Outcome after heart-lung or lung transplantation in patients with Eisenmenger syndrome

Objective The optimal timing for transplantation is unclear in patients with Eisenmenger syndrome (ES). We investigated post-transplantation survival and transplantation-specific morbidity after heart-lung transplantation (HLTx) or lung transplantation (LTx) in a cohort of Nordic patients with ES to aid decision-making for scheduling transplantation. Methods We performed a retrospective, descriptive, population-based study of patients with ES who underwent transplantation from 1985 to 2012. Results Among 714 patients with ES in the Nordic region, 63 (9%) underwent transplantation. The median age at transplantation was 31.9 (IQR 21.1-42.3) years. Within 30 days after transplantation, seven patients (11%) died. The median survival was 12.0 (95% CI 7.6 to 16.4) years and the overall 1-year, 5-year, 10-year and 15-year survival rates were 84.1%, 69.7%, 55.8% and 40.6%, respectively. For patients alive 1 year post-transplantation, the median conditional survival was 14.8 years (95% CI 8.0 to 21.8), with 5-year, 10-year and 15-year survival rates of 83.3%, 67.2% and 50.0%, respectively. There was no difference in median survival after HLTx (n=57) and LTx (n=6) (14.9 vs 10.6 years, p=0.718). Median cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis/kidney transplantation-free survival rates were 11.2 (95% CI 7.8 to 14.6), 6.9 (95% CI 2.6 to 11.1) and 11.2 (95% CI 8.8 to 13.7) years, respectively. The leading causes of death after the perioperative period were infection (36.7%), bronchiolitis obliterans syndrome (23.3%) and heart failure (13.3%). Conclusions This study shows that satisfactory post-transplantation survival, comparable with contemporary HTx and LTx data, without severe comorbidities such as cardiac allograft vasculopathy, bronchiolitis obliterans syndrome and dialysis, is achievable in patients with ES, with a conditional survival of nearly 15 years.Peer reviewe

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio

Transcutaneous electrical stimulation therapy and genetic analysis in Dercum’s disease A pilot study

Dercum’s disease (DD), or adiposis dolorosa, is a rare condition of unknown etiology characterized by growth of painful subcutaneous adipose tissue. No specific treatment exists. Pain is often invalidating and resistant to analgesic drugs. We tested the efficacy of Frequency Rhythmic Electrical Modulation System (FREMS) therapy on pain relief. Subcutaneous biopsies were performed for genetic analysis. Nine DD patients were enrolled. Five cycles of FREMS at 3-month intervals during 1 year were administered. Visual analogue scale (VAS), Bartel Index Questionnaire and Short Form 36 questionnaire were used to measure pain and general health status at baseline, 6 and 12 months. Dual-energy X-ray absorptiometry (DEXA) quantified fat mass. Next-Generation Sequencing (NGS) was performed on adipose tissue biopsies and peripheral blood sample to search for somatic variants and specific protein pathway mutation. Seven patients were included in the final analysis. FREMS induced a reduction in VAS score (from 92 to 52.5, P = .0597) and a significant improvement in SF-36 domains (Physical functioning, Role limitation due to physical health, Body pain, Vitality, Social functioning, P G variant, occasionally identified in patients with multiple symmetric lipomatosis, was excluded in all subjects. On the other hand, we observed variants in genes belonging to signaling pathways involved in cell cycle and proliferation (Phosphoinositide 3-kinase/AKT/mTOR, MAPK/ERK, and Hippo). FREMS can be a useful tool to alleviate pain and improve overall quality of life in patients with DD. Genetic analysis highlighted the molecular heterogeneity of lipomas

The excludon: a new concept in bacterial antisense RNA-mediated gene regulation

International audienceIn recent years, non-coding RNAs have emerged as key regulators of gene expression. Among these RNAs, the antisense RNAs (asRNAs) are particularly abundant, but in most cases the function and mechanism of action for a particular asRNA remains elusive. Here, we highlight a recently discovered paradigm termed the excludon, which defines a genomic locus encoding an unusually long asRNA that spans divergent genes or operons with related or opposing functions. Because these asRNAs can inhibit the expression of one operon while functioning as an mRNA for the adjacent operon, they act as fine-tuning regulatory switches in bacteria