Efficacy Of Treatment Research Articles

Clinical characteristics and prognosis of type 1 infratentorial superficial siderosis

A total of 7 patients with type 1 infratentorial superficial siderosis(iSS-1)in Memory Clinic at Huashan Hospital, Fudan University from March 2019 to March 2023 were respectively collected to analyze the clinical characteristics and treatment, and followed up for 12 months. There were 7 patients, 2 males and 5 females, aged 56 (49-60) years. The 4 patients who underwent cognitive assessment had varying degree of cognitive impairment, with 2 patients exhibiting severe executive function impairment. Magnetic resonance myelography imaging was used to screen the etiology of iSS-1 patients. Four patients had clear dural defects, 3 of whom accepted autologous blood patch treatment. And all 3 patients were relieved from postural headache and dizziness within 3 months after treatment; symptoms such as hearing loss, unstable walking, ataxia and cognitive impairment remained stable, and 1 patient showed significant improvement in cognitive assessment scores. The efficacy and safety of autologous blood patch treatment still need to be further confirmed by RCT studies of expanded samples.

Global visualization of adolescent idiopathic scoliosis treatment: a bibliometric analysis

ObjectiveThe objective of this study is to present a comprehensive overview of current advancements, prominent areas of interest, emerging trends, and frontiers in global research concerning the treatment of adolescent idiopathic scoliosis. The aim is to offer valuable insights and guidance for future research endeavors in this field.MethodsWe conducted a literature search on the treatment of adolescent idiopathic scoliosis using the Web of Science Core Collection database spanning from 2009 to 2024. Visualization of countries, institutions, authors, and keywords was performed using CiteSpace.Results1,002 English articles were included in this study. Between 2009 and 2020, publications remained relatively low and stable. However, in 2021, interest in the treatment of adolescent idiopathic scoliosis began to surge, a noticeable increase in publications, with a peak reached in 2022. The United States emerged as the leading contributor among countries, institutions, and authors. Nanjing University and Peter O. Newton were the most prolific institutions and authors, respectively. The academic journal with the highest number of published articles was Spine. Notably, areas such as Cobb angle measurement, the efficacy of non-surgical treatments for AIS, and factors influencing the success of brace treatment garnered significant attention as hot topics in adolescent idiopathic scoliosis treatment.ConclusionThe prognosis remains consistent across patients with varying degrees of curvature in adolescent idiopathic scoliosis. Given the limited understanding of its etiology, the relationship between curvature and prognosis, as well as the exploration of its underlying causes, could emerge as new research directions in the future.

Clinical management of Psoriasis (Eka Kushtha) through Ayurvedic interventions: A case study highlighting the efficacy of Shila Sindura and Integrative Therapies

Background: Psoriasis, a chronic autoimmune condition, manifests as erythemato-squamous lesions with significant physical and psychological distress. In Ayurveda, psoriasis can be correlated with Eka Kushtha, primarily caused by vitiated Vata and Kapha Doshas. This case study evaluates the efficacy of an Ayurvedic intervention comprising Shila Sindura, Bakuchi Rasayana, and adjunct therapies in the management of Eka Kushtha (psoriasis). Case Presentation: A 20-year-old male presented with an 8-year history of extensive red and white scaly plaques affecting his feet, knees, hands, elbows, and upper back. Symptoms included severe itching, burning sensations, and joint stiffness. Despite prior treatments, recurrence persisted. Clinical assessment using the Psoriasis Area and Severity Index (PASI) revealed a baseline score of 26.4. Treatment Protocol: The patient underwent a one-month Ayurvedic regimen consisting of Shila Sindura (250 mg BD), Bakuchi Rasayana (750 mg BD), and Avipattikara Churna (3 g BD). External applications included Gandhaka Malahara and Jatyadi Taila. Dietary modifications and lifestyle adjustments were emphasized to complement treatment. Out Comes: Follow-up assessments demonstrated significant clinical improvement, with the PASI score decreasing from 26.4 to 1.0 after two months. Marked reductions in erythema, scaling, and plaque thickness were observed across all body regions. Hematological and biochemical parameters remained stable, with minor fluctuations in renal and hepatic markers, warranting continued monitoring. Conclusion: This case study highlights the potential of Ayurvedic management for psoriasis, emphasizing systemic detoxification, dosha balancing, and localized care. Future controlled clinical trials are recommended to validate these findings and further explore the mechanisms of action.

Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysis

BackgroundOur study was designed to determine the safety, efficacy, and immunological effects of perioperative pembrolizumab in early-stage NSCLC.MethodsThis is a single-arm phase II study of perioperative pembrolizumab in patients with...

Comparative Effectiveness of Pharmacologic Treatments for the Prevention of Episodic Migraine Headache: A Systematic Review and Network Meta-analysis for the American College of Physicians.

Various treatments for preventing episodic migraine are available. To evaluate the comparative effectiveness and harms of pharmacologic prevention of episodic migraine, focusing on treatments already determined to be superior to placebo. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception until April 2024. Randomized trials evaluating selected efficacious pharmacologic treatments in adults with episodic migraine. Selection was done independently by 2 reviewers. Data were extracted by 1 reviewer and checked by a second. Risk of bias and certainty of the evidence were assessed using the Cochrane Risk of Bias tool and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, respectively. Sixty-one studies (20 680 patients) evaluating 16 treatments were included. Nineteen studies had low risk of bias. All selected treatments were deemed efficacious against placebo on the basis of previous systematic reviews. In network meta-analyses, calcitonin gene-related peptide antagonist monoclonal antibodies (CGRP-mAbs) probably resulted in fewer discontinuations due to adverse events than topiramate (risk difference, -16.2% [95% CI, -18.4% to -12.8%]; moderate-certainty evidence), and CGRP-mAbs may result in less migraine-related disability and improved quality of life compared with gepants (mean differences, -4.12 [CI, -9.30 to 1.05] and 2.25 [CI, -0.85 to 5.34], respectively; low-certainty evidence). For other outcomes and comparisons, there was moderate- or low-certainty evidence of no clinically important differences, uncertain evidence, or no evidence. Limited literature was available to determine the minimal important differences. The number of head-to-head comparisons of treatments was limited. No high-certainty evidence favored one pharmacologic treatment for prevention of episodic migraine over another. Evidence was mostly insufficient or of low certainty. American College of Physicians. (PROSPERO: CRD42023414305).

Effects of Radiation Dose of Photon and Electron Beam Energies and Angles in Radiation Therapy

This study explores the effects of varying radiation beam energy levels and angles on the doses administered to adjacent healthy tissues and tumors during cancer treatment. While electron beams are best suited for superficial tumors because of their shallow penetration depth, photon beams produced by linear accelerators are useful for deep-seated tumors. Radiation doses were measured at different angles with 6 MV and 15 MV photon beams at 0° and 60° and with 6 MeV, 12 MeV, and 15 MeV electron beams at 0° and 15°. The findings demonstrate that larger angles and higher energy produce higher doses at different positions in photon therapy. Energy levels in electron therapy have a greater effect on dose distribution than angles. Our linear regression model analysis found that energy level angles and dose measurements in photon therapy strongly correlate with high R2 scores (above 0.8). Substantial and inconsistent correlations were observed with electron therapy. Despite these variations, a positive correlation was seen between various dose measurements for both treatments. These results emphasize the significance of choosing the right angles and energy levels to maximize treatment efficacy and minimize harm to healthy tissues. The use of these treatment protocols in clinical settings is supported by comparing our results with international standards which guarantee safety and efficacy.

Evaluation of Hematological Parameters Pre and Post Chemotherapy in Breast Cancer Patients at the National Cancer Institute in Sudan at Khartoum state, Sudan

Introduction: Breast cancer is the most common malignancy among women worldwide, including in Sudan. Chemotherapy, a primary treatment modality, often results in hematological toxicity, impacting patients' overall health and treatment efficacy. This study aims to evaluate the changes in hematological parameters in breast cancer patients before and after chemotherapy in the Sudanese population. Materials and Methods: A case control study was conducted at the National Cancer Institute in Sudan at Khartoum state, Sudan. During the period of June 2022 to December 2022. A total of one hundred (N=100) female breast cancer patients scheduled for chemotherapy were enrolled.50 sample before initiation chemotherapy, and fifty (50) samples after first cycle of chemotherapy from same patients. And fifty (50) samples from the healthy individuals as control group. Venous blood was obtained, then CBC determined using hematology analyzer (Sysmex: XP-300). Hematological parameters, including Red blood cell count (RBC), white blood cell (WBC) count, and platelet count, and differential counts, were measured before the initiation of chemotherapy and after the completion of the first cycle. Data were analyzed using paired t-tests to determine the significance of changes in these parameters. Results: Significant reductions were observed in RBC levels (mean pre-chemotherapy: (3.8± 1.1) g/dL, mean post-chemotherapy: (2.1± 1.1); p<0.001) and WBC counts (mean pre-chemotherapy: 13.9 ± 1.9 x 10^3/μL, mean post-chemotherapy: 4.1 ± 1.9 x 10^3/μL; p<0.001). Platelet counts also decreased significantly (mean pre-chemotherapy: 661.8 ± 128.5 x 10^3/μL, mean post-chemotherapy: 182.4 ± 125.5 x 10^3/μL; p<0.01). Breast cancer patients before initiation the first cycle of chemotherapy show significant low in RBCs count (3.8 ± 1.1) when compared with control group (4.8 ± 0.4) (p = 0.000). Also, significant high in WBCS count (13.9 ± 1.9) when compared with control group (5.9 ± 1.3) (p = 0.000) and high PLTs count (661.8 ± 128.5) when compared with control group (262.7 ± 73.4) (p =0.000). And decrease in three parameters (pancytopenia) RBCs, WBCS, and PLTs count (2.7 ± 0.7) (4.1 ± 2.3) (182.4 ± 102.4) respectively when compared with control group (4.8 ± 0.4) (5.9 ± 1.3) (262.7 ± 73.4) (p =0.000) to all, when start the first cycle of chemotherapy. Conclusion: Chemotherapy in breast cancer patients leads to significant hematological changes, predominantly anemia, leukopenia, and thrombocytopenia. These findings underscore the need for close monitoring of hematological parameters during chemotherapy to manage potential toxicities and optimize treatment outcomes for breast cancer patients in Sudan.

The effectiveness of dyadic interventions for health outcomes of prostate cancer patients and informal caregivers: a systematic review and meta-analysis

BackgroundProstate cancer is a worldwide health issue, and current prostate cancer care extends to the patient‒caregiver dyadic setting, where individuals are interdependent and interact with each other as well as possible negative psychological and behavioural outcomes. However, the impact of dyadic care interventions on health outcome indicators for prostate cancer patients and their informal caregivers has yet to be examined.AimTo describe the characteristics of dyadic interventions involving patients with prostate cancer and their informal caregivers and investigate their effects on psychosocial health, sexual health, and dyadic relationships.MethodsTen electronic databases (Web of Science, Cochrane Library, PsycINFO, PubMed, Embase, CINAHL, CNKI, Wanfang, VIP, and SinoMed) were thoroughly searched for related publications published between the database’s founding and April 2024. The risk of bias for the included studies was evaluated using the Cochrane risk-of-bias tool, and a meta-analysis was performed using RevMan 5.4.ResultsThis study identified and evaluated 19 RCTs reporting 22 different interventions, as well as outcome indicators for the three aspects of psychosocial health, sexual health, and dyadic relationships in prostate cancer patients and informal caregivers. A meta-analysis of pooled data revealed that for prostate cancer patients, the intervention improved dyadic coping (SMD95% CI [95% CI] = 0.22 [0.01;0.42], p = 0.04), and for informal caregivers the dyadic care intervention reduced anxiety (SMD95% CI [95% CI] = -0.35 [-0.65;-0.06], p = 0.02), enhanced self-efficacy (SMD [95% CI] = 0.22 [0.01;0.43], p = 0.04), and improved sexual functioning (SMD [95% CI] = 0.29 [0.05;0.54], p = 0.02). No statistically significant overall effects were observed for the other outcome indicators.ConclusionThe results of this review indicate that dyadic care interventions benefit prostate cancer patients and informal caregivers. However, given features such as research quality and sample size, further randomized controlled trials with excellent study designs are needed in the future to evaluate and validate the efficacy of dyadic care treatments for patients with prostate cancer.Trial registrationThe protocol for this study is registered in PROSPERO with registration number (CRD42024567542).

Current and Evolving Concepts in the Management of Complex Regional Pain Syndrome: A Narrative Review

Background/Objectives: Complex regional pain syndrome (CRPS) is characterized by severe pain and reduced functionality, which can significantly affect an individual’s quality of life. The current treatment of CRPS is challenging. However, recent advances in diagnostic and treatment methods show promise for improving patient outcomes. This review aims to place the question of CRPS in a broader context and highlight the objectives of the research for future directions in the management of CRPS. Methods: This study involved a comprehensive literature review. Results: Research has identified three primary pathophysiological pathways that may explain the clinical variability observed in CRPS: inflammatory mechanisms, vasomotor dysfunction, and maladaptive neuroplasticity. Investigations into these pathways have spurred the development of novel diagnostic and treatment strategies focused on N-Methyl-D-aspartate Receptor Antagonists (NMDA), Toll-like receptor 4 (TLR-4), α1 and α2 adrenoreceptors, as well as the identification of microRNA (miRNA) biomarkers. Treatment methods being explored include immune and glial-modulating agents, intravenous immunoglobulin (IVIG) therapy, plasma exchange therapy, and neuromodulation techniques. Additionally, there is ongoing debate regarding the efficacy of other treatments, such as free radical scavengers, alpha-lipoic acid (ALA), dimethyl fumarate (DMF), adenosine monophosphate-activated protein kinase (AMPK) activators such as metformin, and phosphodiesterase-5 inhibitors such as tadalafil. Conclusions: The controversies surrounding the mechanisms, diagnosis, and treatment of CRPS have prompted researchers to investigate new approaches aimed at enhancing understanding and management of the condition, with the goal of alleviating symptoms and reducing associated disabilities.

Targeting the hERG1/β1 integrin complex in lipid rafts potentiates statins anti-cancer activity in pancreatic cancer

Plasma membrane macromolecular complexes function as signaling hubs that regulate cell behavior, which is particularly relevant in cancer. Our study provides evidence that the complex formed by the hERG1 potassium channel and the β1 subunit of integrin receptors preferentially localizes in Lipid Rafts (LRs) in Pancreatic Ductal Adenocarcinoma (PDAC) cell lines and primary samples. The complex recruits the p85 subunit of phosphatidyl-inositol-3-kinase (PI3K), activating phosphoinositide metabolism and triggering an intracellular signaling pathway centered on Akt. This pathway ultimately affects cancer cell proliferation through cyclins and p21, and cell migration through the small GTPase Rac-1 and f-actin organization. The hERG1/β1 integrin complex in LRs can be dissociated and the downstream signaling pathway can be inhibited by either disrupting LRs through methyl-beta-cyclodextrin (MβCD) or inhibiting cholesterol synthesis by statins. Treatment with a single chain bispecific antibody—scDb-hERG1-β1—specifically targeting the complex significantly potentiates the effects of both MβCD and statins on intracellular signaling. Consequently, these treatments decrease PDAC cell proliferation and motility in vitro. From a pharmacological perspective, different statins produce anti-neoplastic effects in synergy with scDb-hERG1-β1. Such combination also enhances tumor sensitivity to chemotherapeutic drugs, such as gemcitabine and oxaliplatin. The efficacy of these combination treatments depends on the amount of the hERG1/β1 integrin complex present on the plasma membrane of cancer cells. Finally, the combined treatment with statins and scDb-hERG1-β1 significantly reduces tumor growth and improves survival in vivo, in a preclinical mouse model. These results suggest that the combination of scDb-hERG1-β1 and statins represent a potential novel strategy for treating PDAC patients.

Efficacy of Educational Intervention on Parental Expertise Regarding Prevention of Hypovitaminosis of Retinol (Vitamin A) and Vision Impairment Among Mothers of Preschool Children

ABSTRACT Background: Vitamin A deficiency (VAD) is a leading cause of childhood blindness in developing countries, contributing significantly to morbidity and mortality from common early-life illnesses, even at sub-clinical levels. The need for effective interventions to address VAD is critical, especially in communities where awareness is low. Objective: This study aimed to assess the impact of a community-based educational intervention on improving maternal knowledge about vitamin A and its role in preventing childhood blindness and related health issues. Methods: The study was conducted in Choolai, Chennai, during March and April 2024, over four weeks. A total of 100 mothers of preschool children were enrolled, with equal numbers assigned to an experimental group (receiving community-based educational intervention) and a control group (receiving standard treatment). Data was collected using a semi-structured questionnaire and the PRASHAT vision disability checklist. Statistical analysis was performed using SPSS version 22. Results: The pre-test scores for both groups were similar. However, post-intervention, the experimental group showed a significant improvement in knowledge, with coherence scores increasing from 13.90 to 23.54, compared to minimal improvements in the control group. Demographic factors, such as age, education, and occupation, were significantly correlated with the improvement in the experimental group. Conclusion: The study demonstrated that community-based educational interventions significantly enhance maternal knowledge about vitamin A, thereby reducing the risk of vitamin A deficiency and improving vision health among preschool children. These findings highlight the importance of such interventions in preventing hypervitaminosis and promoting optimal child health.

Efficacy of e-cigarettes for smoking cessation in populations with psychiatric and/or substance use problems: A secondary analysis of a randomized controlled trial.

People with psychiatric and substance use disorders are more likely to smoke and less likely to quit than smokers in the general population. We evaluated the efficacy of e-cigarettes for abstinence from tobacco smoking in people with psychiatric and substance use problems. We analyzed data collected in the larger 'Efficacy, Safety, and Toxicology of ENDS as an Aid for Smoking Cessation' (ESTxENDS) trial (n=1246): the intervention group received e-cigarettes and e-liquids, plus standard-of-care smoking cessation counseling (SOC) for 6 months; the control group received SOC and a voucher. The primary outcome was biochemically validated continuous self-reported abstinence at 6 months; secondary outcomes included 6-month and 7-day self-reported abstinence. We calculated adjusted relative risks (ARR) for two subsamples meeting these conditions at the baseline visit: 1) psychotropic medication use; and 2) problematic substance or polysubstance use. Among the participants using psychotropic medications (n=239), the ARR for validated abstinence was 2.62 (95% CI: 1.40-4.90) in the intervention group versus the control group, 2.95 (95% CI: 1.72-5.07) for 6-month and 2.96 (95% CI: 1.92-4.55) for 7-day self-reported abstinence, while among participants with problematic substance or polysubstance use (n=818), the ARR was 1.57 (95% CI: 1.20-2.04), 1.42 (95% CI: 1.15-1.74), and 1.53 (95% CI: 1.31-1.79), respectively. Adding e-cigarettes to standard-of-care counseling increased the likelihood that participants with psychiatric and substance use problems would abstain from smoking, but larger studies should test the efficacy and safety of smoking cessation interventions in this often-marginalized population.

Comparative Efficacy and Safety of Netarsudil-Containing Interventions for Intraocular Pressure Control: A Systematic Review and Network Meta-Analysis.

Netarsudil has been approved for lowering elevated intraocular pressure (IOP), showing effectiveness through two distinct mechanisms. It is also effective when used in combination with other therapies to enhance outcomes. This study aims to compare the drug's effectiveness with other treatments, both as a standalone and in combination therapies, while also assessing potential adverse effects to evaluate its overall safety and suitability.We systematically searched PubMed, Cochrane, Web of Science, and Scopus till the 7th of October.Data from eligible studies were extracted and combined using a frequentist network meta-analysis, presented asmean differences (MDs) for continuous outcomes and risk ratios (RRs) along with their 95% confidence intervals (CIs). We used the Cochrane risk-of-bias (ROB) tool to assess the quality of the included RCTs.Netarsudil 0.02%/latanoprost 0.005% fixed-dose combination (FDC) q.d. was the most effective in reducing IOP in one-, two-, and six-week follow-ups in addition to the three-month follow-up. The netarsudil-containing medication was associated with higher adverse events compared to other arms.Netarsudil 0.02%/latanoprost 0.005% FDC q.d. and bimatoprost 0.03%/timolol 0.5% FDC emerged as the most effective therapies for lowering IOP, with each showing significant advantages at different follow-up points. Both FDCs achieved substantial reductions in IOP and a high proportion of patients reaching target IOPs. However, safety profiles indicate that traditional therapies like latanoprost 0.005% and timolol 0.5% may have fewer side effects, including lower incidences of blurred vision, conjunctival hemorrhage, and conjunctival hyperemia.

Age and Sex Differences in Efficacy of Treatments for Type 2 Diabetes: A Network Meta-Analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors improve hyperglycemia, and SGLT2 inhibitors and GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACEs) among individuals with type 2 diabetes. It is not clear whether efficacy varies by age or sex. To assess whether age or sex are associated with differences in the efficacy of SGLT2 inhibitors, GLP-1 receptor agonists, and DPP4 inhibitors. The MEDLINE and Embase databases and US and Chinese clinical trial registries were searched for articles published from inception to November 2022; in August 2024, the search was updated to capture the trial results. Two reviewers screened for randomized clinical trials of SGLT2 inhibitors, GLP-1 receptor agonists, or DPP4 inhibitors vs a placebo or active comparator in adults with type 2 diabetes. Individual participant data and aggregate data were used to estimate age × treatment interactions and sex × treatment interactions in multilevel network meta-regression models. Hemoglobin A1c (HbA1c) and MACEs. Of the 601 eligible trials identified (592 trials with 309 503 participants reported HbA1c; mean age, 58.9 [SD, 10.8] years; 42.3% were female and 23 trials with 168 489 participants reported MACEs; mean age, 64.0 [SD, 8.6] years; 35.3% were female), individual participant data were obtained for 103 trials (103 reported HbA1c and 6 reported MACEs). The use of SGLT2 inhibitors (vs placebo) was associated with less HbA1c lowering with increasing age for monotherapy (absolute reduction [AR], 0.24% [95% credible interval {CrI}, 0.10% to 0.38%] per 30-year increment in age), for dual therapy (AR, 0.17% [95% CrI, 0.10% to 0.24%]), and for triple therapy (AR, 0.25% [95% CrI, 0.20% to 0.30%]). The use of GLP-1 receptor agonists was associated with greater HbA1c lowering with increasing age for monotherapy (AR, -0.18% [95% CrI, -0.31% to -0.05%] per 30-year increment in age) and for dual therapy (AR, -0.24% [95% CrI, -0.40% to -0.07%]), but not for triple therapy (AR, 0.04% [95% CrI, -0.02% to 0.11%]). The use of DPP4 inhibitors was associated with slightly better HbA1c lowering in older people for dual therapy (AR, -0.09% [95% CrI, -0.15% to -0.03%] per 30-year increment in age), but not for monotherapy (AR, -0.08% [95% CrI, -0.18% to 0.01%]) or triple therapy (AR, -0.01% [95% CrI, -0.06% to 0.05%]). The relative reduction in MACEs with use of SGLT2 inhibitors was greater in older vs younger participants per 30-year increment in age (hazard ratio, 0.76 [95% CrI, 0.62 to 0.93]), and the relative reduction in MACEs with use of GLP-1 receptor agonists was less in older vs younger participants (hazard ratio, 1.47 [95% CrI, 1.07 to 2.02]). There was no consistent evidence for sex × treatment interactions with use of SGLT2 inhibitors and GLP-1 receptor agonists. The SGLT2 inhibitors and GLP-1 receptor agonists were associated with lower risk of MACEs. Analysis of age × treatment interactions suggested that SGLT2 inhibitors were more cardioprotective in older than in younger people despite smaller reductions in HbA1c; GLP-1 receptor agonists were more cardioprotective in younger people.

Model-informed repurposing of eliglustat for treatment and prophylaxis of Shiga toxin-producing Escherichia coli hemolytic-uremic syndrome (STEC-HUS) in children.

Shiga toxin-producing Escherichia coli hemolytic-uremic syndrome (STEC-HUS) is a severe illness predominantly affecting young children, with limited treatment options beyond supportive care. Eliglustat, approved for Gaucher disease, shows potential in reducing Shiga toxin binding to target glomerular endothelial cells in vitro, prompting interest as a treatment for STEC-HUS. However, it remains unknown what dose is likely to be effective and safe for treatment of STEC-HUS in the pediatric population. We hypothesize that effective and safe levels of eliglustat can be reached in children. We identified pharmacokinetic targets of efficacy for treatment and prophylaxis of STEC-HUS based on a preclinical model and human cardiac safety data. Then, we developed oral and intravenous dosing regimens using population pharmacokinetic (popPK) simulations based on an existing model enriched to allow extrapolation to a simulated virtual pediatric population. These dosing regimens were then confirmed using a verified physiologically based pharmacokinetic (PBPK) model. We simulated, using popPK data, oral and intravenous dosing regimens resulting in adequate target exposure in > 90% of all patients, with minimal expected risk for cardiotoxicity. Confirmation of these dosing regimens with PBPK modeling resulted in very similar exposure, with lower interindividual variability and minimal toxicity potential. Based on pharmacokinetic modeling, we developed oral and intravenous eliglustat dosing regimens that are likely safe and effective for treatment of STEC-HUS and prophylaxis in case of outbreaks of STEC infections. Clinical evaluation of these dosing regimens in children suspected of or diagnosed with STEC-HUS is required and should include assessment of pharmacokinetics, efficacy, and safety (e.g., ECG monitoring).

Step-by-step causal analysis of EHRs to ground decision-making.

Causal inference enables machine learning methods to estimate treatment effects of medical interventions from electronic health records (EHRs). The prevalence of such observational data and the difficulty for randomized controlled trials (RCT) to cover all population/treatment relationships make these methods increasingly attractive for studying causal effects. However, researchers should be wary of many pitfalls. We propose and illustrate a framework for causal inference estimating the effect of albumin on mortality in sepsis using an Intensive Care database (MIMIC-IV) and comparing various sensitivity analyses to results from RCTs as gold-standard. The first step is study design, using the target trial concept and the PICOT framework: Population (patients with sepsis), Intervention (combination of crystalloids and albumin for fluid resuscitation), Control (crystalloids only), Outcome (28-day mortality), Time (intervention start within 24h of admission). We show that too large treatment-initiation times induce immortal time bias. The second step is selection of the confounding variables based on expert knowledge. Increasingly adding confounders enables to recover the RCT results from observational data. As the third step, we assess the influence of multiple models with varying assumptions, showing that a doubly robust estimator (AIPW) with random forests proved to be the most reliable estimator. Results show that these steps are all important for valid causal estimates. A valid causal model can then be used to individualize decision making: subgroup analyses showed that treatment efficacy of albumin was better for patients >60 years old, males, and patients with septic shock. Without causal thinking, machine learning is not enough for optimal clinical decision on an individual patient level. Our step-by-step analytic framework helps avoiding many pitfalls of applying machine learning to EHR data, building models that avoid shortcuts and extract the best decision-making evidence.

Cellular Epigenetic Targets and Epidrugs in Breast Cancer Therapy: Mechanisms, Challenges, and Future Perspectives

Breast cancer is the most common malignancy affecting women, manifesting as a heterogeneous disease with diverse molecular characteristics and clinical presentations. Recent studies have elucidated the role of epigenetic modifications in the pathogenesis of breast cancer, including drug resistance and efflux characteristics, offering potential new diagnostic and prognostic markers, treatment efficacy predictors, and therapeutic agents. Key modifications include DNA cytosine methylation and the covalent modification of histone proteins. Unlike genetic mutations, reprogramming the epigenetic landscape of the cancer epigenome is a promising targeted therapy for the treatment and reversal of drug resistance. Epidrugs, which target DNA methylation and histone modifications, can provide novel options for the treatment of breast cancer by reversing the acquired resistance to treatment. Currently, the most promising approach involves combination therapies consisting of epidrugs with immune checkpoint inhibitors. This review examines the aberrant epigenetic regulation of breast cancer initiation and progression, focusing on modifications related to estrogen signaling, drug resistance, cancer progression, and the epithelial–mesenchymal transition (EMT). It examines existing epigenetic drugs for treating breast cancer, including agents that modify DNA, inhibitors of histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone demethyltransferases. It also delves into ongoing studies on combining epidrugs with other therapies and addresses the upcoming obstacles in this field.

Mitochondria-targeting of oxidative phosphorylation inhibitors to alleviate hypoxia and enhance anticancer treatment efficacy.

Hypoxia is a common feature of solid tumors and is associated with a poor response to anticancer therapies. Hypoxia also induces metabolic changes, such as a switch to glycolysis. This glycolytic switch causes acidification of the tumor microenvironment (TME), thereby attenuating the anticancer immune response. A promising therapeutic strategy to reduce hypoxia and thereby sensitize tumors to irradiation and/or antitumor immune responses is pharmacological inhibition of oxidative phosphorylation (OXPHOS). Several OXPHOS inhibitors (OXPHOSi) have been tested in clinical trials. However, moderate responses and/or substantial toxicity has hampered clinical implementation. OXPHOSi tested in clinical trials inhibit the oxidative metabolism in tumor cells as well as healthy cells. Therefore, new strategies are needed to improve the efficacy of OXPHOSi while minimizing side effects. To enhance the therapeutic window, available OXPHOSi have, for instance, been conjugated to triphenylphosphonium (TPP+) to preferentially target the mitochondria of cancer cells, resulting in increased tumor uptake compared to healthy cells, as cancer cells have a higher mitochondrial membrane potential. However, OXPHOS inhibition also induces reactive oxygen species (ROS), and subsequent antioxidant responses, which may influence the efficacy of therapies, such as platinum-based chemotherapy and radiotherapy. Here, we review the limitations of the clinically tested OXPHOSi metformin, atovaquone, tamoxifen, BAY 87-2243 and IACS-010759 and the potential of mito-targeted OXPHOSi and their influence on ROS production. Furthermore, the effect of the mitochondria-targeting moiety TPP+ on mitochondria is discussed as this affects mitochondrial bioenergetics.

Ménétrier Disease: A Scoping Review of Case Reports over the Last 10 Years

Abstract Objective This scoping review aims to map existing recent case reports on Menetrier’s disease examining clinical features, treatment strategies, potential etiological factors, and other associations to enhance understanding and inform future research directions. Methods We conducted a systematic search of PubMed, SCOPUS, Web of Science and Google Scholar for case reports on Menetrier’s disease published in English between January 2014 and October 2024. Eligible cases required histopathological confirmation, comprehensive clinical details, and unrestricted access, while pediatric cases and inaccessible records were excluded. Results Among 59 patients, 67.8% presented with Hypoalbuminemia, 37.3% were anemic. Regarding etiology, 20.3% tested positive for Helicobacter pylori suggesting a weaker link between the agent and Menetrier’s disease which highlights the need to explore other causes. 71.2% received pharmacological treatment of which 38% experienced full success, defined by both morphological and symptomatic improvements, while 66.6% experienced only symptomatic relief after treatment. Surgical Intervention was necessary for 35.6% of patients. The variability in clinical presentation and treatment outcomes, along with the lack of standardized approaches, implicate a need for further research to improve diagnostic and therapeutic strategies for Ménétrier’s disease. Conclusions This scoping review identifies critical research gaps in Ménétrier’s disease, including the need for further investigation into genetic predispositions, the role of etiological agents, treatment efficacy of emerging therapies, and the timing of surgical interventions, alongside the importance of cancer surveillance.

Interval Analysis-Based Optimization: A Robust Model for Intensity-Modulated Radiotherapy (IMRT)

Background: Cancer remains one of the leading causes of mortality worldwide, with radiotherapy playing a crucial role in its treatment. Intensity-modulated radiotherapy (IMRT) enables precise dose delivery to tumors while sparing healthy tissues. However, geometric uncertainties such as patient positioning errors and anatomical deformations can compromise treatment accuracy. Traditional methods use safety margins, which may lead to excessive irradiation of healthy organs or insufficient tumor coverage. Robust optimization techniques, such as minimax approaches, attempt to address these uncertainties but can result in overly conservative treatment plans. This study introduces an interval analysis-based optimization model for IMRT, offering a more flexible approach to uncertainty management. Methods: The proposed model represents geometric uncertainties using interval dose influence matrices and incorporates Bertoluzza’s metric to balance tumor coverage and organ-at-risk (OAR) protection. The θ parameter allows controlled robustness modulation. The model was implemented in matRad, an open-source treatment planning system, and evaluated on five prostate cancer cases. Results were compared against traditional Planning Target Volume (PTV) and minimax robust optimization approaches. Results: The interval-based model improved tumor coverage by 5.8% while reducing bladder dose by 4.2% compared to PTV. In contrast, minimax robust optimization improved tumor coverage by 25.8% but increased bladder dose by 23.2%. The interval-based approach provided a better balance between tumor coverage and OAR protection, demonstrating its potential to enhance treatment effectiveness without excessive conservatism. Conclusions: This study presents a novel framework for IMRT planning that improves uncertainty management through interval analysis. By allowing adjustable robustness modulation, the proposed model enables more personalized and clinically adaptable treatment plans. These findings highlight the potential of interval analysis as a powerful tool for optimizing radiotherapy outcomes, balancing treatment efficacy and patient safety.