Therapeutics and Clinical Risk Management最新文献

Myelofibrosis (MF) is a hematologic malignancy characterized by abnormal proliferation of myeloid cells and the release of pro-inflammatory cytokines, leading to progressive bone marrow dysfunction. The introduction of ruxolitinib just over a decade ago marked a significant advancement in MF therapy, with JAK inhibitors now being the first-line treatment for reducing spleen size and managing symptoms. However, early JAK inhibitors (ruxolitinib and fedratinib) are often associated with cytopenias, particularly thrombocytopenia and anemia, which limit their tolerability. To address these complications, pacritinib has been developed and recently approved for patients with thrombocytopenia, while momelotinib is in development for those with anemia. Although JAK inhibitors have significantly improved the quality of life of MF patients, they have not demonstrated the ability to reduce leukemic transformation and their impact on survival is debated. Numerous drugs are currently being developed and investigated in clinical trials, both as standalone therapy and in combination with JAK inhibitors, with promising results enhancing the benefits of JAK inhibitors. In the near future, MF treatment strategies will involve selecting the most suitable JAK inhibitor based on individual patient characteristics and prior therapy. Ongoing and future clinical trials are crucial for advancing the field and expanding therapeutic options for MF patients.

Objective: To determine the factors influencing proximal radial artery occlusion (PRAO) right radial artery after coronary intervention.

Methods: This is a single-center prospective observational study. A total of 460 patients were selected to undergo coronary angiography (CAG) or percutaneous coronary intervention (PCI) via the proximal transradial approach (PTRA) or distal transradial approach (DTRA). The 6F sheath tube were received by all patients. Radial artery ultrasound was performed 1 day before procedure and 1-4 days after procedure. Patients were divided into the PRAO group (42 cases) and the non-PRAO group (418 cases). General clinical data and preoperative radial artery ultrasound indexes of the two groups were compared to analyze related factors leading to PRAO.

Results: The total incidence of PRAO was 9.1%, including 3.8% for DTAR and 12.7% for PTRA. The PRAO rate of DTRA was significantly lower than that of PTRA (p < 0.05). Female, low body weight, low body mass index (BMI) and CAG patients were more likely to develop PRAO after procedure (p < 0.05). The internal diameter and cross-sectional area of the distal radial artery and proximal radial artery were smaller in the PRAO group than in the non-PRAO group, and the differences were statistically significant (p < 0.05). Multifactorial model analysis showed that the puncture approach, radial artery diameter and procedure type were predictive factors of PRAO, and the receiver operating characteristic curve showed a good predictive value.

Conclusion: A larger radial artery diameter and DTRA may reduce the incidence of PRAO. Preoperative radial artery ultrasound can guide the clinical selection of appropriate arterial sheath and puncture approach.

Dystrophic epidermolysis bullosa (DEB) is one of the major types of EB, a rare hereditary group of trauma-induced blistering skin disorders. DEB is caused by inherited pathogenic variants in the COL7A1 gene, which encodes type VII collagen, the major component of anchoring fibrils which maintain adhesion between the outer epidermis and underlying dermis. DEB can be subclassified into dominant (DDEB) and recessive (RDEB) forms. Generally, DDEB has a milder phenotype, while RDEB patients often have more extensive blistering, chronic inflammation, skin fibrosis, and a propensity for squamous cell carcinoma development, collectively impacting on daily activities and life expectancy. At present, best practice treatments are mostly supportive, and thus there is a considerable burden of disease with unmet therapeutic need. Over the last 20 years, considerable translational research efforts have focused on either trying to cure DEB by direct correction of the COL7A1 gene pathology, or by modifying secondary inflammation to lessen phenotypic severity and improve patient symptoms such as poor wound healing, itch, and pain. In this review, we provide an overview and update on various therapeutic innovations for DEB, including gene therapy, cell-based therapy, protein therapy, and disease-modifying and symptomatic control agents. We outline the progress and challenges for each treatment modality and identify likely prospects for future clinical impact.

Purpose: A central aspect of the treatment of non-unions is the filling of bone defects. The quantity of available autologous bone for this purpose is limited. Alternatively, or additionally, bone substitutes may be used. The aim of this retrospective, single-center study including 404 non-unions in 393 patients is to investigate the effect of tricalcium phosphate (TCP) on the healing of non-unions. Furthermore, the influence of gender, age, smoking status, comorbidities, type of surgical procedure, presence of infection, and length of treatment was investigated.

Methods: We evaluated three groups of patients. Group 1 received TCP + BG, group 2 received BG alone and group 3 received no augmentation. Bone stability was assessed 1 and 2 years after non-union revision surgery through analysis of radiographs using the Lane Sandhu Score. Scores ≥3 were rated as stable Other influencing factors were collected from the electronic medical record.

Results: In 224 non-unions, bone defects were filled with autologous bone and TCP (TCP+BG). In 137 non-unions, bone defects were filled with autologous bone (BG), and in 43 non-unions presenting non-relevant defects, neither autologous bone nor TCP were used (NBG). After 2 years, 72.7% of the TCP+BG patients, 90.1% of the BG patients and 84.4% of the NBG patients achieved a consolidation score ≥3. Advanced age, presence of comorbidities and longer treatment period had a significantly negative effect on consolidation 1 year after surgery. Longer treatment periods also showed a negative significant effect after 2 years. It is notable that larger defects, mainly treated with the combination of autologous bone and TCP, showed similar healing rates to that of smaller defects after 2 years.

Conclusion: The combination of TCP and autologous bone-grafts shows good results in the reconstruction of complicated bone-defects, but patience is required since the healing period exceeds 1 year in most patients.

Polypharmacy increases the risk of unbearable side effects, drug-drug interactions, and hospitalizations in geriatric patients. The iatrogenic risk of inadequate management of antidepressants is very important in this population. Therefore, primary care physicians and geriatricians have the responsibility of the optimization of antidepressants prescriptions. Our work is a literature review of the European and the international guidelines regarding the management of antidepressants. We reviewed the PubMed database and Google scholar for articles and reviews from 2015. We also screened relevant articles for more references and searched the web for available European guidelines relevant to our topic. We divided our findings into four main inquiries that are Indication, effectiveness, tolerability, and iatrogenic risks. Poor or absence of effectiveness should lead to a readjustment of the treatment plan. In case of unbearable side effects, antidepressants should be stopped, and alternative non-pharmacological therapies should be proposed. Doctors should look out for drug-drug interaction risks in this population and constantly adjust the prescription. Prescription of antidepressants is not always evidence based which leads to heavy iatrogenic consequences. We suggest a simple 4-questions-algorithm that aims to remind doctors of the basics of good practice and helps in the process of deprescribing an antidepressant in older adults.

Objective: This study aimed to assess the predictive value of preoperative diffusion tensor imaging (DTI) data for surgical outcomes of patients with supratentorial glioma in the motor function area.

Patients and methods: This is a retrospective study of 43 patients receiving navigation-guided surgery for histopathologically demonstrated supratentorial glioma in the motor function area. All patients underwent preoperative 3 Tesla magnetic resonance imaging examinations with conventional and DTI sequences. Data on preoperative imaging and pre- and postoperative clinical characteristics of patients were retrospectively collected. Univariate and multivariate linear regressions were applied to analyze the relationships between preoperative parameters and pre- and postoperative muscle strength and the Karnofsky Performance Status (KPS) score.

Results: Fourteen patients had low-grade gliomas and 29 had high-grade gliomas. Although the corticospinal tract (CST) score did not differ significantly between tumor grades, edema and deviation were common in low-grade gliomas (64.3%), while destroyed and infiltrated lesions were common in high-grade gliomas (58.6%). Muscle strength improved after surgery in the deviated tract group (40%) more than in the infiltrated tract group (33.3%). Two independent indices, preoperative muscle strength (p = 0.000) and glioma-to-CST distance (p = 0.001), were linearly related to postoperative muscle strength. The preoperative KPS score was the only indicator that affected the postoperative KPS score (p = 0.000).

Conclusion: DTI should be considered in surgical management of supratentorial gliomas in the motor function area to determine the appropriate surgical strategy and predict the nature of the tumor and postoperative motor function.

Purpose: Gefitinib resistance limits the therapeutic efficacy of gefitinib to lung adenocarcinoma (LUAD). The goal of this research is to learn more about the lncRNA AFAP1-AS1 and how it functions in gefitinib-resistant LUAD cells.

Methods: RT-qPCR was performed to test the expression of AFAP1-AS1, miR-653-5p and AGR2 in LUAD tissues with acquired resistance to gefitinib or not as well as in gefitinib-resistant LUAD cells. Cell proliferation, invasion and apoptosis were measured by CCK8 assays, transwell invasion assays and flow cytometry, respectively. Luciferase reporter assay showed that miR-653-5p and AFAP1-AS1 or AGR2 interactions.

Results: In gefitinib-resistant LUAD cells and tissues, AFAP1-AS1 was overexpressed. Meanwhile, silencing AFAP1-AS1 reduced proliferation and migration while increasing apoptosis and gefitinib sensitivity. Mechanically, AFAP1-AS1 sequestered the miR-653-5p and blocked the inhibition of miR-653-5p to AGR2 and stepwise upregulated AGR2 overexpression in LUAD gefitinib resistant cells, resulting gefitinib resistance in LUAD.

Conclusion: AFAP1-AS1 promotes gefitinib-resistance LUAD cells through a previously unrecognized miR-653-5p/AGR2 axis, suggesting targeting AFAP1-AS1/miR-653-5p/AGR2 axis might be a promising way for LUAD intervention.

Background: To date, no study evaluated the cost-effectiveness of palbociclib (PAL) plus fulvestrant (FUL) vs ribociclib (RIB) plus FUL and abemaciclib (ABM) plus FUL in Italy. Cost-effectiveness analysis comparing the three cyclin-dependent 4/6 kinase inhibitors in combination with endocrine therapies for the management of postmenopausal women with HR+, HER2- advanced or metastatic breast cancer in Italy was developed.

Material and methods: To assess the cost-effectiveness of PAL plus FUL vs RIB plus FUL and ABM plus FUL, a cost-minimization has been carried out with a conservative scenario considering three CDK4/6 inhibitors with equal effectiveness in terms of overall survival (OS) (MAIC, Rugo et al 2021). Adverse events (AEs) associated with all therapies were obtained from clinical trials. Ad-hoc analysis was performed to estimate the cost-effectiveness considering the quality-of-life (QoL) data (Lloyd et al 2006).

Results: Cost-minimization inputs were drugs, visits and exams, AE monitoring and best supportive care (BSC) before the progression state, active and BSC in the progression and terminal phase of the last two weeks of life. Given the comparability of PAL, RIB and ABM in terms of efficacy, this analysis demonstrated slight economic savings over a lifetime for PAL. Results showed saving per patient of €305 (lifetime) when PAL is compared with RIB; for PAL vs ABM a saving of €243 (lifetime) in a conservative scenario. Results of a budget impact analysis showed a potential savings of €319,563 for PAL vs RIB and €297,544 for PAL vs ABM. When QoL data were considered, results may favor PAL due to the lower impact of AE with savings and improvement in the QoL related to fewer AE.

Conclusion: From the Italian perspective, a cost-saving profile associated with the use of PAL+FUL for the management of advanced/metastatic HR+/HER2- breast cancer compared to RIB+FUL and ABM+FUL emerged.

Purpose: Oral rehydration solutions (ORSs) are effective in replacing fluids and electrolytes and are widely used. OS-1 Jelly (Otsuka Pharmaceutical Factory, Tokushima, Japan) is a jelly drink corresponding to code 2-1 of the 2021 Japanese Dysphagia Diet. Although jelly drinks are less likely to be aspirated than liquids, their physical properties vary depending on the product. Therefore, the severity of dysphagia may affect intake status. This study aimed to investigate the association between the intake status of ORS jelly and swallowing function.

Patients and methods: Thirty-six patients with dysphagia who required videoendoscopic swallowing evaluation at our university hospital were enrolled. Videoendoscopic swallowing evaluation was performed, and each participant swallowed 5 mL of OS-1 Jelly or thickened water modified to International Dysphagia Diet Standardization Initiative (IDDSI) level 2 three times. Statistical analysis was performed to determine the difference in the number of swallows, time until the swallowing reflex, position for inducing the swallowing reflex, presence of pharyngeal residue, penetration, or aspiration between ORS jelly and thickened water.

Results: The time until the swallowing reflex was induced and the position of the swallowing reflex triggered were significantly earlier for ORS jelly (p=0.012, p=0.001). The incidence of pharyngeal residue was significantly lower with ORS jelly (p=0.002). The Penetration-Aspiration Scale score was similar for both samples (p=0.062), and no aspiration was observed in either sample.

Conclusion: Patients with dysphagia who can swallow thickened water modified to IDDSI level 2 can consume ORS jelly. ORS jelly, which requires no thickening and can be easily and safely consumed, is effective for water and electrolyte intake in patients with dysphagia.