A Brief Digital Screening and Intervention Tool for Parental and Adolescent Tobacco and Electronic Cigarette Use in Pediatric Medical Care in Canada: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Though rates of tobacco smoking have decreased consistently over the past 3 decades, cigarette use remains the top preventable cause of premature death in North America. The Clinical Effort Against Secondhand Smoke Exposure (CEASE) is a medical clinic-based intervention that systematically screens parents for tobacco use and offers them direct access to evidence-based smoking cessation services. While the effectiveness of CEASE for parents who smoke has already been demonstrated in the United States, the CEASE model has not yet been tested in Canada, among parents who use e-cigarettes, or among adolescents who use cigarettes and e-cigarettes. OBJECTIVE: We aim to demonstrate the feasibility and evaluate the preliminary effectiveness of the CEASE program for parental smoking cessation and its adapted version for adolescent smoking cessation and adolescent and parental vaping cessation. METHODS: We will approach parents or guardians of children aged between 0 and 17 years, as well as adolescent patients aged between 14 and 17 years, from a tertiary care pediatric hospital in Montreal, Quebec, Canada, for participation in this single-blinded, pilot randomized controlled trial. Eligible participants are those who report using tobacco cigarettes or e-cigarettes at least once in the last 7 days and present to an outpatient pediatric clinic for a scheduled appointment. Our recruitment target is 100 participants: 50 parents or guardians of children aged 17 years or younger, and 50 adolescents aged between 14 and 17 years. The feasibility of implementation of the CEASE model will be measured by recruitment and retention rates for all 4 participant groups (stratified as follows: parents who use cigarettes, parents who use e-cigarettes exclusively, adolescents who use cigarettes, and adolescents who use e-cigarettes exclusively). Parent and adolescent participants within each group are randomized to the intervention and control groups using a 1:1 ratio through a computer-generated randomization list. Preliminary effectiveness outcomes include self-reported smoking and e-cigarette cessation, use of cessation resources, changes in smoking and e-cigarette use, motivation to quit, and quit attempts among participants. Participants complete electronic questionnaires on a tablet in the clinic at baseline as well as electronic follow-up questionnaires at 1, 3, and 6 months. Individuals reporting successful quit attempts are invited to provide a urine sample for cotinine testing to biochemically confirm quit. Analyses include descriptive statistics as well as exploratory trajectory analyses of smoking, e-cigarette use, and motivation to quit. RESULTS: Research activities began in June 2022. Participant enrollment and data collection began in February 2023 and are expected to be completed in 15 months. CONCLUSIONS: There is a strong need for effective and cost-effective smoking and vaping cessation interventions for parents and adolescents. If successful, this study will help inform the preparation of a fully powered randomized controlled trial of CEASE in Canada in these populations. TRIAL REGISTRATION: Clinicaltrials.gov NCT05366790; https://www.clinicaltrials.gov/study/NCT05366790. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47978.

Quality of life in monogenic autoinflammatory diseases. A review.

BACKGROUND: Systemic autoinflammatory diseases (SAIDs) are a group of disorders related to defective regulation of the innate immune system. Recurrence of inflammation can severely affect the patients' outcomes with a direct or indirect impact on their physical and mental health and/or global quality of life (QoL). We therefore sought to identify currently available QoL studies for these diseases as well as measurement tools at our disposal. BASIC PROCEDURES: A systematic literature review was carried out with a focus on monogenic SAIDs. We inventoried the study designs developed in the selected publications, grouped them into similar topics, and listed the different outcome measures used for QoL. MAIN FINDINGS: We recorded 53 bibliographic references evaluating the impact of monogenic SAIDs on the patients' QoL. These publications revealed 150 different study designs and 82 outcome measures used for their assessment. The best-explored topics were the overall patients' QoL, followed by the evaluation of their psychosocial and physical functioning. We found fair coverage of familial Mediterranean fever, poor investigation of the mixed hereditary recurrent fever (HRF) group, cryopyrin-associated periodic diseases and cherubism, and almost no study of the other monogenic SAIDs. CONCLUSIONS: This work revealed areas requiring further investigation such as homogenization of concepts, study of uncommon or more recent diseases, and development of more specific and validated outcome measures for SAIDs.

Helicobacter pylori serology is associated with worse overall survival in patients with melanoma treated with immune checkpoint inhibitors.

The microbiome is now regarded as one of the hallmarks of cancer and several strategies to modify the gut microbiota to improve immune checkpoint inhibitor (ICI) activity are being evaluated in clinical trials. Preliminary data regarding the upper gastro-intestinal microbiota indicated that Helicobacter pylori seropositivity was associated with a negative prognosis in patients amenable to ICI. In 97 patients with advanced melanoma treated with ICI, we assessed the impact of H. pylori on outcomes and microbiome composition. We performed H. pylori serology and profiled the fecal microbiome with metagenomics sequencing. Among the 97 patients, 22% were H. pylori positive (Pos). H. pylori Pos patients had a significantly shorter overall survival (p = .02) compared to H. pylori negative (Neg) patients. In addition, objective response rate and progression-free survival were decreased in H. pylori Pos patients. Metagenomics sequencing did not reveal any difference in diversity indexes between the H. pylori groups. At the taxa level, Eubacterium ventriosum, Mediterraneibacter (Ruminococcus) torques, and Dorea formicigenerans were increased in the H. pylori Pos group, while Alistipes finegoldii, Hungatella hathewayi and Blautia producta were over-represented in the H. pylori Neg group. In a second independent cohort of patients with NSCLC, diversity indexes were similar in both groups and Bacteroides xylanisolvens was increased in H. pylori Neg patients. Our results demonstrated that the negative impact of H. pylori on outcomes seem to be independent from the fecal microbiome composition. These findings warrant further validation and development of therapeutic strategies to eradicate H. pylori in immuno-oncology arena.

Stereotactic Ablative Radiotherapy for oligo-progressive disease refractory to systemic therapy in Non-Small Cell Lung Cancer: A registry-based phase II randomized trial (SUPPRESS-NSCLC).

BACKGROUND: Management of Non-Small Cell Lung Cancer (NSCLC) patients with oligoprogression remains controversial. There is limited data to support the strategy of Stereotactic Ablative Radiotherapy (SABR) targeting the oligoprogressive disease in combination with ongoing systemic treatment. We aim to assess the benefit of this approach compared to standard of care in the treatment of oligoprogressive NSCLC. METHODS: This phase II study will enroll 68 patients with oligoprogressive NSCLC, defined as 1-5 progressive extracranial lesions ≤5 cm involving ≤3 organs. Patients on active systemic therapy (chemotherapy, immunotherapy, targeted therapy or a combination) will be randomized 1:1 to either continue their current systemic therapy in combination with SABR to all lesions or the standard of care (switch to the next line of treatment, continue same treatment or observation). The co-primary endpoints are progression-free survival (PFS) and overall survival (OS). Secondary endpoints include time to next systemic treatment, patient-reported quality of life, cost effectiveness as well as translational analysis to characterize both adaptive immunity and immunogenic cell death markers in the peripheral blood. DISCUSSION: There is an unmet need to carefully examine the efficacy, safety and quality of life impact of SABR in the context of oligoprogressive disease. The present study will provide higher level randomized evidence on the role of SABR in oligoprogressive NSCLC.

Intraductal Carcinoma of the Prostate as a Cause of Prostate Cancer Metastasis: A Molecular Portrait.

Intraductal carcinoma of the prostate (IDC-P) is one of the most aggressive types of prostate cancer (PCa). IDC-P is identified in approximately 20% of PCa patients and is associated with recurrence, metastasis, and PCa-specific death. The main feature of this histological variant is the colonization of benign glands by PCa cells. Although IDC-P is a well-recognized independent parameter for metastasis, mechanisms by which IDC-P cells can spread and colonize other tissues are not fully known. In this review, we discuss the molecular portraits of IDC-P determined by immunohistochemistry and genomic approaches and highlight the areas in which more research is needed.

Iron-catalyzed synthesis of cyclopropanes by in situ generation and decomposition of electronically diversified diazo compounds.

The modular synthesis of a variety of trans 1,2-disubstituted cyclopropanes in a safe and user-friendly one-pot iron-catalyzed cyclopropanation reaction is described. Easily synthesized N-nosylhydrazones are used as diazo precursors, allowing the in situ generation of electron-rich diazo compounds under mild reaction conditions and their direct participation in the cyclopropanation reaction.