Relevant Trials Research Articles

Role of Cardiac Magnetic Resonance in Inflammatory and Infiltrative Cardiomyopathies: A Narrative Review.

Cardiac magnetic resonance (CMR) has acquired a pivotal role in modern cardiology. It represents the gold standard for biventricular volume and systolic function assessment. Moreover, CMR allows for non-invasive myocardial tissue evaluation, highlighting tissue edema, fibrosis, fibro-fatty infiltration and iron overload. This manuscript aims to review the impact of CMR in the main inflammatory and infiltrative cardiomyopathies, providing details on specific imaging patterns and insights regarding the most relevant trials in the setting.

Molecular tumor board: Real-world experience in a tertiary cancer centre in Singapore.

107 Background: Genomic profiling is increasingly employed to support diagnosis and treatment of cancer. Our Molecular tumor boards (MTBs) serves as a collaborative platform for a multi-disciplinary team of oncologists, pathologists, scientists, bioinformaticians, genetic counsellors and research coordinators to discuss and match patients to the most relevant therapies and/or clinical trials. We report here the evaluation of our MTBs for year 2023 with the aim of identifying challenges and opportunities for successful implementation of precision oncology. Methods: Regular monthly MTBs were conducted to discuss molecular profiles from predominantly advanced-stage patients enrolled to the IMPACT study (Individualized Molecular Profiling for Allocation to Clinical Trials NCT02806388). Next-generation sequencing was performed either in-house using Oncomine or commercial FoundationOne panels. Additional tests such as whole transcriptome sequencing (WTS), immunohistochemistry (IHC) and fluorescent in-situ hybridization (FISH) were also performed where indicated. MTB recommendations were documented for follow-up and analysis. Results: A total of 102 out of 611 profiled patients were discussed in MTBs in 2023, with an average of 8.6 patients per month. Top 3 cancer types were gastrointestinal (32%), breast (18%) and lung (18%). 65/102 (63.7%) cases had MTB recommendations, of which 21 (20.6%) had multiple recommendations. Overall uptake rate for recommendations was 23.8% (29/122). Conclusions: MTB plays an important role in identifying therapeutic opportunities by factoring in patient variables, available data and physician experience while at the same time provides an avenue for further investigation to gather cumulative evidence. Frequent reasons encountered for not adopting the recommendations include: (1) insufficient sample to proceed with further investigations, (2) limited access to off-label treatments, and (3) additional considerations to participate in clinical trials. To fully realize the value of MTB, we will focus on (1) defining the molecular tests for efficient profiling, (2) crafting a route for special access to treatments and (3) increasing awareness and understanding of clinical trials. [Table: see text]

Comparative Effectiveness of Bimekizumab and Risankizumab in Patients with Psoriatic Arthritis at 52 Weeks Assessed Using a Matching-Adjusted Indirect Comparison.

The relative efficacy of bimekizumab and risankizumab in patients with PsA who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR) was assessed at 52weeks (Wk52) using matching-adjusted indirect comparisons (MAIC). Relevant trials were systematically identified. For patients who were bDMARD naïve, individual patient data (IPD) from BE OPTIMAL (NCT03895203; N = 431) were matched with summary data from KEEPsAKE-1 (NCT03675308; N = 483). For patients who were TNFi-IR, IPD from BE COMPLETE (NCT03896581; N = 267) were matched with summary data from the TNFi-IR patient subgroup in KEEPsAKE-2 (NCT03671148; N = 106). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted to match the baseline characteristics of patients in the risankizumab trials. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Recalculated bimekizumab Wk52 outcomes for American College of Rheumatology (ACR) 20/50/70 response criteria and minimal disease activity (MDA) index (non-responder imputation) were compared with risankizumab outcomes via non-placebo-adjusted comparisons. In patients who were bDMARD naïve, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR50 (odds ratio [95% confidence interval]: 1.52 [1.11, 2.09]) and ACR70 (1.80 [1.29, 2.51]). In patients who were TNFi-IR, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR20 (1.78 [1.08, 2.96]), ACR50 (3.05 [1.74, 5.32]), ACR70 (3.69 [1.82, 7.46]), and MDA (2.43 [1.37, 4.32]). Using MAIC, bimekizumab demonstrated a greater likelihood of efficacy in most ACR and MDA outcomes than risankizumab in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52. NCT03895203, NCT03896581, NCT03675308, NCT03671148.

Comparative Effectiveness of Bimekizumab and Ustekinumab in Patients with Psoriatic Arthritis at 52 Weeks Assessed Using a Matching-Adjusted Indirect Comparison.

A matching-adjusted indirect comparison (MAIC) was conducted to assess the relative efficacy at 52weeks (Wk52) of bimekizumab 160mg every 4weeks (Q4W) and ustekinumab 45 or 90mg every 12weeks (Q12W) in patients with psoriatic arthritis (PsA) who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or who had a previous inadequate response or an intolerance to tumor necrosis factor inhibitors (TNFi-IR). Relevant trials were systematically identified. Individual patient data from the bimekizumab trials BE OPTIMAL (NCT03895203; N = 431) and BE COMPLETE (NCT03896581; N = 267) were matched with summary data on patients receiving ustekinumab in the PSUMMIT 1 trial (NCT01009086; 45mg, N = 205; 90mg; N = 204) and a subgroup of TNFi-IR patients receiving ustekinumab in the PSUMMIT 2 trial (NCT01077362; 45mg, N = 60; 90mg, N = 58), respectively. Patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of the ustekinumab trial patients. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Non-placebo-adjusted comparisons of recalculated bimekizumab and ustekinumab outcomes for the American College of Rheumatology (ACR) 20/50/70 response criteria (non-responder imputation) were analyzed. In patients who were bDMARD naïve, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (odds ratio [95% confidence interval] 45mg: 2.14 [1.35, 3.40]; 90mg: 1.98 [1.24, 3.16]), ACR50 (45mg: 2.74 [1.75, 4.29]; 90mg: 2.29 [1.48, 3.55]), and ACR70 (45mg: 3.33 [2.04, 5.46]; 90mg: 3.05 [1.89, 4.91]). In patients who were TNFi-IR, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (45mg: 4.17 [2.13, 8.16]; 90mg: 4.19 [2.07, 8.49]), ACR50 (45mg: 5.00 [2.26, 11.05]; 90mg: 3.86 [1.70, 8.79]), and ACR70 (45mg: 9.85 [2.79, 34.79]; 90mg: 6.29 [1.98, 20.04]). Using MAIC, bimekizumab showed greater efficacy than ustekinumab in achieving all ACR responses in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52. NCT03895203, NCT03896581, NCT01009086, NCT01077362.

Cutaneous Lupus Erythematosus Treatment Revolution: Exploring the Latest Nano Lipid Drug Delivery Innovations

Abstract: This review article aims to explore recent advancements in the treatment of Cutaneous Lupus Erythematosus (CLE) by focusing on the innovative use of Nano Lipid Carrier formulations. It assesses the efficacy, safety, and potential therapeutic benefits of these novel formulations in managing CLE symptoms. A comprehensive search was conducted across various scientific databases, including PubMed, MEDLINE, and Google Scholar, to identify relevant studies, clinical trials, and reviews pertaining to CLE treatment, particularly those involving various NLC formulations. Studies were selected based on their relevance to CLE treatment, with a specific emphasis on recent innovations. Data extraction involved gathering information on study design, intervention methods, outcomes, and conclusions related to the efficacy and safety of novel formulations in managing CLE symptoms. The synthesized data reveal promising outcomes associated with the use of NLC in treating CLE. These formulations offer enhanced drug delivery, improved skin penetration, and targeted therapy, resulting in better symptom management and reduced adverse effects compared to conventional treatments. Various studies demonstrate the efficacy of NLC embedded in reducing inflammation, controlling disease activity, and improving the quality of life for CLE patients. The latest advancements in CLE treatment, using novel methods, present a significant revolution in managing this chronic autoimmune skin condition. The reviewed literature highlights the potential of Nano lipid carrier embedded hydrogel as a promising therapeutic approach for CLE, offering improved efficacy, safety, and patient compliance. Further research and clinical trials are warranted to validate these findings and establish NLC as a standard treatment modality for CLE.

A personalised algorithm predicting the risk of intravenous corticosteroid failure in acute ulcerative colitis.

An episode of acute ulcerative colitis (UC) represents an important watershed moment in a patient's disease course. To derive a personalised algorithm for identifying patients at high risk of corticosteroid non-response from variables available at hospital presentation using a large prospectively collected acute UC patient database and machine learning-based techniques. We analysed data from 682 consecutive presentations of acute UC. We used an Akaike information criterion-based elastic net model to select variables based on the 419 earliest presentations of acute UC (1996-2017). We constructed two risk-scoring algorithms, with and without utilising additional endoscopic variables, using logistic regression models. We validated these risk scores on separate cohorts of 181 (2018-2022) and 82 (2015-2022) acute UC presentations. The partial risk of rescue (ROR) score included the admission indices of oral corticosteroid treatment, bowel frequency ≥6/24 h, albumin, CRP ≥12 mg/mL and log10CRP. The full ROR score incorporates the same variables with the addition of the Mayo endoscopic subscore and disease extent. The AUCs in the main validation cohort were 0.76 (95% CI: 0.69-0.83) and 0.78 (95% CI: 0.71-0.85) for the partial and full ROR scores, respectively. These pragmatic personalised risk scores (available at www.severecolitis.com) have comparably strong performance characteristics and usability enabling the identification of individuals at high risk of corticosteroid non-response before or after endoscopic assessment. The ROR scores have the potential to challenge conventional acute UC treatment paradigms by identifying patients who may benefit from early rescue therapy or participation in relevant clinical trials.

The current therapeutic cancer vaccines landscape in non-small cell lung cancer.

Currently, conventional immunotherapies for the treatment of non-small cell lung cancer (NSCLC) have low response rates and benefit only a minority of patients, particularly those with advanced disease, so novel therapeutic strategies are urgent deeded. Therapeutic cancer vaccines, a form of active immunotherapy, harness potential to activate the adaptive immune system against tumor cells via antigen cross-presentation. Cancer vaccines can establish enduring immune memory and guard against recurrences. Vaccine-induced tumor cell death prompts antigen epitope spreading, activating functional T cells and thereby sustaining a cancer-immunity cycle. The success of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rendered cancer vaccines a promising avenue, especially when combined with immunotherapy or chemoradiotherapy for NSCLC. This review delves into the intricate antitumor immune mechanisms underlying therapeutic cancer vaccines, enumerates the tumor antigen spectrum of NSCLC, discusses different cancer vaccines progress and summarizes relevant clinical trials. Additionally, we analyze the combination strategies, current limitations, and future prospects of cancer vaccines in NSCLC treatment, aiming to offer fresh insights for their clinical application in managing NSCLC. Overall, cancer vaccines offer promising potential for NSCLC treatment, particularly combining with chemoradiotherapy or immunotherapy could further improve survival in advanced patients. Exploring inhaled vaccines or prophylactic vaccines represents a crucial research avenue.

Decompressive Craniectomy with or Without Dural Closure: Systematic Review and Meta-analysis.

Decompressive craniectomy is used to alleviate intracranial pressure in cases of traumatic brain injury and stroke by removing part of the skull to allow brain expansion. Traditionally, this procedure is followed by a watertight dural suture, although evidence supporting this method is not strong. This meta-analysis examines the feasibility of the open-dura (OD) approach versus the traditional closed-dura (CD) technique with watertight suturing. A systematic review and comparative meta-analysis were conducted on OD and CD dural closure techniques. Medline, Embase, and Cochrane were searched for relevant trials. The primary end point was the rate of complications, with specific analyses for infection and cerebrospinal fluid (CSF) leaks. Mortality, poor neurological outcomes, and operation duration were also assessed. Odds ratios with 95% confidence intervals (CIs) were calculated using a random-effects model. Following a comprehensive search, 930 studies were screened, from which four studies and a total of 368 patients were ultimately selected. The primary outcome analysis showed a reduced likelihood of complications in the OD group when compared with the CD group (368 patients, odds ratio 0.54 [95% CI 0.32-0.90]; I2 = 17%; p < 0.05). Specific analysis of infections and CSF leaks did not show statistically significant results, as well as the evaluation of the mortality rates and poor neurological outcome differences between groups. Assessment of operation duration, however, demonstrated a significant difference between techniques, with a mean reduction of 52.50min favoring the OD approach (mean difference - 52.50 [95% CI - 92.13 to - 12.87]; I2 = 96%). This study supports the viability of decompressive craniectomy without the conventional time-spending watertight duraplasty closure, exhibiting no differences in the rate of infections or CSF leaks. Furthermore, this approach has been associated with improved rates of complications and faster surgery, which are important aspects of this technique, particularly in its potential to reduce both costs and procedure length.

The role of everolimus in metastatic breast cancer and possibilities of moving forward-a narrative review.

In hormone-receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer endocrine-based therapies are preferred over chemotherapy. One of the treatment options is the combination of everolimus with exemestane or other endocrine drug in later lines mainly based on progression-free survival (PFS) results of the phase 3 BOLERO-2 trial. Altogether, clinical trials did not prove an overall survival (OS) benefit and considerable side effects hampered its application in the day-by-day practice. In recent years CDK4/6-inhibitors became a first-choice combination partner to the endocrine treatment, everolimus still has a place within the treatment armamentarium. Although everolimus is a targeted drug, there is no accepted predictive biomarker and further patient selection is not possible. However, several directions can be defined how to optimally use everolimus. For update information on everolimus treatment in breast cancer I have performed a literature search. I used the keywords "breast cancer" and "everolimus" and extended the search in PubMed from 01/01/2014 to 10/02/2023. I considered all phase 3 trials, the phase 1-2 trials with not repetitive information, studies with biomarker results and I also checked review articles to identify potential relevant other clinical trial reports. I also have made a search in clinicaltrials.gov for recently completed and ongoing trials. I summarized the search results in this concise and brief report focusing on main trial results and ongoing research with everolimus. The most promising research directions seem to be further investigations for useable predictive biomarkers, for combinations with other targeted drugs (even in a triple combination) and for the feasibility of pharmacologically guided dosing method.

Salvianolic acid B in fibrosis treatment: a comprehensive review.

Fibrosis is a public health issue of great concern characterized by the excessive deposition of extracellular matrix, leading to the destruction of parenchymal tissue and organ dysfunction that places a heavy burden on the global healthcare system due to its high incidence, disability, and mortality. Salvianolic acid B (SalB) has positively affected various human diseases, including fibrosis. In this review, we concentrate on the anti-fibrotic effects of SalB from a molecular perspective while providing information on the safety, adverse effects, and drug interactions of SalB. Additionally, we discuss the innovative SalB formulations, which give some references for further investigation and therapeutic use of SalB's anti-fibrotic qualities. Even with the encouraging preclinical data, additional research is required before relevant clinical trials can be conducted. Therefore, we conclude with recommendations for future studies. It is hoped that this review will provide comprehensive new perspectives on future research and product development related to SalB treatment of fibrosis and promote the efficient development of this field.

Dairy and Headaches: What is the Connection?

Headaches represent a prevalent and burdensome health condition, affecting individuals of all ages worldwide. While dietary factors have been implicated in headache pathophysiology, the association between dairy consumption and headaches remains controversial and inadequately understood. This comprehensive review systematically examines the existing literature to elucidate the relationship between dairy intake and headaches, addressing methodological challenges, potential biases, and gaps in the current knowledge. A thorough search of electronic databases identified relevant observational studies, clinical trials, and mechanistic investigations exploring the impact of dairy consumption on headache incidence, frequency, severity, and duration. Methodological considerations, including study design, measurement of exposure and outcome variables, confounding factors, and sources of bias, were critically evaluated to assess the strength of evidence and validity of findings. Despite heterogeneity across studies, emerging evidence suggests a complex and multifaceted relationship between dairy intake and headaches, influenced by individual characteristics, dietary patterns, headache subtype, and study context. While some studies report a positive association between dairy consumption and headaches, others indicate no significant effect or potential therapeutic benefits of dairy restriction. Mechanistic insights suggest plausible biological mechanisms, including neuroinflammatory pathways, neurotransmitter modulation, vascular effects, and gut-brain interactions, which may mediate the observed associations. Future research directions encompass longitudinal studies, mechanistic investigations, stratified analyses, randomized controlled trials, and exploration of the gut microbiota to further elucidate the underlying mechanisms and inform evidence-based dietary recommendations for headache management. This integrative review underscores the importance of interdisciplinary collaboration and personalized approaches to address the complex interplay between diet, headaches, and overall health.

The Effect of Virtual Reality Application on Pain and Anxiety During Episiotomy Repair: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is a rising trend among women towards nonpharmacological approaches owing to their minimally invasive nature and limited adverse effects. Virtual reality (VR) has recently gained popularity as a new technology for reducing pain and anxiety in medical settings. Our research sought to investigate the impact of VR on pain and anxiety levels while undergoing episiotomy repair. A comprehensive search was carried out across PubMed, Scopus, Cochrane Library, and ISI Web of Science to find relevant randomized clinical trials (RCTs) up to January 2024. These trials investigated the use of VR as a treatment during episiotomy repair compared with a control group that did not receive VR intervention. Meta-analysis was performed using Review Manager software to analyze the data collected. Our primary outcomes were pain scores reported during and after episiotomy repair measured by a visual analog scale. Secondary outcomes analyzed included anxiety scores during and after the procedure, as well as the duration of episiotomy repair. Seven RCTs, involving 578 patients, met the inclusion criteria. VR resulted in a significant reduction in pain scores both during and after episiotomy repair (p < 0.001). Additionally, anxiety levels during and after the procedure were significantly reduced in the VR group compared with the control group. Moreover, the duration of episiotomy repair was significantly shorter in the VR group. Using VR has proven to be an effective technique in reducing pain and anxiety during and after episiotomy repair, as well as potentially speeding up the procedure.

Chinese Expert Consensus on the Standardized Diagnosis and Treatment of Non‑small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations (2024 Edition)

The standard clinical practice of managing the non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations was elaborated in Chinese expert consensus on non‑small cell lung cancer with EGFR exon 20 insertion mutations (2023 edition), and this rare subset has gradually attracted attention recently. With the deepening of treatment area exploration and the approval of new targeted drugs, there are more options for the diagnosis and treatment of EGFR ex20ins positive NSCLC patients. Therefore, based on the previous version of consensus, the expert panel has updated this consensus on the standardized clinical diagnosis and treatment of EGFR ex20ins mutation NSCLC through reference to literature and clinical data, and combined with the experts' own clinical experience. The updated recommendations includes disease congnition, testing methods, therapy and recent relevant clinical trials for NSCLC patients with EGFR ex20ins mutation, in order to provide better medication reference for clinical physicians. .

Application of network pharmacology and dock of molecules on the exploration of the mechanism of frankincense-myrrh for lumbar intervertebral disc degeneration: A review.

To investigate the efficacy of Frankincense-Myrrh in lumbar Intervertebral degenerative diseases (LIDD). The active components of frankincense-myrrh was retrieved with a unique system pharmacology platform for Traditional Chinese Medicine Systems Pharmacology (TCMSP). The LIDD-related target genes were screened with DisGeNET and Genecards databases. Then, STRING & Cytoscape were used for analyzing the Protein-Protein Interaction network. DAVID was used for analyzing Gene Ontology (GO) & Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, molecules of AutoDockVina and Pymol were used for docking the molecules for verifying active ingredients and key targets' binding force. The 105 LIDD-related targets identified in Ruxiang (RX)-Moyao (MY) involve 53 active ingredients. In addition, topological analysis was conducted for identifying the 12 key targets. According to the analysis results of GO & KEGG, RX-MY is significant for treating LIDD through participating in many pathways and biological processes, such as signaling pathways of inflammatory response reactive process, MAP kinase activity, TNF, and MAPK, etc. According to the dock results, the active components oxo-tirucalic, acid, isofouquierone, (7S, 8R, 9S, 10R, 13S, 14S,17Z)-17-ethylidene-7-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta [a] phenanthrene-3,16-dion in RX-MY binds actively. The basic pharmacological action and RX-MY-related mechanism in the treatment of LIDD was revealed in this study for the first time. It is predicted that the results may provide a treatment plan for RX-MY with replacement of NSAIDs and warrant investigation of new therapeutic alternatives for LIDD. However, these predictions should be validated by relevant pharmacological trials.

Budesonide Versus Mesalamine in Microscopic Colitis: A Comparative Meta-analysis of Randomized Controlled Trials.

Microscopic colitis (MC) is an inflammatory bowel disease of autoimmune origin that causes chronic watery diarrhea. Medications, including budesonide, mesalamine, loperamide, cholestyramine, and bismuth subsalicylate, are first-line therapies. Meanwhile, azathioprine, 6-mercaptopurine, and methotrexate are indicated for refractory MC. We aim to assess the efficacy and safety of budesonide compared with mesalamine for induction of remission in MC patients. We searched the Cochrane Library, Scopus, Web of Science, and PubMed for relevant clinical trials comparing either mesalamine or budesonide with a control group. We included the following outcomes: clinical remission (3 or fewer stools/day), daily stool weight, daily stool frequency, number of patients with clinical response <50% in the disease activity, and daily stool consistency. Safety end points included: any adverse event, serious adverse events, any adverse event-related discontinuation, abdominal discomfort, constipation, flatulence, nausea, dizziness, headache, bronchitis, nasopharyngitis, and depression. We conducted a meta-analysis model using the generic inverse variance method and performed a subgroup analysis based on the intervention administered. Nineteen randomized clinical trials were included. We found that after 6 weeks of follow-up, budesonide is associated with increased clinical remission rates compared with mesalamine [RR=2.46 (2.27, 2.67), and RR=2.24 (1.95, 2.57), respectively]. However, the test of subgroup difference revealed that the difference is not significant (P=0.25). After 8 weeks of follow-up, budesonide showed significantly higher clinical remission rates than mesalamine RR=2.29 (2.14, 2.45), and RR=1.7 (1.41, 2.05), respectively (P=0.003). Regarding the daily stool weight, patients in the budesonide group showed nonsignificant less stool weight [MD=-351.62 (-534.25, -168.99)] compared with mesalamine [MD=-104.3 (-372.34, 163.74)], P=0.14. However, daily stool frequency was significantly less in the budesonide group compared with mesalamine (P<0.001). Budesonide is associated with a significantly lower incidence of adverse events compared with mesalamine (P=0.002). Analysis of other safety endpoints was not significant between both groups. Budesonide was found to be better than mesalamine in MC patients in terms of clinical remission rate, especially after 8 weeks of follow-up. Budesonide also showed less incidence of adverse events. There is an urgent need for randomized, double-blinded clinical trials to provide direct and reliable evidence.

Mechanistic in silico explorations of the immunogenic and synergistic effects of radiotherapy and immunotherapy: a critical review.

Immunotherapy is a rapidly evolving field, with many models attempting to describe its impact on the immune system, especially when paired with radiotherapy. Tumor response to this combination involves a complex spatiotemporal dynamic which makes either clinical or pre-clinical in vivo investigation across the resulting extensive solution space extremely difficult. In this review, several in silico models of the interaction between radiotherapy, immunotherapy, and the patient's immune system are examined. The study included only mathematical models published in English that investigated the effects of radiotherapy on the immune system, or the effect of immuno-radiotherapy with immune checkpoint inhibitors. The findings indicate that treatment efficacy was predicted to improve when both radiotherapy and immunotherapy were administered, compared to radiotherapy or immunotherapy alone. However, the models do not agree on the optimal schedule and fractionation of radiotherapy and immunotherapy. This corresponds to relevant clinical trials, which report an improved treatment efficacy with combination therapy, however, the optimal scheduling varies between clinical trials. This discrepancy between the models can be attributed to the variation in model approach and the specific cancer types modeled, making the determination of the optimum general treatment schedule and model challenging. Further research needs to be conducted with similar data sets to evaluate the best model and treatment schedule for a specific cancer type and stage.

Stereotactic ablative radiotherapy versus conventional fractionated radiotherapy for clinical early-stage non-small-cell lung cancer: a population-based study.

The use of stereotactic ablative radiotherapy (SABR) over conventional fractionated radiotherapy (CFRT) for early-stage non-small-cell lung cancer (NSCLC) has been advocated, but is also debated in the literature. In this retrospective cohort study, we adopted a target trial emulation framework to identify eligible patients diagnosed between 2011 and 2021 using the Taiwan Cancer Registry. In the primary analysis, the overall survival (OS) was the primary endpoint, whereas incidences of lung cancer mortality and radiation pulmonary toxicity were the secondary endpoints. Extensive supplementary analyses were also conducted. We included 351 patients in the primary analysis and found that the OS was not significantly different between the SABR (n = 290) and CFRT (n = 61) groups. The propensity score weighting adjusted hazard ratio of death was 0.75 (95% confidence interval 0.53-1.07, p = 0.118). The secondary endpoints and supplementary analyses showed no significant differences. The OS of patients with early-stage NSCLC treated with SABR was not significantly different from that of patients treated with CFRT alone. The results of the relevant ongoing clinical trials are eagerly awaited.

Preemptive oral analgesia with steroidal and nonsteroidal anti-inflammatory drugs in periodontal surgery: a systematic review.

Introduction: Periodontal procedures can promote prolonged intense pain, particularly in clinical situations requiring surgical procedures. In this context, preemptive analgesia has also been assessed for its utility in controlling post-operative pain and discomfort in patients undergoing periodontal invasive procedures. This study assessed the efficacy and safety of preemptive oral analgesia with steroidal and non-steroidal anti-inflammatory drugs in periodontal surgeries. Methods: This systematic review performed a search in the following electronic sources: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), EMBASE (via Ovid), Web of Science, Virtual Health Library and in clinical trials electronic databases for relevant randomized clinical trials (RCTs); published up to July 2023. Primary outcomes assessed were post-operative pain, edema and trismus. A narrative synthesis of the findings was carried out. Results: Six RCTs, involving a total of 250 participants, were included. The studies reviewed had a high risk of bias, particularly due to allocation concealment and blinding of participants and personnel. The RCTs reported only the outcome pain. The preemptive use of dexamethasone 8mg, etoricoxib 90mg or 120mg and ketorolac 20mg seems to be more effective for controlling post-operative pain than placebo. Discussion: The anti-inflammatory drugs evaluated proved to be effective for controlling post-operative pain. However, given the limitations regarding lack of studies, methodological biases, disparities in drugs and doses, report restricted the pain outcome; further RCTs confirming the effectiveness and safety of these drugs in periodontal surgical procedures are warranted.

A Comprehensive Review of Biologics in Phase III and IV Clinical Trials for Atopic Dermatitis.

Atopic dermatitis (AD) is a skin condition characterized by significant challenges and a substantial deterioration in the life quality for affected patients. The therapeutic landscape for AD has witnessed a transformative shift with the emergence of biologic therapies. Our focus centers on biologics currently undergoing phase III and IV clinical trials, deeming them to hold the highest potential for significant clinical relevance. To identify biologic drugs under development in phase III and IV clinical trials, we searched ClinicalTrials.gov. Additional relevant trials were identified through JapicCTI/ Japan Registry of Clinical Trials (jRCT) with a citation search. A search in MEDLINE and EMBASE was performed. There have been 76 clinical trials identified concerning biologic drugs: dupilumab (34 trials), lebrikizumab (14 trials), tralokinumab (10 trials), rocatinlimab (7 trials), amlitelimab (2 trials), nemolizumab (6 trials), MG-K10 (1 trial), CM310 (1 trial), 611 (1 trial). A search in MEDLINE revealed 132 articles concerning phase III and IV clinical trials for AD treatment. A total of 39 articles concerned biologic drugs covering 23 clinical trials. A search in EMBASE revealed 268 relevant articles, allowing us to identify results of an additional six clinical trials. The safety and efficacy of these biologics are comprehensively addressed in this review. This comprehensive review aims to explore the current landscape of biologic therapies for AD, delving into the latest research findings, clinical trial outcomes, and the diverse mechanisms of action employed by these novel interventions.

Efficacy and safety of romosozumab: a meta-analysis of placebo-controlled trials.

We aimed to comprehensively compile placebo-controlled trials on the efficacy and safety of romosozumab (210mg, subcutaneously, once monthly) in postmenopausal women and men with osteoporosis. PubMed, Google Scholar, and ClinicalTrials.gov were searched for relevant placebo-controlled trials (as of January 1, 2024). Percent change in bone mineral density (BMD), falls, fractures, and adverse events (AEs) after drug administration were collected. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Six trials (7990 patients; follow-up period, 6-12months) were included. Compared with placebo, romosozumab significantly increased lumbar spine BMD (MD = 12.69; 95% CI 11.10-14.29), total hip BMD (MD = 4.42; 95% CI 3.03-5.80), and femoral neck BMD (MD = 3.99; 95% CI 2.42-5.57) at 12months. Romosozumab significantly decreased falls (RR = 0.80; 95% CI 0.68-0.93) and major osteoporotic fractures (RR = 0.37; 95% CI 0.25-0.54), but increased injection-site reactions (RR = 1.83; 95% CI 1.46-2.30) within 12months. No significant differences were observed in other AEs (including cardiovascular AEs) within 12months. Romosozumab treatment resulted in a significant BMD gain, reduced falls and major osteoporotic fractures. It was generally well-tolerated, including the cardiovascular aspects. However, clinicians should consider the occurrence of minor AEs (e.g., injection-site reactions).