Integrated transcriptomic landscape of the effect of anti-steatotic treatments in high-fat diet mouse models of non-alcoholic fatty liver disease.

High-fat diet (HFD) mouse models are widely used in research to develop medications to treat non-alcoholic fatty liver disease (NAFLD), as they mimic the steatosis, inflammation, and hepatic fibrosis typically found in this complex human disease. The aims of this study were to identify a complete transcriptomic signature of these mouse models and to characterize the transcriptional impact exerted by different experimental anti-steatotic treatments. For this reason, we conducted a systematic review and meta-analysis of liver transcriptomic studies performed in HFD-fed C57BL/6J mice, comparing them with control mice and HFD-fed mice receiving potential anti-steatotic treatments. Analyzing 21 studies broaching 24 different treatments, we obtained a robust HFD transcriptomic signature that included 2,670 differentially expressed genes and 2,567 modified gene ontology biological processes. Treated HFD mice generally showed a reversion of this HFD signature, although the extent varied depending on the treatment. The biological processes most frequently reversed were those related to lipid metabolism, response to stress, and immune system, whereas processes related to nitrogen compound metabolism were generally not reversed. When comparing this HFD signature with a signature of human NAFLD progression, we identified 62 genes that were common to both; 10 belonged to the group that were reversed by treatments. Altered expression of most of these 10 genes was confirmed in vitro in hepatocytes and hepatic stellate cells exposed to a lipotoxic or a profibrogenic stimulus, respectively. In conclusion, this study provides a vast amount of information about transcriptomic changes induced during the progression and regression of NAFLD and identifies some relevant targets. Our results may help in the assessment of treatment efficacy, the discovery of unmet therapeutic targets, and the search for novel biomarkers. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Promoter profiles in plasma CfDNA exhibits a potential utility of predicting the efficacy of neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. METHOD: First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. RESULTS: The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978-0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. CONCLUSION: These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.

Reporting on patient's body mass index (BMI) in recent clinical trials for patients with breast cancer: a systematic review.

BACKGROUND: The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the potential differential efficacy of most drugs according to the body mass index (BMI). Here, we conducted a systematic review on recent clinical drug trials to document the dosing regimen of recent drugs, the reporting of BMI and the possible exclusion of patients according to BMI, other adiposity measurements and/or diabetes (leading comorbidity of obesity). We further explored whether treatment efficacy was evaluated according to BMI. METHODS: A search of Pubmed and ClinicalTrials.gov was performed to identify phase I-IV trials investigating novel systemic breast cancer treatments. Dosing regimens and exclusion based on BMI, adiposity measurements or diabetes, documentation of BMI and subgroup analyses according to BMI were assessed. RESULTS: 495 trials evaluating 26 different drugs were included. Most of the drugs (21/26, 81%) were given in a fixed dose independent of patient weight. BMI was an exclusion criterion in 3 out of 495 trials. Patients with diabetes, the leading comorbidity of obesity, were excluded in 67/495 trials (13.5%). Distribution of patients according to BMI was mentioned in 8% of the manuscripts, subgroup analysis was performed in 2 trials. No other measures of adiposity/body composition were mentioned in any of the trials. Retrospective analyses on the impact of BMI were performed in 6 trials. CONCLUSIONS: Patient adiposity is hardly considered as most novel drug treatments are given in a fixed dose. BMI is generally not reported in recent trials and few secondary analyses are performed. Given the prevalence of patients with obesity and the impact obesity can have on pharmacokinetics and cancer biology, more attention should be given by investigators and study sponsors to reporting patient's BMI and evaluating its impact on treatment efficacy and toxicity.

Impact of proton pump inhibitors on the efficacy of androgen receptor signaling inhibitors in metastatic castration-resistant prostate cancer patients.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups. RESULTS: The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered. CONCLUSIONS: The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.

Training the microbiota to increase immune checkpoint blockade and to reduce toxicity.

There is no doubt that immunotherapy, particularly immune checkpoint blockade (ICB), has drastically improved treatment of metastatic cancer patients. Microbiota composition has been proposed to be one of the reasons for failure or success. ICB works via the activation or reactivation of T cells that are "switched off" by tumor cells or by the tumor microenvironment. Even advanced metastatic disease, previously considered as untreatable, can benefit from cancer immunotherapy. However, still a good proportion of patients does not respond to therapy or acquires resistance during treatment. Some genera or species of bacteria have been associated with treatment response or toxicity, but as the composition of the microbiota is not static, rather, it is very dynamic there is promise that by changing the microbiota composition, or by harnessing the microbiota 'secrete' tricks, one can improve treatment efficacy or reduce toxicity. Several players, including diet, prebiotics, probiotics, and postbiotics, have been proposed to shape the microbiota. In this minireview, we summarize very recent data on how to train the microbiota to increase ICB efficacy and reduce toxicity.

Effect of gender and age on bDMARD efficacy for axial spondyloathritis patients: a meta-analysis of randomized controlled trials.

OBJECTIVE: To study the therapeutic variations of biological and targeted synthetic disease-modifying antirheumatic drugs(b/tsDMARDs) between genders and across age stages in axial spondyloarthritis (axSpA) patients through meta-analysis. METHODS: Randomized controlled trials (RCTs), published by Pubmed, Scopus, and Embase before August 10, 2023, testing the efficiency of b/tsDMARDs in axSpA, were searched and systematically reviewed. The Assessment of Spondyloarthritis International Society ≥40% improvement (ASAS40) response was used as the primary outcome of treatment response. RESULTS: : Only one study meet the inclusion criteria was related to tsDMARD, which was excluded from further data combination. Nine studies of bDMARDs, with the involvement of 4127 patients, were included for final analysis. When compared with placebo, both males (OR = 3.14; 95%CI, 2.66-3.70) and females (2.32; 1.82-2.82), younger (4.00; 2.50-6.40) and older (2.21; 1.15-4.22) patients, presented significantly better responses to bDMARDs. Besides, the efficacies were more evident in males (1.89; 1.56-2.30) and younger patients (2.07; 1.42-3.02). Subgroup analysis revealed that gender difference in efficacy was more obvious in non-radiographic-axSpA (nr-axSpA) patients (Pheterogeneity=0.03, I2=78.1%). Moreover, males with radiographic-axSpA (r-axSpA) and nr-axSpA shared similar responses to bDMARDs (Pheterogeneity=0.87, I2=0%), while females with r-axSpA showed greater response than those with nr-axSpA (Pheterogeneity=0.005, I2=87.4%). CONCLUSIONS: BioDMARDs were efficient in all axSpA patients regardless of gender or age stage. However, the treatment responses were more evident in male and younger patients. Besides, females with r-axSpA had greater responses than those with nr-axSpA, whereas no relevant difference was observed in males, indicating that the gender difference on efficacy was larger in nr-axSpA patients.

Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

Indirect treatment comparisons of the gene therapy etranacogene dezaparvovec versus extended half-life factor IX therapies for severe or moderately severe haemophilia B.

INTRODUCTION: Etranacogene dezaparvovec gene therapy for haemophilia B demonstrated superior efficacy at 24 months in reducing bleeds versus a ≥6-month lead-in period of prophylaxis with FIX products in the phase 3 trial, HOPE-B. In the absence of head-to-head comparisons of etranacogene dezaparvovec versus FIX products, indirect treatment comparisons (ITC) can be used. AIM: To compare the efficacy of etranacogene dezaparvovec versus rIX-FP, rFIXFc and N9-GP using ITC, and support HOPE-B results. METHODS: Data were leveraged from Phase 3 pivotal trials: HOPE-B, PROLONG-9FP, B-LONG and Paradigm 2. Annualised bleeding rates (ABR), spontaneous (AsBR) and joint (AjBR) bleeding rates, percentage of patients with no bleeds, and FIX consumption were assessed using inverse probability of treatment weighting and matching adjusted indirect comparisons. RESULTS: Etranacogene dezaparvovec demonstrated statistically significantly lower bleeding rates versus all comparators. Rate ratios for ABR, AsBR and AjBR versus rIX-FP were 0.19 (p < .0001), 0.08 (p < .0001) and 0.09 (p < .0001), respectively. Rate ratios for ABR, AsBR and AjBR versus rFIXFc were 0.14 (p < .0001), 0.13 (p = .0083) and 0.15 (p = .0111), respectively. Rate ratios for ABR and AsBR, versus N9-GP were 0.24 (p = .0231) and 0.13 (p = .0071), respectively. Etranacogene dezaparvovec demonstrated significantly higher percentage of patients with no bleeds versus rIX-FP and rFIXFc; odds ratios: 17.60 (p < .0001) and 5.65 (p = .0037), respectively. Etranacogene dezaparvovec resulted in significantly lower FIX consumption than all comparators. CONCLUSIONS: ITC suggests that etranacogene dezaparvovec offers patients with haemophilia B (≤2% of normal FIX expression) a single dose treatment that can significantly reduce bleeding rates and eliminate routine infusions associated with FIX therapies.

Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, and phase 2b trial (IASOS).

BACKGROUND: Orismilast is a novel oral phosphodiesterase-4 (PDE4) B/D inhibitor being investigated as a potential treatment for moderate-to-severe psoriasis. OBJECTIVE: To evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis. METHODS: This multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy end points were analyzed using multiple imputation. RESULTS: Of 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast vs placebo. Orismilast showed significant improvements in the primary end point, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast -52.6% to -63.7% and placebo, -17.3%; all P <.001). Greater proportions receiving orismilast achieved PASI75 (39.5%-49.0%; P <.05) and PASI90 (22.0%-28.3%; P <.05 for 20 and 40 mg) vs placebo (PASI75, 16.5% and PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed. LIMITATIONS: Small sample size, disease severity imbalance between groups, limited duration and diversity in study population. CONCLUSION: Orismilast demonstrated greater efficacy vs placebo and a safety profile in line with PDE4 inhibition.

Evaluation of the associations of interlukin-7 genetic variants with toxicity and efficacy of immune checkpoint inhibitors: A replication study of a Japanese population, based on the findings of a European genome-wide association study.

AIM: Recent genome-wide association studies of European populations have identified rs16906115, a single-nucleotide polymorphism in the interleukin-7 gene, as a predictor of immune-related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single-nucleotide polymorphism in a Japanese population. METHODS: From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow-up ≥12 weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non-responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non-responders. RESULTS: In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non-responders (p = 0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p = 0.015) in the univariate analysis and 0.315 (p = 0.023) in the multivariate analysis. CONCLUSIONS: In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry with the number UMIN000043798.

IMbrave152/SKYSCRAPER-14: a Phase III study of atezolizumab, bevacizumab and tiragolumab in advanced hepatocellular carcinoma.

Atezolizumab plus bevacizumab is a standard of care, first-line therapy for advanced hepatocellular carcinoma (HCC). Myeloid and T regulatory cells are key immunosuppressive cell types within the hepatic tumor microenvironment associated with clinical resistance to atezolizumab and bevacizumab therapy for HCC and overall poor prognosis. Therapeutic targeting of TIGIT, which is highly expressed in these cells, with tiragolumab may overcome the immunosuppressive environment and improve clinical benefit, a hypothesis supported by positive efficacy signals in the Phase Ib/II MORPHEUS-Liver study. This paper describes the rationale and design of IMbrave152/SKYSCRAPER-14, a randomized, double-blind, placebo-controlled Phase III study comparing atezolizumab and bevacizumab with tiragolumab or placebo in patients with HCC and no prior systemic treatment.Clinical Trial Registration: NCT05904886 (ClinicalTrials.gov).

This research study is designed to test a new treatment combination for liver cancer, specifically for patients whose cancer cannot be removed with surgery or has spread. The treatment involves three medications: atezolizumab, bevacizumab and tiragolumab.Atezolizumab and bevacizumab are already used together as a standard treatment for liver cancer. Tiragolumab is designed to block the TIGIT receptor, which is normally involved in holding back the immune cells that would attack the tumor. Because tiragolumab may restore the immune response against the tumor, adding tiragolumab might make the treatment more effective.The study is being done worldwide and includes patients who have not received any previous systemic treatment for their advanced liver cancer. Patients participating in the study will be randomly placed into two groups. One group will receive the new combination of three medications, while the other group will receive the standard treatment of two medications plus a placebo (a treatment with no active ingredient). The main goal is to see if the new combination helps patients live longer and slows the cancer's growth compared with the standard treatment. Safety and how patients feel during the treatment are also important parts of the study.

Prospective study to evaluate radioactive iodine of 20 mCi vs 10-15 mCi in Graves' disease.

OBJECTIVES: To assess whether increasing radioactive iodine dose can increase treatment efficacy in Graves' disease. METHODS: A prospective study was conducted, including 106 patients receiving 20 mCi (740 MBq) radioactive iodine (RAI), compared with a retrospective data, including 113 patients receiving 10-15 mCi (370-555 MBq) RAI. Remission and failure rates were evaluated at 6 months post-RAI. Statistical analysis was performed using logistic regression and Kaplan-Meier curves. RESULTS: Patients receiving 20 mCi RAI demonstrated a significantly higher remission rate compared to the 10-15 mCi group (82.1% vs 66.4%, p = 0.009). Median time to remission was shorter in the 20 mCI group (3 vs 4 months, p = 0.002). Hypothyroidism at 6 months was more prevalent in the 20 mCi group (67% vs 53%, p = 0.03). Larger thyroid size (> 60 g) was associated with treatment failure (p = 0.02). CONCLUSIONS: Higher dosage (20 mCi) RAI showed superior efficacy in achieving remission compared to lower dosages (10-15 mCi) in Graves' disease treatment.

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.

Clinical Practice of Photodynamic Therapy for Non-Small Cell Lung Cancer in Different Scenarios: Who Is the Better Candidate?

BACKGROUND: Photodynamic therapy (PDT) is a relatively safe and highly selectivity antitumor treatment, which might be increasingly used as a supplement to conventional therapies. A clinical overview and detailed comparison of how to select patients and lesions for PDT in different scenarios are urgently needed to provide a basis for clinical treatment. SUMMARY: This review demonstrates the highlights and obstacles of applying PDT for lung cancer and underlines points worth considering when planning to initiate PDT. The aim was to make out the appropriate selection and help PDT develop efficacy and precision through a better understanding of its clinical use. KEY MESSAGES: Increasing evidence supports the feasibility and safety of PDT in the treatment of non-small cell lung cancer. It is important to recognize the factors that influence the efficacy of PDT to develop individualized management strategies and implement well-designed procedures. These important issues should be worth considering in the present and further research.

The efficacy of hybrid neuroprostheses in the rehabilitation of upper limb impairment after stroke, a narrative and systematic review with a meta-analysis.

BACKGROUND: Paresis of the upper limb (UL) is the most frequent impairment after a stroke. Hybrid neuroprostheses, i.e., the combination of robots and electrical stimulation, have emerged as an option to treat these impairments. METHODS: To give an overview of existing devices, their features, and how they are linked to clinical metrics, four different databases were systematically searched for studies on hybrid neuroprostheses for UL rehabilitation after stroke. The evidence on the efficacy of hybrid therapies was synthesized. RESULTS: Seventy-three studies were identified, introducing 32 hybrid systems. Among the most recent devices (n = 20), most actively reinforce movement (3 passively) and are typical exoskeletons (3 end-effectors). If classified according to the International Classification of Functioning, Disability and Health, systems for proximal support are expected to affect body structures and functions, while the activity and participation level are targeted when applying Functional Electrical Stimulation distally plus the robotic component proximally. The meta-analysis reveals a significant positive effect on UL functions (p < 0.001), evident in a 7.8-point Mdiff between groups in the Fugl-Meyer assessment. This positive effect remains at the 3-month follow-up (Mdiff = 8.4, p < 0.001). CONCLUSIONS: Hybrid neuroprostheses have a positive effect on UL recovery after stroke, with effects persisting at least three months after the intervention. Non-significant studies were those with the shortest intervention periods and the oldest patients. Improvements in UL functions are not only present in the subacute phase after stroke but also in long-term chronic stages. In addition to further technical development, more RCTs are needed to make assumptions about the determinants of successful therapy.

Factors associated with a better treatment efficacy among psoriasis patients: a study based on decision tree model and logistic regression in Shanghai, China.

BACKGROUND: Many effective therapies for psoriasis are being applied in clinical practice in recent years, however, some patients still can't achieve satisfied effect even with biologics. Therefore, it is crucial to identify factors associated with the treatment efficacy among psoriasis patients. This study aims to explore factors influencing the treatment efficacy of psoriasis patients based on decision tree model and logistic regression. METHODS: We implemented an observational study and recruited 512 psoriasis patients in Shanghai Skin Diseases Hospital from 2021 to 2022. We used face-to-face questionnaire interview and physical examination to collect data. Influencing factors of treatment efficacy were analyzed by using logistic regression, and decision tree model based on the CART algorithm. The receiver operator curve (ROC) was plotted for model evaluation and the statistical significance was set at P < 0.05. RESULTS: The 512 patients were predominately males (72.1%), with a median age of 47.5 years. In this study, 245 patients achieved ≥ 75% improvement in psoriasis area and severity index (PASI) score in week 8 and was identified as treatment success (47.9%). Logistic regression analysis showed that patients with senior high school and above, without psoriasis family history, without tobacco smoking and alcohol drinking had higher percentage of treatment success in patients with psoriasis. The final decision tree model contained four layers with a total of seventeen nodes. Nine classification rules were extracted and five factors associated with treatment efficacy were screened, which indicated tobacco smoking was the most critical variable for treatment efficacy prediction. Model evaluation by ROC showed that the area under curve (AUC) was 0.79 (95%CI: 0.75 ~ 0.83) both for logistic regression model (0.80 sensitivity and 0.69 specificity) and decision tree model (0.77 sensitivity and 0.73 specificity). CONCLUSION: Psoriasis patients with higher education, without tobacco smoking, alcohol drinking and psoriasis family history had better treatment efficacy. Decision tree model had similar predicting effect with the logistic regression model, but with higher feasibility due to the nature of simple, intuitive, and easy to understand.

Patient preference, efficacy, and compliance with zoledronic acid for glucocorticoid-induced osteoporosis in patients with autoimmune diseases.

PURPOSE: We evaluated the preference, patient satisfaction, and efficacy of zoledronic acid compared with oral bisphosphonates (BPs) for glucocorticoid-induced osteoporosis (GIOP) in patients with autoimmune diseases. METHODS: We enrolled 50 patients with new fractures or osteoporosis detected on follow-up bone densitometry after at least 1 year of oral BP use among patients diagnosed with GIOP during treatment for autoimmune diseases. After 1 year of zoledronic acid treatment, patients completed a survey for preference and satisfaction assessment. Treatment efficacy was analysed by comparing bone mineral density changes and fractures with those in a control group of patients who continued oral BP use. RESULTS: Age, sex, treatment duration, and medication history did not differ significantly between the two groups. Among the participants, 86.7% preferred and were more satisfied with intravenous zoledronic acid than with oral BPs, primarily because of the convenience of its administration interval. Only two patients (4%) reported infusion-related adverse events with zoledronic acid. Furthermore, no significant differences were observed in the annualized percentage change in the bone mineral density of the lumbar spine, femur neck, and hip between patients receiving zoledronic acid and those receiving oral BPs. The occurrence of new fractures was consistent across both groups, with two cases in each, showing no significant differences. CONCLUSION: Patients showed a preference for and greater satisfaction with zoledronic acid, and its efficacy in treating osteoporosis was comparable to that of oral BPs. Therefore, zoledronic acid is a suitable treatment option for GIOP in patients with autoimmune diseases.

Enhancing traumatic brain injury emergency care: the impact of grading and zoning nursing management.

OBJECTIVE: This research aimed to evaluate the impact of grading and zoning nursing management on traumatic brain injury (TBI) patients' emergency treatment outcomes. METHODS: This randomized controlled trial included 200 TBI patients. They were treated with a conventional care (control group, n = 100) and a novel grading and zoning approach (study group, n = 100), respectively. This innovative model organized care into levels based on urgency and complexity, facilitating targeted medical response and resource allocation. Key metrics compared included demographic profiles, consultation efficiency (time metrics and emergency treatment rates), physiological parameters (HR, RR, MAP, SpO2, RBS), and patient outcomes (hospital and ICU stays, complication rates, and emergency outcomes). RESULTS: The study group demonstrated significantly improved consultation efficiency, with reduced times for physician visits, examinations, emergency stays, and specialist referrals (all p < 0.001), alongside a higher emergency treatment rate (93% vs. 79%, p = 0.004), notably better physiological stability, improved HR, RR, MAP, SpO2 and RBS (p < 0.001), shorter hospital and ICU stays, fewer complications, and superior emergency outcomes. CONCLUSION: Grading and zoning nursing management substantially enhances TBI patients' emergency care efficiency and clinical outcomes, suggesting a viable model for improving emergency treatment protocols.

The efficacy, safety, and beneficiary population of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum-resistant ovarian cancer patients: A comparative cohort study.

AIM: Angiogenesis inhibitor apatinib targets vascular endothelial growth factor receptors and improves the outcomes of patients with gynecologic malignancy. This study aimed to evaluate the efficacy and safety of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum-resistant ovarian cancer (RPR-OC) patients. METHODS: This study retrieved 67 RPR-OC patients who received apatinib plus chemotherapy or chemotherapy alone and divided them into apatinib + chemo (N = 30) and chemo alone (N = 37) groups according to the actual medication. RESULTS: Objective response rate (36.7% vs. 16.2%, p = 0.056) and disease control rate (80.0% vs. 59.5%, p = 0.072) showed an increased trend in apatinib + chemo group versus chemo alone group. The progression-free survival (PFS) (p = 0.010) and overall survival (OS) (p = 0.042) were prolonged in apatinib + chemo group versus chemo alone group. The median (95%confidence interval [CI]) PFS was 5.9 (5.5-6.3) months in apatinib + chemo group and 3.8 (2.0-5.6) months in chemo alone group. The median (95%CI) OS was 20.5 (16.5-24.5) months in apatinib + chemo group and 13.6 (8.6-18.6) months in chemo alone group. Apatinib plus chemotherapy was independently related with better PFS (hazard ratio [HR]: 0.354, p < 0.001) and OS (HR: 0.116, p < 0.001). Subgroup analyses indicated that patients with a more serious disease condition might benefit more from apatinib plus chemotherapy. No difference was found in adverse events of all grade or grade ≥3 between the two groups (all p > 0.05). CONCLUSION: Angiogenesis inhibitor apatinib plus chemotherapy shows better treatment efficacy than chemotherapy alone with controllable safety profile in RPR-OC patients.

Symptom Assessment of Candidates for Sacral Neuromodulation Therapy With Urologic and Colorectal Conditions: Time for a Holistic Approach? Results and Findings From a Prospective Single-Center Study.

OBJECTIVES: Sacral neuromodulation (SNM) has evolved as a therapeutic intervention for various pelvic floor dysfunctions. However, the traditional approach primarily assesses discipline-specific symptoms, potentially overlooking holistic symptom improvement. We aimed to investigate whether a more comprehensive evaluation of pelvic floor symptoms enhances the assessment of SNM's test phase. MATERIAL AND METHODS: A prospective single-center trial (Optimization of Lower Urinary Tract Symptoms study) assessed SNM efficacy from March 2018 to December 2021 in patients from the urology department (UD) and colorectal surgery department (CRD) with a follow-up of 12 months. Objective and subjective outcomes were examined using diaries and patient-reported outcome measures. Statistical analyses were conducted to determine predictive factors for treatment success, expressed by the patient global impression of change. SPSS 29.0 was used. RESULTS: A total of 85 participants were included, displaying concomitant pelvic floor symptoms. After the first phase, significant improvements on all pelvic floor domains questionnaires were seen for both patients from UD and those from CRD. Although improvements were observed in bladder and bowel diaries, the traditional criteria for success (≥50% improvement in diary variables) did not consistently correlate with the patients' global impression of change. The absolute reductions in bother sum scores from multiple domains were significant predictors for the patients' global impression of change, outperforming discipline-specific assessments. Patients from UD benefit from both a urologic and pelvic pain symptom evaluation, and those from CRD, from both a urologic and bowel symptom evaluation. CONCLUSIONS: SNM shows positive effects across various pelvic floor domains, even beyond the primary intended indication of implantation. The rather rigid approach of patient selection of discipline-specific symptoms alone can be questioned. A more comprehensive evaluation encompassing various pelvic floor symptoms with the emphasis on subjective outcome measures could enhance SNM's efficacy assessment during the test phase. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT05313984.