high rates of morbidity and mortality. Current approaches to detecting and treating Cardiovascular Diseases (CVD) often focus on symptomatic management and are initiated after the disease has progressed. Personalized medicine, which tailors medical interventions to individual characteristics, has emerged as a promising strategy for improving cardiovascular health outcomes. This article provides an overview of personalized medicine in the context of CVD, with a specific emphasis on FDA-approved interventions. It explores the potential benefits, challenges, and future directions of personalized medicine in cardiovascular disorders. By reviewing the advancements in this field, this article underscores the importance of early detection, intervention, and innovative treatment options in reducing the impact of CVD on individuals and society.

Virtual reality modelling in a child after multiple interventions for hypoplastic aortic arch and coarctation.

We present the benefits of advanced multimodality imaging and virtual reality modelling in the diagnosis and treatment planning of a child with aneurysms after numerous interventions for treatment of a hypoplastic aortic arch and coarctation.