Obesity leads to higher risk of sperm DNA damage in infertile patients

There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be altered in case of high body mass index （BMI）. A few studies assessing the impact of BMI on sperm DNA integrity have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI, through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling （TUNEL） assay, we observed an increased rate of sDerm DNA damage in obese men （odds ratio （95% confidence interval）： 2.5 （1.2-5.1））.     

Smoking is a risk factor of organ/space surgical site infection in orthopaedic surgery with implant materials

Purpose

In recent guidelines, smoking is reported as a factor increasing the risk of surgical site infection (SSI). The accurate analysis of the literature shows that this recommendation relies on low level of evidence in orthopaedic surgery with material implantation (arthroplasty components or implants for internal fixation). This study aimed to assess the attributable risk of smoking on organ/space SSI in orthopaedic surgery with implants.

Methods

Risk factors of organ/space SSI were studied in a prospective cohort including 3,908 patients from June 2003 to December 2006.

Results

Smoking was found as a significant risk factor for organ/space SSI. We also observed a significant difference between smokers and non-smokers for surgical wound complications (hematoma, discharge or wound dehiscence) during the period between surgical procedure and discharge from hospital.

Conclusion

This is the first large prospective report of a significant association between smoking and organ/space SSI in orthopaedic surgery with implants.     

Biobanking for research in surgery: are surgeons in charge for advancing translational research or mere assistants in biomaterial and data preservation?

Background

High-quality biospecimens of human origin with annotated clinical and procedural data are an important tool for biomedical research, not only to map physiology, pathophysiology and aetiology but also to go beyond in translational research. This has opened a new special field of research known as ‘biobanking’, which focuses on how to collect, store and provide these specimens and data, and which is substantially supported by national and European funding.

Purpose

An overview on biobanking is given, with a closer look on a clinical setting, concerning a necessary distinction from clinical trials and studies as well as a comparison of prospective sample collection with secondary use of archived samples from diagnostics. Based on a summary of possible use and scientific impact of human tissue in research, it is shown how surgical expertise boosts the scientific value of specimens and data. Finally, an assessment of legal and ethical issues especially from a surgical perspective is given, followed by a model of interdisciplinary biobanking within a joint ‘centre’ that as synergistic structure merges essential input from surgery as well as laboratory medicine, pathology and biometry.

Conclusion

Within the domain of biobanking, surgeons have to develop a better awareness of their role within translational research, not only on the level of medical faculties but also as nationally and internationally funded initiatives. Therefore, the authors suggest a platform for biobanking within the German association of surgeons in analogy to the existing special interest group for clinical trials.     

The impact of changes in job security on mental health across gender and family responsibility: evidence from the UK Household Longitudinal Study

Purpose

While there is strong evidence that job insecurity leads to mental distress, little is known about how gender and parental responsibilities may exacerbate this relationship. Examining their contribution as potential effect modifiers may provide insights into gender inequalities in mental health and inform gender-sensitive labour policies to ameliorate the negative effects of job insecurity. Our study addresses this gap by examining the longitudinal association between job insecurity and mental health across different configurations of gender and parental responsibilities.

Methods

Our sample includes 34,772 employed participants over the period of 2010–2018. A gender-stratified fixed-effect regression was used to model the within-person change over time in mental health associated with loss of job security, and effect modification by parent–partner status (e.g. childfree men, partnered father, etc.).

Results

Loss of job security was associated with a moderate decrease in mental health functioning for partnered fathers, partnered mothers, and childfree men and women ranging between a reduction in MCS-12 by 1.00 to 2.27 points (p < 0.05). Lone fathers who lose their job security experienced a higher decrease in mental health functioning at − 7.69 (95% CI − 12.69 to − 2.70), while lone mothers did not experience any change.

Conclusion

The effects of job insecurity on mental health is consistent across gender and parent–partner status with the exception of lone fathers and lone mothers. Future studies should investigate the effects of policies that may reduce mental distress in the face of the threat of job loss such as reducing wait time for payment of unemployment benefits.

     

(R)-2-Phenylpyrrolidine Substituted Imidazopyridazines: A New Class of Potent and Selective Pan-TRK Inhibitors

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A phase III randomized trial of high‐dose CEOP + filgrastim versus standard‐dose CEOP in patients with non‐Hodgkin lymphoma: 10‐year follow‐up data: Australasian Leukaemia and Lymphoma Group (ALLG) NHL07 trial

Increasing dose intensity (DI) of chemotherapy for patients with aggressive non‐Hodgkin lymphoma (NHL) may improve outcomes at the cost of increased toxicity. This issue was addressed in a randomized trial aiming to double the DI of myelosuppressive drugs. Between 1994 and 1999, 250 patients with previously untreated aggressive NHL were randomized to treatment with six cycles of 3‐weekly standard (s) or intensive (i) chemotherapy: s‐CEOP–cyclophosphamide 750, epirubicin 75, vincristine 1.4 mg/m² all on day 1, and prednisolone 100 mg days 1–5; i‐CEOP–cyclophosphamide 1,500, epirubicin 150, vincristine 1.4 mg/m² all on day 1, and prednisolone 100 mg days 1–5. Primary endpoint was 5‐year overall survival (OS). Relative to s‐CEOP patients, i‐CEOP patients achieved a 78% increase in the DI of cyclophosphamide and epirubicin. Despite this, there was no significant difference in any outcome: 5‐year OS (56.7% i‐CEOP; 55.1% s‐CEOP; P = 0.80), 5‐year progression free survival (PFS; 41% i‐CEOP; 43% s‐CEOP; P = 0.73), 5‐year time to progression (TTP; 44% i‐CEOP; 47% s‐CEOP; P = 0.72), or complete remission (CR) + unconfirmed CR (CRu) rates (53% i‐CEOP; 59% s‐CEOP; P = 0.64). Long‐term follow up at 10 years also showed no significant differences in OS, PFS, or TTP. The i‐CEOP arm had higher rates of febrile neutropenia (70 vs. 26%), hospitalisations, blood product utilisation, haematological and gastrointestinal toxicities, and lower quality of life scores during treatment, although without significant differences 6‐month later. In the treatment of aggressive NHL in the prerituximab era, increasing DI did not result in improved outcomes, while at the same time lead to increased toxicity. Am. J. Hematol. 89:536–541, 2014. © 2014 Wiley Periodicals, Inc.     

Genetic variability of VEGF pathway genes in six randomized phase III trials assessing the addition of bevacizumab to standard therapy

Background

Despite extensive translational research, no validated biomarkers predictive of bevacizumab treatment outcome have been identified.

Methods

We performed a meta-analysis of individual patient data from six randomized phase III trials in colorectal, pancreatic, lung, renal, breast, and gastric cancer to explore the potential relationships between 195 common genetic variants in the vascular endothelial growth factor (VEGF) pathway and bevacizumab treatment outcome.

Results

The analysis included 1,402 patients (716 bevacizumab-treated and 686 placebo-treated). Twenty variants were associated (P < 0.05) with progression-free survival (PFS) in bevacizumab-treated patients. Of these, 4 variants in EPAS1 survived correction for multiple testing (q < 0.05). Genotype-by-treatment interaction tests revealed that, across these 20 variants, 3 variants in VEGF-C (rs12510099), EPAS1 (rs4953344), and IL8RA (rs2234671) were potentially predictive (P < 0.05), but not resistant to multiple testing (q > 0.05). A weak genotype-by-treatment interaction effect was also observed for rs699946 in VEGF-A, whereas Bayesian genewise analysis revealed that genetic variability in VHL was associated with PFS in the bevacizumab arm (q < 0.05). Variants in VEGF-A, EPAS1, and VHL were located in expression quantitative loci derived from lymphoblastoid cell lines, indicating that they affect the expression levels of their respective gene.

Conclusions

This large genetic analysis suggests that variants in VEGF-A, EPAS1, IL8RA, VHL, and VEGF-C have potential value in predicting bevacizumab treatment outcome across tumor types. Although these associations did not survive correction for multiple testing in a genotype-by-interaction analysis, they are among the strongest predictive effects reported to date for genetic variants and bevacizumab efficacy.