Contemporary epidemiology of infective endocarditis in patients with congenital heart disease: A UK prospective study.

OBJECTIVES: Infective endocarditis is a life-threatening complication of congenital heart disease (CHD), but there are few studies concerning the contemporary risk profile, preceding invasive procedures and outcomes in this patient population. The aim of this study was to investigate the epidemiology of infective endocarditis (IE) in patients with CHD. METHODS: Cases of IE in children and adults with CHD were prospectively recorded as part of the UK National Institute for Cardiovascular Outcomes Research (NICOR) National Congenital Heart Disease Audit. Patients were entered into the database between April 2008 and March 2016. RESULTS: Eight hundred episodes of IE were recorded in 736 patients with CHD. Sixty-five patients (9%) were infants (aged <1 year), 235 (32%) were children (aged 1-15 years), and 436 (59%) were adults (aged >15 years). The most common diagnoses were Tetralogy of Fallot (n = 150, 22.8%), ventricular septal defect (n = 129, 19.6%) and bicuspid aortic valve (n = 70, 10.7%). Dental procedures preceded 67 of 635 episodes (11%) of IE, and non-dental invasive procedures preceded 177 of 644 episodes (27.4%). The most common causative organisms were streptococci, accounting for 40% of cases. Overall in-hospital mortality was 6.7%. On multivariable analysis, adverse factors associated with in-hospital mortality were staphylococcal infection and presence of an underlying atrioventricular septal defect. CONCLUSIONS: Infective endocarditis in patients with CHD is an ongoing clinical challenge. In contemporary practice in tertiary congenital centers, 1 of 15 patients do not survive to hospital discharge. Streptococci remain the most common causative organism, and antecedent dental or medical procedures were undertaken in a significant minority in the 3 months before diagnosis. The presence of an atrioventricular septal defect or staphylococcal infection is associated with significantly increased risk of early mortality.

Preservation of forelimb function by UPF1 gene therapy in a rat model of TDP-43-induced motor paralysis.

Nonsense-mediated mRNA decay (NMD) is an RNA surveillance mechanism that requires upframeshift protein 1 (UPF1). This study demonstrates that human UPF1 exerts protective effects in a rat paralysis model based on the amyotrophic lateral sclerosis (ALS)-associated protein, TDP-43 (transactive response DNA-binding protein 43 kDa). An adeno-associated virus vector (AAV9) was used to express TDP-43 throughout the spinal cord of rats, inducing reproducible limb paralysis, to recapitulate the paralysis in ALS. We selected UPF1 for therapeutic testing based on a genetic screen in yeast. The expression of human TDP-43 or human UPF1 in the spinal cord was titrated to less than twofold over the respective endogenous level. AAV9 human mycUPF1 clearly improved overall motor scores in rats also expressing TDP-43. The gene therapy effect of mycUPF1 was specific and reproducible compared with groups receiving either empty vector or green fluorescent protein vector controls. The gene therapy maintained forelimb motor function in rats that would otherwise become quadriplegic. This work helps validate UPF1 as a novel therapeutic for ALS and other TDP-43-related diseases and may implicate UPF1 and NMD involvement in the underlying disease mechanisms.

Phosphonate utilization by the globally important marine diazotroph Trichodesmium.

The factors that control the growth and nitrogen fixation rates of marine diazotrophs such as Trichodesmium have been intensively studied because of the role that these processes have in the global cycling of carbon and nitrogen, and in the sequestration of carbon to the deep sea. Because the phosphate concentrations of many ocean gyres are low, the bioavailability of the larger, chemically heterogeneous pool of dissolved organic phosphorus could markedly influence Trichodesmium physiology. Here we describe the induction, by phosphorus stress, of genes from the Trichodesmium erythraeum IMS101 genome that are predicted to encode proteins associated with the high-affinity transport and hydrolysis of phosphonate compounds by a carbon-phosphorus lyase pathway. We show the importance of these genes through expression analyses with T. erythraeum from the Sargasso Sea. Phosphonates are known to be present in oligotrophic marine systems, but have not previously been considered to be bioavailable to marine diazotrophs. The apparent absence of genes encoding a carbon-phosphorus lyase pathway in the other marine cyanobacterial genomes suggests that, relative to other phytoplankton, Trichodesmium is uniquely adapted for scavenging phosphorus from organic sources. This adaptation may help to explain the prevalence of Trichodesmium in low phosphate, oligotrophic systems.

Quantitative studies on menstrual blood loss in IUD users.

Despite the introduction of new intrauterine devices (IUDs), the most important complication involving their use continues to be excessive menstrual bleeding. IUD use in developing countries with women who are already depleted in body iron stores may prove to be deleterious to their health. Mean amounts of menstrual blood loss (MBL) for women not using contraception in the western world is about 32 ml. This mean is increased to 52-72 ml with use of the Lippes loop and other non-medicated devices up to 24 months after insertion. For the Copper-7 and Copper-T-200 devices this mean increase is to 37-40 ml in the first month, decreasing to 30-38 ml at 12 months after IUD insertion. In the users of the Multiload-250 IUD at one month post-insertion the MBL is from 56 to 63 ml and from 36 to 39 ml at 24 months of use. The mean Multiload-375 device users at one month after insertion lose a mean of 45-73 ml at 24 months, 35-50 ml. With the progestogen-releasing IUD mean MBL is 27-36 ml at 1 month and 9-13 ml at 12 months post-insertion. Intermenstrual blood loss is significant only in the first month of use for all IUDs. Discontinuation rates for pain and bleeding with non-medicated IUDs are from 11.0-19.6 per 100 women per year, and for the copper IUDs 4.4 to 6.8 per 100 women in the first year of use. The main problem with prolonged menstrual bleeding is depletion of the body iron stores; this is highly significant with non-medicated devices, less important with copper devices and conversely, iron stores are increased in users of progestogen-releasing devices. This is based on serum ferritin measured up to 24 months after insertion. The ferritin values correlated well with the volumes of MBL. It is suggested, especially for women with low body iron stores, that there is an order of preference for IUDs to be used. This should be: firstly, the progestogen-releasing devices; secondly, the Copper-T and Copper-7 IUDs; thirdly the larger surface copper devices (Cu-T-220C, Multiload 250 and 375, Cu-T-380). Non-medicated devices are not to be recommended for these women.

The management of cryptogenic stroke in pregnancy.

Cerebrovascular accidents (CVAs) during pregnancy are uncommon but can have devastating consequences. The causes of CVA in both the pregnant and the non-pregnant state are diverse and require thorough investigation. Recent studies have indicated that embolic stroke in young adults may be caused by paradoxical emboli through a patent foramen ovale (PFO), suggesting that the presence of a PFO should be specifically sought in pregnant or postpartum women presenting with CVA. This review will outline the causes of CVAs in pregnancy and the role of paradoxical emboli, with a focus on PFO.

[Clinical evaluation of the progesterone T intrauterine device]. / Evaluación clínica del dispositivo intrauterino "T de progesterona".

PIP: This study describes a clinical evaluation of the Progesterone T IUD which releases a daily dose of 65 mcg of progesterone. The device is made of a copolymer of ethylene vinyl and has a transversal arm measuring 3.18 cm and a longitudinal arm 3.61 cm. The longitudinal arm contains 38 mg of natural progesterone, Barium sulfate, and silicone acetate. 146 new users of the Progesterone T were compared with 149 using the Copper 7 Gravigarde. Patients in both groups ranged in age from 17-40 years with an average of 27.2 for Progesterone T and 27.1 for Copper 7 users. Parity ranged from 1-11 with an average of 2.8 for the Progesterone T group and from 1-10 with an average of 2.7 for the Copper 7 group. The average number of spontaneous abortions was .7 for the Progesterone T group and .5 for the Copper 7 group. The groups were also comparable in previous contraceptive usage. In another study, 51 Lippes Loop D users, 52 Progesterone T users, and 50 Copper 7 users were evaluated for menstrual and intermenstrual blood loss in the 3 months prior to and the 1st, 2nd, 4th, 6th, 9th, and 12th months after insertion. At the end of 12 months, the Progesterone T and Copper 7 users respectively had pregnancy rates of 1.4 and 1.5, expulsion rates of 4.2 and 5.8, rates of removal for medical reasons of 2.8 and 3.0, and continuation rates of 87.2 and 84.6. After 1569 women-months of Progesterone T use and 1558 of Copper 7 use there were no statistically significant differences. With the Progesterone T there was 1 removal for pain, 1 for pelvic inflammation, and 2 for menstrual alterations. 4 Copper 7s were removed for bleeding. The average duration of menstrual bleeding was 6.0 days with the Progesterone T and 6.2 with the Copper 7. The number of days of true bleeding were 4.8 on average for the Progesterone T and 5.3 for the Copper 7. Intermenstrual bleeding was twice as common for the Progesterone T. There was no statistically significant difference in incidence of pain reported by the 2 groups at the beginning and end of the study. Both groups had a decline in pain at the end of the study, with the Progesterone T having a slightly more pronounced decline. The average volume of menstrual blood loss increased by 87.8% after insertion of the Lippes Loop D and by 24.3% with the Copper 7 but declined by 44.5% for the Progesterone T.^ieng