NCT Number Research Articles

Effect of Male Partner-Targeted Breastfeeding Education and Support Interventions on Optimal Breastfeeding Practices in Central Ethiopia: A Cluster Randomized Controlled Trial.

A male partner or husband is the most influential person in the family, especially in Ethiopia. The role of a male partner or husband in promoting and supporting breastfeeding has hardly been investigated in low- and middle-income countries, including Ethiopia. Therefore, the objective of this study was to evaluate the effect of breastfeeding education and support interventions that focus on male partners, with the goal of promoting optimal breastfeeding practices in central Ethiopia. A two-arm parallel design cluster randomized controlled trial was carried out among couples in a community setting in the Hadiya Zone, Central Ethiopia. Fathers and mothers in the intervention group received breastfeeding education and support via social events, home visits and using printed materials, while those in the control group received existing routine care. A total of 408 couples from 16 clusters were randomly assigned to either the intervention group (n = 204) or the control group (n = 204). A Generalized Estimating Equation (GEE) model was used to evaluate the effectiveness of the interventions. At the end of the interventions, the proportion of optimal breastfeeding practice increased by 19.5% in the intervention group and by 2% in the control group. The differences-in-difference in optimal breastfeeding practice between the intervention and control groups was 17.5% [95% CI: 13.8%-21.2%; p = 0.001]. In the GEE model, babies born to mothers in the mother-father pair group had a 38% higher likelihood [RR = 1.38, 95% CI (1.106, 1.723)] of being optimally breastfed at the sixth month compared with babies born to mothers who received standard care. Breastfeeding education and support interventions targeting male partners in low-resource settings improve optimal breastfeeding practices, highlighting the need to give due emphasis to integrating breastfeeding promotion and counselling for male partners into existing maternal and child health services. Trial Registration: ClinicalTrials.gov identifier (NCT number): NCT05173454, First registered on 30/12/2021.

CTNI-39. UPDATE ON GBM AGILE: A GLOBAL, PHASE 2/3 ADAPTIVE PLATFORM TRIAL TO EVALUATE MULTIPLE REGIMENS IN NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMA

Abstract BACKGROUND GBM AGILE (Glioblastoma Adaptive, Global, Innovative Learning Environment) is a biomarker based, multi-arm, international, seamless Phase 2/3 platform trial designed to rapidly identify and confirm experimental therapies that improve overall survival for approval along with their associated biomarker signatures. GBM AGILE is a collaboration between academic investigators, patient organizations, and industry to support new drug applications for newly diagnosed (ND) and recurrent glioblastoma. METHODS The primary objective of GBM AGILE is to identify therapies that improve the overall survival in patients with ND or recurrent glioblastoma. Bayesian response adaptive randomization is used within subtypes of the disease to assign participants to investigational arms based on their performance. GBM AGILE operates under a Master Protocol allowing multiple drugs to be evaluated simultaneously and over time against a common control. New experimental therapies are added as information about promising new drugs is identified, while therapies are removed as they complete evaluation. Six investigational arms have been included to date. Along with an adaptive trial design, shared control arm and operational processes, GBM AGILE continues to incorporate new design and operational elements. One recent design element added to the Master Protocol for consideration for future arms is an extended evaluation period, of up to 11 months, for arms that reach maximum sample size in Stage 1 (Stage 1: learn most responsive signature) without having reached a decision for futility or graduation. Allowing data to mature and additional events to accumulate may increase the ability of the trial to detect efficacy, and if appropriate, for an arm to graduate to Stage 2 (Stage 2: confirm activity in graduating signature). Using improved and flexible processes, GBM AGILE continues to serve as a global trial that supports the efficient and rapid incorporation and evaluation of new experimental therapies for patients with glioblastoma. NCT number: NCT03970447.

Clinical outcomes in patients in any phase of CML treated with ponatinib in France-Data from the TOPASE observational study.

The TOPASE study was set up to evaluate the outcomes of chronic myeloid leukaemia [CML] patients treated with ponatinib (PON) in a real-world setting in France. One hundred and twenty CML patients, 105 in chronic phase (CP), 8 in accelerated phase (AP) and 7 in blastic phase (BP) were included. Fifty-one (49%) of the CP-CML patients were in third line of treatment. The trigger for PON initiation in CP-CML was 'poor response' in 67 patients, 'poor tolerance' in 28 patients and 'response enhancement' in seven patients. The median dose at initiation was 30 mg/day [Q1; Q3 = 15; 30] in CP-CML and 45 mg/day [Q1; Q3 = 30; 45] in AP/BP-CML. Of 98 CP-CML evaluable patients, 72 (73.5%) were considered as responders (MMR) at one time point at least once, especially for those in second line of treatment and/or presenting a T315I mutation. Ninety-six of 120 (80%) patients reported at least one adverse event. An arterial occlusive event (AOE) was reported in 11 patients (9.2%). Thus, these real-life data confirm the potency of ponatinib in resistant or intolerant patients with an acceptable safety profile in non-selected patients. NCT number: NCT04048564.

The effectiveness and outcomes of epidural analgesia in patients undergoing open liver resection: a propensity score matching analysis

BackgroundOpen liver resection necessitates a substantial upper abdominal inverted-L incision, resulting in severe pain and compromising patient recovery. Despite the efficacy of epidural analgesia in providing adequate postoperative analgesia, the potential epidural-related adverse effects should be carefully considered. This study aims to compare the efficacy and safety of continuous epidural analgesia and intravenous analgesia in open liver resection.MethodsA retrospective study was conducted, collecting data from patients who underwent open liver resection between 2007 and 2017. Propensity score matching was implemented to mitigate confounding variables, with patients being matched in a 1:1 ratio based on propensity scores. The primary outcome was the comparison of postoperative morphine consumption at 24, 48, and 72 hours between the two groups. Secondary outcomes included pain scores, postoperative outcomes, and epidural-related adverse effects.ResultsA total of 612 patients were included, and after matching, there were 204 patients in each group. Opioid consumption at 24, 48, and 72 hours postoperatively was statistically lower in the epidural analgesia group compared to the intravenous analgesia group (p < 0.001). However, there was no significant difference in pain scores (p = 0.422). Additionally, perioperative hypotension requiring treatment, as well as nausea and vomiting, were significantly higher in the epidural analgesia group compared to the intravenous analgesia group (p < 0.001).ConclusionsEpidural analgesia is superior to intravenous morphine in terms of reducing postoperative opioid consumption within the initial 72 h after open liver resection. Nevertheless, perioperative hypotension, which necessitates management, should be approached with consideration and vigilance.Trial registrationThe study was registered in the Clinical Trials Registry at www.clinicaltrials.gov/, NCT number: NCT06301932.

SciScribe: Automating and contextualizing literature reviews in cardiac surgery

BackgroundThe task of writing structured content reviews and guidelines has grown stronger and more complex. We propose to go beyond search tools and toward curation tools by automating time-consuming and repetitive steps of extracting and organizing information. MethodsSciScribe is built as an extension of IBM's Deep Search platform, which provides document processing and search capabilities. This platform was used to ingest and search full-content publications from PubMed Central (PMC) and official, structured records from the ClinicalTrials and OpenPayments databases. Author names and NCT numbers, mentioned within the publications, were used to link publications to these official records as context. Search strategies involve traditional keyword-based search as well as natural language question and answering via large language models (LLMs). ResultsSciScribe is a web-based tool that helps accelerate literature reviews through key features: (1) accumulating a personal collection from publication sources, such as PMC or other sources; (2) incorporating contextual information from external databases into the presented papers, promoting a more informed assessment by readers; (3) semantic questioning and answering of documents to quickly assess relevance and hierarchical organization; and (4) semantic question answering for each document within a collection, collated into tables. ConclusionsEmergent language processing techniques are opening new avenues to accelerate and enhance the literature review process, for which we have demonstrated a use case implementation in cardiac surgery. SciScribe automates and accelerates this process, mitigates errors associated with repetition and fatigue, and contextualizes results by linking relevant external data sources instantaneously.

Effectiveness of male partner-targeted breastfeeding education and support interventions on mothers' breastfeeding self-efficacy in central Ethiopia: a cluster-randomized controlled trial

The purpose of this study was to evaluate the effect of male partners’ targeted antenatal and postnatal breastfeeding education and support interventions on maternal breastfeeding self-efficacy in central Ethiopia. A two-arm parallel group cluster randomized controlled trial was carried out among couples in a community setting in the Hadiya Zone, central Ethiopia. A total of 408 couples from 16 clusters were randomly assigned to either the intervention (n = 204) or control group (n = 204). The analysis was conducted using an intention-to-treat approach. A generalized estimating equation (GEE) analysis was done to evaluate the effectiveness of the interventions. Maternal BFSE was significantly higher among mothers whose male partner received breastfeeding education and support interventions than those who did not receive the interventions (130 (65.0%) v 90 (45.9%), P < 0.001). The net effect of the intervention on improving maternal BFSE was 20.9% [95% CI: 16.9%–24.9%]. In the GEE model, maternal BFSE was 48% [RR = 1.48, 95% CI: 1.23, 1.79] higher in the intervention group than the control group. Involving male partners in breastfeeding promotion activities can enhance the mother's self-efficacy and confidence in breastfeeding.Trial registration: ClinicalTrials.gov identifier (NCT number), NCT05173454. Registered on 30/12/2021.

Exploring the effects of post operative hyperoxic intermittent stimuli on reticulocyte levels in cancer patients: a randomized controlled study

BackgroundAnemia is common among hospitalized critically ill and surgical oncological patients. The rising incidence of cancer and aggressive treatments has increased the demand for blood products, further strained by a dwindling donor pool. The normobaric oxygen paradox (NOP) has emerged as a potential avenue to increase EPO levels. While some studies support its efficacy, research remains limited in clinical settings. This study aims to assess the effectiveness of a NOP protocol in stimulating erythropoiesis, as measured by changes in reticulocyte counts, in cancer patients undergoing abdominal surgeries.MethodsThis is a post hoc analysis of a prospective, single-center, controlled, randomized study. A total of 49 patients undergoing abdominal surgery were analyzed at the Institut Jules Bordet. Adult patients admitted to the intensive care unit (ICU) for at least 24 h were enrolled, excluding those with severe renal insufficiency or who received transfusions during the study period. Participants were randomized into two groups: a normobaric oxygen paradox (OXY) group who received 60% oxygen for 2 h on days 1, 3, and 5 post-surgery and a control (CTR) group who received standard care. Data on baseline characteristics, surgical details, and laboratory parameters were collected. Statistical analysis included descriptive statistics, chi-square tests, t-tests, Mann–Whitney tests, and linear and logistic regression.ResultsThe final analysis included 33 patients (median age 62 [IQR 58–66], 28 (84.8%) males, with no withdrawals or deaths during the study period. No significant differences were observed in baseline surgical characteristics or perioperative outcomes between the two groups. In the OXY group (n = 16), there was a significant rise (p = 0.0237) in the percentage of reticulocyte levels in comparison to the CTR group (n = 17), with median values of 36.1% (IQR 20.3–57.8) versus − 5.3% (IQR − 19.2–57.8), respectively. The increases in hemoglobin and hematocrit levels did not significantly differ between the groups when compared to their baselines’ values.ConclusionsThis study provides preliminary evidence supporting the potential of normobaric oxygen therapy in stimulating erythropoiesis in cancer patients undergoing abdominal surgeries. While the OXY group resulted in increased reticulocyte counts, further research with larger sample sizes and multi-center trials is warranted to confirm these findings.Trial registrationThe study was retrospectively registered under NCT number 06321874 on The 10th of April 2024.

P-103 Sperm selection for ICSI by rheotaxis and thermotaxis in In-Situ handmade microfluidics of fluidic walls: preliminary results of a Randomized Controlled Trial

Abstract Study question Does sperm selection by rheotaxis and thermotaxis in In-Situ handmade microfluidics of fluidic walls optimize ICSI outcomes and workflow? Summary answer In-Situ handmade rheo/thermotaxis microfluidics of fluidic walls is as effective and more time-efficient than centrifugation density gradients to support pre-implantation embryonic development to blastocyst. What is known already Microfluidics technologies stand as the latest sperm selection methodology for ICSI. To outline their application in ART we conceived a lab-on-a-chip approach for sperm selection by In-Situ handmade microfluidics of fluidic walls (isM) in the same ICSI plate which integrates two operative zones: one to allow seminal plasma dispersion and sperm thermotaxis and another one to allow sperm rheotaxis. Our microfluidics system can be prepared with any media suitable for ICSI, disregarding centrifugation, washing, plasticware and other cells. The isM protocol proved non-inferior to centrifugation density gradients (CDG) to support embryonic development and implantation in a previous sibling-oocyte study. Study design, size, duration The present RCT was approved by our ethical committee for research with medical products (CEIm approval number 2023/394). This preliminary analysis aims to detect deviations in the pre-defined primary outcomes: Normal Fertilization Rate, Day 5/6 usable blastocyst rate per MII, and per zygote. This analysis includes data from 21 couples undergoing an ICSI treatment in our center during December 2023-January 2024. Only patients without clinical or analytical suspicion of sperm DNA fragmentation were included. Participants/materials, setting, methods Patients were randomly allocated to isM (n 9) or to CGD (n 12) groups. All participants signed an informed consent. Sperm samples were processed directly after liquefaction. For CGD, samples were prepared in 80-40% PureSperm® layers by isopycnic centrifugation followed by washing and dilution steps. The isM system was prepared by displaying three microdroplets of different volumes following a L-shape interconnection and allowing a temperature gradient of 2ºC between the first and the second microdroplet. Main results and the role of chance Sperm characteristics showed the following total mean values for the isM and CGD groups, respectively: concentration (58,2±38,0 × 106/ml and 52,7±29,1 × 106/ml) and progressive sperm concentration (16,6±17,0 × 106/ml and 16,8±13,4 × 106/ml). Women average age was 36,7±2,9 isM and 35,8±2,5 CDG. This analysis includes a total of 168 MII oocytes (n = 69 isM and n = 99 CDG), with a mean number of MII oocytes per patient of 7,4±2,1 isM and 8,3±1,9 CDG. Comparisons between the two groups showed that isM protocol optimizes ICSI outcomes by means of Normal Fertilization Rate: 88,4% vs 76,8%; p &amp;lt; 0,05, Day 5 A/B grade blastocyst rate: 36,1 vs 31,6%; ns, Day 5/6 usable blastocyst rate per MII: 58,0% vs 44,4%; ns and Day 5/6 usable blastocyst rate per diploid zygote: 65,6% vs 57,9%; ns. The isM protocol also optimizes the IVF workflow compared to CDG, as the time to obtain sperm for ICSI after liquefaction was 26 vs 77 minutes, respectively. Limitations, reasons for caution The study aims for a total size of 50 ICSI cycles to validate statistically our data at a power of 80%. The isM protocol depends on a free hand preparation. A ready-to-use surface would benefit the operability, albeit the use of templates and the training reduces inter and intra-operator variability. Wider implications of the findings The potential benefits of the isM protocol on fertilization could be significant for patients with a limited number of available oocytes for ICSI. According to the literature, microfluidics reduce the DNA fragmentation index in the selected sperm fraction. The isM method could be especially beneficial in patients with this pathology. Trial registration number NCT number assignment pending

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Single Vaccination of Ad26.RSV.preF-Based Regimen in Japanese Adults Aged 60 Years and Older.

Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of lower respiratory tract disease (LRTD) in older adults. The Ad26.RSV.preF/RSV preF protein vaccine demonstrated protective efficacy against RSV related LRTD in a Phase 2b study in the United States. Hence, Ad26.RSV.preF/RSV preF protein vaccine candidate was evaluated in the Japanese older adult population. This Phase 1 study evaluated safety, reactogenicity, and immunogenicity of Ad26.RSV.preF/RSV preF protein vaccine at dose level of 1 × 1011 vp/150 μg in Japanese healthy adult aged ≥60 years. The study included a screening Phase, vaccination, 28-day follow up Phase, a 182-day follow-up period, and final visit on Day 183. A total of 36 participants were randomized in a 2:1 ratio to receive Ad26.RSV.preF/RSV preF protein vaccine (n = 24) or placebo (n = 12). After study intervention administration, the safety and immunogenicity analysis were performed as per planned schedule. Immune responses including virus-neutralizing and preF-specific binding antibodies were measured on Days 1, 15, 29, and 183. There were no deaths, SAEs, or AEs leading to discontinuation reported during the study. The Ad26.RSV.preF/RSV preF protein vaccine had acceptable safety and tolerability profile with no safety concern in Japanese older adults. The Ad26.RSV.preF/RSV preF protein vaccine induced RSV-specific humoral immunity, with increase in antibody titers on Days 15 and 29 compared with baseline which was well maintained until Day 183. A single dose of Ad26.RSV.preF/RSV preF protein vaccine had an acceptable safety and tolerability profile and induced RSV-specific humoral immunity in Japanese healthy adults. NCT number: NCT04354480; Clinical Registry number: CR108768.

Multiplex analysis of the immune environment before and after neoadjuvant durvalumab as a prognostic factor in resectable non-small cell lung cancer (NSCLC) in the IFCT-1601 IONESCO phase 2 trial.

8022 Background: Immune checkpoint inhibitors (ICI) are currently included in the peri-operative standard of care for NSCLC with the objective of a curative strategy. In early stages of NSCLC, biomarkers predicting ICI efficacy should be more stringent than PD-L1 tumoral expression in order to improve the benefit-toxicity ratio. We deeply analyzed the tumor microenvironment of patients included in the IONESCO multicenter phase 2 trial (stage IB &gt; 4cm–IIIA, non N2 resectable NSCLC). Diagnostic biopsies and surgical resection specimen after 3 cycles of Durvalumab were available. We previously showed that the % of residual viable tumor cells (RVT) was associated with disease free survival (DFS) and overall survival (OS). PD-L1 tumor positive score was not correlated to RVT nor survival. Methods: 46 patients were included in the IONESCO trial. Among them, diagnostic biopsy (n = 32), surgical resection specimen post durvalumab (n = 39) and paired tumor samples (n = 31) were analyzed. Immune environment was assessed using 7 quantitative 7-plex immunofluorescence panels generating 349 different cellular phenotypes in 3 different compartments (whole tumor, intra cytokeratin and stroma), focusing on T and B lymphocytes, macrophages, immune checkpoint, NK cells, apoptosis, innate and adaptive immunity, dendritic cells. Densities of cells were quantified using Fluorescent Multiplex immunohistochemistry performed on Leica Bond RX, using OpalTM technology. A fisher's exact test or chi2 test was used for demographics variables and RVT. HRs and 95% CIs were estimated using a Cox model. NCT number: NCT03030131. Results: With median follow-up of 4.5 years, 16/31 patients had a disease recurrence. Histology, sex, stage and survival were significantly associated with intra-tumor densities of CD3, CD8, PD1, TIM3, and CD163 cells in the diagnostic biopsy, and with the delta of CD3, FoxP3, CD4, CD163PD1, TIM3, PDL1 on immune cells and TIM3PDL1 cells, between biopsy and surgical specimen. DFS was significantly associated with high density of CD8+TIM3+ in biopsies (HR = 0.25 [0.09-0.71], p = 0.0092) and with the high density of CD20+ cells in surgical specimen (HR = 0.36 [0.13-0.97], p = 0.04). The RVT was significantly associated with CK+Caspase3- cells and CK+PDL1+ cells in the surgical specimen. No biomarker was associated with OS. Conclusions: Multiparameter analysis of the immune NSCLC environment of patients treated with neoadjuvant anti-PDL1 allows identification of markers associated with clinical, pathological parameters and DFS. Our findings highlight the substantial impact of high CD8+TIM3+ cell density pre-durvalumab and of high CD20+ cell density post-durvalumab on DFS. These findings deserve to be assessed in patients treated with neoadjuvant combined immunotherapy chemotherapy. Clinical trial information: NCT03030131 .

Characterization of cancer clinical trials in the community setting.

e13506 Background: Extending clinical trials to community oncology sites is an imperative to meet accrual goals, ensure generalizable results, and facilitate optimal and equitable clinical care. The types of trials attractive to and successful in the community, however, are likely different from those run primarily at academic centers. We analyzed the characteristics of clinical trials open at a network of community oncology practices across the United States in the last 2 years, in order to inform both sponsors and sites about the studies most well-suited for a community setting. Methods: We analyzed characteristics from every clinical trial entered in OncoTrials, a clinical trial screening and tracking tool utilized exclusively by US community oncology practices, between 9/1/2021 through 10/09/2023 via knowledge of the trial NCT number and data available through API from clinicaltrials.gov. Descriptive statistics, including median and range for continuous variables and percentages for categorical variables are reported. Results: 1,310 clinical trials were open across 64 community oncology practices. Sponsors were classified as 80% industry (n=1,054), 15% NIH (n=195), 1% network (n=13) and 5% other (n=48). 93% of studies were interventional, 5% observational, 1% registry and 1% expanded access. Types of interventional studies (n=1,215) and the number of sites that ran them are shown (Table). The median target enrollment across all studies was 235 patients. Individual trials were open at a median of 2 community practices in our cohort (range 1-22 practices); 521 clinical trials (40%) were open at only one practice and 34 trials (2.6%) were open at more than 10 practices. The mean number of unique trials open at a practice during our 2 year observation period was 54 (median 35, range 1-264). Among these trials, the most commonly associated tumor types were lung (15%), pan-solid tumors (14%), breast (11%), lymphoma (6%), colorectal (6%), prostate (5%), gynecologic (4%), bladder (4%), head and neck (4%) and melanoma (4%). Conclusions: Community oncology practices supported a robust portfolio of clinical trials, most commonly focused on treatment of solid tumors. The vast majority were interventional (phase 2-3) and industry-sponsored. Half of sites ran Phase I trials, and Phase IV trials were uncommon but had broad participation across sites. Notably, a large proportion of studies were only open at one single site in a cohort of 64 community oncology practices. This highlights the opportunity for sponsors to leverage networks, consortia, and further research to ensure that appropriate studies are accessible among a broader range of community research sites. [Table: see text]

Effectiveness of dental floss in the management of gingival health: A 6-month follow-up of a randomized controlled clinical trial.

To evaluate, (i) if subjects submitted to a structured oral hygiene training program (OHt) maintain adopted habits over 180 days without professional guidance; and (ii) in perspective whether flossing provides additional benefits to toothbrushing on gingival health. Seventy-five adult subjects showing approximately 40% proximal gingival bleeding were randomized to receive OHt (1 session weekly over 8 weeks) using toothbrush and dental floss or toothbrush alone. The subjects were then followed over 180 days without professional guidance. Primary outcomes were mean interproximal Gingival Index (GI) and GI = 2 (gingival bleeding). Mixed linear models were used for the comparison between groups (p < 0.05). 68 subjects received OHt, 48 subjects completed the 180-day follow-up. Subjects maintained adequate oral hygiene routines. Besides a reduction in gingival inflammation, no alterations in gingival status were observed among groups, subjects additionally instructed to use dental floss showing a mean interproximal GI = 2 of 12.8 ± 2.5 compared with 19.8 ± 2.2 for subjects limited to tooth brushing alone. OHt intensive training promotes gingival health and maintenance lasting at least 6 months without professional supervision reinforcing important principles: (i) dental health professionals should dedicate time training and motivating their patients to reach adequate self-performed plaque control; and (ii) the adjunctive use of dental floss appears essential to reduce interproximal gingival inflammation in subjects with intact interdental papillae. Dentists need to invest time in training/motivating/engage their patients to achieve adequate OH; adjunct flossing in subjects with papilla filling the interdental space appears essential to reach and maintain gingival health. GOV : (53831716.5.0000.5346). The protocol registration was filed May 9, 2018 (# 538,311,716.5.0000.5346) on ClinicalTrials.gov. An NCT number (NCT04909840) was generated upon completed registration.

Abstract PS17-02: Elacestrant vs standard-of-care in ER+/HER2- advanced or metastatic breast cancer (mBC) with ESR1 mutation: key biomarkers and clinical subgroup analyses from the phase 3 EMERALD trial

Abstract Background: The EMERALD trial reported significantly prolonged progression-free survival (PFS) and a manageable safety profile with elacestrant vs standard of care (SOC) endocrine therapy in patients (pts) with ER+/HER2− ESR1 mutated (ESR1-mut) mBC following progression on prior endocrine therapy (ET). EMERALD is the only pivotal oral SERD clinical trial where prior CDK4/6i usage was mandated. Duration of prior CDK4/6i was shown to be a predictor of efficacy in patients with ESR1 mutations (ESR1-mut) receiving elacestrant, with median PFS (mPFS) for patients with ESR1-mut receiving at least 12 months of CDK4/6i achieved 8.61 months (elacestrant) vs 1.91 months (SOC) (SABCS 2022). This analysis evaluates the clinical benefit of single-agent elacestrant in key clinically relevant subgroups, including biomarkers, usually associated with poorer prognosis. Methods: Patients with ER+/HER2- advanced or mBC who previously had 1-2 lines of endocrine therapy, and prior CDK4/6i, were randomized 1:1 to receive elacestrant or SOC (aromatase inhibitor or fulvestrant). A subgroup analysis was performed on patients with ESR1-mut, by prior duration of CDK4/6i plus ET with at least 12 months in the advanced or metastatic setting, with concomitant presence of liver and/or lung metastases, PIK3CA mutations, TP53 mutation, and HER2 low expression. Results: Overall, 478 patients were randomized to elacestrant (n=239) or SOC (n=239), 228 pts (47.7%) had ESR1-mut, and 159 pts (71.6%) received at least 12 months of prior CDK4/6i. Out of these 159 pts, 113 pts (71%) had liver and/or lung metastases, 62 pts (39%) had a PIK3CA-mut, 61 pts (38%) had TP53m, and 77 pts (48%) had HER2 low expression. A clinically meaningful improvement in PFS favoring elacestrant compared to SOC was consistent across all relevant subgroups in pts with ESR1-mut. Conclusions: Elacestrant showed significantly greater PFS when prior treatment duration with CDK4/6i was at least 12 months, suggesting prior exposure to CDK4/6i is a surrogate marker for endocrine sensitivity. In this population, elacestrant demonstrated superior efficacy, compared to SOC, even in patients with concomitant PIK3CA or TP53 mutations, expression of HER2 low, or presence of liver and/or lung metastases. These results suggest an active ER-driven pathway for this group despite the presence of other resistance mechanisms, where single-agent oral elacestrant could be an attractive option compared to combination therapies or intravenous HER2 low-targeted ADCs. NCT number: NCT03778931 Table. a. Includes E545K, H1047R, E542K amongst others b. HER2 IHC 1+, and 2+ with no ISH amplification Citation Format: Aditya Bardia, Joyce O'Shaughnessy, Francois-Clement Bidard, Patrick Neven, José Ángel García-Sáenz, Philippe Aftimos, Javier Cortés, Janice Lu, Giulia Tonini, Kathy Puvana Theall, Alessandro Paoli, Virginia Kaklamani. Elacestrant vs standard-of-care in ER+/HER2- advanced or metastatic breast cancer (mBC) with ESR1 mutation: key biomarkers and clinical subgroup analyses from the phase 3 EMERALD trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS17-02.

Abstract CT257: Hyperprogressive disease following bintrafusp alfa and DNA damaging chemotherapy in relapsed small cell lung cancer

Abstract Background: Small cell lung cancer (SCLC) is the most aggressive type of lung cancer. Current therapies have limited efficacy in SCLC, and despite a highly mutated genome, SCLC is largely unresponsive to immunotherapy. We sought to leverage the immune surveillance triggered by DNA damage in patients with relapsed SCLC using bintrafusp alfa, a bifunctional fusion protein targeting both PD-L1 and TGF-beta. Hyperprogressive disease (HPD), characterized by the rapid acceleration of tumor growth, has been reported in approximately 13% of patients treated with immune checkpoint inhibitors. However, the mechanistic basis is poorly understood. Methods: This is a safety run-in and phase II clinical trial. Cohort 1 enrolled patients with relapsed SCLC across Arms A (bintrafusp alfa 2400 mg q3 wks), B (bintrafusp alfa 2400 mg on D1 plus topotecan 1 mg/m2/day on D1-5 q3 wks), and C (bintrafusp alfa 1200 mg on D1 q2 wks plus temozolomide 200 mg/m2/day on D1-5 q4 wks). The primary endpoint was objective response rate (ORR). Results: Thirty-seven patients enrolled. Grade 3 treatment-related adverse events (TRAE) included transaminitis (27.0%), anemia (24.4%), lymphopenia (10.8%), and maculopapular rash (5.4%). Grade 4 TRAE included thrombocytopenia (8.1%), lymphopenia (5.4%) and transaminitis (5.4%). One patient experienced grade 5 tumor hemorrhage. By RECIST 1.1, partial responses were observed in 5 (13.5%), stable disease in 11 (29.7%), and progressive disease in 21 (56.8%) patients. Importantly, 13 (35.1%) patients developed HPD (≥ 2x increase in tumor growth rate from pre-trial vs on-trial, time to treatment failure ≤ 2 months, and ≥ 50% increase tumor burden). Changes in circulating cell-free DNA (n=20) tumor fraction using DELFI-TF, a mutation-independent, low-coverage whole genome sequencing approach, correlated with treatment responses. Pre-treatment serum from HPD (n=10 vs. 9 non-HPD) patients showed significantly lower levels of inflammatory cytokines (CXCL10, CCL13, CCL8, CCL19, TRAIL) and Granzyme H, and higher levels of anti-inflammatory cytokine IL10. Consistently, pre-treatment tumor transcriptomes of HPD (n=5 vs. 7 non-HPD) patients revealed suppression of IFN-gamma response, allograft rejection, and inflammatory response pathways. Conclusions: Concomitant TGF-beta and PD-L1 blockade is associated with a high frequency of HPD in SCLC patients. cfDNA could be critical for monitoring HPD. Tumor and blood immune signatures may inform the likelihood of HPD, with immune excluded tumors more likely to develop HPD. NCT Number: NCT03554473 Bintrafusp alfa was provided by EMD Serono (CrossRef Funder ID: 10.13039/100004755) Citation Format: Brett Schroeder, Nobuyuki Takahashi, Howard Yang, Renee Donahue, Zachary Skidmore, Alissa Konicki, Michael Nirula, Max Greenberg, George Chrisafis, Yang Zhang, Yo-Ting Tsai, Linda Sciuto, Samantha Nichols, Melissa Abel, Parth Desai, Rajesh Kumar, Christopher Schultz, Danielle Pinkiert, Chante Graham, Ajit Sharma, Justin Malin, Manan Krishnamurthy, Sophie Zhuang, Maxwell Lee, Lorenzo Rinaldi, Jeffrey Schlom, Lalage Wakefield, Anish Thomas. Hyperprogressive disease following bintrafusp alfa and DNA damaging chemotherapy in relapsed small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT257.

Predictors of adherence to exercise interventions in people with schizophrenia

Exercise interventions are nowadays considered as effective add-on treatments in people with schizophrenia but are usually associated with high dropout rates. Therefore, the present study investigated potential predictors of adherence from a large multicenter study, encompassing two types of exercise training, conducted over a 6-month period with individuals with schizophrenia. First, we examined the role of multiple participants’ characteristics, including levels of functioning, symptom severity, cognitive performance, quality of life, and physical fitness. Second, we used K-means clustering to identify clinical subgroups of participants that potentially exhibited superior adherence. Last, we explored if adherence could be predicted on the individual level using Random Forest, Logistic Regression, and Ridge Regression. We found that individuals with higher levels of functioning at baseline were more likely to adhere to the exercise interventions, while other factors such as symptom severity, cognitive performance, quality of life or physical fitness seemed to be less influential. Accordingly, the high-functioning group with low symptoms exhibited a greater likelihood of adhering to the interventions compared to the severely ill group. Despite incorporating various algorithms, it was not possible to predict adherence at the individual level. These findings add to the understanding of the factors that influence adherence to exercise interventions. They underscore the predictive importance of daily life functioning while indicating a lack of association between symptom severity and adherence. Future research should focus on developing targeted strategies to improve adherence, particularly for people with schizophrenia who suffer from impairments in daily functioning.Clinical trials registration The study of this manuscript which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112, https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804.

Late-onset pulmonary complications following allogeneic hematopoietic cell transplantation in pediatric patients: a prospective multicenter study.

The primary objective of our multicenter prospective study was to describe the incidence of late-onset non-infectious pulmonary complications (LONIPCs) in children undergoing hematopoietic cell transplantation (HCT) using sensitive criteria for pulmonary function test (PFT) abnormalities including the non-specific pattern of airflow obstruction. Secondary objectives were to assess the factors associated with LONIPC occurrence and the sensitivity of the 2014 NIH-Consensus Criteria of bronchiolitis obliterans syndrome (BOS). PFT and clinical assessment were performed prior to HCT and at 6, 12, 24, and 36 months post-HCT. LONIPC diagnosis was validated by an Adjudication Committee. The study comprised 292 children from 12 centers. Thirty-two individuals (11%, 95% CI: 8-15%) experienced 35 LONIPCs: 25 BOS, 4 interstitial lung diseases, 4 organizing pneumonia and 2 pulmonary veno-occlusive diseases. PFT abnormalities were obstructive defects (FEV1/FVC z-score < -1.645; n = 12), restrictive defects (TLC < 80% predicted, FEV1 and FVC z-scores < -1.645; n = 7) and non-specific pattern (FEV1 and FVC z-score< -1.645, FEV1/FVC z-score > -1.645, and TLC > 80% predicted; n = 8). HCT for malignant disease was the only factor associated with LONIPC (P = 0.04). The 2014 NIH-Consensus Criteria would only diagnose 8/25 participants (32%) as having BOS. In conclusion, 11% of children experienced a LONIPC in a prospective design. Clinical Trials.gov identifier (NCT number): NCT02032381.

Effect of rosuvastatin on sortilin and fetuin-A in type 2 diabetic patients: a randomized controlled trial

Abstract Objective Rosuvastatin is a drug used for decreasing the risk of cardiovascular complications in type 2 diabetes mellitus (T2DM) patients. It is hypothesized that fetuin-A encourages lipid-induced insulin resistance and sortilin may increase the risk of atherosclerotic-related disorders. The aim of this study is to investigate the safety and efficacy of rosuvastatin co-treatment in T2DM patients and its effect on levels of sortilin and fetuin-A. Methods Seventy T2DM patients treated with glimepiride and metformin were randomly assigned to either co-treated with rosuvastatin 10 mg tablets (rosuvastatin group, n = 40), or placebo (placebo group, n = 30) daily for 3 months in a parallel, double-blind randomized controlled trial. Blood was collected for biochemical analysis. Serum sortilin and fetuin-A levels, glycemic and lipid profiles were measured before and 3 months after intervention. Results Fasting blood glucose (FBG, mg/dl) significantly decreased in placebo and rousvastatin groups from (104 ± 7.24 to 96.67 ± 7.14 vs 102.8 ± 6.43 to 93.0 ± 4.71), respectively, compared with baseline (p &lt; 0.05). BMI and HbA1c decreased in placebo vs rosuvastatin group (29.20 ± 3.18 to 28.10 ± 3.08, p=0.08 vs 28.67 ± 3.56 to 27.66 ± 3.16, p = 0.27), and (6.59 ± 0.27 to 6.36 ± 0.27 vs 6.56 ± 0.26 to 6.29 ± 0.25), respectively, compared with baseline (p ≤ 0.001) with no significance difference between both groups (p = 0.58 and p = 0.25, respectively). Sortilin and fetuin-A levels significantly decreased in rosuvastatin vs placebo group from (1.77 ± 0.41 to 0.64 ± 0.37 vs 1.70 ± 0.36 to 1.65 ± 0.36) and from (295.33 ± 52.04 to 179.75 ± 60.22 vs 307.22 ± 50.11 to 288.94 ± 49.53), respectively, compared with baseline with significance difference between both groups (p &lt; 0.001) compared with placebo. Significant positive correlation was found between sortilin with fetuin-A, low-density lipoprotein (LDL-C), and atherogenic index (p &lt; 0.001). Significant positive correlation was observed between fetuin-A with FBG (p &lt; 0.05) and atherogenic index (p &lt; 0.001). Conclusion Rosuvastatin co-treatment in T2DM patients improves glycemic control and aids in decreasing the atherogenic biomarkers sortilin and fetuin-A levels, so it can be considered tolerable and efficient in improving lipid profile and atherogenic index. Trial registration ClinicalTrials.gov identifier (NCT number): NCT03907423, (The registration date: April 9, 2019). https://clinicaltrials.gov/ct2/show/NCT03907423.

Mesenchymal stromal cell therapy for COVID-19 acute respiratory distress syndrome: a double-blind randomised controlled trial.

Mesenchymal stromal cells (MSC) have immunomodulatory and tissue-regenerative properties and have shown promising results in acute respiratory distress syndrome (ARDS) of multiple causes, including COVID-19. We conducted a randomised (1:1), placebo-controlled, double-blind clinical trial to assess the efficacy and safety of one bone marrow-derived MSC infusion in twenty patients with moderate to severe ARDS caused by COVID-19. The primary endpoint (increase in PaO2/FiO2 ratio from baseline to day 7, MSC 83.3 versus placebo 57.6) was not statistically significant, although a clinical improvement at day 7 in the WHO scale was observed in MSC patients (5, 50% vs 0, 0%, p = 0.033). Median time to discontinuation of supplemental oxygen was also shorter in the experimental arm (14 versus 23 days, p = 0.007), resulting in a shorter hospital stay (17.5 versus 28 days, p = 0.042). No significant differences were observed for other efficacy or safety secondary endpoints. No infusion or treatment-related serious adverse events occurred during the one-year follow-up. This study did not meet the primary endpoint of PaO2/FiO2 increase by day 7, although itsuggests that MSC are safe in COVID-19 ARDS and may accelerate patients' clinical recovery and hospital discharge. Larger studies are warranted to elucidate their role in ARDS and other inflammatory lung disorders.Trial Registration: EudraCT Number: 2020-002193-27, registered on July 14th, 2020, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002193-27/ES . NCT number: NCT04615429, registered on November 4th, 2020, https://clinicaltrials.gov/ct2/show/NCT04615429 .

Assessment of different continence definitions in the context of the randomized multicenter prospective LAP-01 trial—Does the best definition change over time?

BackgroundA uniform definition of continence is urgently needed to allow the comparison of study results and to estimate patient outcomes after radical prostatectomy (RP). To identify a practical definition that includes both objective and subjective aspects in a tangible way, we assessed different continence definitions and evaluated which best reflects the patients’ subjective perception of continence.MethodsOur analyses included 718 patients that underwent either robot-assisted radical prostatectomy (RARP) or laparoscopic radical prostatectomy (LRP) in a multicenter randomized patient-blinded trial. Continence was assessed through patient questionnaires prior to and at 3, 6 and 12 months after surgery which included the number of pads used per day, the ICIQ-SF and the question “Do you suffer from incontinence? (yes/no)” to assess subjective continence. We used Krippendorff’s Alpha to calculate the agreement of different continence definitions with the subjective perception.ResultsAt 3 months, the “0/safety pad” definition shows the highest agreement by alpha = 0.70 (vs. 0.63 for “0 pads” and 0.37 for “0–1 pad”). At 6 and 12 months “0 pads” is the better match, with alpha values of 0.69 (vs. 0.62 and 0.31) after 6 months and 0.70 (vs. 0.65 and 0.32) after 12 months. The ICIQ-SF score shows good correlation with the subjective continence at 3 months (alpha = − 0.79), the coefficient then decreasing to − 0.69 and − 0.59 at 6 and 12 months.ConclusionThe best continence definition according to the patients’ perspective changes over time, “0 pads” being the superior criterion in the long-term. We recommend using the 0-pad definition for standardized continence reporting, as it is simple yet as accurate as possible given the inevitably high subjectivity of continence perception.Trial registration The LAP-01 trial was registered with the U.S. National Library of Medicine clinical trial registry (clinicaltrials.gov), NCT number: NCT03682146, and with the German Clinical Trial registry (Deutsches Register Klinischer Studien), DRKS ID number: DRKS00007138

Incidence and Burden of Herpes Zoster in Sweden: A Regional Population-Based Register Study.

Herpes zoster (HZ) is a painful disease that mainly affects individuals whose immune system has been weakened because of increasing age (> 50years) or certain diseases or treatments. We estimated the complete burden of HZ. This population-based register study analysed healthcare data from the VEGA and Digitalis databases of Västra Götaland Region (VGR), Sweden. The VEGA database includes all patients in VGR, covering both hospital and primary care. The Digitalis records prescribed medications. The study population included patients aged ≥ 18years with at least one registered primary or secondary HZ diagnosis (based on International Classification of Diseases [ICD] codes) between 2005 and 2021. Incidence rates (95% confidence intervals [CI]) were stratified by age, sex and diagnosis/analgesic prescription. Overall HZ incidence increased from 2.5 (95% CI 2.4-2.6) in 2005 to 4.2 (95% CI 4.1-4.3) in 2021. The increase in incidence was rapid from 2005 to 2013, followed by a plateauing trend. From 2014-2019, the lifetime risk of HZ, excluding recurrent cases, was 36.5% (95% CI 35.5-37.4%). Municipal differences ranged from 34.4% (95% CI 32.5-36.4%) to 43.6% (95% CI 39.9-47.4%). Recurrence rates of HZ were 8.7% and 9.1% with follow-up periods of 5.5 and 10.5years, respectively. Reported postherpetic neuralgia (PHN) cases increased five-fold over the study period. In 2019, 19% of all HZ patients developed HZ-related neuropathic pain; 13.6% had signs of persistent pain (> 90days; i.e. PHN). An increased occurrence of cerebral and cardiovascular disease was observed in HZ patients. Among high-risk groups the occurrence of HZ peaked among those with inflammatory and autoimmune diseases. HZ and PHN risk in Sweden is comparable to that in other European countries prior to implementing HZ national vaccination programs. Municipal differences suggest that the lifetime risk of HZ in Sweden is at least 36.5%. NCT Number ( www. gov ).