Journal of Personalized Medicine最新文献

Background: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Despite the implementation of the treat-to-target (T2T) strategy and the introduction of several classes of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), a considerable proportion of patients continues to exhibit active, refractory disease. In 2021, the European Alliance of Associations for Rheumatology (EULAR) defined this condition as Difficult-to-Treat Rheumatoid Arthritis (D2T-RA). This study aimed to identify clinical, laboratory, and therapeutic factors associated with D2T-RA. Methods: A total of 344 patients with established RA were retrospectively evaluated. Among them, 164 fulfilled the 2021 EULAR criteria for D2T-RA (D2T group), while 180 did not (NO-D2T group). Clinical (age, sex, disease duration, BMI, smoking, comorbidities), laboratory (RF, ACPA, ESR, CRP), clinimetric (DAS28, CDAI, PhGA, PGA, HAQ), and therapeutic data (glucocorticoid use, methotrexate treatment and dose, monotherapy, advanced therapy exposure, number of failed advanced therapies, current DMARD regimen) were analyzed. Results: Factors significantly associated with D2T-RA included female sex, longer disease duration, higher RF and ACPA titers, elevated ESR levels, glucocorticoid therapy, and a greater number of failed advanced therapies. Although both groups achieved low disease activity or remission by DAS28 and CDAI, JAK inhibitors-particularly Filgotinib and Upadacitinib-were significantly more common in the D2T cohort and appeared associated with clinical stabilization. Conclusions: This study strengthens the understanding of the predictive profile of D2T-RA, confirming the role of disease chronicity and persistent inflammation in the development of treatment resistance. Importantly, the observed trend toward clinical stabilization achieved under JAK inhibitor therapy reinforces their potential to address unmet therapeutic needs in D2T-RA, providing a mechanistically grounded strategy for patients refractory to conventional and biologic DMARDs.

Background: Embolization is a key therapeutic option in interventional radiology for the management of acute arterial bleeding and solid organ injuries. While various embolic agents exist, there is a persistent clinical need for materials that are not only highly effective but also biocompatible, easy to deliver, and cost-effective. We aim to evaluate a new eco-friendly dry foam agar-based embolization agent (ABEA) in an uncontrolled solid organ hemorrhage model. Material and Methods: Ten pigs underwent a controlled splenic injury. After a 5 min free-bleeding period, five pigs were treated with splenic artery ABEA embolization, while the remaining five received no treatment and served as the control group. Follow-up angiography was performed immediately after embolization and at 5 and 15 min in the treated pigs. Mean arterial pressures and average blood loss volumes were evaluated for 120 min. Results: The control group showed continuous blood loss, leading to a significantly higher total blood loss than the ABEA-treated group (1451 mL vs. 611 mL at 120 min, p < 0.05). Mean arterial pressure (MAP) remained below the hemorrhagic shock threshold throughout the procedure in the control group, validating the model of uncontrolled hemorrhage. In addition, a significant stabilization of MAP was observed in treated pigs, remaining above the critical level of hemorrhagic shock and differed significantly from control group values. Conclusions: Embolization with ABEA maintained MAP above critical levels and significantly reduced blood loss volume in a hemorrhagic model. These results support the technical feasibility and short-term hemostatic performance of ABEA in an acute setting. While preliminary, this proof-of-concept has provided the basis for a validated clinical study currently underway to evaluate its effectiveness and safety in human patients.

Background/Objectives: Alzheimer's disease (AD) exhibits high heritability (60-80%), yet individual-level genetic risk prediction remains challenging. While APOE ε4 is the strongest genetic risk factor, incomplete penetrance complicates risk assessment. Methods: We analyzed seven blood-related members across three generations using the Korean Chip v2.0 genotyping (~1.2 M SNPs) and Illumina EPICv2 DNA methylation profiling. Genetic burden score (GBS) was calculated by summing risk alleles across 320 variants in six AD-associated genes (APOE, PICALM, CLU, CR1, BIN1, and ABCA7). Results: An unexpected pattern was observed in this family: the affected individual (J-003) had the lowest GBS (39 alleles), while individuals with higher genetic burden (51-61 alleles) remained cognitively healthy. J-003 also exhibited lower APOE methylation (β = 0.495) compared to the family mean (β = 0.523). CR1 contributed the most risk alleles across the family, followed by PICALM. Conclusions: This single-case observation cannot establish causality, generalizability, or biological significance. The affected individual's lower APOE methylation may represent a causal factor, disease consequence, or coincidental variation-scenarios that cannot be distinguished from this dataset. Validation in larger cohorts with multiple affected individuals is required to determine whether integrated multi-omics approaches can inform personalized risk assessment in familial contexts.

Diabetes prevalence in older people residing in care homes is rising. This cohort of patients is characterised by multiple morbidities, polypharmacy, and frailty. As a result, they are exposed to an increasing burden of hypoglycaemia, which leads to unnecessary hospital visits and negative consequences. In addition, due to their high baseline morbidities, the risk of cardiovascular events increases. The newly introduced therapy of SGLT-2 inhibitors and GLP-1RA has a very low risk of hypoglycaemia and a significant cardiovascular protective effect. This makes it an appealing choice to be used in older people with complex morbidities, such as care home residents. So far, the current use of these agents is suboptimal in these settings because clinicians are cautious of side effects and tolerability, and also, clinical studies have not included this population. Furthermore, the guidelines in this area lack a personalised approach and are too general, with no clear specific description of which patients are suitable for such therapy. The currently available little evidence is indirect, which confirms the superior benefits of such therapy in frail compared with robust subjects, especially in those who are overweight or obese. The demographic mix of care homes is largely heterogeneous in terms of variations in body composition. In addition to malnourished, frail phenotype subjects, the prevalence of individuals with obesity living in these settings is increasing. Therefore, there is scope for increased use of these new agents in residents who have at least a normal or higher body weight. Because of the high baseline cardiovascular risk, these patients will benefit most from such therapy. Otherwise, these agents are better when less used for frail patients who are anorexic and malnourished because of the risk of inducing further weight loss, volume loss, low blood pressure, falls, and fractures.

Background: Intraventricular tumors represent a minority in the context of brain tumors, but their surgical treatment is particularly complex due to their vascularization and visualization, especially in deep localization. The characteristics of these tumors make them ideal candidates for minimally invasive surgical strategies such as the tubular retractor technique, above all in the elderly population. Objectives: A 1-year multi-center, retrospective case series was performed: the authors describe their preliminary experience using a neuronavigated tubular retractor in the management of 11 cases of intraventricular meningiomas. Methods: Clinical and radiological findings were examined to define the outcomes. We used an alternative tubular retractor system obtained using a modified preexisting general surgery trocar (ENDOPATH XCEL 15 mm trocar) or the NICO System BrainPath. Results: Gross total resection, defined as the removal of all the tumor visible from the brain scans, was achieved in all cases. Ten out of eleven of the patients did not experience major complications or permanent neurological deficits. Four patients presented transitory post-operative agitation, visual blurring and transient hemiparesis. All patients (mean age 72.6 years) were discharged from the hospital in 5-7 days. Conclusions: Our preliminary experience suggests that the use of navigated tubular retractors, by displacing the fibers and hence minimizing the damage to the surrounding cerebral parenchyma, is feasible and safe, representing a minimally invasive technique for a personalized and patient-tailored approach. The use of the selective ultrasonic aspirator makes it possible to excise the tumor through the narrow corridor of the tubular lumen of around 2 cm, and this technique can also be improved using both endoscope and microscope guidance.

Background/Objectives: Cardiac arrhythmias are among the leading causes of sudden cardiac death (SCD). Pathogenic variants in potassium channel genes play a key role in inherited arrhythmia syndromes, yet their contribution in Central Asian populations remains poorly characterized. Methods: We performed targeted next-generation sequencing (NGS) using a 96-gene custom Haloplex panel in 79 Kazakhstani patients with clinically diagnosed arrhythmias, including atrioventricular block, sick sinus syndrome, and atrial fibrillation. Detected variants in potassium channel genes were classified according to ACMG guidelines and correlated with clinical phenotypes. Results: A total of 52 variants were identified across 11 potassium channel genes. Two likely pathogenic variants (KCNH2 p.Cys66Gly and p.Arg176Trp) and six variants of uncertain significance (VUS) in KCNQ1, KCNE2, KCNE3, and KCNJ8 were detected. Two novel previously unreported variants were found in KCNE5 and KCND3. Patients harboring pathogenic variants commonly presented with early-onset arrhythmias or a positive family history of cardiovascular disease. Carriers of KCNH2 variants exhibited mild QT prolongation and recurrent syncope. Conclusions: This is the first genetic study of potassium channel gene mutations in Kazakhstani patients with cardiac arrhythmias. The detection of pathogenic and novel variants highlights the clinical utility of integrating genetic testing into diagnostic and management pathways for arrhythmia syndromes. Population-specific genomic data are essential for improving risk stratification, guiding medication safety, and enabling cascade family screening in Central Asia.

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Background: Identification of patients at risk and prevention of acute postoperative pain (APOP) are central to individualized anesthesia and analgesia. Venous cannulation pain (VCP) has shown promise as a predictor of APOP. In the PeriOPerative Individualization Trial (POPIT), VCP was evaluated as a pain-sensitivity stratification method to guide anesthesia and reduce postoperative pain. This report presents a predefined secondary analysis with the primary aim to evaluate VCP as a method for postoperative pain prediction. As a secondary aim, we sought to explore factors that influence VCP. Methods: 271 patients were stratified into two cohorts, high-risk (VCP ≥ 2.0) and low-risk (VCP < 2.0), for APOP, based on their VCP. Within each group, patients were randomized to receive either: standard care or opioid-free anesthesia (low-risk cohort), and standard care or multimodal anesthesia with opioids (high-risk cohort). Differences in acute and persistent pain, quality of recovery, postoperative opioid consumption, and proportion of patients experiencing moderate to severe APOP depending on VCP levels were investigated. The predictive capacity of VCP was evaluated and adjusted for in terms of potential confounders. Results: High-risk patients, grading VCP ≥ 2.0 (VAS units) experienced more APOP on the day of surgery (difference 0.9 NRS-units, 95% CI 0.2-1.6, p = 0.009) and after 24 h during movement (difference 0.6 NRS-units, 95% CI 0.0-1.3, p = 0.048). Patients grading VCP < 2.0 had better quality of recovery after 24 hr (difference 7, 95% 1-13, p = 0.002) and lower postoperative opioid consumption (difference 7.5 mg, 95% 5.7-9.3, p < 0.001). The OR for VCP ≥ 2.0 to predict APOP in PACU was 1.76 (95% CI 1.02-3.04, p = 0.043), but in a multivariate model, adjusted for age, VCP ≥ 2, gender, pain catastrophizing, preoperative pain, and pain on the day of surgery, female gender was the only independent predictor of APOP (OR 2.65 (95% CI 1.33-5.29), p = 0.006). Conclusions: Pain during venous cannulation as a predictor of acute pain after surgery was significant in univariate regression, but the results were lost when adjusting for confounders like gender and current pain. However, VCP continues to show potential in associated postoperative recovery outcomes such as opioid consumption. The level of pain associated with venous cannulation is influenced by gender, preoperative pain, and current pain on the day of surgery. Pain sensitivity stratification needs refinement before implementation in clinical practice.