Sodium-Glucose Cotransporter Type 2 Inhibitors Use in Elderly Polypathological Patients with Acute Heart Failure: PROFUND-IC Registry.

Background/Objectives: Heart failure (HF) is a highly prevalent clinical syndrome with serious morbidity and mortality. Furthermore, acute heart failure (AHF) is the main cause of hospital admission in people aged 65 years or more. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) have been shown to improve the survival and quality of life in patients with HF regardless of left ventricular ejection fraction (LVEF). Our aims were to describe the characteristics of adults with multiple pathologies admitted with acute heart failure as the main diagnosis and of the population treated with SGLT2is, as well as to evaluate if their use was associated with lower readmission and mortality rates. Methods: A prospective study of patients from the PROFUND-IC registry who were admitted with AHF as the main diagnosis was conducted. Clinical and analytical characteristics were analyzed, as well as readmissions and mortality. Descriptive and bivariate analyses of the sample between those taking SGLT2is and those who were not were performed, using the chi-square test for qualitative variables and Welch's test for quantitative measures, as well as the Fisher and Wilcoxon tests as indicated for nonparametric tests. Kaplan-Meier curves were constructed to analyze the readmission and mortality of patients at 12 months based on SGLT2i treatment. Finally, a propensity score matching was performed, guaranteeing that the observed effect of the drug was not influenced by the differences in the characteristics between the groups. Results: There were 750 patients included: 58% were women, and the mean age was 84 years. Functional class II according to the NYHA scale predominated (54%), and the mean LVEF was 51%. SGLT2 inhibitors were prescribed to only 28% of patients. Most of the patients were men (48.6% vs. 39.8%, p = 0.029), they were younger (82 vs. 84 years, p = 0.002), and their LVEF was lower (48% vs. 52%, p < 0.001). Lower mortality was observed in the group treated with SGLT2is, both during baseline admission (2.4% vs. 6.9%, p = 0.017) and at the 12-month follow-up (6.2% vs. 13%, p = 0.023); as well as a lower readmission rate (23.8% vs. 38.9%, p < 0.001). After the propensity score matching, a decrease in the 12-month readmission rate continued to be observed in the group treated with SGLT2is (p = 0.03). Conclusions: SGLT2is use was associated with lower readmission rates at the 12-month follow-up in older adults with multiple pathologies admitted with acute heart failure.

TIGIT+Tfh show poor B-helper function and negatively correlate with SARS-CoV-2 antibody titre.

Circulating follicular helper T cells (cTfh) can show phenotypic alterations in disease settings, including in the context of tissue-damaging autoimmune or anti-viral responses. Using severe COVID-19 as a paradigm of immune dysregulation, we have explored how cTfh phenotype relates to the titre and quality of antibody responses. Severe disease was associated with higher titres of neutralising S1 IgG and evidence of increased T cell activation. ICOS, CD38 and HLA-DR expressing cTfh correlated with serum S1 IgG titres and neutralising strength, and interestingly expression of TIGIT by cTfh showed a negative correlation. TIGIT+cTfh expressed increased IFNγ and decreased IL-17 compared to their TIGIT-cTfh counterparts, and showed reduced capacity to help B cells in vitro. Additionally, TIGIT+cTfh expressed lower levels of CD40L than TIGIT-cTfh, providing a potential explanation for their poor B-helper function. These data identify phenotypic changes in polyclonal cTfh that correlate with specific antibody responses and reveal TIGIT as a marker of cTfh with altered function.

Paraproteinaemic keratopathy simulating a crystalline keratopathy.

BACKGROUND: Paraproteinemic keratopathy is a rare disorder characterized by the bilateral accumulation of polychromatic deposits diffusely in all corneal layers together or not with diffuse or patchy pseudo lipid deposits. We present an atypical case of paraproteinemic keratopathy which lead to an initial misdiagnosis of infectious crystalline keratopathy. CASE PRESENTATION: a 69-year-old woman with an asymptomatic keratopathy detected during a cataract intervention. Slit-lamp examination revealed several hyper refringent subepithelial foci with fern-shaped branches, resembling crystalline keratopathy, in her left eye. Anterior segment optical coherence tomography revealed exclusively subepithelial hyperreflective lesions limited to the anterior stroma. The progressive bilateralization and progression of the condition prompted us to include other entities with crystalline corneal deposits in our differential diagnosis. Hematological analysis showed a high number of free Kappa light chains. Despite the typical clinical appearance of crystalline keratopathy, the atypical evolution and test results led us to consider that monoclonal gammopathy could be the cause of this entity. CONCLUSIONS: Paraproteinemic keratopathy may present in its early stages as a unilateral subepithelial crystalline keratopathy. Thus, it must always be taken into account in the differential diagnosis of any crystalline keratopathy, particularly when there are no predisposing factors for an infectious crystalline keratopathy. Early recognition of this rare entity is important to address the associated potentially serious systemic disease.

Changes In Serum CXCL13 Levels Are Associated With Outcomes of Colorectal Cancer Patients Undergoing First-Line Oxaliplatin-Based Treatment.

Metastatic colorectal cancer (mCRC) currently lacks reliable biomarkers for precision medicine, particularly for chemotherapy-based treatments. This study examines the behavior of 11 CXC chemokines in the blood of 104 mCRC patients undergoing first-line oxaliplatin-based treatment to pinpoint predictive and prognostic markers. Serum samples were collected before treatment, at response evaluation (EVAR), and at disease progression or last follow-up. Chemokines were assessed in all samples using a Luminex® custom panel. CXCL13 levels increased at EVAR in responders, while in non-responders it decreased. Increasing levels of CXCL13 at EVAR, independently correlated with improved progression-free survival (PFS) and overall survival (OS). Nanostring® analysis in primary tumor samples showed CXCL13 gene expression's positive correlation not only with gene profiles related to an immunogenic tumor microenvironment, increased B cells and T cells (mainly CD8+) but also with extended OS. In silico analysis using RNAseq data from liver metastases treated or not with neoadjuvant oxaliplatin-based combinations, and deconvolution analysis using the MCP-counter algorithm, confirmed CXCL13 gene expression's association with increased immune infiltration, improved OS, and Tertiary Lymphoid Structures (TLSs) gene signatures, especially in neoadjuvant-treated patients. CXCL13 analysis in serum from 36 oxaliplatin-treated patients from the METIMMOX study control arm, reported similar findings. In conclusion, the increase of CXCL13 levels in peripheral blood and its association with the formation of TLSs within the metastatic lesions, emerges as a potential biomarker indicative of the therapeutic efficacy in mCRC patients undergoing oxaliplatin-based treatment.

Yogurt, in the context of a healthy diet, for the prevention and management of diabetes and obesity: a perspective from Argentina.

Diabetes is a non-communicable chronic, but preventable, disease whose occurrence is related to unhealthy lifestyles, including inadequate diet. Obesity is a risk factor for diabetes. In Argentina, 12.7% of the population is living with diabetes. In this work, we aimed at giving a perspective on the role of yogurt, as part of a healthy lifestyle, for the prevention and management of obesity and diabetes. The intake of yogurt declined in the last decade in Argentina. In the context of the global diet, the contribution of a moderate increase of yogurt consumption has the potential to improve up to 10% the nutritional density of the Argentine population's diet, given its present low diversity and wide gaps in nutritive foods. The consumption of yogurt can be beneficial in the prevention and management of obesity and T2DM. The ready availability of yogurt and its easy introduction to diverse diets suggests that educating the general public to incorporate this fermented milk as part of a healthy diet may potentially contribute to improved public health through prevention of NCDs and the costs associated with them.

Left ventricular shape index and eccentricity index with ECG-gated Nitrogen-13 ammonia PET/CT in patients with myocardial infarction, ischemia, and normal perfusion.

BACKGROUND: LV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function. METHODS AND RESULTS: One hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05). CONCLUSIONS: Shape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling.

CHAMPP4KIDS: Mixed methods study protocol to evaluate acceptability and feasibility of Parenting for Lifelong Health materials in a Canadian context.

BACKGROUND: Parents and caregivers play a key role in children's healthy development and well-being. Traditional parenting interventions promote positive parenting practices and are key to preventing child maltreatment. However, numerous barriers can limit access to programs, barriers which were further exacerbated by the COVID-19 pandemic. The Parenting for Lifelong Health group developed mass media and public health communication materials to promote positive caregiving behaviours on a population level. The Champions of Positive Parenting 4 Kids (CHAMPP4KIDS) study will examine the acceptability and feasibility of these materials for service providers and caregivers of children aged 2-6 years in Ontario, Canada. METHODS: This study will use a convergent mixed-methods design. Consenting service providers (n = 200) and caregivers (n = 100) will complete a quantitative survey to rate, rank and give feedback on Parenting for Lifelong Health tip sheets and social media ads. Caregivers will also complete self-report scales measuring depression and anxiety. We will hold focus group discussions with a sub-sample of surveyed providers (n = 40) and caregivers (n = 25). An adapted Trials of Improved Practices methodology will explore caregiver perspectives after implementing the tip sheets. Primary quantitative outcomes will be descriptive statistics of rankings, Likert Scale scores and descriptive analysis of caregiver depression and anxiety. Qualitative data will be analyzed using Rapid Qualitative Inquiry and triangulated through a convergent coding matrix. DISCUSSION: The Parenting for Lifelong Health COVID-19 parenting materials offer succinct, engaging parenting information in a mass media format that addresses some challenges associated with accessing in-person programming. The CHAMPP4KIDS study will provide mixed methods insights on the materials' acceptability and feasibility from different groups in a Canadian context, with a focus on marginalized families. The use of Trials of Improved Practices methodology could prove a useful tool for participant-led adaptation of existing parenting, early childhood development and other health intervention materials.

An umbrella review of systematic reviews on interventions of physical activity before pregnancy, during pregnancy, and postpartum to control and/or reduce weight gain.

BACKGROUND: The increasing prevalence of overweight and obesity worldwide represents a (chronic) complex public health problem. This is also seen among women of childbearing age despite increased efforts to promote physical activity (PA) interventions. Excessive gestational weight gain (GWG) is associated with negative health outcomes for both mothers and offspring. OBJECTIVES: To summarize current systematic reviews (SRs) on PA interventions during pregnancy and postpartum to prevent excessive GWG and identify the most effective approaches. SEARCH STRATEGY: A literature search was conducted on major electronic databases (MEDLINE/Pubmed, Cochrane, Web of Science, Epistemonikos) from inception to March 2023. SELECTION CRITERIA: This study included SRs and meta-analyses of studies involving women aged 18 years or older from diverse ethnic backgrounds, who were either in the preconception period, pregnant, or within 1 year postpartum and who had no contraindications for exercise. Women with chronic diseases, such as pre-existing diabetes (type 1 or type 2) were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data from selected studies assessing the impact of PA in preconception, pregnancy, and postpartum. Methodologic quality was assessed with the AMSTAR-2 tool. A narrative summary of results addresses relationships between PA and weight before, during, and after pregnancy, informing future research priorities for preventing excessive weight gain. This study is registered on PROSPERO (CRD420233946666). MAIN RESULTS: Out of 892 identified articles, 25 studies were included after removing duplicates, unrelated titles, and screening titles and abstracts for eligibility. The results demonstrate that PA can help prevent excessive GWG and postpartum weight retention. Structured and supervised moderate-intensity exercise, at least twice a week, and each session lasting a minimum of 35 min seems to provide the greatest benefits. CONCLUSIONS: Women who comply with the PA program and recommendations are more likely to achieve adequate GWG and return to their pre-pregnancy body mass index after delivery. Further research is warranted to explore how preconception PA influences pregnancy and postpartum outcomes given the absence of identified preconception-focused interventions.

Validation of the inventory: lockdown and its impact on the university Community.

BACKGROUND: Significant consequences of COVID-19 within academic/professional life are, at the psychological level, related to worry, tension, stress; coping strategies and lifestyle changes. This study describes the process of design and validation of an inventory (QPIC), which aims to assess the psychological impact that a situation of confinement can produce among university students and teachers. METHODS: Design of the instrument and psychometric tests. A sample of 862 students and 229 professors affiliated to Spanish and Colombian universities was used. Data were collected in April 2020 with the request of the favourable Bioethics Committee IR/2020. RESULTS: Six experts carried out the content validation. A confirmatory factor analysis of the theoretical dimensions proposed for the scales was performed and the internal consistency of each of the three initial scales was confirmed (0.866, 0.813 and 0.834). CONCLUSION: A rigorous and reliable instrument is achieved, consisting of two final scales: (a) Worry, tension and stress scale (b) Coping scale, which helps to measure individual psychological effects in housebound situations. It is an instrument designed, constructed ad hoc to assess the impact of confinement and subjected to validation. The factor structure and reliability of the instrument are examined and good psychometric properties are obtained. The application of this inventory will make it possible to assess the impact on people's mental health during a period of confinement.

Field-based molecular detection of Batrachochytrium dendrobatidis in critically endangered Atelopus toads and aquatic habitats in Ecuador.

Batrachochytrium dendrobatidis (Bd) is a lethal fungal species that parasitizes vertebrates and is associated with the worldwide decline of amphibian populations. The development of sensitive, rapid detection methods, particularly DNA-based techniques, is critical for effective management strategies. This study evaluates the efficacy of DNA extraction and a portable PCR device in a mountable field laboratory setup for detecting Bd near the habitats of three critically endangered Atelopus toad species in Ecuador. We collected skin swabs from Atelopus balios, A. nanay, and A. bomolochos, and environmental DNA (eDNA) samples from streams in Andean and coastal regions of Ecuador. For eDNA, a comparison was made with duplicates of the samples that were processed in the field and in a standard university laboratory. Our findings revealed Bd detection in eDNA and swabs from 6 of 12 water samples and 10 of 12 amphibian swab samples. The eDNA results obtained in the field laboratory were concordant with those obtained under campus laboratory conditions. These findings highlight the potential of field DNA-based monitoring techniques for detecting Bd in amphibian populations and their aquatic habitats, particularly in remote areas. Furthermore, this research aligns with the National Action Plan for the Conservation of Ecuadorian Amphibians and contributes to the global effort to control this invasive and deadly fungus.

A longitudinal study examining the associations between prenatal and postnatal maternal distress and toddler socioemotional developmental during the COVID-19 pandemic.

Elevated psychological distress, experienced by pregnant women and parents, has been well-documented during the COVID-19 pandemic. Most research focuses on the first 6-months postpartum, with single or limited repeated measures of perinatal distress. The present longitudinal study examined how perinatal distress, experienced over nearly 2 years of the COVID-19 pandemic, impacted toddler socioemotional development. A sample of 304 participants participated during pregnancy, 6-weeks, 6-months, and 15-months postpartum. Mothers reported their depressive, anxiety, and stress symptoms, at each timepoint. Mother-reported toddler socioemotional functioning (using the Brief Infant-Toddler Social and Emotional Assessment) was measured at 15-months. Results of structural equation mediation models indicated that (1) higher prenatal distress was associated with elevated postpartum distress, from 6-weeks to 15-months postpartum; (2) associations between prenatal distress and toddler socioemotional problems became nonsignificant after accounting for postpartum distress; and (3) higher prenatal distress was indirectly associated with greater socioemotional problems, and specifically elevated externalizing problems, through higher maternal distress at 6 weeks and 15 months postpartum. Findings suggest that the continued experience of distress during the postpartum period plays an important role in child socioemotional development during the COVID-19 pandemic.

ncRNAs Orchestrate Chemosensitivity Induction by Neddylation Blockades.

We performed an integrative transcriptomic in silico analysis using lung adenocarcinoma A549 cells treated with the neddylation inhibitor MLN4924 and the gefitinib-resistant PC9 cell line (PC9GR). We focused on the transcriptional effects of the top differentially expressed ncRNA biotypes and their correlating stemness factors. Interestingly, MLN4924-treated cells showed a significant upregulation of mRNAs involved in carcinogenesis, cell attachment, and differentiation pathways, as well as a parallel downregulation of stemness maintenance and survival signaling pathways, an effect that was inversely observed in PC9GR cells. Moreover, we found that stemness factor expression could be contrasted by selected up-regulated ncRNAs upon MLN4924 treatment in a dose and time-independent manner. Furthermore, upregulated miRNAs and lncRNA-targeted mRNAs showed an evident enrichment of proliferation, differentiation, and apoptosis pathways, while downregulated ncRNA-targeted mRNAs were implicated in stem cell maintenance. Finally, our results proved that stemness (KLF4 and FGFR2) and epithelial-mesenchymal transition (ZEB2, TWIST2, SNAI2, CDH2, and VIM) factors, which are highly expressed in PC9GR cells compared to gefitinib-sensitive PC9 cells, could be abrogated with the neddylation inhibitor MLN4924 mainly through activation of epithelial differentiation pathways, thus exerting a protective role in lung cancer cells and chemosensitivity against lung tumorigenic transformation.

Peroxisomal Localization of a Truncated HMG-CoA Reductase under Low Cholesterol Conditions.

3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase, HMGCR) is one of the rate-limiting enzymes in the mevalonate pathway required for cholesterol biosynthesis. It is an integral membrane protein of the endoplasmic reticulum (ER) but has occasionally been described in peroxisomes. By co-immunofluorescence microscopy using different HMGCR antibodies, we present evidence for a dual localization of HMGCR in the ER and peroxisomes in differentiated human monocytic THP-1 cells, primary human monocyte-derived macrophages and human primary skin fibroblasts under conditions of low cholesterol and statin treatment. Using density gradient centrifugation and Western blot analysis, we observed a truncated HMGCR variant of 76 kDa in the peroxisomal fractions, while a full-length HMGCR of 96 kDa was contained in fractions of the ER. In contrast to primary human control fibroblasts, peroxisomal HMGCR was not found in fibroblasts from patients suffering from type-1 rhizomelic chondrodysplasia punctata, who lack functional PEX7 and, thus, cannot import peroxisomal matrix proteins harboring a type-2 peroxisomal targeting signal (PTS2). Moreover, in the N-terminal region of the soluble 76 kDa C-terminal catalytic domain, we identified a PTS2-like motif, which was functional in a reporter context. We propose that under sterol-depleted conditions, part of the soluble HMGCR domain, which is released from the ER by proteolytic processing for further turnover, remains sufficiently long in the cytosol for peroxisomal import via a PTS2/PEX7-dependent mechanism. Altogether, our findings describe a dual localization of HMGCR under combined lipid depletion and statin treatment, adding another puzzle piece to the complex regulation of HMGCR.

Routine screening for adverse childhood experiences (ACEs) still doesn't make sense.

When a serious health or social problem is identified as both prevalent and in need of attention, a common response is to propose that various systems implement routine identification, such as universal screening. However, these well-intentioned responses often fail to consider the key requirements necessary to determine whether benefits outweigh harms. Unfortunately, this continues to be the case for calls to implement routine screening for Adverse Childhood Experiences (ACEs). Persistent evidence gaps for this type of screening include the lack of any randomized controlled trials demonstrating that ACEs screening programs lead to any benefits. Rather than being informed by established screening principles, the calls to proceed with ACEs screening appear to rely on the assumption that simply identifying risk factors can lead to beneficial outcomes that outweigh any risk of harms. This may reflect a gap in understanding that patterns identified at the population level (e.g., that more ACEs are associated with more health and social problems) cannot be directly translated to practices at the level of the individual. This commentary does not question the importance of ACEs; rather it identifies that directing limited resources to screening approaches for which there is no evidence that benefits outweigh harms is problematic. Instead, we advocate for the investment in high-quality trials of prevention interventions to determine where best to direct limited resources to reduce the occurrence of ACEs, and for the prioritization of evidence-based treatment services for those with existing health and social conditions, whether or not they are attributed to ACEs.

Physical activity and unexpected weight change in Ontario children and youth during the COVID-19 pandemic: A cross-sectional analysis of the Ontario Parent Survey 2.

The objective of this study was to investigate the association between children's parent-reported physical activity levels and weight changes during the COVID-19 pandemic among children and youth in Ontario Canada. A cross-sectional online survey was conducted in parents of children 5-17 years living in Ontario from May to July 2021. Parents recalled their child's physical activity and weight change during the year prior to their completion of the survey. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multinomial logistic regression for the association between physical activity and weight gain or loss, adjusted for child age and gender, parent ethnicity, current housing type, method of school delivery, and financial stability. Overall, 86.8% of children did not obtain 60 minutes of moderate-to-vigorous physical activity per day and 75.4% of parents were somewhat or very concerned about their child's physical activity levels. For all physical activity exposures (outdoor play, light physical activity, and moderate-to-vigorous physical activity), lower physical activity was consistently associated with increased odds of weight gain or loss. For example, the adjusted OR for the association between 0-1 days of moderate-to-vigorous physical activity versus 6-7 days and child weight gain was 5.81 (95% CI 4.47, 7.56). Parent concern about their child's physical activity was also strongly associated with child weight gain (OR 7.29; 95% CI 5.94, 8.94). No differences were observed between boys and girls. This study concludes that a high proportion of children in Ontario had low physical activity levels during the COVID-19 pandemic and that low physical activity was strongly associated with parent reports of both weight gain and loss among children.

Outcomes for clinical trials involving adults with chronic kidney disease: a multinational Delphi survey involving patients, caregivers, and health professionals.

BACKGROUND: Many outcomes of high priority to patients and clinicians are infrequently and inconsistently reported across trials in CKD, which generates research waste and limits evidence-informed decision making. We aimed to generate consensus among patients/caregivers and health professionals on critically important outcomes for trials in CKD prior to kidney failure and the need for kidney replacement therapy, and to describe the reasons for their choices. METHODS: Online two-round international Delphi survey. Adult patients with CKD (all stages and diagnoses), caregivers and health professionals, who could read English, Spanish, or French were eligible. Participants rated the importance of outcomes using a Likert scale (7-9 indicating critical importance) and a best-worst scale. The scores for the two groups were assessed to determine absolute and relative importance. Comments were analysed thematically. RESULTS: In total, 1 399 participants from 73 countries completed Round 1 of the Delphi survey including 628 (45%) patients/caregivers and 771 (55%) health professionals. In Round 2, 790 participants (56% response rate) from 63 countries completed the survey including 383 (48%) patients/caregivers and 407 (52%) health professionals. The overall top five outcomes were: kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death. In the final round, patients/caregivers indicated higher scores for most outcomes (17/22 outcomes), and health professionals gave higher priority to mortality, hospitalization, and cardiovascular disease (mean difference > 0.3). Consensus was based upon the two groups yielding median scores of ≥ 7 and mean scores > 7, and the proportions of both groups rating the outcome as 'critically important' being greater than 50%. Four themes reflected the reasons for their priorities: imminent threat of a health catastrophe, signifying diminishing capacities, ability to self-manage and cope, and tangible and direct consequences. CONCLUSION: Across trials in CKD, the outcomes of highest priority to patients, caregivers, and health professionals were kidney function, need for dialysis/transplant, life participation, cardiovascular disease, and death.

Real-world treatment outcomes of immune checkpoint inhibitors used off-label in oncology: A comprehensive cancer institution experience.

Off-label use (OLU) is quite common in oncology due to the complexity of cancer and the time-consuming regulatory process. However, outcomes of OLU in cancer treatment remain unclear. This study aimed to evaluate the overall survival (OS), event-free survival (EFS), duration of treatment (DOT), and reason for treatment discontinuation in patients receiving immune checkpoint inhibitors (ICI) as OLU for solid tumors from 2011 to 2020. The study collected data on 356 episodes (353 patients), with a median age of 64.4 years, 36.2% women, and 14.6% ECOG ≥ 2. Median OS was 15.7 (11.9-18.7) months, and median EFS was 5.4 (3.8-6.6) months. Men, patients with metastatic disease or ECOG-PS higher than 1, had worse survival outcomes. The findings derived from this study provide valuable information regarding the real-world use of ICI-OLU and contributes to enhancing the decision-making process for individuals with cancer. Further research on immunotherapy outcomes of OLU in cancer is needed.

Social support buffers the impact of pregnancy stress on perceptions of parent-infant closeness during the COVID-19 pandemic.

Pregnant individuals and parents have experienced elevated mental health problems and stress during COVID-19. Stress during pregnancy can be harmful to the fetus and detrimental to the parent-child relationship. However, social support is known to act as a protective factor, buffering against the adverse effects of stress. The present study examined whether (1) prenatal stress during COVID-19 was associated with parent-infant closeness at 6 months postpartum, and (2) social support moderated the effect of prenatal stress on the parent-infant relationship. In total, 181 participants completed questionnaires during pregnancy and at 6 months postpartum. A hierarchical linear regression analysis was conducted to assess whether social support moderated the effect of stress during pregnancy on parent-infant closeness at 6 months postpartum. Results indicated a significant interaction between prenatal stress and social support on parents' perceptions of closeness with their infants at 6 months postpartum (ß = .805, p = .029); parents who experienced high prenatal stress with high social support reported greater parent-infant closeness, compared to those who reported high levels of stress and low social support. Findings underscore the importance of social support in protecting the parent-infant relationship, particularly in times of high stress, such as during the COVID-19 pandemic.

Individuos y progenitores en estado de embarazo experimentan elevados problemas de salud mental y estrés durante el COVID­19. El estrés durante el embarazo puede ser dañino para el feto y perjudicial para la relación progenitor­niño. Sin embargo, es sabido que el apoyo social actúa como un factor de protección, sirviendo como agente amortiguador contra los adversos efectos del estrés. El presente estudio longitudinal examinó si 1) el estrés prenatal durante el COVID­19 se asociaba con la cercanía madre­infante a los seis meses después del parto, y 2) el apoyo social moderaba el efecto del estrés prenatal en la relación madre­infante. Un total de 181 participantes completaron cuestionarios durante el embarazo y a los seis meses después del parto. Un análisis de regresión lineal jerárquico se llevó a cabo para evaluar si el apoyo social moderaba el efecto del estrés durante el embarazo en cuanto a la cercanía progenitor­infante a los seis meses después del parto. Los resultados indicaron una interacción significativa entre el estrés prenatal y el apoyo social sobre las percepciones que los progenitores tenían de la cercanía con sus infantes a los seis meses después del parto (ß = .805, p = .029); los progenitores que experimentaron un alto estrés prenatal con un alto apoyo social reportaron una mayor cercanía progenitor­infante, comparados con aquellos que reportaron altos niveles de estrés y bajo apoyo social. Los resultados subrayan la importancia del apoyo social para proteger la relación progenitor­infante, particularmente en épocas de alto estés, tal como durante la pandemia del COVID­19.

Les personnes enceintes et les parents font l'expérience de plus grands problèmes de santé mentale et de plus de stress durant la crise du COVID­19. Le stress durant la grossesse peut être néfaste pour le foetus et vient au détriment de la relation parent­enfant. Cependant l'on sait que le soutien social est un facteur de protection, faisant tampon face aux effets adverses du stress. Cette étude longitudinale a examiné si 1) le stress prénatal durant le COVID­19 était lié à la proximité mère­nourrisson à six mois postpartum, et 2) le soutien social a modéré l'effet du stress prénatale sur la relation mère­nourrisson. En tout 181 participants ont rempli des questionnaires durant la grossesse et à sic mois postpartum. Une analyse de régression linéaire hiérarchique a été faite pour évaluer si le soutien social a modéré l'effet du stress durant la grossesse sur la proximité parent­nourrisson à six mois postpartum. Les résultats ont indiqué une interaction importante entre le stress prénatal et le soutien social sur les perceptions des parents de la proximité avec leurs nourrissons à six mois postpartum (ß = ,805, p = ,029); les parents qui ont fait l'expérience d'un stress prénatal élevé avec un soutien social élevé ont signalé une plus grande proximité parent­nourrisson, comparé à ceux ayant signalé des niveaux de stress élevés et un faible soutien social. Les résultats soulignent l'importance du soutien social dans la protection de la relation parent­nourrisson, particulièrement en temps de stress élevé, comme durant la pandémie de COVID­19.

Next-Generation Sequencing Trends among Adult Patients with Select Advanced Tumor Types: A Real-World Evidence Evaluation.

There are limited data on the prevalence of next-generation sequencing (NGS) in the United States, especially in light of the increasing importance of identifying actionable oncogenic variants due to molecular biomarker-based therapy approvals. This retrospective study of adult patients with select metastatic solid tumors and central nervous system tumors from the Optum Clinformatics Data Mart US health care claims database (January 1, 2014, to June 30, 2021; N = 63,209) examined NGS use trends over time. A modest increase in NGS was observed across tumor types from 2015 (0.0% to 1.5%) to 2021 (2.1% to 17.4%). A similar increase in NGS rates was also observed across key periods; however, rates in the final key period remained <10% for patients with breast, colorectal, head and neck, soft tissue sarcoma, and thyroid cancers, as well as central nervous system tumors. The median time to NGS from diagnosis was shortest among patients with non-small-cell lung cancer and longest for patients with breast cancer. Predictors of NGS varied by tumor type; test rates for minorities in select tumor types appeared comparable to the White population. Despite improving payer policies to expand coverage of NGS and molecular biomarker-based therapy approvals, NGS rates remained low across tumor types. Given the potential for improved patient outcomes with molecular biomarker-based therapy, further efforts to improve NGS rates are warranted.

Effectiveness of nurse-home visiting in improving child and maternal outcomes prenatally to age two years: a randomised controlled trial (British Columbia Healthy Connections Project).

BACKGROUND: We investigated the effectiveness of Nurse-Family Partnership (NFP), a prenatal-to-age-two-years home-visiting programme, in British Columbia (BC), Canada. METHODS: For this randomised controlled trial, we recruited participants from 26 public health settings who were: <25 years, nulliparous, <28 weeks gestation and experiencing socioeconomic disadvantage. We randomly allocated participants (one-to-one; computer-generated) to intervention (NFP plus existing services) or comparison (existing services) groups. Prespecified outcomes were prenatal substance exposure (reported previously); child injuries (primary), language, cognition and mental health (problem behaviour) by age two years; and subsequent pregnancies by 24 months postpartum. Research interviewers were masked. We used intention-to-treat analyses. (ClinicalTrials.gov, NCT01672060.) RESULTS: From 2013 to 2016 we enrolled 739 participants (368 NFP, 371 comparison) who had 737 children. Counts for child injury healthcare encounters [rate per 1,000 person-years or RPY] were similar for NFP (223 [RPY 316.17]) and comparison (223 [RPY 305.43]; rate difference 10.74, 95% CI -46.96, 68.44; rate ratio 1.03, 95% CI 0.78, 1.38). Maternal-reported language scores (mean, M [SD]) were statistically significantly higher for NFP (313.46 [195.96]) than comparison (282.77 [188.15]; mean difference [MD] 31.33, 95% CI 0.96, 61.71). Maternal-reported problem-behaviour scores (M [SD]) were statistically significantly lower for NFP (52.18 [9.19]) than comparison (54.42 [9.02]; MD -2.19, 95% CI -3.62, -0.75). Subsequent pregnancy counts were similar (NFP 115 [RPY 230.69] and comparison 117 [RPY 227.29]; rate difference 3.40, 95% CI -55.54, 62.34; hazard ratio 1.01, 95% CI 0.79, 1.29). We observed no unanticipated adverse events. CONCLUSIONS: NFP did not reduce child injuries or subsequent maternal pregnancies but did improve maternal-reported child language and mental health (problem behaviour) at age two years. Follow-up of long-term outcomes is warranted given that further benefits may emerge across childhood and adolescence.