Clinical Management Of Patients Research Articles

TB Anywhere, TB Everywhere. The First Case of pre-Extensively Drug Resistant Tuberculosis Treated with BPaL in Italy: Challenges and Opportunities for Transborder Collaboration.

Even if in the past years new effective, safe, and orally administrable drugs are available to create shorter regimens, drug-resistant (DR) tuberculosis (TB) treatment remains a critical issue and a major challenge faced by clinicians worldwide. We present the first case of transborder pulmonary pre-extensively drug-resistant (pre-XDR)-TB treated in Italy with the bedaquiline-pretomanid-linezolid regimen. Diagnosis and treatment were started in Ukraine, and, after a month of treatment, due to the Russo-Ukrainian war, the patient moved to Italy, where the diagnosis was confirmed both by genotypic and phenotypic drug susceptibility tests, and treatment continued. In this short report, we highlight challenges and future opportunities to improve the clinical management of patient with DR-TB.

Integrated Analysis of Gene Expression and Immune Cell Infiltration Reveals Dysregulated Genes and miRNAs in Acute Kidney Injury.

Acute Kidney Injury (AKI) is a multifaceted condition characterised by rapid deterioration of renal function, often precipitated by diverse etiologies. A comprehensive understanding of the molecular underpinnings of AKI is pivotal for identifying potential diagnostic markers and therapeutic targets. This study utilised bioinformatics to elucidate gene expression and immune infiltration in AKI. Publicly available mRNA and miRNA datasets were harnessed to discern differentially expressed genes (DEGs) and miRNAs in AKI. The CIBERSORT algorithm was employed to quantify immune cell infiltration in AKI samples. Functional enrichment analyses were conducted to unravel the implicated biological processes. Furthermore, the expression of identified genes and miRNAs was validated by quantitative real-time PCR in an AKI model. Our study revealed significant dysregulation of three genes (Aspn, Clec2h, Tmigd1) and two miRNAs (mmu-miR-21a-3p, mmu-miR-223-3p) in AKI, each with p < 0.0001. These molecular markers are implicated in immune responses, tissue remodelling, and inflammation. We observed notable disturbances in specific immune cells, including activated and immature dendritic cells, M1 macrophages, and subsets of T cells (Treg, Th1, Th17). These alterations correlated significantly with AKI pathology, with dendritic cells and M1 macrophages showing p < 0.01, and T cell subsets demonstrating p < 0.05. These results highlight the intricate involvement of the immune system in AKI and indicate significant enrichment of pathways related to immune response, inflammation, and tissue remodelling, pointing to their pivotal roles in AKI pathophysiology. Our study underscored the significance of immune cell infiltration and dysregulated gene and miRNA expression in AKI. The identified genes (Clec2h, Aspn, and Tmigd1) and miRNAs (mmu-miR-21a-3p and mmu-miR-223-3p) offer potential diagnostic markers and therapeutic avenues for AKI. Subsequent investigations targeting these genes and miRNAs, along with the elucidated pathways, may augment the clinical management and outcomes for AKI patients.

CRISPR-Cas9 screening identified novel subtypes of cutaneous melanoma based on essential cancer genes.

Our primary objective was to identify genes critical for cutaneous melanoma (CM) and related typing, based on essential genes, to generate novel insights for clinical management and immunotherapy of patients with CM. We analyzed RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), and sequencing data of 29 CM cell line from Cancer Cell Line Encyclopedia (CCLE) databases. Combined with DepMap database, 406 CM essential cancer genes were finally obtained. Based on the expression of essential genes in cancer, the patients included in TCGA and Gene Expression Omnibus (GEO) databases were divided into three different molecular subtypes (C1, C2, and C3) by the NMF algorithm. Data analysis from TCGA and GEO datasets revealed that subtype C3 had the poorest prognosis, while subtype C1 exhibited the best prognosis. Combined with the CIBERSORT, ESTIMATE and ssGSEA algorithm, patients with different molecular subtypes can be divided into two immune subtypes (hot and cold). We found that subtype C1 was characterized by hot tumors, in contrast to subtypes C2 and C3, which were characterized by cold tumors. Then, we used univariate Cox regression, LASSO, and multifactor Cox regression analysis to select risk genes and constructed a prognostic model based on eight genes: RABIF, CDCA8, FOXM1, SPRR2E, AIP, CAP1, CTSW, and IFITM3. All patients were divided into two risk subtypes (high and low ) according to the median of risk scores. We found that most hot tumor subtypes were found in the low-risk subtypes and most patients with this subtype survived for longer. Ultimately, we selected RABIF, which exhibits the highest risk coefficient, for histological and cytological verification. The results showed that RABIF was overexpressed in melanoma. Inhibition of RABIF expression could suppress the proliferation and invasion of melanoma cells and promote the apoptosis of melanoma cells. In conclusion, we used CRISPR-Cas9 screening to verify the association between molecular subtypes (C1, C2, and C3), immune subtypes (hot and cold), and risk subtypes (high and low) in patients with CM, particularly in distinguishing survival and prognosis. These findings can be used to guide clinical management and immunotherapy of patients with CM.

International consensus statement on microbiome testing in clinical practice.

There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field. We aimed to establish a framework to regulate the provision of microbiome testing and minimise the use of inappropriate tests and pave the way for the evidence-based development and use of human microbiome diagnostics in clinical medicine.

Developing a nearly automated open-source pipeline for conducting computational fluid dynamics simulations in anterior brain vasculature: a feasibility study

Intracranial aneurysms (IA) pose significant health risks and are often challenging to manage. Computational fluid dynamics (CFD) simulation has emerged as a powerful tool for understanding lesion-specific hemodynamics in and around IAs, aiding in the clinical management of patients with an IA. However, the current workflow of CFD simulations is time-consuming, complex, and labor-intensive and, thus, does not fit the clinical environment. To address these challenges, we have developed a semi-automated pipeline integrating multiple open-source software packages to streamline the CFD simulation process. Specifically, the study utilized medical angiography data from 18 patients. An in-house open-source DL image segmentation model (ARU-Net) was employed to generate 3D computer models of the anterior circulation. The segmented intracranial vasculature models, including IAs, were further refined using the Vascular Modeling Toolkit (VMTK), an open-source Python package. This step involved smoothing the surface of the models and extending the inlet and outlet regions to ensure a realistic representation of the vascular geometry. The refined vascular models were then converted into computational meshes using an open-source mesh generator known as TetGen. This process was nearly automated and required minimal user interaction(s). Blood flow simulations of the cerebral vascular models were performed using established SimVascular solvers (an open-source finite element platform for vascular applications) through an application programming interface (API). The CFD simulation process was also conducted using the manual workflow for comparative purposes. The initial assessment compared the geometries derived from manual and DL-based segmentation. The DL-based segmentation demonstrated reliable performance, closely aligning with manually segmented results, evidenced by excellent Pearson correlation coefficient (PCC) values and low relative difference (RD) values ranging from 3% to 10% between the computed geometrical variables derived from both methods. The statistical analysis of the computed hemodynamic variables, including velocity informatics and WSS-related variables, indicated good to excellent reliability for most parameters (e.g., ICC of 0.85–0.95). Given the data investigated, the proposed automated workflow streamlines the process of conducting CFD simulations. It generates results consistent with the current standard manual CFD protocol while minimizing dependence on user input.

Investigation of the relationships between peri-implant diseases, periodontal diseases, and conditions: a cross-sectional study.

Peri-implant and periodontal conditions share common underlying factors, including risk factors, microbiology, immunology, and treatment approaches. This study aims to investigate the potential co-occurrence of peri-implant and periodontal conditions. One hundred twenty-three implants were divided into three groups: peri-implantitis (41 implants), peri-implant mucositis (41 implants), and peri-implant health (41 implants). Peri-implant and periodontal statuses were assessed using the 2017 AAP/EFP World Workshop on Classification of Periodontal and Peri-implant Diseases and Conditions. All measurements were performed by a single clinician (T.Ş.). One-way analysis of variance was used to compare the study groups according to the data. An assessment was conducted regarding the coexistence of periodontal and peri-implant conditions. Patients with peri-implant mucositis predominantly had gingivitis, whereas those with peri-implant health exhibited periodontal health. In contrast, patients with peri-implantitis mostly had gingivitis, with a lower occurrence of periodontitis. A significant difference was observed between the peri-implant and periodontal groups (p = 0.003). Significant differences were observed between peri-implant and periodontal evaluations for plaque indices, gingival indices, probing depth, gingival recession, and clinical attachment level (p = 0.001), (p = 0.006). The findings of this study underscore the intricate influence of implant treatment on periodontal health. This observation emphasizes the importance of elucidating the underlying factors to improve clinical management and outcomes in patients with periodontal and peri-implant diseases, highlighting the relevance and potential impact of this research in the field.

Patient-derived induced pluripotent stem cells to study non-canonical splicing variants associated with Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiomyopathy and a leading cause of sudden death. Genetic testing and familial cascade screening play a pivotal role in the clinical management of HCM patients. However, conventional genetic tests primarily focus on the detection of exonic and canonical splice site variation. Oversighting intronic non-canonical splicing variants potentially contributes to a proportion of HCM patients remaining genetically undiagnosed. Here, using a non-integrative reprogramming strategy, we generated induced pluripotent stem cell (iPSC) lines from four individuals carrying one of two variants within intronic regions of MYBPC3: c.1224-52G > A and c.1898-23A > G. Upon differentiation to iPSC-derived cardiomyocytes (iPSC-CMs), mis-spliced mRNAs were identified in cells harbouring these variants. Both abnormal mRNAs contained a premature termination codon (PTC), fitting the criteria for activation of nonsense mediated decay (NMD). However, the c.1898-23A > G transcripts escaped this mRNA quality control mechanism, while the c.1224-52G > A transcripts were degraded. The newly generated iPSC lines represent valuable tools for studying the functional consequences of intronic variation and for translational research aimed at reversing splicing abnormalities to prevent disease progression.

18F‐FAPI versus 18F‐FDG PET/CT in the Diagnosis of Relapsing Polychondritis

ABSTRACTRelapsing polychondritis (RP) is a rare immune‐mediated systemic inflammatory disease with diverse clinical manifestations. Independent involvement of the respiratory system in RP is uncommon. In the event of respiratory involvement as the initial airway‐only manifestation, the diagnosis of RP is challenging and might be delayed, and patients with respiratory involvement exhibit a poor prognosis. However, no specific diagnostic method is currently available for RP with respiratory system involvement as the main clinical manifestation. We present a 49‐year‐old female with the complaint of chronic dry cough accompanied by shortness of breath after exercise that has persisted for over a year. The patient was treated using corticosteroids. The patient's symptoms improved rapidly with the administration of 5 days of methylprednisolone sodium succinate at a dose of 40 mg/day. The treatment was then switched to methylprednisolone tablets at a dose of 40 mg/day, and the dosage was reduced by 4 mg every week until the cessation of therapy. Meanwhile, oral cyclophosphamide tablets were administered once every day at a dose of 100 mg each time. After 1 month of treatment, the symptoms of cough disappeared, the modified british medical research council (mMRC) grade dropped from 4 to 2, and the COPD assessment test (CAT) score dropped from 30 to 17. Repeated CT of the chest revealed that the tracheal wall thickening had alleviated. No recurrence was revealed in the follow‐up visit 12 months after drug withdrawal. The patient underwent 18F‐FDG PET/CT examination before hormone and immunosuppressive therapy, and 18F‐FAPI PET/CT examination was performed 5 days later. The 18F‐FDG PET/CT method revealed slight thickening of the local wall of the trachea and the left and right main bronchus, with no increase in the FDG metabolism, and no abnormalities in the rest of the cartilage. 18F‐FAPI PET‐CT imaging showed increased FAPI uptake in various parts of the body, including trachea and bronchus. The present study reports that compared to 18F‐FDG PET/CT, the 18F‐FAPI PET/CT revealed more lesions and provided a better image contrast, suggesting the latter as a suitable diagnostic method for RP, which could assist in improving the clinical management of RP patients.

Study of clinical profile and management of patients with pulmonary thromboembolism at tertiary care center in Western India.

Study of clinical profile and management of patients with pulmonary thromboembolism at tertiary care center in Western India.

A Cross-Sectional Study of Variant Interpretation and Reporting of NGS Data Using Tertiary Analysis Software: Navify® Mutation Profiler.

Personalized medicine has revolutionized the clinical management of patients with solid tumors. However, the large volumes of molecular data derived from next-generation sequencing (NGS) and the lack of harmonized bioinformatics pipelines drastically impact the clinical management of patients with solid tumors. A possible solution to streamline the molecular interpretation and reporting of NGS data would be to adopt automated data analysis software. In this study, we tested the clinical efficiency of the Navify Mutation Profiler (nMP) software in improving the interpretation of NGS data analysis in diagnostic routine samples from patients with solid tumors. This study included one coordinating institution (Federico II University of Naples) and five other Italian institutions. Variant call format (VCF) files from reference standard samples previously tested by the coordinating institution and from n = 8 diagnostic routine samples (n = 2 from colorectal carcinoma; n = 2 from non-small cell lung cancer; n = 2 from advanced melanoma; and n = 2 from patients with gastrointestinal stromal tumors)and previously analyzed by each participating institution (n = 5) with standardized internal analysis workflows were uploaded onto the Navify® Mutation Profiler (nMP) system (Roche Sequencing Solutions, Pleasanton, CA, USA) for automated analysis and interpretation of DNA and RNA molecular alterations analytical parameters, molecular profiling, and clinical interpretation were carried out by the nMP system and compared with the standard workflow data analyzed by the participating institutions. Overall, all VCF files were successfully submitted and interpreted by the nMP system. A concordance agreement rate of 89.6% was observed between the automated and standard workflow systems. In particular, DNA and RNA molecular profiles obtained with the nMP system matched those obtained with standardized approaches in 44 out of 48 patients (91.7%) and in 11 out of 12 (91.7%) cases, respectively. In addition, the nMP system evidenced wild-type variants in 6 out of 7 (85.7%) cases. The nMP system represents a valid, easily manageable, and clinically useful system to interpret NGS data on diagnostic routine samples from patients with solid tumors.

A Molecular‐Targeting Photosensitizer to Inhibit DNA Damage Repair System and Induce cGAS‐STING Pathway Activation for Photo‐Immunotherapy of Ovarian Cancer

AbstractPoly(ADP‐ribose) polymerase (PARP) inhibitors are commonly utilized in the clinical management of patients with platinum‐sensitive recurrent and late‐stage ovarian cancer, which constitutes a significant proportion of gynecological cancer‐related mortality. Nonetheless, the constraints of their monofunctional properties and limited therapeutic efficacy observed in advanced cancer cases necessitate the exploration of more potent therapeutic strategies for the management of ovarian cancer. The present study describes the development of QTABI, a PARP‐targeting photosensitizer capable of producing reactive oxygen species with light irradiation. Simultaneously, it exhibits significant inhibition of PARP activity, induction of deoxyribonucleic acid (DNA) damage, and consequent synthetic lethality. Furthermore, QTABI can effectively promote the accumulation of cytosolic DNA and activate the cyclicGMP‐AMP synthase (cGAS)‐stimulator of interferon gene (STING) pathway under light irradiation, thereby eliciting potent anti‐tumor immune responses and ultimately boosting anti‐cancer efficacy. Collectively, these findings suggest that QTABI is a multi‐functional photosensitizer, which targets the DNA‐damaging repair system and activates the cGAS‐STING pathway, offering a promising combination photo‐immunotherapy strategy for treating ovarian cancer.

Changes in clinical presentation, management, and survival outcomes in patients affected by colorectal cancer following COVID-19 pandemic.

As an extended analysis of the COVID-DELAY study, we aimed to assess the impact of the COVID-19 pandemic on diagnosis, staging, and survival outcomes among patients with colorectal cancer (CRC) diagnosis performed from 2019 to 2022. All consecutive newly diagnosed CRC patients referred to 11 Italian Oncology Departments between March and December 2019, 2020, 2021, and 2022 were enrolled. Access rate, demographics, diagnostic-therapeutic temporal intervals, and first-line progression-free survival (PFS) and OS among metastatic patients were assessed. Compared to 2019 (n = 690), an initial global reduction in new CRC cases in 2020 (n = 564, -18.3%) was observed, followed by a progressive increase in new CRC diagnoses in 2021 (n = 748, + 8.4%) and 2022 (n = 756, + 9.6%); a higher rate of TNM stage IV tumors was diagnosed in 2020 (35.4%) and 2021 (31.0%) compared to 2019 (29.6%), with normalization in 2022 (26.4%) (P < .001). Not clinically relevant differences between histological diagnosis and first oncological examination, cytohistological diagnosis and systemic treatment start, first oncological appointment and systemic treatment start, treatment start and first radiological assessment between 2020 and 2021-2022 years were found. After propensity score matching according to the year of diagnosis, median OS was significantly worse in 2020, 2021, and 2022 compared to 2019 (27.6 vs 24.8 vs not reached vs 38.9 months, respectively) (P < .001). Concordantly, the median PFS was significantly worse with each passing year: 13.0 vs 11.1 vs 9.2 vs 7.2 months in 2019, 2020, 2021, and 2022, respectively (P = .00027). A progressive normalization in the rate of new CRC diagnosis as well as TNM stages at diagnosis, in 2021 and 2022 compared to 2020 and 2019, was found. The increase in new CRC cases might have affected some diagnostic-therapeutic time intervals in 2021-2022 years compared to 2020. Significantly, compared to the pre-pandemic phase, pandemic years were independently associated with worse PFS and OS outcomes in patients affected by metastatic disease.

Prognostic and predictive value of pathohistological features in gastric cancer and identification of SLITRK4 as a potential biomarker for gastric cancer

The aim of this study was to develop a quantitative feature-based model from histopathologic images to assess the prognosis of patients with gastric cancer. Whole slide image (WSI) images of H&E-stained histologic specimens of gastric cancer patients from The Cancer Genome Atlas were included and randomly assigned to training and test groups in a 7:3 ratio. A systematic preprocessing approach was employed as well as a non-overlapping segmentation method that combined patch-level prediction with a multi-instance learning approach to integrate features across the slide images. Subjects were categorized into high- or low-risk groups based on the median risk score derived from the model, and the significance of this stratification was assessed using a log-rank test. In addition, combining transcriptomic data from patients and data from other large cohort studies, we further searched for genes associated with pathological features and their prognostic value. A total of 165 gastric cancer patients were included for model training, and a total of 26 features were integrated through multi-instance learning, with each process generating 11 probabilistic features and 2 predictive labeling features. We applied a 10-fold Lasso-Cox regression model to achieve dimensionality reduction of these features. The predictive accuracy of the model was verified using Kaplan-Meyer (KM) curves for stratification with a consistency index of 0.741 for the training set and 0.585 for the test set. Deep learning-based resultant supervised pathohistological features have the potential for superior prognostic stratification of gastric cancer patients, transforming image pixels into an effective and labor-saving tool to optimize the clinical management of gastric cancer patients. Also, SLITRK4 was identified as a prognostic marker for gastric cancer.

Strategies for improving treatment retention for buprenorphine/naloxone for opioid use disorder: a qualitative study of issues and recommendations from prescribers

BackgroundOpioid use disorder (OUD) remains a significant public health issue as the number of opioid-related overdose deaths continues to reach new highs each year. Buprenorphine/Naloxone is a medication that has been shown to be highly effective for the treatment of OUD. However, the clinical management of patients on this medication is challenging as many patients discontinue treatment prematurely. We conducted a qualitative study focusing on experienced prescribers of buprenorphine to learn about what they believe are key challenges in prescribing this medication to patients with OUD and related strategies for improving treatment outcomes.MethodsWe conducted two rounds of interviews with 12 prescribers who were either trained as a primary care physician, nurse practitioner, or physician assistant. These prescribers were recruited from an academically-based treatment program, a community health center, and a commercial substance use disorder treatment facility. Interview data were coded and analyzed in accordance with a grounded theory approach.ResultsKey findings and related recommendations emerged for patient monitoring, integration of behavioral health with prescribing, patient volume requirements, and use of telehealth.ConclusionThe interviews generated a number of recommendations for improving patient outcomes from buprenorphine treatment. Some of these recommendations can be implemented quite readily whereas others entail more substantial resources and time commitments.

Study protocol for a randomized controlled trial evaluating the effectiveness of a mother-child intervention model of neurogenic tremor as an add-on to treatment for emotional disorders in adolescents

BackgroundAdolescents exhibit a high prevalence of mental health disorders, with more than half of all cases emerging before the age of 14 years. Since the advent of the COVID-19 pandemic, there has been a marked upsurge in anxiety and depression among adolescents across several nations. Emotional disorders often lead to severe outcomes, including school absenteeism, self-harm, and suicidal tendencies. The suboptimal efficacy of pharmacotherapy, compounded by limited availability and substantial costs associated with individual psychotherapy, underscores the critical need for identifying simple yet efficacious psychotherapeutic interventions suitable for both individual and group settings. Tension and Trauma Release Exercise (TRE) is a mind-body therapeutic approach that efficiently alleviates symptoms of anxiety and depression. This randomized controlled trial (RCT) aims to evaluate the effectiveness of a mother-child intervention model using TRE in enhancing the clinical management of adolescent patients diagnosed with emotional disorders.Methods This study recruits 140 dyads of adolescents with emotional disorders and their mothers, randomly assigned to intervention or control groups. The intervention arm combines eight weeks of standard pharmacotherapy with an eight-week TRE group therapy, assessing at baseline, post-8-week treatment, and three-month follow-up. Initially, controls receive eight weeks of standard medication with parallel assessments, later transitioning to the same TRE intervention while maintaining continuous evaluation. The study further examines the influence of maternal emotional health on adolescent treatment response and investigates associated neurophysiological and psychological mechanisms.DiscussionThis research endeavors to identify a straightforward and potent body-oriented psychological intervention that could improve the clinical outcomes for adolescent patients with emotional disorders. Such findings would carry profound implications not only for the healthy development of teenagers but also for potentially mitigating the burden on families, educational institutions, and society as a whole.Trial registrationChiCTR2100044553, Registered March 24, 2021.

Virtual Gene Panels Have a Superior Diagnostic Yield for Inherited Rare Diseases Relative to Static Panels.

Exome- or genome-based panels-also known as slices or virtual panels-are now a popular approach that involves comprehensive genomic sequencing while restricting analysis to subsets of genes based on patients' phenotypes. This flexible strategy enables frequent gene updates based on novel disease associations as well as reflexing to analyzing other genes up to the whole exome or genome. With recent improvements addressing limitations associated with virtual panels, the advantages of this approach, relative to static custom-based panels, remain to be systematically characterized. Here we perform slice testing on 1014 patients (50.5% females; average age 17 years) referred from multiple pediatric clinics within a single center in the Middle East (83% Arab population). Initial analysis uncovered molecular diagnoses for 235 patients for a diagnostic yield of 23% (235/1014). "On the fly" focused analysis in most negative cases (N = 779) identified clinically significant variants correlating with patients' presentations in genes outside the originally ordered panel for another 35 patients (3.5% or 35/1024) increasing the overall diagnostic yield to 27%. The pathogenic variants underlying the additional cases (13% of all positive cases) were excluded from the original "panel" gene list, mainly as result of issues related to panel selection, novel gene-disease associations, phenotype spectrum broadening, or gene lists variability. The additional findings led to changes in clinical management in most patients (94%). Our findings support slice testing as an efficient and flexible platform that facilitates updates to gene lists to achieve high clinical sensitivity and utility.

Epidemiology, clinical characteristics and potential mechanism of ibrutinib-induced ventricular arrhythmias.

The Bruton's Tyrosine Kinase Inhibitor, ibrutinib, has been widely employed due to its significant efficacy in B-cell lymphoma. However, the subsequent cardiac complications, notably atrial fibrillation (AF) and ventricular arrhythmias (VAs),associated with ibrutinib treatment have emerged as a major concern in cardio-oncology and hematology. Ibrutinib-induced AF has been well described, whereas mechanisms of ibrutinib-induced VAs are still under-investigation. The incidence of ibrutinib-induced VAs can vary vastly due to under-recognition and limitations of the retrospective studies. Recent investigations, including our previous work, have proposed several potential mechanisms contributing to this adverse event, necessitating further validation. The development of effective strategies for the prevention and treatment of ibrutinib-induced VAs still requires in-depth exploration. This review aims to establish a comprehensive framework encompassing the epidemiology, mechanistic insights, and clinical considerations related to ibrutinib-induced VAs. This article outlines potential strategies for the clinical management of patients undergoing ibrutinib therapy based on suggested mechanisms.

Proteomic and phosphoproteomic identified structural and functional changes in the aorta associate with age-dependent hypertension in male Sprague Dawley rats.

Guillain-Barré syndrome (GBS) and cardiovascular diseases (CVDs) have been observed to have a potential association, with GBS potentially leading to cardiovascular complications. However, these observational studies may be influenced by confounding factors. This study aimed to assess the causal relationship between GBS and CVDs, including heart failure (HF), atrial fibrillation (AF), and coronary artery disease (CAD), using a two-sample bidirectional Mendelian randomization (MR) analysis. Datasets for GBS and CVDs were retrieved from the United Kingdom Biobank and analyzed using selected instrumental variables (IVs) related to genetic variations. Sensitivity tests, including heterogeneity and horizontal pleiotropy tests, were conducted to ensure the reliability of the selected IVs. The analysis results were then visualized to illustrate the causal relationships. The study identified genetic variants as IVs for both GBS and CVDs. MR analysis revealed a significant causal effect of GBS on the increased risk of HF (Inverse variance weighted [IVW], p<0.05), but no significant causal relationship was found between GBS and AF or CAD. Similarly, no causal effect of CVDs on the occurrence of GBS was observed. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy, supporting the robustness of the results. This bidirectional MR analysis suggests a causal relationship between GBS and an increased risk of HF but not with AF or CAD, nor was a reverse causal effect of CVDs on GBS observed. These findings underscore the importance of considering cardiovascular complications, particularly HF, in the clinical management of patients with GBS in European populations.

Examining the relationships between patients’ multimorbidity trajectories and prognostic outcomes after the initial hip fracture

Hip fractures significantly affect patients’ health and quality of life. Despite therapeutic treatments, many patients continue to experience poor prognoses that include recurrent fractures and mortality, especially the older ones. Therefore, understanding important factors associated with post-fracture prognoses is critical. This study focuses on patients’ multimorbidity trajectories and examines how the trajectory’s time span, number of coexisting chronic diseases, and sequential disease patterns relate to distinct prognostic outcomes. From the National Health Insurance Research Database in Taiwan, we obtain a sample of 128,822 patients who suffered an initial hip fracture between 1996 and 2011. We use this sample to analyze the relationships between multimorbidity trajectories and prognostic outcomes after an initial hip fracture. The results reveal that a patient’s multimorbidity trajectory’s time span and number of chronic diseases significantly associate with his or her post-fracture prognosis. In addition, essential sequential patterns of chronic diseases relate to post-fracture prognoses too. We then leverage the discovered relationships to develop a cross-attention neural network method for estimating patients’ post-fracture prognoses and demonstrate its predictive utilities relative to several prevalent machine leaning methods. This study underscores the importance of leveraging the time span, number of chronic diseases, and sequential disease patterns in patients’ multimorbidity trajectory profile to estimate their prognoses within three years of an initial hip fracture, which can support physicians’ clinical decisions and patient management.

A retrospective study for clinical characteristics of 293 patients with dermatomyositis.

This retrospective study aimed to investigate differences in clinical characteristics between different antibody phenotypes in patients with dermatomyositis (DM). Two hundred and ninety-three patients with DM were included in this study from September 2018 to September 2023. We collected basic clinical data from the patients, using statistical methods to analyze the clinical characteristics, and used survival analysis and COX regression to assess the prognosis of the patients. In the 293 patients, the antibody distribution was as follows: antibody negative (50, 20.3%), anti-melanoma differentiation-associated gene 5 (MDA5) antibody (104, 42.3%), anti-transcription intermediary factor γ (TIF-γ) antibody (41, 16.7%), anti-complex nucleosome remodeling histone deacetylase (Mi2) antibody (28, 11.4%), anti-nuclear matrix protein 2 (NXP2) antibody (19, 7.7%), anti-small ubiquitin-like modifier activating enzyme (SAE) antibody (4, 1.6%). Interstitial pneumonia (P < .001), lung infection (P < .001), respiratory symptoms (P < .001), arthralgia (P < .001), and fever (P < .001) were more likely to be seen in patients with anti-MDA5 antibody. Malignancy (P < .001) and V-sign (P = .017) were more likely to occur in anti-TIF1-γ antibody positive patients. Anti-NXP2 antibody-positive patients showed more symptoms of muscle involvement, such as myasthenia (P = .002), myalgia (P = .003) and dysphagia (P = .001). In the analysis of prognosis, age at onset (hazard ratio = 1.096, 95% CI: 1.064-1.129, P < .001), fever (hazard ratio = 2.449, 95% CI: 1.183-5.066, P = .016), γ-glutamyl transferase level (hazard ratio = 1.005, 95% CI: 1.002-1.008, P < .001), eosinophil level (hazard ratio = 0.000, 95% CI: 0.000-0.324, P = .024), and complement 3 (C3) level (hazard ratio = 0.115, 95% CI: 0.023-0.575, P = .008) had a statistically significant effect on survival time. The clinical features of DM are associated with myositis-specific antibodies. At the same time, advanced age, fever, elevated γ-glutamyl transferase levels, and reduced C3 and eosinophil levels may be associated with poor prognosis in patients with DM. These data may provide useful information for clinical management of patients with DM.