Individualized Treatment Strategies Research Articles

The use of glucocorticoids in Behçet’s disease

Behçet’s disease (BD) is a chronic, multifactorial inflammatory disorder characterized by episodic involvement of multiple systems, including mucocutaneous, ocular, vascular, gastrointestinal, joint, and neurological domains. Glucocorticoids (GC) play a pivotal role in managing BD, especially during acute flares and severe organ involvement. This review highlights the tailored use of GC across various manifestations of BD. For mucocutaneous lesions, topical GC are effective, where as short-term low-dose systemic GC are reserved for colchicine-resistantcases. In ocular BD, systemic GC are in dispensable for sight-threatening conditions, often combined with disease-modifying anti-rheumatic drugs (DMARDs) or biologics to minimize GC dependency. In vascular involvement, particularly pulmonary artery aneurysms, high-dose or pulse GC are essential to control vessel wall inflammation, often alongside immunosuppressive agents like cyclophosphamide. Neurological BD necessitate surgent high-dose GC therapy, complemented by DMARDs for sustained control. Joint involvement can be managed with intraarticular GC, reducing systemic exposure. In gastrointestinal BD, GC use is limited due to potential mucosal irritation, with biologics and DMARDs serving as adjunctive options. Across all manifestations, GC tapering is prioritized to mitigate adverse effects, while combination therapy with DMARDs or biologics ensures comprehensive disease control. This comprehensive review underscores the critical role of GC in BD management, advocating for individualized treatment strategies to balance efficacy and safety.

The Impact of Clinical Parameters on LSTM-based Blood Glucose Estimate in Type 1 Diabetes

Accurate forecasting of blood sugar levels is essential for managing diabetes, especially Type-1 reducing incidences, and diminishing care, costs in patients. In this study, a Long Short-Term Memory Recurrent Neural Network (LSTM) model has been employed to predict blood glucose levels using clinical data. The research focuses on identifying and analyzing several key parameters that play a significant role in determining future blood glucose levels, ensuring a robust and reliable prediction framework. We have considered patient-specific features: Insulin-Sensitivity-Factor (ISF), total daily dose (TDD) of insulin, HbA1C levels, height and weight of a patient, and age and gender while analyzing the prediction performance for Blood Glucose. We thought training LSTM models on a large dataset and studying the most important predictors with their predictive power would be beneficial. The results indicate that including these clinical parameters improves the accuracy of blood glucose prediction and provides valuable information for individuals to control diabetes. This analysis highlights the efficiency of LSTM networks in making use of patient data to improve prediction models, eventually aiding more effective and individualized treatment strategies for Type 1 diabetic patients (T1D). This work also examines the extent to which each parameter influences the prediction of future blood glucose levels, providing deeper insights into their relative impact and significance in the predictive model.

Vascular Cognitive Impairment

ABSTRACT OBJECTIVE Vascular cognitive impairment is a major contributor to age-associated cognitive decline, both independently and as a contributor to mixed dementia syndromes. This article reviews the current understanding of how vascular dysfunction contributes to cognitive impairment and dementia risk in older individuals and includes updated diagnostic criteria and treatment recommendations. LATEST DEVELOPMENTS Clinical and research criteria have been evolving to more accurately determine the full prevalence of vascular cognitive impairment. The Boston Criteria version 2.0 for cerebral amyloid angiopathy now includes multiple punctate MRI T2 white matter hyperintensities and MR-visible perivascular spaces in addition to previously described T2* hemorrhagic signatures. MR-visible perivascular spaces are associated with both vascular cognitive impairment and Alzheimer disease, potentially linking cerebrovascular dysfunction to neurodegenerative disorders through its role in brain waste clearance. The American Heart Association’s goal for cardiovascular health promotion, “Life’s Essential 8,” has been updated to include sleep health and acknowledges psychological well-being and social determinants of health as fundamental components necessary to achieve optimal cardiovascular health for all adults. ESSENTIAL POINTS Vascular cognitive impairment is a common and often underrecognized contributor to cognitive impairment in older individuals, with heterogeneous etiologies requiring individualized treatment strategies. Effective cerebrovascular disease risk factor modification starting in midlife is critical to reducing the risk of Alzheimer disease and related dementias, with the goal of preventing vascular brain injury and maintaining cognitive reserve in the presence of nonvascular age-related brain pathologies.

New insights into gestational diabetes: genetic and epigenetic factors

ABSTRACT Gestational diabetes is generally diagnosed between the 24th and 28th weeks of pregnancy because of hormonal changes leading to insulin resistance. Key risk factors include obesity, a family history of diabetes and ethnicity, as well as genetic and epigenetic influences. Epigenetic modifications, such as DNA methylation and histone acetylation, alongside environmental factors like diet and exposure to endocrine disruptors, contribute to the risk. Effective management of gestational diabetes is crucial to prevent complications such as macrosomia, birth trauma, and an increased risk of caesarean delivery. This management requires dietary changes, regular blood glucose monitoring, and sometimes insulin therapy. Current research focuses on understanding genetic and epigenetic influences to improve prediction and develop targeted therapies, highlighting the necessity for personalised approaches to managing and preventing gestational diabetes. Advances in this area could lead to more effective and individualised treatment strategies, benefiting both mothers and their babies.

Endoscopic nasal multilevel skull base reconstruction combined with lumbar cistern drainage in the treatment of infection caused by cerebrospinal fluid leakage: A case report.

Traumatic cerebrospinal fluid leakage can cause complications such as meningitis, ventriculitis and brain abscess. It is necessary to formulate individualized treatment strategies, such as the use of antibiotics and skull base reconstruction methods. The application of nasal septum mucosal flap can significantly reduce the incidence of cerebrospinal fluid leakage. Neuroendoscope has been widely used in the treatment of skull base diseases, and the application of continuous lumbar cistern drainage technology has effectively controlled cerebrospinal fluid leakage. This paper introduces a case of long-term cerebrospinal fluid leakage complicated with infection. Neuroendoscopic multilevel skull base reconstruction combined with lumbar cistern drainage has achieved good clinical results, and this combined treatment is rarely reported in the literature. In order to promote the surgical effect of cerebrospinal fluid leakage, this combined treatment scheme is introduced here. A 43-year-old male was admitted with headache for 7 days, aggravation with fever and vomiting for 2 days. Cerebrospinal fluid culture suggests central nervous system infection, history and symptoms suggest traumatic cerebrospinal fluid rhinorrhea, and computed tomography (CT) shows old skull base fracture. Intracranial infection was controlled after anti-infection treatment with sensitive antibacterial drug ceftriaxone sodium. Repair of cerebrospinal fluid rhinorrhea by transsphenoidal endoscope. Continuous lumbar cistern drainage (LCD) was performed after operation to promote the healing of the leak. After comprehensive treatment, the patient did not have CSF rhinorrhea again and was discharged. Antibiotics combined with endoscopic multi-segment skull base reconstruction and lumbar cistern drainage are effective in treating infection caused by cerebrospinal fluid leakage.

Sequential Use of Sorafenib and Regorafenib in Hepatocellular Cancer Recurrence After Liver Transplantation: Treatment Strategies and Outcomes.

During liver transplantation, hepatocellular carcinoma (HCC) recurrence remains a critical challenge for patient survival. Targeted therapies, such as sorafenib and regorafenib, have been utilized to manage relapsed HCC in this unique setting. This study aimed to assess the efficacy of Sorafenib and Regorafenib in patients with HCC who experienced recurrence after liver transplantation. We focused on survival outcomes, treatment responses, and the management of side effects in this patient group. We conducted a retrospective analysis of 73 patients who experienced HCC recurrence post-liver transplantation between 2012 and 2022 across 11 oncology centers in Turkey. Patients were categorized according to Child-Pugh classification and treated with sorafenib as first-line therapy and Regorafenib in case of progression. Survival rates were analyzed using the Kaplan-Meier method, and risk factors were evaluated using Cox regression analysis. Of the 73 patients included in the study, 62 were male (84.9%), and 11 were female (15.1%), with a mean age of 61.5 ± 10.9 years. All patients received sorafenib as first-line treatment. Among patients who experienced progression with sorafenib or discontinued treatment due to toxicity, 45.2% (n = 33) continued treatment with regorafenib. The median progression-free survival (PFS1) time with sorafenib was 5.6 months, and the one-year survival rate was 24.3%. The median progression-free survival (PFS2) time with regorafenib, which was administered as second-line treatment, was also calculated as 5.9 months. Overall survival (OS) duration was determined as 35.9 months. The most common side effects associated with both drugs included fatigue, hand and foot syndrome, and hypertension. Significantly better survival outcomes were shown in the Child-Pugh A group compared to other patients. These results suggest that Sorafenib and Regorafenib treatments offer a survival advantage in patients with relapsed HCC post-transplantation. However, individualized treatment strategies and close follow-up are crucial for optimizing outcomes. Further studies are needed to refine therapeutic protocols and enhance the care of this specific patient group.

Evaluating Surgical Approaches for Hemimandibular Hyperplasia Associated with Osteochondroma: A Systematic Literature Review.

Background/Objectives: Hemimandibular hyperplasia (HH) associated with osteochondroma presents complex challenges in maxillofacial surgery, including facial asymmetry, occlusal instability, and temporomandibular joint (TMJ) dysfunction. Surgical interventions vary widely in approach and outcomes, underscoring the need for a systematic evaluation of effectiveness. This systematic review assesses the effectiveness of surgical approaches for managing HH associated with osteochondroma, focusing on techniques including condylectomy, orthognathic surgery, distraction osteogenesis, total joint replacement (TJR), and genioplasty. Methods: Following PRISMA 2020 guidelines, a comprehensive search was conducted in PubMed, Scopus, and Web of Science for studies published from 2000 to 2023. Eligibility criteria were based on the PICO framework, with primary outcomes evaluated for facial symmetry, occlusal correction, mandibular function, and recurrence rates. The Cochrane Risk of Bias Tool assessed study quality, while the GRADE framework evaluated the certainty of evidence. This review was not registered due to exclusion criteria for certain dental topics in PROSPERO. Results: Of 145 studies identified, 18 met inclusion criteria, totaling 214 patients. High and low condylectomy both effectively corrected asymmetry, with high condylectomy reducing recurrence risk but often requiring reconstruction. Orthognathic surgery, combined with condylectomy, significantly enhanced facial symmetry and occlusal function. Distraction osteogenesis proved valuable for mandibular lengthening in cases of severe deformities, while TJR offered definitive solutions for extensive joint involvement. Genioplasty corrected chin asymmetry, contributing to improved facial balance. Limitations included small sample sizes and variable follow-up durations. Conclusions: Surgical approaches tailored to individual patient needs show effectiveness in treating HH associated with osteochondroma, achieving functional and esthetic outcomes. Future studies should prioritize larger cohorts and standardized follow-up protocols to better assess long-term efficacy. Advances in 3D surgical planning and individualized treatment strategies show promise for optimized patient-specific care.

Frailty as a predictor of mortality and morbidity after cholecystectomy: A systematic review and meta-analysis of cohort studies.

Although cholecystectomy is a common surgery, it carries higher risks of postoperative complications and mortality for older adults. Age alone is not a reliable predictor of postoperative outcomes, whereas frailty may provide a more accurate assessment of a patient's health and functional status. Frailty, characterized by physical deterioration and reduced resilience, has been shown to predict mortality, prolonged recovery, and morbidity after various surgeries, including cholecystectomy. Thus, incorporating frailty evaluations into preoperative assessments can improve patient outcomes by individualizing treatment strategies. This systematic review and meta-analysis aims to evaluate how well frailty predicts postoperative outcomes following cholecystectomy. In accordance with PRISMA guidelines, we searched PubMed, Embase, and Web of Science on August 14th, 2024, without restrictions on publication year or language. The quality of the studies was assessed using the Newcastle-Ottawa scale, and meta-analysis was conducted using odds ratios with 95% confidence intervals as the effect size, employing a random-effects model. Nine cohort studies comprising a total of 128,421 participants were included. The pooled results showed significantly higher odds of short-term mortality (OR: 5.54, 95% CI: 1.65-18.60, p = 0.006), postoperative morbidity (OR: 2.65, 95% CI: 1.51-4.64, p = 0.001), major morbidity (OR: 3.61, 95% CI: 1.52-8.59), and respiratory failure (OR: 3.85, 95% CI: 1.08-13.79) among frail patients. Additionally, frail patients had longer hospital stays (mean difference: 2.98 days, 95% CI: 1.91-4.04) and significantly higher odds of postoperative infection and sepsis. However, no association was evident with reoperation rates. This study highlights the value of utilizing frailty assessment tools in preoperative settings for predicting outcomes after cholecystectomy. These tools could improve decision-making in both emergency and elective situations, aiding in the choice between surgical and medical management, as well as between open and laparoscopic procedures tailored to each patient.

Phenotype-Genotype Correlation in Morquio A Syndrome: Protocol for a Meta-Analysis.

Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome, is a rare lysosomal storage disease characterized by autosomal recessive inheritance of mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. This leads to a deficiency of the GALNS enzyme, causing the accumulation of glycosaminoglycans in tissues. Morquio A syndrome primarily affects the skeletal system and joints but can also impact various organs, resulting in symptoms such as hearing and vision loss, respiratory issues, spinal cord compression, heart diseases, and hepatomegaly. The genotype-phenotype relationship is diverse, with studies highlighting variants associated with classic, nonclassic, or intermediate phenotypes. Understanding these genetic factors is crucial for predicting disease prognosis and tailoring effective treatment strategies for individuals with Morquio A syndrome. The aim of this meta-analysis is to comprehend the relationship between the severity of the phenotype and the genotype of patients with MPS IVA, considering factors such as the type of variant and its location in the different domains of the protein. This meta-analysis will include articles featuring participants of all genders and age groups who have a molecular diagnosis of MPS IVA and a description of the phenotype. Literature published in English, Spanish, and Portuguese will be considered. Exclusion criteria will encompass studies lacking full-text availability and those involving patients with an MPS IVA diagnosis but without phenotype information. The databases to be searched include PubMed, MEDLINE, ScienceDirect, and Scopus. The screening of literature, paper selection, and data extraction will involve 2 independent reviewers, who will conduct the process blindly. In the event of disagreements between the 2 reviewers at any stage, resolution will be sought through discussion or with the involvement of an additional reviewer. The final selection of manuscripts will be based on consensus. The results of the review will be presented using descriptive statistics, and the information will be organized in either diagrammatic or tabular formats, following the guidelines provided by the Joanna Briggs Institute. Genotype-phenotype relationships will be analyzed using IBM SPSS Statistics, using chi-square tests, Fisher exact tests, and regression analysis to interpret the data. A literature search conducted in January 2024 produced 760 results. The review is expected to be completed by the end of 2024. This meta-analysis will gather and analyze information on the phenotype-genotype relationship in patients diagnosed with MPS IVA. The data collection and resulting analyses will make a substantial contribution to understanding the underlying mechanism of the disease, enabling the prediction of the syndrome's progression and severity. DERR1-10.2196/56649.

Spectral CT-based nomogram for preoperative prediction of Lauren classification in locally advanced gastric cancer: a prospective study.

To develop a nomogram based on clinical features and spectral quantitative parameters to preoperatively predict the Lauren classification for locally advanced gastric cancer (LAGC). Patients diagnosed with LAGC by postoperative pathology who underwent abdominal triple-phase enhanced spectral computed tomography (CT) were prospectively enrolled in this study between June 2023 and December 2023. All the patients were categorized into intestinal- and diffuse-type groups according to the Lauren classification. Traditional characteristics, including demographic information, serum tumor markers, gastroscopic pathology, and image semantic features, were collected. Spectral quantitative parameters, including iodine concentration (IC), effective atomic number (Zeff), and slope of the energy spectrum curve from 40 keV to 70 keV (λ), were measured three times for each patient by two blinded radiologists in arterial/venous/delayed phases (AP/VP/DP). Differences in traditional features and spectral quantitative parameters between the two groups were compared using univariable analysis. Independent predictors of the Lauren classification of LAGC were screened using multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used to assess the discriminating capability. Ultimately, the nomogram, including clinical features and spectral CT quantitative parameters, was developed. Gender, nIC in AP (APnIC), and λ in DP (λd) were independent predictors for Lauren classification. The nomogram based on these indicators produced the best performance with an area under the curve of 0.841 (95% confidence interval: 0.749-0.932), specificity of 85.3%, accuracy of 76.4%, and sensitivity of 68.4%. The nomogram based on clinical features and spectral CT quantitative parameters exhibits great potential in the preoperative and non-invasive assessment of Lauren classification for LAGC. Question Can the proposed nomogram, integrating clinical features and spectral quantitative parameters, preoperatively predict the Lauren classification in locally advanced gastric cancer (LAGC)? Findings The nomogram, based on gender, arterial phase normalized iodine concentration, and slope of the energy spectrum curve in the delayed phase showed satisfactory predictive ability. Clinical relevance The established nomogram could contribute to guiding individualized treatment strategies and risk stratification in patients by predicting the Lauren classification for LAGC before surgery.

Outcomes of Conservative Treatments Evaluations for Lumbar Radiculopathy

Background: Lumbar Radiculopathy (LR) is a condition characterized by motor, reflex and sensory changes, often causing significant pain and disability. Conservative treatments are commonly recommended as initial management options. This study aims to evaluate the outcomes of various conservative treatments for LR. Materials and methods: This prospective cohort study involved 100 patients diagnosed with LR who underwent conservative treatments between January 2023 and December 2023 at our Physical Medicine Department, Institute of Applied Health Sciences (IAHS). Treatments included physical therapy, NSAIDs, epidural steroid injections and activity modification. Baseline data, including demographic information, pain intensity (VAS) functional status (ODI) and quality of life (SF-36), were collected. Follow-up assessments were conducted at 6 weeks, 3 months and 6 months. Primary outcomes were changes in VAS, ODI and SF-36 scores. Secondary outcomes included patient satisfaction and the need for additional interventions. Data were analyzed using descriptive statistics, paired t-tests and ANOVA. Results: The mean age of participants was 45.3 years, with a slight male predominance (56%). At baseline, mean VAS was 7.8, ODI was 45.6 and SF-36 was 62.5. Significant reductions in VAS (2.6), ODI (18.7), and improvements in SF-36 physical (80.3) and mental (81.7) scores were observed at 6 months (p<0.05). Patient satisfaction at 6 months was highest for epidural injections (90%), followed by NSAIDs (85%), physical therapy (80%) and activity modification (70%). The need for additional interventions decreased to 8%. The incidence of adverse events was low, with physical therapy showing the lowest rates. Initial ODI score was a significant predictor of positive outcomes (p=0.03). Conclusion: Conservative treatments for LR are effective in reducing pain and disability and improving quality of life. All treatment modalities showed comparable efficacy, with low adverse event rates, supporting their use as first-line treatments. Initial disability levels should be considered in treatment planning to optimize outcomes. Further research is needed to refine predictive models and enhance individualized treatment strategies. IAHS Medical Journal Vol 7(1), June 2024; 80-85

Challenges in metastatic hepatocellular carcinoma: beyond tumor stage in guiding treatment.

Extrahepatic metastases in hepatocellular carcinoma (HCC) often signify a poor prognosis. This case details the five-year survival of a patient with HCC and adrenal metastasis managed with an aggressive multimodal approach, including ablation, systemic therapy, and surgical resection. Despite therapeutic advances, metastatic HCC management remains a clinical challenge, underscoring the need for individualized treatment strategies beyond traditional staging systems. Further research is essential to determine the role of surgical resection and other treatment modalities in the metastatic setting.

Anticoagulation vs Antiplatelets Across Subgroups of Embolic Stroke of Undetermined Source: A Meta-Analysis of Randomized Controlled Trials.

The term "embolic stroke of undetermined source" (ESUS) encompasses a substantial but heterogeneous population of patients with ischemic stroke, underscoring the importance of identifying personalized treatment strategies. In subgroups of patients randomized in ESUS trials, we evaluated the effectiveness of anticoagulation compared with antiplatelet therapy in secondary ischemic stroke prevention. A study-level meta-analysis was conducted on randomized controlled trials of patients with ESUS, comparing anticoagulation with antiplatelet therapy. The primary efficacy outcome was recurrent ischemic stroke, and safety outcomes were major bleeding and death. Subgroups assessed were age, sex, presence of patent foramen ovale (PFO), left atrial enlargement (LAE), and atrial cardiopathy. Pooled risk ratios (RRs) were meta-analyzed. Cochrane Risk of Bias Tool 2.0 was used for risk-of-bias assessment. A total of 7 randomized controlled trials involving 14,804 patients were analyzed, with 7,406 patients treated with anticoagulation and 7,398 treated with antiplatelet therapy. Compared with antiplatelet therapy, anticoagulation was associated with a similar rate of recurrent ischemic stroke (RR 0.91, 95% CI 0.80-1.05; I2 = 0%). In ESUS with PFO, anticoagulation was associated with significantly lower risk of ischemic stroke (RR 0.59, 95% CI 0.35-0.98; I2 = 0%). Heterogeneity was present in those with LAE: antiplatelet therapy was superior in trials allowing cardiac monitoring after randomization (RR 6.65, 95% CI 1.26-35.08; I2 = 0%), but anticoagulation was superior in trials prohibiting cardiac monitoring after randomization (RR 0.25 95% CI 0.07-0.89). Subgroups based on age, sex, or presence of atrial cardiopathy did not benefit from anticoagulation over antiplatelet therapy. In this meta-analysis, an empiric anticoagulation approach is not beneficial for patients with ESUS. This finding highlights the importance of an individualized treatment strategy. Such a strategy should include prolonged cardiac monitoring for atrial fibrillation, particularly in patients with moderate-to-severe LAE. Anticoagulation treatment showed promise in patients with medically treated PFO. Other subgroups did not benefit from anticoagulation therapy. Large prospective studies within ESUS subgroups are needed to validate our findings.

Spontaneous cerebrospinal fluid rhinorrhoea: a case report and literature review

BackgroundCerebrospinal fluid rhinorrhea is a rare condition characterized by the abnormal leakage of cerebrospinal fluid from the intracranial space into the sinonasal cavity. It includes various etiologies, including traumatic, iatrogenic, and spontaneous causes, each with distinct epidemiological and clinical characteristics.Case presentationA 40-year-old Asian female presented with a three-month history of watery discharge from her left nostril and dull headaches localized to the left side of her head. Despite the initial diagnosis of allergic rhinitis, symptoms persisted, leading to further evaluation and eventual diagnosis of cerebrospinal fluid rhinorrhea. Detailed history, physical examination, and diagnostic tests including fluid analysis and imaging confirmed the diagnosis. The patient underwent a successful surgical repair after failed conservative management, highlighting the importance of timely intervention.ConclusionCerebrospinal fluid rhinorrhea poses significant risks if left untreated, including meningitis. Prompt recognition, accurate diagnosis, and individualized treatment strategies are crucial in mitigating complications and improving patient outcomes. A multidisciplinary approach, incorporating both conservative and surgical interventions tailored to the underlying cause, is essential for the successful management of cerebrospinal fluid rhinorrhea.

INNV-19. MULTIMODAL THERAPY FOR BRAF V600E MUTANT MELANOMA BRAIN METASTASES: CHARACTERIZATION OF CHRONOLOGICAL TREATMENT STRATEGIES AND ASSOCIATIONS WITH OVERALL SURVIVAL

Abstract BACKGROUND B-raf proto-oncogene (BRAF)-mutant melanoma brain metastases (BRAF MBM) are associated with poor prognosis. Amidst our large institutional experience treating patients with BRAF MBM with multimodality therapy, our aim was to identify disease and treatment-related prognostic features, accounting for longitudinal sequence of events, to inform clinical decision-making. METHODS We retrospectively reviewed electronic health records of 100 patients with primary cutaneous melanoma diagnosed with BRAF MBM. Demographic, disease, and clinical factors including treatment sequencing were tabulated. Descriptive statistics were used to summarize the study population and non-parametric tests were used to evaluate differences across groups. A multivariable Cox regression identified factors associated with overall survival (OS) following BRAF MBM diagnosis. RESULTS Median follow-up was 22 months and median OS was 33.5 months. Patients received an average [standard deviation (SD)] of 3.36 [1.06] unique therapies. After adjustment for covariates, greater number of brain metastases at initial diagnosis (hazard ratio (HR) 2.3 [1.14-4.62], p=0.01 for 3-10 metastases and HR 2.54 [1.01-6.36], p=0.04 for >10 metastases, respectively), receipt of combination IO and targeted therapy prior to BRAF MBM diagnosis (HR 2.91 [1.08-7.86], p=0.03), and receipt of no unique subsequent therapy after initial management strategy (HR 3.89 [1.48-10.16], p=0.005) were significantly associated with worse OS. CONCLUSIONS Despite heterogeneity in individual treatment sequences, patients with greater intracranial disease burden and those receiving combination targeted and immunotherapy prior to BRAF MBM diagnoses had the worst outcomes. Dynamic changes in therapy resistance may inform optimal treatment strategies for individuals with BRAF MBM.

Integrating transcriptomic data and digital pathology for NRG-based prediction of prognosis and therapy response in gastric cancer

Background Cancer is characterized by its ability to resist cell death, and emerging evidence suggests a potential correlation between non-apoptotic regulated cell death (RCD), tumor progression, and therapy response. However, the prognostic significance of non-apoptotic RCD-related genes (NRGs) and their relationships with immune response in gastric cancer (GC) remain unclear. Methods In this study, RNA-seq gene expression and clinical information of GC patients were acquired from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Cox and LASSO regression analyses were used to construct the NRG signature. Moreover, we developed a deep learning model based on ResNet50 to predict the NRG signature from digital pathology slides. The expression of signature hub genes was validated using real-time quantitative PCR and single-cell RNA sequencing data. Results We identified 13 NRGs as signature genes for predicting the prognosis of patients with GC. The high-risk group, characterized by higher NRG scores, demonstrated a shorter overall survival rate, increased immunosuppressive cell infiltration, and immune dysfunction. Moreover, associations were observed between the NRG signature and chemotherapeutic drug responsiveness, as well as immunotherapy effectiveness in GC patients. Furthermore, the deep learning model effectively stratified GC patients based on the NRG signature by leveraging morphological variances, showing promising results for the classification of GC patients. Validation experiments demonstrated that the expression level of SERPINE1 was significantly upregulated in GC, while the expression levels of GPX3 and APOD were significantly downregulated. Conclusion The NRG signature and its deep learning model have significant clinical implications, highlighting the importance of individualized treatment strategies based on GC subtyping. These findings provide valuable insights for guiding clinical decision-making and treatment approaches for GC.

Prognostic characteristics and drug sensitivity analysis of hepatocellular carcinoma based on histone modification-related genes: a multi-omics integrated study revealing potential therapeutic targets and individualized treatment strategies.

Hepatocellular carcinoma (HCC) ranks among the most prevalent and lethal malignancies worldwide. Histone modifications (HMs) play a pivotal role in the initiation and progression of HCC. However, our understanding of HMs in HCC remains limited due to the disease's heterogeneity and the complexity of HMs. We integrated multi-omics data from multiple cohorts, including single-cell RNA sequencing, bulk RNA sequencing, and clinical information. Weighted gene co-expression network analysis (WGCNA) and consensus clustering were employed to identify histone-related genes. We developed a histone modification-related signature (HMRS) using 117 machine learning methods. Comprehensive analyses of molecular characteristics, immune landscape, and drug sensitivity associated with the HMRS were performed. Through integrative analysis, we defined 110 histone-related genes and identified 45 HCC-HM-related genes (HCC-HMRgenes). The HMRS demonstrated robust prognostic value across multiple cohorts. Patients with high HMRS scores exhibited distinct genomic alterations, including higher tumor heterogeneity and TP53 mutations. The high-risk group showed enrichment in cell cycle, DNA repair, and metabolic pathways. Immune landscape analysis revealed significant differences in immune cell infiltration and pathway activities between high- and low-risk groups. Drug sensitivity prediction suggested potential therapeutic strategies for different risk groups. Our study provides a comprehensive understanding of HMs in HCC and establishes a robust prognostic signature. The HMRS not only stratifies patients into distinct risk groups but also offers insights into underlying molecular mechanisms, immune characteristics, and potential therapeutic strategies, paving the way for personalized medicine in HCC.

Construction of a novel mitochondrial oxidative stress-related genes prognostic system and molecular subtype characterization for breast cancer

PurposeBreast cancer (BRCA) is the most common malignant tumor among women, characterized by high incidence rates and mortality rates. Oxidative stress and immunity, particularly in relation to mitochondria, have emerged as pivotal factors in breast carcinogenesis. Nonetheless, limited research has explored the specific contribution of mitochondrial oxidative stress to the prognosis of BRCA.MethodIn this study, we conducted univariate and multivariate Cox regression analyses to pinpoint independent prognostic genes associated with mitochondrial oxidative stress (MOSRGs) and their correlation with BRCA clinical outcomes. Subsequently, we developed a robust and accurate MOS scoring system for BRCA patients based on these identified independent prognostic MOSRGs.ResultOur findings were further substantiated by immune infiltration and somatic mutation analyses, providing additional evidence that the MOS scoring system holds predictive value for clinical outcomes in patients and correlates directly with three subtypes of BRCA. In vitro experiments in the MCF7 cell and breast tissue further verified the mRNA and protein expression level of independent prognostic genes, validating the consistency of the MOS prognostic signatures in BRCA.ConclusionThis research has unveiled a novel prognostic scoring system, providing valuable insights for improving patient prognosis assessment and developing individualized treatment strategies in BRCA patients.

The Management of Interstitial Lung Disease in the ICU: A Comprehensive Review.

Interstitial lung disease (ILD) encompasses a diverse group of parenchymal lung diseases characterized by varying degrees of inflammation and/or fibrosis. Patients with ILD frequently require hospitalization, with many needing intensive care unit (ICU) admission, most often due to respiratory failure. The diagnosis and management of ILD in the ICU present unique challenges. Diagnosis primarily relies on chest CT imaging to identify fibrosis and inflammation. Acute exacerbations, whether in idiopathic pulmonary fibrosis (IPF) or non-IPF ILD, require careful evaluation of potential triggers and differential diagnoses. Bronchoalveolar lavage may provide valuable information, such as the identification of infections, but carries risks of complications. Biopsies, whether transbronchial or surgical, can also be informative but pose significant procedural risks. Corticosteroids are the cornerstone of treatment for acute exacerbations of IPF, with higher doses potentially benefiting non-IPF ILD. Additional immunosuppressive agents may be used in cases with evidence of inflammation. Oxygen supplementation, particularly with high-flow nasal cannula, is often employed to manage severe hypoxemia, while noninvasive ventilation can be useful for worsening hypoxemia and/or hypercapnia. When mechanical ventilation is used, it is recommended to target low tidal volumes to minimize lung injury; high PEEP may be less effective and even associated with increased mortality. Prone positioning can improve oxygenation in severely hypoxemic patients. In addition to ventilatory strategies, careful fluid management and addressing concomitant pulmonary hypertension are essential components of care. Extracorporeal membrane oxygenation is a high-risk intervention reserved for the most severe cases. Lung transplantation may be considered for end-stage ILD patients in the ICU, with outcomes dependent on the urgency of transplantation and the patient's overall condition. Managing ILD in the ICU requires a multidisciplinary approach, and despite recent advances, mortality remains high, emphasizing the need for continued research and individualized treatment strategies.

Predictive modeling of preoperative acute heart failure in older adults with hypertension: a dual perspective of SHAP values and interaction analysis

BackgroundIn older adults with hypertension, hip fractures accompanied by preoperative acute heart failure significantly elevate surgical risks and adverse outcomes, necessitating timely identification and management to improve patient outcomes.Research objectiveThis study aims to enhance the early recognition of acute heart failure in older hypertensive adults prior to hip fracture surgery by developing a predictive model using logistic regression (LR) and machine learning methods, optimizing preoperative assessment and management.MethodsEmploying a retrospective study design, we analyzed hypertensive older adults who underwent hip fracture surgery at Hebei Medical University Third Hospital from January 2018 to December 2022. Predictive models were constructed using LASSO regression and multivariable logistic regression, evaluated via nomogram charts. Five additional machine learning methods were utilized, with variable importance assessed using SHAP values and the impact of key variables evaluated through multivariate correlation analysis and interaction effects.ResultsThe study included 1,370 patients. LASSO regression selected 18 key variables, including sex, age, coronary heart disease, pulmonary infection, ventricular arrhythmias, acute myocardial infarction, and anemia. The logistic regression model demonstrated robust performance with an AUC of 0.753. Although other models outperformed it in sensitivity and F1 score, logistic regression’s discriminative ability was significant for clinical decision-making. The Gradient Boosting Machine model, notable for a sensitivity of 95.2%, indicated substantial capability in identifying patients at risk, crucial for reducing missed diagnoses.ConclusionWe developed and compared efficacy of predictive models using logistic regression and machine learning, interpreting them with SHAP values and analyzing key variable interactions. This offers a scientific basis for assessing preoperative heart failure risk in older adults with hypertension and hip fractures, providing significant guidance for individualized treatment strategies and underscoring the value of applying machine learning in clinical settings.