A real-world retrospective-prospective analysis of efficacy and safety of combined ixazomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma: The northern Italy experience.

INTRODUCTION: Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE-MM1. OBJECTIVES AND METHODS: We conducted a retrospective-prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life. RESULTS: At IRd initiation, 34% of pts were aged ≥75 (median 72.5), 8.5% had an ECOG performance status ≥2, 54.7% of evaluable pts carried high-risk cytogenetic abnormalities [del17p and/or t(4;14) and/or t(14;16) and/or 1 g gain/amp], 60.2% had received ≥2 prior lines of therapy (pLoT), 57.5% were lenalidomide (Len)-exposed (including both Len-sensitive and Len-refractory pts), and 22% were Len-refractory. Main G ≥3 adverse events (AEs) were thrombocytopenia (16%) and neutropenia (12.3%). G ≥3 non-hematologic AEs included infections (9.4%) and GI toxicity (diarrhea 5.7%, hepatotoxicity 2.8%), VTE, skin rash, and peripheral neuropathy were mainly G1-2. The overall response rate was 56.4% (≥VGPR 30%). With a median follow-up of 38 m, median PFS (mPFS) was 16 m and the 1-year OS rate was 73%. By subgroup analysis, an extended PFS was observed for pts achieving ≥VGPR (mPFS 21.2 m), time from diagnosis to IRd ≥5 years (26.2 m), 1 pLoT (34.4 m), Len-naïve (NR), age ≥70 (20 m). In pts exposed to Len, non-refractory in any prior line and immediately prior to IRd, mPFS was 16 and 18 m, respectively. An inferior PFS was seen in Len-refractory pts (4.6 m). By multivariate analysis, independent predictors of PFS were age ≥70 (HR 0.6), time from diagnosis ≥5 years (HR 0.32), refractoriness to Len in any prior line (HR 3.33), and immediately prior (HR 4.31). CONCLUSION: IRd might be effective and safe in RRMM pts with an indolent disease, in early lines of treatment, and who proved Len-sensitive, independent of age, and cytogenetic risk.

Efficacy of Microneedling and CO2 Laser for Acne Scar Remodelling: A Comprehensive Review.

Acne scarring is a prevalent issue affecting millions worldwide, with significant psychological and social implications. Microneedling and CO2 laser therapy have emerged as promising modalities for acne scar remodelling. Microneedling induces controlled micro-injuries to stimulate collagen production, while CO2 laser therapy precisely ablates scar tissue. This comprehensive review evaluates the efficacy, safety, and comparative benefits of microneedling and CO2 laser therapy. Literature synthesis reveals both modalities to improve acne scars, albeit with different mechanisms and risks. Factors influencing treatment selection and the role of combination therapy are discussed. Future directions include optimising protocols and exploring novel techniques. Overall, microneedling and CO2 laser therapy offer valuable options for acne scar management, empowering individuals to address the physical and emotional burden of scarring.

Information literacy in the digital age: information sources, evaluation strategies, and perceived teaching competences of pre-service teachers.

Introduction: Information literacy has become indispensable in navigating today's fast-paced media environment, with teachers playing a pivotal role in fostering reflective and critical digital citizenship. Positioned as future gatekeepers, pre-service teachers are the key to teaching media skills and especially information literacy to future generations of pupils. Given the particular challenges facing educators today compared to previous generations, it is important to determine whether the next generation of teachers feel adequately prepared and perceive themselves as competent to pass on these skills to their future pupils. However, previous research has highlighted deficiencies in formal learning opportunities at universities, underscoring the need for further investigation into pre-service teachers' information acquisition, evaluation practices as well as their perceived relevance to teaching, and person-related factors associated with their perceived competence in teaching information literacy. Method: An online questionnaire was presented to participants, employing a mixed-method approach. We qualitatively examined the sources of information used by pre-service teachers and the evaluation strategies they employ, while quantitatively analyzing relationships between pre-service teachers' person-related factors and their perceived teaching competence. Participants assessed their perceived teaching competence, perceived learning opportunities, self-efficacy (general and related to information assessment), perceived informedness, selective exposure, need for cognition, need for cognitive closure, and mistrust in media coverage. Results: Data from 371 participants revealed digital media dominance in information acquisition over traditional sources, albeit with a prevalence of surface-level evaluation strategies over reflective approaches. Two distinct dimensions of perceived competence in teaching information literacy emerged: one focusing on information assessment while the other centers on the understanding of news creation processes. Perceived competence in teaching information literacy was significantly associated with self-efficacy in information assessment, perceived informedness, selective exposure to information as well as perceived learning opportunities focusing on information evaluation. Moreover, pre-service teachers employing diverse information evaluation strategies demonstrated a heightened sense of perceived competence in teaching information assessment. Discussion: Our results provide valuable insights into the multifaceted nature of pre-service teachers' perceived competence in teaching information literacy. Theoretical implications for future research as well as practical implications for teacher education and the structure of future curricula are discussed.

A survey on the effects of patient safety training programs based on SBAR and FMEA techniques on the level of self-efficacy and observance of patient safety culture in Iran hospital, Shiraz in 2022-2023.

BACKGROUND AND OBJECTIVE: Patient safety and medical personnel self-efficacy are among the main factors involved in providing quality health services. Moreover, safety culture in an organization is considered one of the most critical factors regarding patients' safety. Therefore, the present study aimed to determine the effects of patient safety programs based on Situation, Background, Assessment, Recommendation (SBAR) and Failure Model Effects Analysis (FMEA) techniques on self-efficacy and patient safety culture in Iran Hospital of Shiraz in 2022-2023. MATERIALS AND METHODS: This two-stage quasi-experimental study was conducted in 2022-2033. Considering inclusion criteria, the present study included 80 nurses working in Iran Hospital. The participants were divided into groups of SBAR (40 participants) and FMEA (40 participants). All the data were collected using a Hospital Survey on Patient Safety Culture questionnaire and Sherer General Self-Efficacy Scale. Then, the collected data were analyzed using SPSS 13, Fisher's exact test, paired t-test, and independent t-test with a significant level of P < 0.05. RESULTS: The mean score of total patient safety culture between the two groups was insignificant before the intervention (P = 0.58). However, it was more significant in the FMEA group than the SBAR group after the intervention (P < 0/05). In addition, the mean self-efficacy score between the two groups was insignificant before the intervention (P = 0.80). However, after the intervention, the mean score of the FMEA group was significantly higher than the SBAR group (P < 0.05). CONCLUSION: According to the findings of this study, there is a meaningful relationship between patient safety training programs based on SBAR and FMEA techniques on patient safety and self-efficacy of nurses; however, FMEA training has more positive effects on self-efficacy and patient safety compared to other techniques. As a result, these techniques, along with other plans, are recommended to authorities in order to help improve patient safety.

Long-term outcomes with emicizumab in hemophilia A without inhibitors: results from the HAVEN 3 and 4 studies.

Background: Emicizumab, a bispecific monoclonal antibody, bridges activated factor (F) IX and FX, mimicking the function of missing or deficient activated FVIII in people with hemophilia A (HA). Objectives: To evaluate the long-term efficacy and safety of emicizumab prophylaxis in people with HA without FVIII inhibitors in the HAVEN 3 and 4 studies. Methods: HAVEN 3 and 4 were phase 3 open-label studies. Participants received emicizumab maintenance doses of 1.5 mg/kg every week or 3 mg/kg every 2 weeks (HAVEN 3), or 6 mg/kg every 4 weeks (HAVEN 4). Long-term efficacy and safety were assessed. Results: A total of 151 and 40 individuals without FVIII inhibitors received emicizumab in HAVEN 3 and 4, respectively. At the last patient, last visit dates (May 12, 2022 [HAVEN 3] and June 29, 2022 [HAVEN 4]), the median (range) duration of emicizumab exposure across the 2 studies was 248.1 (6.1-287.1) weeks. The mean (95% CI) annualized bleed rate for treated bleeds was 2.0 (0.23-7.15) for weeks 1 to 24, decreasing to 0.9 (0.01-5.28) by weeks 217 to 240. Overall, 188 (98.4%) participants experienced ≥1 adverse event (AE), with 185 treatment-related AEs in 71 (37.2%) participants. Forty-four (23.0%) participants reported a serious AE. Two thromboembolic events were reported, which were deemed unrelated to emicizumab by the investigator. No thrombotic microangiopathies were reported. Conclusion: With nearly 5 years of emicizumab exposure across the HAVEN 3 and 4 studies in people with HA without inhibitors, these data indicate continued bleed control with no new safety signals observed during long-term follow-up.

Predicting early gastric cancer risk using machine learning: A population-based retrospective study.

Background: Early detection and treatment are crucial for reducing gastrointestinal tumour-related mortality. The diagnostic efficiency of the most commonly used diagnostic markers for gastric cancer (GC) is not very high. A single laboratory test cannot meet the requirements of early screening, and machine learning methods are needed to aid the early diagnosis of GC by combining multiple indicators. Methods: Based on the XGBoost algorithm, a new model was developed to distinguish between GC and precancerous lesions in newly admitted patients between 2018 and 2023 using multiple laboratory tests. We evaluated the ability of the prediction score derived from this model to predict early GC. In addition, we investigated the efficacy of the model in correctly screening for GC given negative protein tumour marker results. Results: The XHGC20 model constructed using the XGBoost algorithm could distinguish GC from precancerous disease well (area under the receiver operating characteristic curve [AUC] = 0.901), with a sensitivity, specificity and cut-off value of 0.830, 0.806 and 0.265, respectively. The prediction score was very effective in the diagnosis of early GC. When the cut-off value was 0.27, and the AUC was 0.888, the sensitivity and specificity were 0.797 and 0.807, respectively. The model was also effective at evaluating GC given negative conventional markers (AUC = 0.970), with the sensitivity and specificity of 0.941 and 0.906, respectively, which helped to reduce the rate of missed diagnoses. Conclusions: The XHGC20 model established by the XGBoost algorithm integrates information from 20 clinical laboratory tests and can aid in the early screening of GC, providing a useful new method for auxiliary laboratory diagnosis.

Chinese patent medicine combined with calcium channel blockers in the treatment of essential hypertension:a Bayes network meta-analysis and systematic review.

Backgroud: The co-administration of Chinese patent medicine with calcium channel blockers (CCBs) is a prevalent practice in China for treating essential hypertension (EH). However, robust evidence supporting the efficacy and safety of tailored combinations of different Chinese patent medicines with CCBs, according to individual patient conditions, is still limited. This study sought to elucidate the efficacy and safety of these combinations using a systematic review and network meta-analysis. Materials and methods: Relevant studies were sourced from established databases, incorporating randomized controlled trials published up to 1 February 2023. The ROB2 tool from the Cochrane Collaborative Network was employed to independently assess and cross-verify the quality of the included literature. A network meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 and PRISMA-Network Meta-Analyses (PRISMA-NMA) guidelines. A Bayesian network meta-analysis was utilized to gauge the efficacy and safety of distinct integrations of Chinese patent medicine and CCBs. Primary outcomes were interpreted using a paired fixed-effect meta-analysis. Publication bias was appraised through Egger's test and represented with funnel plots. All statistical analyses were executed within the R statistical framework. Results: Following rigorous selection, data extraction, and bias evaluation, 36 articles were incorporated. Tianma Gouteng Granule, when combined with CCBs, displayed superior efficacy in reducing systolic blood pressure (SBP). In terms of diastolic blood pressure (DBP) reduction, Songling Xuemaikang Capsule combined with CCBs emerged as the most effective. Regarding enhancement of antihypertensive effective rates, Qinggan Jiangya Capsule paired with CCBs demonstrated optimal results. For diminishing Traditional Chinese Medicine syndrome scores, the Qiangli Dingxuan Tablet and CCBs combination proved most beneficial. When aiming to reduce total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels, Tianma Gouteng Granule and CCBs showcased superior results. In contrast, the combination of Songling Xuemaikang Capsule and CCBs was more effective in reducing LDL-C, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Conclusion: This study underscores variability in outcomes from combining Chinese patent medicine and CCBs for hypertension, emphasizing the importance of personalized medicinal combinations, especially Tianma Gouteng Granule and Songling Xuemaikang Capsule. The results offer robust evidence to inform clinical guidelines for essential hypertention and significantly aid clinician in seleting appropriate Chinese patent medicines for treatment.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases.

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

The correlations between parental warmth and children's approaches to learning: a moderated mediation model of self-efficacy and teacher-child closeness.

Researchers have increasingly considered approaches to learning (ATL) a key indicator of school readiness. Our study purposed to examine the impacts of parental warmth on children's approaches to learning, and the mediating role of self-efficacy, as well as the moderating role of teacher-child closeness in this relationship. Using a whole-group sampling method, 414 Chinese children aged 5-6 years participated this research together with their parents and teachers. Parents of those children were asked to fill out in person questionnaires on parental warmth, children's approaches to learning, and self-efficacy. Children's teachers completed the questionnaire regarding teacher-child closeness. Results indicated that children with high parental warmth were more likely to get high approaches to learning and their self-efficacy played a partial mediating role in this link. In addition, teacher-child closeness moderated the correlation between parental warmth and children's self-efficacy. Specifically, the association between parental warmth and children's self-efficacy was stronger for children with high teacher-child closeness than those with low teacher-child closeness. The results extend our understanding of how parental warmth affects children's approaches to learning, revealing that strategies that could enhance self-efficacy would be effective in improving children's approaches to learning.

Electrical impedance tomography as a bedside assessment tool for COPD treatment during hospitalization.

For patients with chronic obstructive pulmonary disease (COPD), the assessment of the treatment efficacy during hospitalization is of importance to the optimization of clinical treatments. Conventional spirometry might not be sensitive enough to capture the regional lung function development. The study aimed to evaluate the feasibility of using electrical impedance tomography (EIT) as an objective bedside evaluation tool for the treatment of acute exacerbation of COPD (AECOPD). Consecutive patients who required hospitalization due to AECOPD were included prospectively. EIT measurements were conducted at the time of admission and before the discharge simultaneously when a forced vital capacity maneuver was conducted. EIT-based heterogeneity measures of regional lung function were calculated based on the impedance changes over time. Surveys for attending doctors and patients were designed to evaluate the ease of use, feasibility, and overall satisfaction level to understand the acceptability of EIT measurements. Patient-reported outcome assessments were conducted. User's acceptance of EIT technology was investigated with a five-dimension survey. A total of 32 patients were included, and 8 patients were excluded due to the FVC maneuver not meeting the ATS criteria. Spirometry-based lung function was improved during hospitalization but not significantly different (FEV1 %pred.: 35.8% ± 6.7% vs. 45.3% ± 8.8% at admission vs. discharge; p = 0.11. FVC %pred.: 67.8% ± 0.4% vs. 82.6% ± 5.0%; p = 0.15. FEV1/FVC: 0.41 ± 0.09 vs. 0.42 ± 0.07, p = 0.71). The symptoms of COPD were significantly improved, but the correlations between the improvement of symptoms and spirometry FEV1 and FEV1/FVC were low (R = 0.1 and -0.01, respectively). The differences in blood gasses and blood tests were insignificant. All but one EIT-based regional lung function parameter were significantly improved after hospitalization. The results highly correlated with the patient-reported outcome assessment (R > 0.6, p < 0.001). The overall acceptability score of EIT measurement for both attending physicians and patients was high (4.1 ± 0.8 for physicians, 4.5 ± 0.5 for patients out of 5). These results demonstrated that it was feasible and acceptable to use EIT as an objective bedside evaluation tool for COPD treatment efficacy.

The mental health self-direction scale: An abridged version and its sensitivity to change.

OBJECTIVE: The Mental Health Self-Direction Scale (MHSD) measures the extent to which clients are able to resolve mental problems by themselves. Because this scale had not yet been evaluated, the aims of this paper were (a) to evaluate and improve the MHSD and (b) to explore the sensitivity to change of the improved scale. METHOD: The MHSD was evaluated and improved by means of confirmatory factor analyses of data from one longitudinal and two cross-sectional outpatient sample. Inconsistent items were removed in a stepwise fashion. Subsequently, the scale's sensitivity to change was explored in the longitudinal sample by using latent growth curve models. RESULTS: The original 31-item scale was reduced to a more stable version with 19 items that yielded four factors named: actorship, demoralization, commitment, and understanding. Throughout clients' treatment, actorship and understanding tended to increase; demoralization tended to decrease; and commitment remained consistently high. CONCLUSIONS: The abridged MHSD scale is stable and sensitive to change. It measures the extent to which clients experience and develop self-direction throughout their treatment. With the use of the new MHSD scale, new views on mental health that emphasize clients' ability to actively engage and cope with health-challenges can be incorporated into clinical treatment.

Emotional Support from Care Recipients, Caring Relationship Quality, and Caregiving Self-Efficacy among Family Caregivers of Older Adults.

We analyzed 756 family caregivers (mean age = 62.3 years), investigating how emotional support from older care recipients was linked to caregivers' self-efficacy through caring relationship qualtiy. Results indicate a significant positive association between emotional support and caregivers' self-efficacy (r = 0.207, p < .01). Caring relationship quality positively correlated with emotional support (r = 0.292, p < .01) and caregivers' self-efficacy (r = 0.141, p < .01). Controlling for socialdemographic and care-related factors, relationship quality partially mediated the association between emotional support from care recipients and caregivers' self-efficacy. This suggests that interventions supporting caregivers' self-efficacy may benefit from considering both care recipients and dyadic relationships.

Scoping review of the use of mesenchymal stem and stromal cell products in cats, Part 2: current scope and efficacy.

A scoping review of published literature found 108 articles related to mesenchymal stem or stromal cell (MSC) use in cats. Twenty-four of the publications summarized the treatment of 192 cats with MSC products for 12 naturally occurring and induced diseases. These trials used a variety of cell sources, administration routes, delivery vehicles, and dosages. The majority of studies did not have a control group. The disease with the largest number of cats administered MSCs thus far is chronic kidney disease (n = 59 cats). The majority of cats had no adverse events associated with treatment, which supports continued interest in the potential use of MSC products to address unmet medical needs. Treatment outcomes of the 192 cats have ranged from no response to long-term cure, depending on the disease being treated and the particular study. Some of these early studies show promise and provide significant information to direct both the design and focus of larger clinical trials investigating the safety and efficacy of MSC treatment for veterinary and human applications.

A digoxin derivative that potently reduces intraocular pressure - efficacy and mechanism of action in different animal models.

Glaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side-effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase. The cyclobutyl derivative (DcB) displays strong selectivity for the human a2 isoform and potently reduces IOP in rabbits. These observations appeared consistent with a hypothesis that in ciliary epithelium DcB inhibits the a2 isoform of Na,K-ATPase, which is expressed strongly in non-pigmented cells, reducing aqueous humor (AH) inflow. This paper extends assessment of efficacy and mechanism of action of DcB using an ocular hypertensive non-human primate model (OHT-NHP) (Macaca fascicularis). In OHT-NHP, DcB potently lowers IOP, in both acute (24 hour) and extended (7-10 day) settings, accompanied by increased aqueous humor flow rate (AFR). By contrast, ocular normotensive animals (ONT-NHP) are poorly responsive to DcB, if at all. The mechanism of action of DcB has been analyzed using isolated porcine ciliary epithelium and perfused enucleated eyes to study AH inflow and AH outflow facility, respectively. (1) DcB significantly stimulates AH inflow although prior addition of 8-Br-cAMP, which raises AH inflow, precludes additional effects of DcB. (2) DcB significantly increases AH outflow facility via the trabecular meshwork (TM). Taken together, the data indicates that the original hypothesis on the mechanism of action must be revised. In the OHT-NHP, and presumably other species, DcB lowers IOP by increasing AH outflow facility rather than by decreasing AH inflow.

Lavender oil preparation Silexan is effective in mild-to-moderate major depression: a randomized, placebo- and reference-controlled trial.

Anxiety and depressive disorders have overlapping symptoms and share common neurobiological pathways. Antidepressant drugs have been demonstrated to be efficacious in anxiety as well. Vice versa, it may also be promising to investigate the efficacy of anxiolytic drugs such as silexan in major depressive disorder (MDD). Patients with a mild or moderate, single or recurrent episode of MDD and a total score of 19-34 points on the Montgomery Åsberg Depression Rating Scale (MADRS) were randomized to receive 1 × 80 mg/d silexan, 1 × 50 mg/d sertraline, or placebo double-blind, double-dummy for 56 days. The primary outcome measure was the MADRS total score change between baseline and treatment end. Treatment groups were compared using a treatment policy estimand. 498 subjects (silexan 170, sertraline 171, placebo 157) were treated and analyzed. After 8 weeks, silexan and sertraline were superior to placebo for MADRS total score reduction, with absolute differences to placebo of 2.17 (95% confidence interval: 0.58; 3.76) points and 2.59 (1.02; 4.17) points, respectively (p < 0.01). Moreover, silexan was superior to placebo for alleviation of functional impairment according to the Sheehan Disability Scale with a difference of 2.40 (1.04; 3.76) points (p < 0.001). Both treatments were well tolerated; eructation was the most frequent adverse effect of silexan. The study confirms the antidepressant efficacy of silexan in mild or moderate MDD, including significant improvements in the subjects' functional capacity. The results for sertraline confirm the assay sensitivity of the trial. Both drugs were well tolerated.Trial registrationEudraCT2020-000688-22 first entered on 12/08/2020.

Evaluation of the efficacy of autogenous tibial periosteal bone grafting in the treatment of osteochondral lesions of the talus and analysis of three-dimensional factors in the necrotic zone.

PURPOSE: This study aims to explore the clinical value of autogenous tibial periosteal bone grafting in the treatment of osteochondral lesions of the talus (OLT) and analyze the three-dimensional factors in the necrotic zone of the talus. METHODS: A retrospective analysis was performed on 36 patients who underwent autogenous tibial periosteal bone grafting in the Foot and Ankle Surgery Department of our hospital between September 2018 and September 2022. The American Orthopaedic Foot and Ankle Society (AOFAS), Visual Analogue Scale (VAS), and Chinese Short-Form 36 Health Survey (SF-36) were used to evaluate treatment efficacy prior to surgery and at the last follow-up. Furthermore, Mimics 21.0 software was employed to measure the three-dimensional data of the necrotic area, including surface area, volume, and depth, in order to investigate their potential impact on patient prognosis. RESULTS: Among the 36 OLT patients who obtained complete follow-up, there were 22 males and 14 females. No complications such as surgical site infection, non-union of cartilage, post-traumatic arthritis, or donor site pain were observed. The AOFAS, VAS, and Chinese SF-36 scores of all patients at the last follow-up showed significant improvement compared to preoperative values. There was no significant correlation between the AOFAS, VAS, and Chinese SF-36 scores at the last follow-up and the depth, surface area, and volume of the necrotic zone. CONCLUSION: The use of autogenous tibial periosteal bone grafting can safely and effectively treat Hepple V OLT. Additionally, there is no significant correlation between the three-dimensional factors of the necrotic area and the prognosis of the patients.

Identification of a risk score model based on tertiary lymphoid structure-related genes for predicting immunotherapy efficacy in non-small cell lung cancer.

BACKGROUND: Tertiary lymphoid structures (TLSs) affect the prognosis and efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC), but the underlying mechanisms are not well understood. METHODS: TLSs were identified and categorized online from the Cancer Digital Slide Archive (CDSA). Overall survival (OS) and disease-free survival (DFS) were analyzed. GSE111414 and GSE136961 datasets were downloaded from the GEO database. GSVA, GO and KEGG were used to explore the signaling pathways. Immune cell infiltration was analyzed by xCell, ssGSEA and MCP-counter. The analysis of WGCNA, Lasso and multivariate cox regression were conducted to develop a gene risk score model based on the SU2C-MARK cohort. RESULTS: TLS-positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029). Both the TLS-positive and TLS-mature groups exhibited genes enrichment in immune activation pathways. The TLS-mature group showed more activated dendritic cell infiltration than the TLS-immature group. We screened TLS-related genes using WGCNA. Lasso and multivariate cox regression analysis were used to construct a five-genes (RGS8, RUF4, HLA-DQB2, THEMIS, and TRBV12-5) risk score model, the progression free survival (PFS) and OS of patients in the low-risk group were markedly superior to those in the high-risk group (p < 0.0001; p = 0.0015, respectively). Calibration and ROC curves indicated that the combined model with gene risk score and clinical features could predict the PFS of patients who have received immunotherapy more accurately than a single clinical factor. CONCLUSIONS: Our data suggested a pivotal role of TLSs formation in survival outcome and immunotherapy response of NSCLC patients. Tumors with mature TLS formation showed more activated immune microenvironment. In addition, the model constructed by TLS-related genes could predict the response to immunotherapy and is meaningful for clinical decision-making.

The efficacy of mindfulness-based programs in reducing anxiety among nurses in hospital settings: A systematic review.

BACKGROUND: The increasing pressure of their professional duties has led to a notable concern regarding the mounting anxiety levels among nurses. The ongoing discussion revolves around the efficacy of mindfulness as a means to alleviate anxiety in nurses. AIM: This systematic review evaluated the effectiveness of mindfulness in reducing anxiety among nurses. METHODS: The evaluation followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. An extensive and comprehensive search was conducted across eight databases to identify studies that utilized randomized controlled trials (RCTs) and were published in English between 2011 and 2022. Independently, two reviewers assessed the validity of the randomized controlled trials using the Consolidated Standards of Reporting Trials criteria. Additionally, two authors independently employed the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-2) method to evaluate the potential bias in the RCTs. RESULTS: Eight randomized controlled trial studies that were deemed eligible were included in the current analysis. Based on the literature review, it was determined that mindfulness-based training can assist nurses in reducing their anxiety levels. Furthermore, the effectiveness of mindfulness-based programs in enhancing nurses' mindfulness and self-compassion has been firmly established. CONCLUSIONS: Based on existing literature, mindfulness-based interventions have proven to be effective in reducing anxiety levels among nurses. However, in order to enhance the overall quality of research, it is necessary to implement more rigorous controlled designs that include randomization. Additionally, larger sample sizes with a diverse range of participants are needed to establish and validate the effectiveness of mindfulness-based programs in alleviating anxiety among nurses. LINKING EVIDENCE TO ACTION: Implementing mindfulness-based training in healthcare organizations can offer numerous benefits. One such advantage is that it can help nurses in reducing anxiety and enhancing their ability to handle the pressures associated with their profession. STUDY REGISTRATION: PROSPERO Protocol registration ID: CRD42023475157.

Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid.

OBJECTIVE: This study aimed to indicate whether a declined plasma concentration of valproic acid (VPA) induced by co-administration of meropenem (MEPM) could affect the antiepileptic efficacy of VPA. METHODS: We retrospectively reviewed data of hospitalized patients who were diagnosed with status epilepticus or epilepsy between 2010 and 2019. Patients co-administered VPA and MEPM during hospitalization were screened and assigned to the exposure group, while those co-administerd VPA and other broad-spectrum antibiotics were allocated to the control group. RESULTS: The exposure group and control group included 50 and 11 patients, respectively. With a similar dosage of VPA, the plasma concentration of VPA significantly decreased during co-administration (24.6 ± 4.3 µg/mL) compared with that before co-administration (88.8 ± 13.6 µg/mL, p < 0.0001), and it was partly recovered with the termination of co-administration (39.8 ± 13.2 µg/mL, p = 0.163) in the exposure group. The inverse probability of treatment weighting estimated the treatment efficacy via changes in seizure frequency, seizure duration, and concomitant use of antiepileptic drugs, which were not significantly different between the exposure and control groups. In the exposure group, there was no significant differences in seizure frequency between the periods of before-during and before-after (p = 0.074 and 0.153, respectively). Seizure duration during VPA-MEPM co-administration was not significantly different from that before co-administration (p = 0.291). CONCLUSIONS: In this study, the reduced plasma concentration of VPA induced by the co-administration of MEPM did not affect the antiepileptic efficacy of VPA. This conclusion should be interpreted with caution, and more research is warranted. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000034567. Registered on 10 July 2020.

Negative Mood is Associated with Sociobehavioral Factors Contributing to Cardiovascular Risk in an Immigrant Population.

Background: Immigrants to the United States, on average, accumulate cardiovascular risk after resettlement, including obesity. There is a need to co-create interventions to address these disparities, and mood may be an important mediating factor. Methods: The Healthy Immigrant Community (HIC) study, set in southeast Minnesota, enrolled 475 adult participants in a weight loss intervention to reduce cardiovascular risk. Baseline questionnaires assessed mood, nutrition, physical activity, self-efficacy for healthy eating and physical activity, social support, and cohesion. A single-item mood rating of poor or fair was considered "negative", while ratings of good, very good, or excellent were considered "positive". Results: A total of 449 HIC participants (268 Hispanic/Latino and 181 Somali) with complete baseline measures and were included in this analysis. Participants endorsing negative mood compared to those endorsing positive mood had lower scores for healthy eating (p = 0.02) and physical activity levels (p = 0.03), lower confidence in eating a healthy diet (p = 0.001), and felt less of a sense of belonging to their community (p = 0.01). Those endorsing negative mood also reported receiving less social support from their family and friends to eat healthy (p = < 0.001) and be physically active (p = 0.01), and less often accessed community resources for healthy eating (p = 0.001) and physical activity (p = < 0.01) compared to participants reporting positive mood. Conclusions: Negative mood was associated with less healthy nutrition, lower confidence in eating healthy, sedentary lifestyle, and perceived lack of belonging to the community. Integrating mood management and self-efficacy strategies may enhance the effectiveness of lifestyle interventions among immigrants who report negative mood. ClinicalTrialsgov registration: NCT05136339; April 23, 2022.