Journal of Personalized Medicine最新文献

Pharmacogenomic (PGx) testing can help personalise psychiatric prescribing and improve on the currently adopted trial-and-error prescribing approach. However, widespread implementation is yet to occur. Understanding factors influencing implementation is pertinent to the psychiatric PGx field. Normalisation Process Theory (NPT) seeks to understand the work involved during intervention implementation and is used by this review (PROSPERO: CRD42023399926) to explore factors influencing PGx implementation in psychiatry. Four databases were systematically searched for relevant records and assessed for eligibility following PRISMA guidance. The QuADS tool was applied during quality assessment of included records. Using an abductive approach to codebook thematic analysis, barrier and facilitator themes were developed using NPT as a theoretical framework. Twenty-nine records were included in the data synthesis. Key barrier themes included a PGx knowledge gap, a lack of consensus in policy and guidance, and uncertainty towards the use of PGx. Facilitator themes included an interest in PGx use as a new and improved approach to prescribing, a desire for a multidisciplinary approach to PGx implementation, and the importance of fostering a climate for PGx implementation. Using NPT, this novel review systematically summarises the literature in the psychiatric PGx implementation field. The findings highlight a need to develop national policies on using PGx, and an education and training workforce plan for mental health professionals. By understanding factors influencing implementation, the findings help to address the psychiatric PGx implementation gap. This helps move clinical practice closer towards a personalised psychotropic prescribing approach and associated improvements in patient outcomes. Future policy and research should focus on the appraisal of PGx implementation in psychiatry and the role of pharmacists in PGx service design, implementation, and delivery.

Background: Autism spectrum disorder (ASD) is related to social communication difficulties, repetitive behaviors, and highly restricted interests beginning early in life. Currently, ASD is more diagnosed than in the past, and new models are needed. The Advanced Integrative Model (AIM) is a new model in which genes and concomitant medical problems to diagnosis (CMPD) and the impact of their rigorous and adequate treatment are considered.

Methods: The role of a dynamic encephalopathy from which the individual response, susceptibilities in the brain and outside the brain, gut barrier and brain-blood-barrier permeabilities, and the plastic nature of the brain is proposed as a tool for diagnosis. The concomitant medical problems (CMP) are those at and outside the brain. The individual response to treatments of CMP is analyzed.

Results: The AIM allows for classification into 3 main groups and 24 subgroups.

Conclusions: The groups and subgroups in ASD are obtained taking into account CMPD treatments and individual response.

Background: This multicentric, retrospective study investigated the use of stereotactic body radiotherapy (SBRT) in patients (pts) with metastatic renal cell carcinoma (mRCC) who experienced oligoprogression during a combination therapy with an immune checkpoint inhibitor (ICI) and a tyrosine-kinase inhibitor (TKI).

Methods: We retrospectively evaluated 34 pts affected by oligoprogressive RCC treated with an ICI-TKI combination between January 2020 and December 2023. SBRT was delivered to each site of oligoprogressive metastatic disease. After SBRT, pts were given follow-up clinical evaluations. 6-12-18-month local control (LC) rates and median next-line treatment-free survival (NEST-FS) were the primary endpoints. The secondary endpoints were overall response rate (ORR), clinical benefits and safety.

Results: After a median follow-up of 24 months, 6-12-18-month LC rates were 100%, 71% and 43%, respectively, and the median NEST-FS was 20 months. ORR was 90%, while clinical benefit was 100%. No > G2 adverse events related to SBRT were recorded.

Conclusions: In our study, SBRT for oligoprogressive mRCC turned out to be a safe and useful treatment which was able to preserve current treatment. Further prospective studies are necessary to explore the effects of the ICIs-TKIs combination and SBRT upon oligoprogressive sites in mRCC.

Background: Distal bile duct cancer is an aggressive malignancy. Tumor-infiltrating immune cells (TIICs) in the tumor microenvironment are crucial for predicting prognosis in various cancers. In this study, we analyzed TIICs based on CD11b, CD163, and CD8 expression, and evaluated their association with clinicopathologic factors and prognosis in distal bile duct cancer. Methods: A total of 90 patients who underwent curative resection for distal bile duct cancer were enrolled. We analyzed CD11b+ tumor-infiltrating myeloid cells (TIMs), CD163+ tumor-infiltrating macrophages (TAMs), and CD8+ tumor-infiltrating lymphocytes (TILs) using immunohistochemistry and tissue microarrays. The correlation between TIICs and clinicopathologic characteristics was assessed. Results: Low levels of CD11b+ TIMs (p < 0.001) and high levels of CD8+ TILs (p = 0.003) were significantly associated with improved overall survival (OS). A combined low level of CD11b+ TIMs and high level of CD8+ TILs was identified as an independent favorable prognostic factor (hazard ratio, 0.159; confidence interval, 0.061-0.410; p < 0.001). Conclusions: CD11b+ TIMs play a crucial role in the tumor microenvironment and the prognosis of distal bile duct cancer. The combined analysis of CD11b+ TIMs and CD8+ TILs can predict survival in patients with distal bile duct cancer.

Objectives: Thyroid eye disease (TED) treatment has been recently revolutionized with the approval of teprotumumab, a targeted insulin growth factor 1 receptor (IGF1R) inhibitor. To date, teprotumumab is the only FDA-approved drug for treating TED. In this article, we would like to temper the current enthusiasm around IGF1R inhibitors. Methods: critical review of the literature by independent academic practitioners. Results: several questions should be raised. First, "how an orphan drug has become a blockbuster with annual sales exceeding $1 billion?" Teprotumumab infusions are expensive, costing about USD 45,000 for one infusion and USD 360,000 for eight infusions in a 75 kg patient. Teprotumumab approval was based on two randomized clinical trials investigating active (clinical activity score ≥ 4) TED patients. Despite this, teprotumumab was approved by the FDA for "the treatment of TED" without distinguishing between active and inactive forms. The second question is as follows: "how can a new drug, compared only to a placebo, become the new standard without being compared to historically established gold standard medical or surgical treatments?" Teprotumumab has never been compared to other medical treatments in active TED nor to surgery in chronic TED. Up to 75% of patients may experience proptosis regression after treatment discontinuation. Finally, ototoxicity has emerged as a potentially devastating side effect requiring frequent monitoring. Investigation into the long-term side effects, especially in women of childbearing age, is also warranted. Conclusions: Teprotumumab is undoubtedly a major treatment option in TED. However, before prescribing a drug, practitioners should assess its benefit/risk ratio based on the following: (i) evidence-based medicine; (ii) their empirical experience; (iii) the cost/benefit analysis; (iv) the long-term outcomes and safety profile.

Introduction: The choice of prosthesis for vertebral body reconstruction (VBR) remains a controversial issue due to the lack of a reliable solution. The subsidence rate of the most commonly used titanium mesh cages (TMC) ranges from 42.5% to 79.7%. This problem is primarily caused by the differences in the elastic modulus between the TMC and bone. This review aims to summarize the clinical and radiological outcomes of new 3D-printed artificial vertebral bodies (3DP AVB). Methods: A literature search of PubMed, Scopus and Google Scholar was conducted to extract relevant studies. After screening the titles and abstracts, a total of 50 articles were selected for full-text analysis. Results: Preliminary data suggest fewer implant-related complications with 3DP AVB. Most comparative studies indicate significantly lower subsidence rates, reduced operation times and decreased intraoperative blood loss. However, the scarcity of randomized clinical trials and the high variability of the results warrant caution. Conclusion: Most literature data show an advantage of 3DP AVB in terms of the operation time, intraoperative blood loss and subsidence rate. However, long manufacturing times, high costs and regulatory issues are this technology's main drawbacks.

Background/objectives: The identification of coronary artery disease (CAD) high-risk individuals is a major clinical need for timely diagnosis and intervention. Many different polygenic scores (PGSs) for CAD risk are available today to estimate the genetic risk. It is necessary to carefully choose the score to use, in particular for studies on populations, which are not adequately represented in the large datasets of European biobanks, such as the Italian one. This work aimed to analyze which PGS had the best performance within the Italian population.

Methods: We used two Italian independent cohorts: the EPICOR case-control study (576 individuals) and the Atherosclerosis, Thrombosis, and Vascular Biology (ATVB) Italian study (3359 individuals). We evaluated 266 PGS for cardiovascular disease risk from the PGS Catalog, selecting 51 for CAD.

Results: Distributions between patients and controls were significantly different for 49 scores (p-value < 0.01). Only five PGS have been trained and tested for the European population specifically. PGS003727 demonstrated to be the most accurate when evaluated independently (EPICOR AUC = 0.68; ATVB AUC = 0.80). Taking into account the conventional CAD risk factors further enhanced the performance of the model, particularly in the ATVB study (p-value = 0.0003).

Conclusions: European CAD PGS could have different risk estimates in peculiar populations, such as the Italian one, as well as in various geographical macro areas. Therefore, further evaluation is recommended for clinical applicability.

The effect of subthalamic stimulation (STN-DBS) on patients' personal satisfaction with life and their Parkinson's disease (PD) treatment is understudied, as is its correlation with quality of life (QoL). Therefore, we tested the hypothesis that STN-DBS for PD enhances satisfaction with life and treatment. In a prospective, multicenter study with a 6-month follow-up involving 121 patients, we measured the main outcomes using the Satisfaction with Life and Treatment Scale (SLTS-7). Secondary outcomes included the eight-item PD Questionnaire (PDQ-8), European QoL Questionnaire (EQ-5D-3L), EQ-Visual Analogue Scale (VAS), Non-Motor Symptom Scale (NMSS), Hospital Anxiety and Depression Scale (HADS), and Unified PD Rating Scale (UPDRS). Longitudinal outcome changes, effect sizes (Cohen's d), and correlations between outcome changes were analyzed. SLTS-7 scores improved at the 6-month follow-up, particularly in the domains of 'satisfaction with physical health' and 'satisfaction with treatment'. Change scores correlated strongly (EQ-VAS), moderately (PDQ-8 SI and HADS), and weakly (UPDRS-activities of daily living and EQ-5D-3L) with other scales. Satisfaction with physical health, psychosocial well-being, or treatment was not related to UPDRS-motor examination. This study provides evidence that STN-DBS enhances patients' personal satisfaction with life and treatment. This satisfaction is associated with improvements in the QoL, daily activities, and neuropsychiatric aspects of PD rather than its motor aspects.

In the original publication [...].

Background: Sleep apnea and nocturnal bruxism belong to sleep disorders that can affect the quality of life. The aim of this study was to investigate the effects on patients with moderate sleep apnea and nocturnal bruxism of Botox injection as monotherapy or associated with wearing thermoformed occlusal splints and to determine the patients' satisfaction degree after the applied treatments. Methods: The selected patients for study were divided into two groups: in the first group, the patients (n = 18) treatment consisted of injecting Botox (Allergan) into the masseter muscle as monotherapy; in the second group, the patients (n = 18) benefited from associated therapy, Botox injections in masseter muscle, and the wear of thermoformed occlusal splints. At baseline, at three weeks, at three months, and six months after the effectuation of therapies, the monitoring sessions were realized. Results: The associated therapy presented better results in decreasing the studied symptoms than the monotherapy. Both therapies improved patient satisfaction. Conclusions: The applied therapies for treating the specific symptomatology in moderate sleep apnea and sleep bruxism were efficacious. Patient satisfaction was very good in both groups after the applied treatments, but the associated therapy presented better results than monotherapy.