MicroRNA Involvement in Immune Activation During Heart Failure

Heart failure is one of the common end stages of cardiovascular diseases, the leading cause of death in developed countries. Molecular mechanisms underlying the development of heart failure remain elusive but there is a consistent observation of chronic immune activation and aberrant microRNA (miRNA) expression that is present in failing hearts. This review will focus on the interplay between the immune system and miRNAs as factors that play a role during the development of heart failure. Several studies have shown that heart failure patients can be characterized by a sustained innate immune activation. The role of inflammatory signaling is discussed and TLR4 signaling, IL-1β, TNFα and IL-6 expression appears to coincide with the development of heart failure. Furthermore, we describe the implication of the renin angiotensin aldosteron system in immunity and heart failure. In the past decade microRNAs (miRNAs), small non-coding RNAs that translationally repress protein synthesis by binding to partially complementary sequences of mRNA, have come to light as important regulators of several kinds of cardiovascular diseases including cardiac hypertrophy and heart failure. The involvement of differentially expressed miRNAs in the inflammation that occurs during the development of heart failure is still subject of investigation. Here, we summarize and comment on the first studies in this field and hypothesize on the putative involvement of certain miRNAs in heart failure. MicroRNAs have been shown to be critical regulators of cardiac function and inflammation. Future research will have to point out if dampening the immune response, and the miRNAs associated with it, during the development of heart failure is a therapeutically plausible route to follow

Ovarian stimulation for fertility treatments and risk of breast cancer: a matched cohort study

Abstract STUDY QUESTION Is there a difference in the breast cancer risk among women who underwent ART treatments compared to those who underwent medically assisted reproduction (MAR) infertility treatments or women of reproductive age in the general population? SUMMARY ANSWER The risk of breast cancer among women treated by ART was similar to the risk among women treated by MAR and women who did not undergo fertility treatments. WHAT IS KNOWN ALREADY Studies investigating breast cancer risk in women who have undergone fertility treatments have provided conflicting results. STUDY DESIGN, SIZE, DURATION A retrospective, population-based cohort study included women who underwent ART or MAR treatments and women who did not undergo fertility treatments from 1994 to 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS Women who underwent ART were matched one to one with women who underwent MAR treatments and one to one with woman from the general population of reproductive age, by year of birth and year of first delivery or nulliparity status. MAR women were also matched to ART women by treatment initiation calendar year. All included women were members of Maccabi Healthcare Services. Data regarding demographics, fertility treatments, BRCA mutation and possible confounders were obtained from the computerized database of electronic health records. The incidence of breast cancer after fertility treatments was compared to the matched controls. MAIN RESULTS AND THE ROLE OF CHANCE Of 8 25 721 women of reproductive age, 32 366 women who underwent ART were matched with patients treated by MAR (n = 32 366) and 32 366 women of reproductive age. A total of 984 women (1.0%) were diagnosed with breast cancer (mean follow-up period, 9.1 ± 6.3 years; interquartile range [IQR], 3.8–13.7 years). The incidence rates of breast cancer per 10 000 person-years were 11.9 (95% CI, 10.7–13.3), 10.7 (95% CI, 9.6–11.9) and 10.7 (95% CI, 9.6–12.0) in the ART group, MAR group and general population, respectively. The crude risk for breast cancer was similar in the ART group compared with the general population (hazard ratio (HR) = 1.10, 95% CI, 0.94–1.28) and in the ART group compared with the MAR group (HR = 1.00, 95% CI, 0.86–1.16). Further adjustment for age, BMI, smoking, socioeconomic status and parity did not substantially impact the hazard rates for breast cancer (ART vs general population: HR = 1.10, 95% CI, 0.94–1.28; ART vs MAR: HR = 0.99, 95% CI, 0.85–1.16). Among women diagnosed with breast cancer, the prevalence of BRCA1/2 mutations and tumour staging did not differ between the ART, MAR and general population groups. Among women who underwent ART, no correlation was found between breast cancer and the number of ART cycles or the use of recombinant medications or urine-derived medications. LIMITATIONS, REASONS FOR CAUTION The mean age of women at the end of follow-up was only 42 years thus the study was not powered to detect potential differences in the risk of postmenopausal breast cancer. In addition, we did not sub-classify the exposed patients by the reason for infertility. WIDER IMPLICATIONS OF THE FINDINGS Breast cancer incidence following ART was comparable to that in the general population or following MAR. Women undergoing fertility treatments and their clinicians may be reassured about the safety of assisted reproduction technologies in terms of premenopausal breast cancer risk. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was used and there are no competing interests. TRIAL REGISTRATION NUMBER N/A. </jats:sec

The effect of prophylaxis with ertapenem versus cefuroxime/metronidazole on intestinal carriage of carbapenem-resistant or third-generation-cephalosporin-resistant Enterobacterales after colorectal surgery

Objectives: Compared to cephalosporin-based prophylaxis, ertapenem prophylaxis lowers the risk of surgical site infection among carriers of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PEs) undergoing colorectal surgery. We aimed to determine whether ertapenem prophylaxis leads to increased postoperative colonization with carbapenem-resistant Enterobacterales (CREs) and third-generation-cephalosporin-resistant Enterobacterales (3GCR-Es). Methods: This study was nested within a quality improvement study of prophylaxis for ESBL-PE carriers undergoing colorectal surgery. Patients were screened 4-6 days after surgery for carriage of ESBL-PEs or other 3GCR-Es and CREs. When CREs were detected, pre-and postsurgical clones were compared using Fourier-transform infrared (FT-IR) spectroscopy. Results: The sample consisted of 56 patients who carried ESBL-PEs before surgery and received cefuroxime/metronidazole prophylaxis (Group 1), 66 who carried ESBL-PEs before surgery and received ertapenem (Group 2), and 103 ESBL-PE non-carriers who received cefuroxime/metronidazole prophylaxis (Group 3). CRE carriage was detected postoperatively in one patient (1.5%) in Group 2 versus eight patients (14.3%) in Group 1 (RD-12.8%; 95%CI-22.4% to-3.1%). For seven out of nine patients, preoperative ESBL-PE and postoperative CRE isolates were compared; in five of them, the pre-and postoperative clones were identical. Postoperative 3GCR-E carriage was detected in 37 patients (56.1%) in Group 2 versus 46 patients in Group 1 (82.1%) (aRD-20.7%, 95%CI-37.3% to-4.1%). Conclusions: Among ESBL-PE carriers undergoing colorectal surgery, detection of short-term postsurgical colonization by CREs and 3GCR-Es was significantly lower among patients who received ertapenem prophylaxis than those who received cephalosporin-metronidazole prophylaxis. Resistance development in a colonizing bacterial clone, rather than carbapenemase acquisition, was the major mechanism of carbapenem resistance.</p

Personalized Ertapenem Prophylaxis for Carriers of Extended-spectrum β-Lactamase-producing Enterobacteriaceae Undergoing Colorectal Surgery

Carriers of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) who receive cephalosporin-based prophylaxis have twice the risk of surgical site infection (SSI) following colorectal surgery as noncarriers. We tested whether ESBL-PE screening and personalized prophylaxis with ertapenem reduces SSI risk among carriers