Cumulative impact of adding frozen-thawed cycles to single versus double fresh embryo transfers

Randomized control trials have shown that single embryo transfer (SET) results in lower live birth rates than double embryo transfer (DET), while observational, retrospective studies find no decrease in overall live birth rate when using a SET policy. The cumulative (fresh transfer followed by frozen - thawed transfers of embryos from the same stimulated cycle) live birth rate after the first and the second stimulated cycle of SET and DET respectively has been analysed. All couples who received their first fresh embryo transfer at Sahlgrenska University Hospital during 2003 and 2004 were included (n = 689). The live birth rates after DET versus SET in the first and second fresh cycles were 29.7 (47/158) versus 23.9% (127/531) and 30.8 (41/133) versus 22.0% (45/205). The cumulative live birth rate per patient after the addition of frozen-thawed embryo transfers were similar: 33.5 (53/158) and 34.8% (185/531) for DET and SET respectively after the first cycle and 32.3 (43/133) versus 32.2% (66/205) after the second cycle. A logistic regression analysis showed no significant correlation for SET or DET with cumulative live birth. Thus, cumulative live birth rates are similar after SET and DET in a routine IVF programme with a majority of SET transfers, although a higher number of frozen-thawed cycles were needed in the SET group.     

Review: Power of big data to improve patient care in gastroenterology

Big data is defined as being large, varied or frequently updated, and usually generated from real-world interaction. With the unprecedented availability of big data, comes an obligation to maximise its potential for healthcare improvements in treatment effectiveness, disease prevention and healthcare delivery. We review the opportunities and challenges that big data brings to gastroenterology. We review its sources for healthcare improvement in gastroenterology, including electronic medical records, patient registries and patient-generated data. Big data can complement traditional research methods in hypothesis generation, supporting studies and disseminating findings; and in some cases holds distinct advantages where traditional trials are unfeasible. There is great potential power in patient-level linkage of datasets to help quantify inequalities, identify best practice and improve patient outcomes. We exemplify this with the UK colorectal cancer repository and the potential of linkage using the National Endoscopy Database, the inflammatory bowel disease registry and the National Health Service bowel cancer screening programme. Artificial intelligence and machine learning are increasingly being used to improve diagnostics in gastroenterology, with image analysis entering clinical practice, and the potential of machine learning to improve outcome prediction and diagnostics in other clinical areas. Big data brings issues with large sample sizes, real-world biases, data curation, keeping clinical context at analysis and General Data Protection Regulation compliance. There is a tension between our obligation to use data for the common good and protecting individual patient’s data. We emphasise the importance of engaging with our patients to enable them to understand their data usage as fully as they wish.     

Face Mask Wastes as Cementitious Materials: A Possible Solution to a Big Concern

After more than two years wearing surgical masks due to the COVID-19 pandemic, used masks have become a significant risk for ecosystems, as they are producing wastes in huge amounts. They are a potential source of disturbance by themselves and as microplastic contamination in the water system. As 5500 tons of face masks are estimated to be used each year, there is an urgent need to manage them according to the circular economy principles and avoid their inadequate disposal. In this paper, surgical wear masks (WM), without any further pretreatment, have been introduced as addition to mortars up to 5% in the weight of cement. Mechanical and microstructural characterization have been carried out. The results indicate that adding MW to the cement supposes a decrease in the properties of the material, concerning both strength and durability behavior. However, even adding a 5% of WM in weight of cement, the aspect of the mortars is quite good, the flexural strength is not significantly affected, and the strength and durability parameters are maintained at levels that—even lower than the reference—are quite reasonable for use. Provided that the worldwide production of cement is around 4.1 Bt/year, the introduction of a 5% of WM in less than 1% of the cement produced, would make it possible to get rid of the mask waste being produced.     

Chromosome banding analysis and genomic microarrays are both useful but not equivalent methods for genomic complexity risk stratification in chronic lymphocytic leukemia patients

Genome complexity has been associated with poor outcome in patients with chronic lymphocytic leukemia (CLL). Previous cooperative studies established five abnormalities as the cut-off that best predicts an adverse evolution by chromosome banding analysis (CBA) and genomic microarrays (GM). However, data comparing risk stratification by both methods are scarce. Herein, we assessed a cohort of 340 untreated CLL patients highly enriched in cases with complex karyotype (CK) (46.5%) with parallel CBA and GM studies. Abnormalities found by both techniques were compared. Prognostic stratification in three risk groups based on genomic complexity (0-2, 3-4 and ≥5 abnormalities) was also analyzed. No significant differences in the percentage of patients in each group were detected, but only a moderate agreement was observed between methods when focusing on individual cases (κ=0.507; P<0.001). Discordant classification was obtained in 100 patients (29.4%), including 3% classified in opposite risk groups. Most discrepancies were technique-dependent and no greater correlation in the number of abnormalities was achieved when different filtering strategies were applied for GM. Nonetheless, both methods showed a similar concordance index for prediction of time to first treatment (TTFT) (CBA: 0.67 vs. GM: 0.65) and overall survival (CBA: 0.55 vs. GM: 0.57). High complexity maintained its significance in the multivariate analysis for TTFT including TP53 and IGHV status when defined by CBA (hazard ratio [HR] 3.23; P<0.001) and GM (HR 2.74; P<0.001). Our findings suggest that both methods are useful but not equivalent for risk stratification of CLL patients. Validation studies are needed to establish the prognostic value of genome complexity based on GM data in future prospective studies.     

Vascular smooth muscle cell-derived adiponectin: a paracrine regulator of contractile phenotype

Adiponectin is a cardioprotective adipokine derived predominantly from visceral fat. We recently demonstrated that exogenous adiponectin induces vascular smooth muscle cell (VSMC) differentiation via repression of mTORC1 and FoxO4. Here we report for the first time that VSMC express and secrete adiponectin, which acts in an autocrine and paracrine manner to regulate VSMC contractile phenotype. Adiponectin was found to be expressed in human coronary artery and mouse aortic VSMC. Importantly, siRNA knock-down of endogenous adiponectin in VSMC significantly reduced the expression of VSMC contractile proteins. Contractile protein deficiency was also observed in primary VSMC isolated from Adiponectin(-/-) mice. This deficiency could be rescued by culturing Adiponectin(-/-) VSMC in conditioned media from wild type (WT) VSMC. Moreover, the paracrine effect of VSMC-derived adiponectin was confirmed as adiponectin neutralizing antibody blocked the rescue. Overexpressed adiponectin also exerted paracrine effects on neighboring untransfected VSMC, which was also blocked by adiponectin neutralizing antibody. Interestingly, adiponectin expression was inducible by the PPARγ agonist rosiglitazone. Our data support an important role for VSMC-derived adiponectin in maintaining VSMC contractile phenotype, contributing to critical cardioprotective functions in the vascular wall. This article is part of a Special Issue entitled "Local Signaling in Myocytes".     

Hiking in Suicidal Patients: Neutral Effects on Markers of Suicidality

Background

Regular physical activity promotes physical and mental health. Psychiatric patients are prone to a sedentary lifestyle, and accumulating evidence has identified physical activity as a supplemental treatment option.

Methods

This prospective, randomized, crossover study evaluated the effects of hiking in high-risk suicidal patients (n = 20) who performed 9 weeks of hiking (2-3 hikes/week, 2-2.5 hours each) and a 9-week control period.

Results

All patients participated in the required 2 hikes per week and thus showed a compliance of 100%. Regular hiking led to significant improvement in maximal exercise capacity (hiking period Δ: +18.82 ± 0.99 watt, P < .001; control period: P = .134) and in aerobic capability at 70% of the individual heart rate reserve (hiking period Δ: +8.47 ± 2.22 watt; P = .010; control period: P = .183). Cytokines, associated previously with suicidality (tumor necrosis factor-α, interleukin-6, S100), remained essentially unchanged.

Conclusions

Hiking is an effective and safe form of exercise training even in high-risk suicidal patients. It leads to a significant improvement in maximal exercise capacity and aerobic capability without concomitant deterioration of markers of suicidality. Offering this popular mode of exercise to these patients might help them to adopt a physically more active lifestyle.     

Gene expression profiles of breast cancer metastasis according to organ site

In advanced breast cancer, biomarker identification and patient selection using a metastatic tumor biopsy is becoming more necessary. However, the biology of metastasis according to the organ site is largely unknown. Here, we evaluated the expression of 771 genes in 184 metastatic samples across 11 organs, including liver, lung, brain, and bone, and made the following observations. First, all PAM50 molecular intrinsic subtypes were represented across organs and within immunohistochemistry‐based groups. Second, HER2‐low disease was identified across all organ sites, including bone, and HER2 expression significantly correlated with ERBB2 expression. Third, the majority of expression variation was explained by intrinsic subtype and not organ of metastasis. Fourth, subtypes and individual subtype‐related genes/signatures were significantly associated with overall survival. Fifth, we identified 74 genes whose expression was organ‐specific and subtype‐independent. Finally, immune profiles were found more expressed in lung compared to brain or liver metastasis. Our results suggest that relevant tumor biology can be captured in metastatic tissues across a variety of organ sites; however, unique biological features according to organ site were also identified and future studies should explore their implications in diagnostic and therapeutic interventions.     

Life events,chronic strain,and psychological distress: Longitudinal causal models

This prospective study examines the causal relations among life events, chronic strain, and psychological distress. The influence of total number of life events; recent events; and undesirable, disruptive, and unanticipated events on marital strain and work/economic strain is assessed using latent variable structural equation modeling. It is hypothesized that chronic strain mediates the effects of life events on psychological distress. The data analyzed are from the first two waves of a prospective study on psychosocial factors and cancer mortality in a sample of skilled blue collar workers exposed to asbestos. A subsample of married and employed men within a relatively narrow age range was selected for this study to facilitate the investigation of the relations among life events, strain, and distress among individuals similarly situated in the life course. The results show that total number of events and recent, undesirable, disruptive, and unanticipated events increase work/economic strain and that, through this increase in strain, life events influence both contemporaneous levels of psychological distress and changes in distress. Life events do not have a direct effect on psychological distress when prior levels of events, work/economic strain, and distress are controlled. In contrast, life events do not have an impact on marital strain; rather, marital strain exerts a direct effect on distress. Undesirable, unanticipated, and disruptive events exert modest but significant direct effects on psychological distress in models including marital strain. These findings are discussed in terms of the place of the sample of workers in the life course, and implications for the design of preventive intervention programs are presented.