Treatment Phase Research Articles

Moving Immunotherapy Into the Treatment of Resectable Non-Small Cell Lung Cancer.

Clinical investigation of immune checkpoint inhibitors (ICIs) has expanded from indications in metastatic non-small cell lung cancer (NSCLC) to add to the treatment of early-stage or resectable NSCLC. Although completed randomized trials supported the approvals of some ICIs as perioperative therapies (ie, adjuvant, neoadjuvant, or neoadjuvant followed by adjuvant), ongoing trials are evaluating other anti-PD-(L)1 antibodies for similar indications, or in combination with stereotactic body radiotherapy (SBRT). The incorporation of immunotherapy brings potential to improve outcomes of patients with resectable NSCLC, but these advances have also increased the complexity of the treatment landscape and created important knowledge gaps. This article reviews the current standards for local therapies in NSCLC, describes the clinical trials exploring the combination of ICIs to SBRT, and explains the recent approvals of ICIs as perioperative therapies. A discussion follows to highlight three important areas of uncertainty: (1) the contribution of ICIs given in each treatment phase (neoadjuvant and adjuvant) to the overall effect of neoadjuvant chemoimmunotherapy followed by adjuvant ICIs; (2) the selection of regimens to serve as comparators in future randomized trials of perioperative therapies; and (3) the role of pathologic complete response as an intermediate end point and aid for selection of patients for adjuvant therapy. Moving forward, stakeholders will need to engage in concerted research efforts to address the relevant clinical questions regarding the optimal management of resectable NSCLC.

Zuberitamab, an innovative anti-CD20 monoclonal antibody, for patients with primary immune thrombocytopenia in China: a randomized, double-blind, placebo-controlled, phase 2 study

Primary immune thrombocytopenia (ITP) is an autoimmune disease, and rituximab (RTX) induces long-term effect as second-line treatments. Zuberitamab is an innovative anti-CD20 monoclonal antibody, which was first developed in China and launched in diffuse large B lymphoma. This study aimed to investigate the safety, efficacy, and anticipated therapeutic dose of zuberitamab in Chinese ITP patients. This randomised, double-blind, placebo-controlled, phase 2 study was conducted at 26 hospitals in China. Eligible patients were aged 18-70 years, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous treatment and had a pre-treatment platelet count of <30×109/L. Patients randomly received zuberitamab in a dose escalation (100/300/600mg) or placebo once-weekly for 4 weeks and followed up to 24 weeks. The primary endpoint is the proportion of patients with a platelet count ≥50×109/L at week 8. Secondary endpoints include the proportion of patients with platelet counts ≥50×109/L or ≥100×109/L at least once within week 12/24, the proportion of patients experiencing platelets increased twice more than baseline as well as ≥30×109/L at least once during the treatment. Adverse events, pharmacokinetic, B cell depletion and immunogenicity were also assessed. This study is registered with https://www.chictr.org.cn/as ChiCTR2100050513. From October 2021 to March 2023, 50 patients were screened for eligibility, of whom 32 patients were enrolled and randomly assigned to placebo (n=4), zuberitamab 100mg (n=10), 300mg (n=8) and 600mg (n=10) groups. The primary endpoint (PLT ≥50×109/L at week 8) was achieved by 40% of patients in the 100mg group, while none in the other groups. Within 12 weeks, the proportions of patients in each treatment group achieving at least one instance of platelet count ≥50×109/L or ≥100×109/L or an increase twice more than baseline as well as ≥30×109/L were (70%, 38%, 50%), (60%, 13%, 30%), and (80%, 50%, 70%) in zuberitamab 100/300/600mg groups, respectively. By week 24, the proportions of patients achieving these secondary endpoints remained relatively stable or showed a mild increase of around 10%. The anticipated therapeutic dose of zuberitamab was 100mg. The plasma concentration of zuberitamab showed an increasing trend with dose (100mg-600mg) and linear pharmacokinetic behavior. CD19+ B cells and CD20+ B lymphocytes rapidly declined to 0% within one week and consistently maintained reduced levels throughout the entire treatment phase in three groups. Adverse events occurred in all patients with most of them were mild to moderate, no severe infections occurred. A slight decrease in immunoglobulins was observed in the 600mg group, but gradually recovered at week 20. Three patients (2 in 100mg and 1 in 600mg group) were tested positive for anti-zuberitamab antibodies. We also observed that women, disease duration <12 months, and MAIPA+patients may have higher response rates. This study preliminarily confirmed that 100mg zuberitamab was safe and effective in treating ITP and was recommended to support further investigation. National Natural Science Foundation of China and Zhejiang Bioray Biopharmaceutical Co. Ltd.

Family-oriented care and health-related quality of life for women with gynaecological cancer: A cross-sectional mixed-method study.

This study aims to describe the experiences of women with gynaecological cancer regarding family-oriented care (FOC) and how they rated their health-related quality of life (HRQoL) using a 15D instrument (15D©). A cross-sectional mixed-method study. The data were collected by electronic surveys of two Finnish cancer associations from gynaecological cancer patients (n = 53). The qualitative data were analysed using thematic analysis. The HRQoL answers were analysed statistically using IBM SPSS Statistics (Version 27). The results emphasized that FOC is not yet part of the care process. Furthermore, comprehensive encounters are lacking, and the experience of being a woman is forgotten during the care process. The results of the HRQoL analysis suggest that distress and the discomfort and symptoms of cancer patients are perceived as significant factors affecting their quality of life during different phases of treatment. Family status also has an impact on perceived quality of life, whereby those living alone gave worse ratings for the depression and vitality dimensions. In part, the quantitative and qualitative data supported each other, but the descriptions provided a more comprehensive view of issues that affect women in a more multidimensional way, such as sexual health issues. More research on the effectiveness of FOC is needed to develop the capacity for effective healthcare. This study was able to identify important areas for improvement in clinical practice from the perspective of patients and their families. This study was prepared and reported according to the STROBE checklist. No patient or public contribution.

Ramosetron as an add-on therapy for refractory fibromyalgia: A randomized, double-blind, placebo-controlled trial.

This study aimed to assess the efficacy and safety of intravenous ramosetron for pain relief in patients with fibromyalgia (FM) unresponsive to conventional treatments. . In this prospective, double-blind, placebo-controlled trial, 80 FM patients were randomly allocated to receive either placebo (n = 40) or ramosetron (n = 40) at a dosage of 0.3 mg/day intravenously for five consecutive days. The primary outcome was the reduction in pain intensity at the end of the treatment period, evaluated using a visual analogue scale (VAS). Secondary outcome measures included the FM Impact Questionnaire, Beck Depression Inventory (BDI), Multi-Dimensional Health Assessment Questionnaire (MDHAQ), EQ-5D, and State-Trait Anxiety Inventory on days 5 (end of treatment), 7, 10, and 28. Safety was continuously monitored throughout the study. . At the end of the treatment phase, the ramosetron group demonstrated a significantly greater reduction in VAS pain scores compared with the placebo group (1.18 ± 1.60 vs 0.54 ± 1.59, p< 0.05). Additionally, the ramosetron group exhibited significant improvements in BDI (4.42 ± 5.18 vs 1.33 ± 4.87, p< 0.05) and MDHAQ pain scale (0.37 ± 0.74 vs 0.04 ± 0.52, p< 0.05) scores. However, these improvements in pain VAS and BDI scores were not sustained through day 28. The safety profile of ramosetron was favorable, with gastrointestinal symptoms, particularly constipation, being the most commonly reported adverse events. . Intravenous administration of ramosetron provided safe and effective short-term relief of pain intensity in FM patients with inadequate response to standard treatments.

#425 Felzartamab (anti-CD38) in patients with IgA Nephropathy—interim results from the IGNAZ study

Abstract Background and Aims Most patients with IgA nephropathy (IgAN) will progress to kidney failure within 10-15 years of diagnosis. Sustained proteinuria is the best predictor of adverse long-term kidney outcomes and is a surrogate marker for efficacy. CD38+ plasma cells are likely the main source of pathogenic Gd-IgA1, and the related autoantibodies in IgAN. Felzartamab (felza; HIB202) is a recombinant purified human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to CD38 on plasma cells and is being studied across immune-mediated kidney diseases such as IgAN, Primary Membranous Nephropathy, Lupus Nephritis, and Antibody Mediated Rejection. The primary aims of the IGNAZ study were to assess: 1) efficacy of felza compared to placebo on urine protein:creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) change from baseline, and 2) the relationship between exposure, safety, and efficacy in each of 3 dose groups vs. placebo. Interim results with 15 months of follow-up from this 24-month trial are presented. Method In Part 1, 48 IgAN subjects were randomized in a 1:1:1:1 ratio across a placebo and 3 active arms in this multicenter, double-blind placebo-controlled, phase IIa trial. The M1, M2, and M3 active arms received 2 doses in 15 days, 5 doses in 2 months, and 9 doses in 5 months, respectively. In Part 2, 6 Japanese subjects received the M3 regimen, open-label, and have been followed for 9 months. Key inclusion criteria included ages 18-80 years, biopsy confirmed diagnosis of IgAN within the past 8 years, proteinuria at screening ≥1.0 g/d, eGFR ≥30 ml/min/1.73 m2 (by CKD-EPI), and background stable and maximally tolerated renin angiotensin system inhibitors. Results 48 randomized subjects were enrolled at 28 sites in the US and in 14 different countries in Europe and in Asia, of which 46 completed the treatment phase. Mean (SD) baseline characteristics (Parts 1 and 2 combined): age 41.6 (12.3) yrs, UPCR 1.67 (1.0) g/g, eGFR 74.6 (30.3) ml/min/1.73 m2. 67% of subjects were male. Intention-to-treat with felza demonstrated rapid, clinically meaningful reductions in UPCR with the maximal treatment effect being observed in the M3 9-dose regimen. In Part 1, percentage change from baseline in UPCR was −14% for placebo and −25% for M3 9-dose arm at month 3, and +9% for placebo and −35% for M3 at month 6 (Fig. A). Reductions in proteinuria observed at month 6 persisted until Month 15, 10 months after the last dose: +6% and −38% mean UPCR change from baseline for placebo and the M3 9-dose arm, respectively (Fig. B). Relatively stable eGFR values were observed for the felza arms compared to loss of eGFR in the placebo arm. Rapid, durable reductions in IgA and Gd-IgA1 levels were seen across the dosing arms, with reductions lasting 10 months after the last dose (Fig. C). IgG recovery occurred faster off-treatment than IgA. Results in the Part 2 subjects were similar to the Part 1 M3 cohort through 9 months. There were no apparent dose-dependent adverse events and no exposure-safety relationship. Treatment-emergent adverse events (TEAEs) were generally of mild or moderate intensity or toxicity grade. The most common TEAE assessed as related by study investigator was infusion related reactions (IRR), most of which occurred on the first infusion. There was one treatment-related serious AE due to an IRR. Five subjects discontinued treatment due to IRRs or drug hypersensitivity; for four of the five subjects, the infusion rate was higher than protocol-specified or had an error in pre-medication. TEAE infections were comparable between placebo and felza arms: Placebo (33.3%), M1 (33.3%), M2 (36.4%), M3 (38.5%), Part 2 (50.0%); all were Grades 1 or 2, and non-serious. Conclusion This proof-of-concept study highlights the potential for disease modification in IgAN with the anti-CD38 mAb felza and supports continued research as a potential treatment for high-risk IgAN patients. Felza treatment resulted in clinically meaningful, prolonged UPCR reductions and eGFR stabilization sustained ≥10 months after dosing was completed. Felza was generally well tolerated with rapid recovery of IgG with durable reductions in IgA and pathogenic Gd-IgA1 levels.

#581 Therapeutic management of patients with GPA and MPA: a nationwide observational study in France

Abstract Background and Aims Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare systemic necrotizing vasculitis. Treatment per rituximab was approved in 2013, and recent guidelines recommend corticosteroids sparing. A real-life pharmacoepidemiologic retrospective study was set up to describe the demographic characteristics of hospitalized GPA and MPA patients and compare the treatments of patients included before rituximab approval (over 2010–2012, Group 1) and after rituximab approval in France (over 2014–2017, Group 2). Method All adult patients hospitalized for GPA or MPA between January 1, 2010 and December 31, 2017 were included from the French National Health Insurance database (SNDS) which covers &amp;gt;97.5% of French population. Patients were separated in 2 groups according to their date of inclusion: (i) Over 2010-2012 for group 1 and (ii) over 2014-2017 for group 2. Descriptive analyses were performed. Kaplan-Meier method was used to model the duration of treatment induction and maintenance. Fine and Gray tests were used to compare treatment phases durations. Results The study involved 4445 prevalent GPA patients (including 1578 incident patients) and 1833 prevalent MPA patients (878 incident patients). Group 1 consisted of 694 and 283 GPA and MPA patients respectively; group 2 included 668 and 463 GPA and MPA patients respectively. Mean age and the sex ratio were stable over time. During the first year after inclusion, the proportion of patients with first-time hospitalized infections, diabetes or renal failure increased between 2010–2012 and 2014–2017. Between the two inclusion periods, the proportions of patients treated with rituximab increased both in the induction and maintenance phases whereas treatment with azathioprine declined (Table 1). As for methotrexate, cyclophosphamide and glucocorticoids, the proportions remained stable. Conclusion According to real-life, pharmacoepidemiologic data in GPA and MPA patients, the introduction of rituximab reduced the use of azathioprine without affecting the use of glucocorticoids, although corticosteroids sparing should become a standard of care with the emerging treatment regimens. No reductions in adverse events were observed with the increased use of rituximab.

RANKL, OPG, and BALP Levels in Gingival Crevicular Fluids as a Biomarker on Alveolar Bone Remodeling in the Retention Phase of Orthodontic Treatment

RANKL, OPG, and BALP Levels in Gingival Crevicular Fluids as a Biomarker on Alveolar Bone Remodeling in the Retention Phase of Orthodontic Treatment

Therapeutic efficacy of candidate antischistosomal drugs in a murine model of schistosomiasis mansoni.

Schistosomiasis is a neglected tropical disease associated with considerable morbidity. Praziquantel (PZQ) is effective against adult schistosomes, yet, it has little effect on juvenile stages, and PZQ resistance is emerging. Adopting the drug repurposing strategy as well as assuming enhancing the efficacy and lessening the doses and side effects, the present study aimed to investigate the in vivo therapeutic efficacy of the widely used antiarrhythmic, amiodarone, and diuretic, spironolactone, and combinations of them compared to PZQ. Mice were infected by Schistosoma mansoni "S. mansoni" cercariae (Egyptian strain), then they were divided into two major groups: Early- [3weeks post-infection (wpi)] and late- [6 wpi] treated. Each group was subdivided into seven subgroups: positive control, PZQ, amiodarone, spironolactone, PZQ combined with amiodarone, PZQ combined with spironolactone, and amiodarone combined with spironolactone-treated groups. Among the early-treated groups, spironolactone had the best therapeutic impact indicated by a 69.4% reduction of total worm burden (TWB), 38.6% and 48.4% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 49%. Whereas, among the late-treated groups, amiodarone combined with PZQ was superior to PZQ alone evidenced by 96.1% reduction of TWB with the total disappearance of female and copula in the liver and intestine, 53.1% and 84.9% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 67.6%. Comparatively, spironolactone was superior to PZQ and amiodarone in the early treatment phase targeting immature stages, while amiodarone had a more potent effect when combined with PZQ in the late treatment phase targeting mature schistosomes.

Single German centre experience with patient journey and care-relevant needs in amyloidosis: The German AMY-NEEDS research and care program.

Amyloidosis is a rare multi-system disorder associated with frequently delayed diagnosis, enormous disease burden and psychosocial distress. Systematic assessment of needs was performed by a subtype-spanning questionnaire-based survey within the AMY-NEEDS research and care program. 118 patients with proven amyloidosis (62.7% ATTR, 22.0% AL, 15.3% other forms) were included in August 2020 until February 2021 (mean age 71.2 ±11.3 years; 30% women). The median diagnostic delay between onset of symptoms and diagnosis was 9.0 (range: 2.5; 33.0) months. Local health care providers (HCPs) play a central role on the way to diagnosis. Diagnosis itself typically requires a clinical but not necessarily a university setting. In the treatment phase, the focus moves to the amyloidosis centre as primary contact and coordinator, with general practitioners (GPs) acting predominantly as a contact point in crisis and link to additional services. About half of patients reported impaired quality of life and one third suffering from anxiety and depressed mood, respectively. The majority of patients talk about their concerns with close caregivers and local HCPs. Advance care planning is a relevant, yet insufficiently met need. The journey of patients with amyloidotic disease, their contact partners and needs at different stages were characterized in detail within the German health care system. An amyloidosis-specific care concept has to master the multitude of interfaces connecting the numerous treatment providers involved with the amyloidosis centre and GPs as key players. Telemedical approaches could be a promising and well-accepted option allowing optimal coordination and communication.

Synergistic neuromodulation therapy for persistent spinal pain: a proof-of-concept trial on the use of spinal cord and dorsal root ganglion stimulation.

Persistent Spinal Pain Syndrome type 2 (PSPS-T2) poses a significant clinical challenge, demanding innovative therapeutic interventions. The integration of Spinal Cord Stimulation (SCS) and Dorsal Root Ganglion Stimulation (DRG-S) is emerging as a potent synergistic strategy for comprehensive pain management. This single patient-blind proof of concept (POC) trial explores the efficacy and synergistic potential of combined SCS and DRG-S in a patient with refractory PSPS-T2. A 45-year-old male with intractable PSPS-T2 underwent a unique, methodically structured study, involving three treatment phases: Phase A with SCS alone, Phase B with DRG-S alone, and Phase C The patient, blinded to the treatment modalities, provided pain assessments using the Visual Analogue Scale (VAS) and Douleur Neuropathique 4 Questions (DN4) conducted by clinical investigators at each phase. Baseline pain scores were ten and nine, respectively. Distinct responses were noted across the phases. Phase A demonstrated moderate pain relief, while Phase B offered further pain intensity reduction. However, Phase C, combining both strategies, yielded the most significant improvement, remarkably enhancing the patient's quality of life and functional capacity. This POC trial underscores the synergistic potential of SCS and DRG-S in managing complex cases of PSPS-T2, suggesting a paradigm shift towards integrated neuromodulation strategies for enhanced pain control. The development of dual intent implantable pulse generators (IPGs) capable of offering combination therapy simultaneously might be effective for pain management in select cases. The significant pain reduction and functional improvement observed advocate for further research in dual neuromodulation therapies. IRB 20190536.

Neferine alleviates ovariectomy-induced osteoporosis by enhancing osteogenic differentiation of bone marrow mesenchymal stem cells via regulation of the p38MAPK pathway

ABSTRACT Objective Osteoporosis, a skeletal ailment marked by bone metabolism imbalance and disruption of bone microarchitecture, Neferine, a bisbenzylisoquinoline alkaloid with diverse pharmacological activities, has received limited attention in the context of osteoporosis treatment. Methods We employed a bilateral ovariectomy (OVX) rat model to induce osteoporosis and subsequently administered Neferine treatment for four weeks following successful model establishment. Throughout the modeling and treatment phases, we closely monitored rat body weights. We assessed alterations in bone tissue microstructure through micro-CT, HE staining, and safranin O-fast green staining. Levels of bone formation and resorption markers in serum were evaluated using ELISA assay. Western blot analysis was employed to determine the expression levels of p38MAPK, p-p38MAPK, and bone formation-related genes in bone tissue. We isolated and cultured OVX rat BMSCs (OVX-BMSCs) and induced osteogenic differentiation while simultaneously introducing Neferine and the p38MAPK inhibitor SB203580 for intervention. Results Neferine treatment effectively curbed the rapid weight gain in OVX rats, ameliorated bone loss, and decreased serum levels of TRAP, CTX-I, PINP, and BALP. Most notably, Neferine promoted the expression of bone formation-related factors in bone tissue of OVX rats, while concurrently activating the p38MAPK signaling pathway. In in vitro experiments, Neferine facilitated the expression of bone formation-related factors in OVX-BMSCs, increased the osteogenic differentiation potential of OVX-BMSCs, and activated the p38MAPK signaling pathway. Nevertheless, SB203580 partially reversed Neferine’s promotive effect. Conclusion Neferine can boost the osteoblastic differentiation of BMSCs and alleviate OVX-induced osteoporosis in rats by activating the p38MAPK signaling pathway.

Comprehensive Virtual Treatment for Severe Anxiety in Youth: A Case Report

Anxiety disorders and obsessive-compulsive disorder (OCD) are among the most common mental health conditions in children and adolescents and are associated with various impairments and long-term consequences. Evidence-based treatments exist but are often lacking in elements needed to effectively treat youth with more severe presentations. This case report illustrates a patient’s treatment course in an innovative program for children, adolescents, and young adults with severe anxiety. The program offers a continuum of outpatient, evidence-based care tailored to the severity of the patient’s condition. The case study focuses on “Jane,” an adolescent female with anxiety as well as obsessive-compulsive spectrum disorders, who had previously received extensive treatment without sustained improvement. Through the program’s three treatment phases, Jane and her parents demonstrated consistent engagement and adherence to treatment. Jane showed significant progress, with rapid reduction in symptoms and functional impairment. This case report underscores key elements of this treatment that address gaps in traditional approaches to care, particularly for patients with severe presentations, including the coordinated, team-based approach; the continuum of evidence-based, phased treatment titrated to need; the utilization of virtual individual, group and parent-focused care and between-session coaching to enhance learning generalization; and the use of measurement-based care. Further research is warranted to evaluate the generalizability and long-term outcomes of this program and its potential to transform the treatment landscape for pediatric anxiety and OCD.

ENDOCARDITIS TEAM? DESIGNING AN ORIGINAL AND TAILORED CLINICAL PATHWAY

Abstract Infective endocarditis (IE) remains a poorly understood disease that primarily affects either native or prosthetic heart valves. Its incidence has increased over the past two decades, now affecting 3 to 10 individuals per 100.000/year in the general population. Despite advances in early diagnosis and surgical intervention, IE continues to pose a significant challenge, often leading to severe complications and carrying a substantial burden of morbidity and mortality. Data from the EURO–Endo registry show a drastic change in IE and provide an accurate picture of IE disease today. In European countries, it tends to affect older patients with a remarkable 12% of cases occurring in those aged ≥ 80 years. The traditional care pathway is often fragmented into multiple and potentially dangerous steps, resulting in delayed diagnosis and treatment. Such a “patchy” approach may cause suboptimal patient management, especially in the subset of frail patients with important concomitant diseases and high surgical risk. Clinical pathways (CPs) are an evidence–based multidisciplinary care plans involving diagnosis, treatment and rehabilitation phases, through which to follow patients from hospital admission to discharge, in order to manage a specific health condition, aiming to optimize patient and hospital/team outcomes, while contributing to a better organized care processes. In 2018, a working group composed by healthcare managers, infectious disease specialists, cardiac surgeons, cardiologists, anesthesiologists, geriatricians and other professionals involved in the care of IE patients have engineered a dedicated CP for IE at our institution. The CP introduced significant changes in the management of patients with IE. As a result, the quality of care and services offered increased, a faster and more appropriate diagnosis and treatment were achieved, patient outcomes and safety improved and a better coordination and continuity of care between different settings was guaranteed. The growing burden of IE in western countries demands an evidence–based multidisciplinary care plan. The creation of a territorial network ensures continuity and appropriateness of care in conjunction with the referring physicians/hospital and rationalization of resources. Although some controversies still exist, we believe that CP will have a positive impact on quality in health care.

Combination Treatment With Varenicline and Nicotine Patch on Smoking Cessation Outcomes in Heavy Drinkers at 26-Week Follow-up.

People who smoke cigarettes and drink alcohol heavily are less likely to quit smoking compared with those who do not drink heavily. The current study examined the effects of a 12-week treatment phase of combination varenicline and nicotine patch compared with placebo and nicotine patch on smoking cessation (primary outcome) and alcohol consumption (secondary outcome) in heavy drinking smokers at 26-week follow-up. Participants were daily smokers who met heavy drinking criteria. They were randomly assigned to receive either varenicline and nicotine patch (n = 61) or placebo and nicotine patch (n = 61) for 12 weeks. At week 26, self-reports of point prevalence cigarette abstinence were biochemically confirmed, and past-month alcohol drinking days and heavy drinking days were assessed. At week 26, smoking quit rates did not differ by treatment group (25% varenicline and 26% placebo). Relative to week 12 outcomes, week 26 quit rates significantly dropped off in the varenicline group but not in the placebo group. Alcohol drinking reductions for the whole sample that were previously observed from baseline to week 12 were sustained at week 26, although they did not differ between treatment groups. In heavy drinking smokers, smoking cessation success was evident in a quarter of the total sample at 3 months postmedication discontinuation. At this time, quit rates were the same between those who received varenicline and nicotine patch and those who received nicotine patch alone. Future research is warranted to examine what may aid in longer-term smoking quit rates in heavy drinking smokers.

Efficacy of EMDR in Body Dysmorphic Disorder and Associated Cognitive-Emotional Features

Body dysmorphic disorder (BDD) is a severe psychological disorder that significantly impacts functioning and quality of life. Eeye movement desensitization and reprocessing (EMDR) presents as an emerging alternate psychological intervention. This study aimed to examine the efficacy of EMDR in BDD symptoms and associated cognitive-emotional features. These features include appearance-based rejection sensitivity, body shame, and self-compassion. Our study utilized a multiple-baseline across-subjects design, monitoring four randomly allocated female patients with BDD over a 10-session/90-minute EMDR treatment phase and two follow-up sessions at 1 and 3 months, respectively. Our results showed that EMDR significantly reduced BDD symptoms (recovery percentage [RP] = 60.54), appearance-based rejection sensitivity (RP = 36.56), and body shame (RP = 54.82) and increased self-compassion (RP = 51.79). Therefore, our study suggests that EMDR may be an effective treatment for BDD patients.

Treatment of localized rectal cancer in 2024

The management of localized rectal cancer has evolved significantly over the last two years. On one hand, intensification of treatments (radio-chemotherapy, chemotherapy, then surgery) for the most advanced tumors has shown an improvement in clinical results compared to less intense regiments. On the other hand, the possibility, as for prostate cancers, of opting for active surveillance without surgery in patients presenting a complete clinical response after a treatment phase, is now accepted. More recently, the Swiss recommendations for the surveillance of rectal cancer have been modified and now differ from those of colon cancers, by incorporating pelvic MRI and rectoscopy in addition, as well as special guidelines for tumors under active surveillance.

Antidyslipidemic effect of ethanol extract of &lt;i&gt;Irvingia wombolu&lt;/i&gt; seeds in high fat diet induced dyslipidemic rat

The antidyslipidemic activity of Irvingia wombolu ethanol seeds extract was studied in high fat diet induced dyslipidemic rats.Forty five (45) Wstar rats were grouped into 5 groups of 9 rats each. The animals were allowed 7 days acclimatization period. Group 1 was the control group and it received normal rat chow and water throughout the study. Groups 2 to 5 were given high fat diet for 14 days after which they were given normal rat chow till the end of the study. At the end of the 14 days, group 2 was not treated while group 3-5 were treated with 250, 500 and 1000mg/kg b.w ethanol extract of Irvingia wombolu seeds respectively for 28 days. The lipid profile of animals was evaluated three times: first after 14 days induction period (phase 1) i.e day 0 of treatment, second was taken 14 days after treatment (phase 2), third was taken 28 days after treatment (phase 3). The study lasted for 49 days and dimethyl sulphoxide was used as a vehicle for the extract. In phase 1, all the groups fed with high fat diet showed an increase in low density lipoprotein (LDL) triglyceride, total cholesterol and a decrease in high density lipoprotein (HDL) levels. In phase 2 there was a decrease in LDL, triglyceride and total cholesterol level in addition to increase in HDL for animals in all the treatment groups. It was observed that in phase 3 only 250mg/kg group showed a progressive decrease in LDL, triglyceride, total cholesterol and an increase in HDL levels while 500 and 1000 mg/kg b.w showed an increase in LDL, triglyceride and total cholesterol level and a decrease in HDL. The result of the present study demonstrated the antidyslipidemic effect of ethanol extract of Irvingia wombolu seeds at lower dose.

Evaluating the Nephroprotective and Hepato-protective Effects of Hypoestes rosea in Acetaminophen-Induced Toxicity in Albino Rats

The leaves of Hypoestes rosea are in use as traditional medicine in the Niger Delta areas in Nigeria and the Western part of Cameroun for the management of different ailments in children, such as anaemia, malaria, fever and other ailments. Regardless of its uses, scanty studies evaluating its organ protective effects exist. Therefore, this research study evaluates the nephroprotective and hepato-protective effects of Hypoestes rosea in acetaminophen-induced toxicity in Albino rats. The objectives of this research study are to evaluate the protective effect of Hypoestes rosea on the kidney and the liver of albino rats. Acetaminophen, which is frequently used as an analgesic and antipyretic drug at high doses, can be harmful to vital organs of the body, affecting the liver and kidneys. In this study, effects of an aqueous extract of Hypoestes rosea (AEHr) on liver function parameters and kidney function parameters of acetaminophen induced-toxicity in albino rats were evaluated using acute (15 days) and sub-chronic (30 days) duration of study and study group comprising of prophylactic (pre-treatment) and therapeutic (post-treatment) phases with six experimental groups in each phase. A total of 112 adult apparently healthy Albino rats weighing (180-220g) were used for this study, divided into six experimental groups of extract control (EC), negative control (NC), positive control (PC), AEHr100mg/kg b w., AEHr 200mg/kg b w., and AEHr 300mg/kg b w. groups each of six rats. At the end of the research study period, blood samples were collected through jugular puncture for liver and kidney function parameters. Results showed that acetaminophen-induced toxicity in albino rats caused toxicity to the kidney and toxicity to the liver, as evidenced by the raised levels of potassium, urea, creatinine and low bicarbonate from the renal function parameters and also as evidenced by significant elevation of bilirubin and liver enzymes with a significantly low total protein and albumin levels from the liver function parameters when compared with other experimental groups. Conversely, AEHr at different concentrations in a dose-dependent pattern at the different treatment phases and different duration periods were able to repair the injury to the kidney and liver caused by acetaminophen induction to normal. Consequently, the findings of this research propose that Hypoestes rosea contains active ingredients accountable for the nephroprotective and hepato-protective abilities in rats and can be recommended for more studies using higher mammals.

Sequential Evaluation of Hematology Markers as a Prognostic Factor in Glioblastoma Patients.

In our study, we investigated the prognostic significance of hematological markers-NLR (Neutrophil-to-Lymphocyte Ratio), PLR (Platelet-to-Lymphocyte Ratio), and RDW-CV (Red Blood Cell Distribution Width-Coefficient of Variation)-in 117 glioblastoma patients. The data collected from January 2016 to December 2018 included demographics, clinical scores, and treatment regimens. Unlike previous research, which often examined these markers solely before surgery, our unique approach analyzed them at multiple stages: preoperative, postoperative, and before adjuvant therapies. We correlated these markers with the overall survival (OS) and progression-free survival (PFS) using statistical tools, including ANOVA, Cox regression, and Kaplan-Meier survival analyses, employing SPSS version 29.0. Our findings revealed notable variations in the NLR, PLR, and RDW-CV across different treatment stages. The NLR and PLR decreased after surgery, with some stabilization post-STUPP phase (NLR: p = 0.007, η2p = 0.06; PLR: p = 0.001, η2p = 0.23), while the RDW-CV increased post-surgery and during subsequent treatments (RDW-CV: p < 0.001, η2p = 0.67). Importantly, we observed significant differences between the preoperative phase and other treatment phases. Additionally, a higher NLR and RDW-CV at the second-line treatment and disease progression were associated with an increased risk of death (NLR at 2nd line: HR = 1.03, p = 0.029; RDW-CV at progression: HR = 1.14, p = 0.004). We proposed specific marker cut-offs that demonstrated significant associations with survival outcomes when applied to Kaplan-Meier survival curves (NLR at 2nd line < 5: p < 0.017; RDW-CV at progression < 15: p = 0.007). An elevated NLR and RDW-CV at later treatment stages correlated with poorer OS and PFS. No significant preoperative differences were detected. These biomarkers may serve as non-invasive tools for glioblastoma management.

Proportion of inflammatory bowel diseases patients withsuboptimal disease control in daily clinical practice-Real-world evidence from the inflammatory bowel diseases-podcast study.

Crohn's disease and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by a progressive nature of the disease resulting in subsequent intestinal damage, limited efficacy of current treatments and suboptimal disease management and a significant burden for patients. The IBD-PODCAST study aims to estimate the proportion of Crohn's disease and UC patients with suboptimal disease control (SDC) in a real-world setting. A non-interventional and cross-sectional study was conducted across 103 sites in 10 countries (Austria, Belgium, Canada, Germany, Greece, Italy, Portugal, Spain, Turkey, and UK). Criteria for SDC were based on STRIDE-II criteria and adapted by an expert panel. 2185 patients (Crohn's disease: n=1,108, UC: n=1077) with a mean (SD) age of 44.0 (14.8) years and mean (SD) disease duration of 12.4 (9.2) years were included (52.2% male). Ileal involvement was present in 39.1% of Crohn's disease patients, 35.3% of UC patients had extensive colitis. 77.3% of Crohn's disease and 65.3% of UC patients were on targeted immunomodulators and, according to STRIDE-II-based treatment phases, 85.6% of Crohn's disease and 85.4% of UC patients were assigned to the long-term treatment phase. SDC was detected in 52.2% of Crohn's disease and 44.3% of UC patients predominantly due to impaired quality of life (QoL), clinically significant extraintestinal manifestations, steroid overuse, signs of active inflammation in UC and Crohn's disease, and active fistulas in Crohn's disease. More than one criterion was seen in 37% of patients with SDC. Opportunities for on-label treatment optimization were observed in 49% of Crohn's disease and 61% of UC patients on advanced therapy. The high percentage of SDC in this global, real-world cohort suggests a large disease burden and high unmet medical need in IBD patients. Future analysis should focus on monitoring and responding to SDC in this cohort and on patients' QoL.