Journal of Personalized Medicine最新文献

Background/Objectives: Primary biliary cholangitis (PBC) is an autoimmune chronic cholestatic disease of the liver that symptomatically can present with pruritus and fatigue. Its established first- and second-line therapies are ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) although they provide limited symptom management. Liver transplantation offers a potentially curative therapeutic option in refractory cases progressing to cirrhosis. Novel research published after the current guidelines highlights the importance of providing an up-to-date analysis of treatment options available. Methods: In this study, we conducted a literature search using Pubmed, Ovid Medline, and SCOPUS to provide a narrative review of first-line, second-line, and emerging therapies in PBC. Results: UDCA has been well established as a long-term, safe therapy within the literature although it is possible that treatment dosage can be further optimised in refractory patients. It has a favourable side effect profile. Despite improving biochemical markers, histopathological profile, and overall outcomes, up to 30-40% of patients are refractory to it. Age and sex are highlighted as independent indicators of non-responsiveness. This necessitates effective second-line therapies. Future trials could aim to investigate UDCA as a co-first-line therapy. Further supporting results for OCA were found in the interim extension trial of the seminal POISE study. The long-term phase 4 COBOLT trial is still awaiting results to further assess the complications, adherence, and potential adverse effects. It is a viable option in UDCA-refractory patients. The high incidence rate of dose-related pruritis indicates that alternative second-line options are needed. Bezafibrate is an off-label antilipemic agent that shows promise as a prospective second-line therapy option. The landmark BEZURSO trial alleviated some efficacy and safety concerns, but it remains associated with elevated serum creatinine; thus, it should be considered with caution. Other prospective second-line therapies are budesonide, triple therapy, and novel agents such as seladelpar and elafibranor. Conclusions: UDCA should remain the treatment of choice for PBC, though perhaps not as monotherapy. With further investigation, BF shows promise as a new second-line therapy alongside OCA, which it may outperform.

Background: This systematic review and meta-analysis aimed to investigate the effects of presurgical orthopedics (PSO) on maxillary arch dimensions in infants with cleft lip and palate during the first year of life. Methods: The review was conducted following PRISMA guidelines. A comprehensive electronic search was performed in MEDLINE, Embase, Cochrane, Scopus, and Google Scholar databases, supplemented by manual searching. Two reviewers independently conducted study selection, data extraction, quality assessment, and risk of bias evaluation. Results: Five studies were included in the meta-analysis. Quantitative analysis was performed based on the primary outcomes. The estimate was calculated using a random-effects model and z distribution (95% confidence interval (CI)). The results showed similar alveolar cleft widths (mean difference, -3.06; 95% CI, -8.03 to 2.70, p = 0.30, I2 = 99%) with clinical differences in favor of PSO, and comparable posterior cleft widths (mean difference, -0.88; 95% CI, -2.06 to 0.30, p = 0.14, I2 = 89%) with and without PSO in CLP babies. Conclusions: This meta-analysis found no statistically significant effects of presurgical orthopedic treatment on maxillary arch dimensions in infants with cleft lip and palate during the first year of life. Further high-quality randomized controlled trials are needed to definitively establish the efficacy of PSO.

Background/Objectives: The integration of pharmacogenetic (PGx) testing into primary care has not been widely implemented, despite its benefits for patients and providers. PGx testing could also reduce health disparities as patients with lower healthcare access are prescribed higher proportions of medications with PGx guidelines. Little is known about the preferences of patients who have experienced PGx testing to inform implementation across the care process. This qualitative study aimed to refine implementation by capturing patient preferences on (1) testing and prescription timing, (2) patient-clinician discussion of results during post-test counseling, and (3) usability of a card during results dissemination. Methods: Interviews were conducted with 25 primary care patients from clinics primarily serving medically underserved populations. Interview transcripts were thematically analyzed using a constant comparative approach. Results: While patients supported both reactive and pre-emptive testing, they valued pre-emptive PGx testing because it is proactive for future health needs, expedites treatment, and is convenient. Patients' preferences for receiving prescriptions depended on several factors: having immediate access to needed medications, avoiding experiencing medication side effects and interactions, avoiding taking ineffective medications, and avoiding inconveniences. Patients identified three issues critical to patient-clinician interactions when receiving testing results: information specific to medications, clarification and further information about their results, and enhanced clinician accessibility related to the results. Lastly, they liked that the results card could facilitate discussions with clinicians and was informative and convenient but said it lacked clarity. Conclusions: These findings should inform implementation strategies for integrating PGx testing in primary care for underserved patients.

Objectives: There remains considerable debate regarding the optimal management of anterior cruciate ligament (ACL) injuries in skeletally immature patients. This study aims to evaluate the clinical outcomes of transphyseal ACL reconstruction in patients with open growth plates. Methods: This retrospective study included skeletally immature patients with full-thickness ACL tears and confirmed open physis. ACL reconstructions were performed using a four-strand semitendinosus autograft, with an additional gracilis tendon graft if needed. The surgical technique emphasized tibial and femoral physeal-sparing tunnel placement to minimize disruption of the growth plates. Clinical assessment included measurements for limb length discrepancy, knee stability, and growth disturbances. Functional outcomes were evaluated using IKDC 2000, Lysholm, and KOOS scores, while ligament stability was assessed with KT-1000 arthrometer measurements at routine follow-up. Results: A total of 31 consecutive patients (15 females, 16 males; mean age 13.6 ± 1.8 years, range 9-16 years) were included. Mean follow-up was 49 ± 26 months (range 18-93 months). The mean time to return to sports was 8.8 ± 4.4 months. Eight patients (26%) experienced ACL graft rupture and underwent revision ACL reconstruction. One additional patient required partial meniscectomy. The overall revision rate was 29%. The mean subjective IKDC score was 91.8 ± 7.2, with Lysholm and KOOS scores of 96.6 ± 7.9 and 94.2 ± 5.3, respectively. No significant growth disturbances were noted. The mean side-to-side difference in KT-1000 testing was 2.2 ± 1.5 mm. Patients who underwent revision ACL reconstruction showed significantly greater length growth compared with those with intact ACL reconstruction (p = 0.02). Spearman correlation revealed a significant association between length growth and anterior tibial translation (p = 0.02, r = 0.46). Conclusions: Transphyseal ACL reconstruction in skeletally immature patients provides favorable clinical and radiological outcomes, with minimal risk of growth disturbance. Most patients returned to pre-injury levels of athletic activity. However, the high revision rate emphasizes the complexity of managing ACL injuries in this population.

Background/Objectives: The etiology and causes of osteoarthritis are still being studied at the cellular and molecular level by many scientists around the world. With advances in knowledge, technology, and the need for complexity, new therapeutic approaches-such as restorative medicine-are being developed to protect the patient from endoprosthesis implantation, aiming to simultaneously restore and maintain physical and psychosocial function. The purpose of this study was to evaluate the effectiveness of physiotherapy after the implantation of CD34+ stem cells into the hip joints of patients with osteoarthrosis. Methods: The study included 71 patients, previously diagnosed with HOA (hip osteoarthritis) and undergoing CD34+ stem cell therapy followed by rehabilitation. The twelve-month prospective follow-up included 23 women and 48 men. Participants were asked to provide information, regarding the quality of their daily functioning, according to the Harris Questionnaire at four time points. Results: In all evaluations and groups of patients, i.e., women and men, and rehabilitated and non-rehabilitated, a significantly high improvement was noted at 3 months after the administration of CD34+ stem cells, while afterwards there was a slight decrease in the value of the results obtained at 6 months after the procedure, which improved at further stages of the study. The value of functioning on the Harris scale did not differ significantly between genders, although there was a trend of better functioning in men after one year, while it was higher in rehabilitation subjects. Conclusions: Patients' daily functioning was better in the rehabilitation group, as reflected by the Harris scale. The absence of adverse symptoms and the small differences in physiotherapy results between the rehabilitated and non-rehabilitated groups testify to the high effectiveness of the stem cell therapy method.

Background/Objectives: Fluid overload is an important risk factor for protein-energy wasting, which could lead to poor outcomes, such as higher morbidity and mortality, in patients with chronic kidney disease (CKD). This study aimed to validate the possible myokine as a biomarker of volume status in patients with non-dialysis CKD. Methods: In total, 151 patients with CKD were enrolled from a single medical center. Demographic data were collected via medical record review. Bioimpedance analysis was performed to measure body composition, and physical performance was assessed by measuring hand grip strength. Results: The physical performance of hand grip strength (21.9 ± 8.7 vs. 19.0 ± 10.1 kg, p = 0.233) and walking speed (1.05 ± 0.29 vs. 0.86 ± 0.52 m/s, p = 0.192) was higher in the low extracellular water/total body water (ECW/TBW) ratio group. Although higher, the median value of the brain-derived neurotrophic factor (BDNF) was not significant in the low ECW/TBW ratio group. Despite that, it had significant negative correlations with the ECW/TBW ratio in Pearson's correlation analyses (r = -0.329, p < 0.001; r = -0.287, p < 0.001; and r = -0.238, p = 0.003). Linear regression analysis showed that the BDNF level had a significant negative relationship with the ECW/TBW ratio and significant associations even after multivariate analysis. Conclusions: Among myokines, BDNF had a significant negative relationship with the ECW/TBW ratio, suggesting that BDNF could be a possible biomarker for volume status in patients with non-dialysis CKD.

Background and Aims: Stroke is the leading cause of seizures and epilepsy in adults; however, current guidelines lack robust recommendations for treating post-stroke seizures (PSSs) and epilepsy (PSE). This study aims to demonstrate the long-term safety and efficacy of lacosamide combined with non-vitamin K antagonist oral anticoagulants (NOACs) in patients with PSE and atrial fibrillation (AF). Methods: In this prospective longitudinal single-center study, 53 patients with concomitant PSE and AF, admitted between 2022 and 2023, received NOACs for AF management and lacosamide for seizure control. A control group of 53 patients with cardioembolic stroke, receiving NOACs (but without PSE), was matched by age, sex, and NIHSS scores to ensure comparability. Results: Over 24 months, 16 patients in the study group and 15 in the control group experienced new embolic events, with no significant difference between groups (p = 0.82). Seizure control improved significantly in the study group, with reduced frequency and severity. No severe adverse events from lacosamide were observed. Conclusions: The combination of NOACs and lacosamide is a safe and effective treatment for patients with AF and PSE and does not increase the risk of recurrent ischemic or hemorrhagic events. Further studies with larger sample sizes and longer follow-ups are needed to confirm these findings and optimize treatment protocols.

Pharmacogenomics (PGx) has revolutionized personalized medicine by empowering the tailoring of drug treatments based on individual genetic profiles. However, the complexity of drug response mechanisms necessitates the integration of additional biological and environmental factors. This article explores integrating epigenetics, nutrigenomics, microbiomes, protein interactions, exosomes, and metabolomics with PGx to enhance personalized medicine. In addition to discussing these scientific advancements, we examine the regulatory and ethical challenges of translating multi-omics into clinical practice, including considerations of data privacy, regulatory oversight, and equitable access. By framing these factors within the context of Medication Adherence, Medication Appropriateness, and Medication Adverse Events (MA³), we aim to refine therapeutic strategies, improve drug efficacy, and minimize adverse effects, with the goal of improving personalized medicine. This approach has the potential to benefit patients, healthcare providers, payers, and the healthcare system as a whole by enabling more precise and effective treatments.

Background/Objectives: Chronic graft-versus-host disease (cGVHD) and oral lichen planus (LPO) are chronic inflammatory conditions with similar oral manifestations. This study aimed to assess whether serum and salivary cytokines (IL-1α, IL-6, IL-17) could serve as reliable biomarkers for cGVHD. Methods: A prospective cohort study was conducted involving cGVHD patients, LPO patients, and healthy controls. Cytokine levels in serum and saliva were measured by ELISA and compared across the groups using the Kruskal-Wallis test. Results: IL-17 levels were significantly elevated in the serum of cGVHD patients compared to LPO patients and controls (p < 0.05). However, IL-6 and IL-1α did not show significant differences among the groups. A comparison of salivary samples between the three groups did not reach statistical significance (p > 0.05). Conclusions: This study suggests that IL-17 could be a potential biomarker for cGVHD-related inflammation, warranting further investigation. Salivary samples do not seem to be a reliable biological marker for the diagnosis of cGVHD. The findings underline the need for larger studies to validate these preliminary results.

Background/Objectives: The complications of hypertension depend not only on the mean blood pressure (BP) but also on its variability (BPV). Recent studies suggest that the choroid may serve as an indicator of systemic vascular damage. These studies have been made possible by the increased availability of optical coherence tomography (OCT). The aim of our study was to analyze the relationship between short-term BP variability (STBPV) and choroid-retinal thickness in hypertensive patients. Methods: A total of 98 patients with a mean age of 49 ± 12 years were enrolled in the study. All participants underwent 24 h blood pressure (BP) monitoring to measure 24 h mean systolic (SBP) and diastolic blood pressure (DBP), along with their respective standard deviations (SD), the weighted SD of 24 h SBP and DBP, and the average real variability (ARV) of 24 h SBP and DBP. The choroid-retinal region was assessed using Swept-Source OCT, with choroidal thickness (ChT) and retinal thickness divided into three concentric rings, and their mean choroidal thickness (ChT-or) was calculated. Results: The choroidal thickness of the concentric rings was found to be inversely correlated with all ARV values of the monitored blood pressure means. In particular, a correlation was observed between the ARV of daytime DBP and ChT-or. This correlation remained statistically significant (β = -0.34; p = 0.02) even after adjustment for various confounding factors. The ARV of daytime DBP was the only STBPV index to maintain a significant association, in the multivariate analysis, with the central ring mean thickness (β = -0.314; p = 0.001) and the inner choroidal ring mean thickness (β = -0.262; p = 0.003). Conclusions: Our study demonstrated an independent negative association between short-term BP variability (STBPV), when expressed as ARV of daytime DBP, and choroidal thickness. This finding confirms the value of choroidal thickness as a marker of cardiovascular risk.