P-wave dispersion in systemic AA amyloidosis of familial Mediterranean fever

Familial Mediterranean fever (FMF) is a hereditary disease characterized by attacks of fever and polyserositis. Recent studies differ as to whether FMF is associated with an abnormally high P-wave duration and P-wave dispersion, markers for supraventricular arrhythmogenicity. The aim of our study was to further evaluate atrial dispersion in FMF patients with amyloidosis. The study groups consisted of 16 patients with FMF and amyloidosis, and 16 age- and sex-matched control subjects. All participants underwent 12-lead electrocardiography under strict standards. P-wave length and P-wave dispersion in each individual patient were computed from a randomly selected beat and an averaged beat constructed from 7 to 12 beats, included in a 10-s electrocardiogram. No statistically significant differences were found between the groups for minimal, maximal, and average P-wave duration and P-wave dispersion, calculated either from a random beat or averaged beats. In conclusion, although a small difference cannot be excluded because of the small study groups, FMF patients with amyloidosis appear to have atrial conduction parameters similar to those of healthy controls, and therefore apparently do not have an increased electrocardiographic risk for developing supraventricular arrhythmias.     

Proximity ligation assays for isoform-specific Akt activation in breast cancer identify activated Akt1 as a driver of progression

The PI3K/Akt signal transduction pathway plays an important role in cancer progression and cell survival. Akt activation is associated with poor outcome in endocrine-treated breast cancer, whereas high levels of cytoplasmic Akt2 are associated with an improved overall survival. Proximity ligation assays (PLAs) were used to determine quantitative expression levels of isoform-specific activation (phosphorylation) of Akt1 and Akt2 in formalin-fixed, paraffin-embedded cell lines and breast cancer tumour tissues in situ. PLAs demonstrated a range of expression in breast cancer samples for total pAkt1 and pAkt2. High levels of pAkt1 were associated with reduced DRFS (HR: 1.45, 95% CI 1.14-1.83, p = 0.002) and OS (HR: 1.42, 95% CI 1.10-1.83, p = 0.007). When PLA results were combined, patients that had high levels of pAkt1 only had a significantly decreased DRFS (HR: 1.92, 95% CI 1.34-2.76, p = 0.005) and OS (HR: 1.94, 95% CI 1.32-2.86, p = 0.008) compared to other patients. Using PLAs to discriminate activation of Akt1 versus Akt2 suggests that Akt1 drives progression in early breast cancers. In cases where both Akt1/Akt2 are activated, Akt2 may act to reverse this effect. Using PLAs, we have measured activation of Akt1 and Akt2 proteins separately in situ in FFPE breast cancer samples.     

Trajectories of PrEP use among men who have sex with men: a pooled analysis of two prospective,observational cohort studies

Introduction

Daily and event-driven oral pre-exposure prophylaxis (PrEP) reduce the risk of HIV acquisition. PrEP use can vary over time, yet little is known about the trajectories of PrEP use irrespective of the chosen PrEP regimens among men who have sex with men (MSM).

Methods

Using data from a mobile, web-based diary application collected daily from 17 August 2015 until 6 May 2018, we analysed PrEP use and sexual behaviour in two large cohorts, AMPrEP (Amsterdam, the Netherlands) and Be-PrEP-ared (Antwerp, Belgium). In both cohorts, participants could choose between daily and event-driven oral PrEP every 3 months. We used group-based trajectory modelling to identify trajectories of PrEP use over time and their determinants. In addition, we estimated the incidence rate of chlamydia, gonorrhoea and syphilis within these trajectories.

Results

We included 516 MSM (n = 322 AMPrEP; n = 194 Be-PrEP-ared), of whom 24% chose event-driven PrEP at PrEP initiation. Participants contributed 225,015 days of follow-up (median = 508 days [IQR = 429−511]). Four distinct PrEP use trajectories were identified: ≤2 tablets per week (“low frequency,” 12% of the total population), 4 tablets per week (“variable,” 17%), “almost daily” (31%) and “always daily” (41%). Compared to participants with “low frequency” PrEP use, participants with “variable” (odds ratio [OR] = 2.18, 95% confidence interval [CI] = 1.04−4.60) and “almost daily” PrEP use were more often AMPrEP participants (OR = 2.64, 95% CI = 1.27−5.49). “Almost daily” PrEP users were more often employed (OR = 6.76, 95% CI = 2.10−21.75) and were younger compared to participants with “low frequency” PrEP use. In addition, the number of days on which anal sex occurred was lower among participants with “low frequency” PrEP use compared to the other groups (all p<0.001). Compared to “low frequency” PrEP users, the incidence rates of chlamydia and gonorrhoea were higher for participants with “almost daily” and “always daily” PrEP use.

Conclusions

We uncovered four distinct PrEP use trajectories, pointing to different patterns of PrEP use in practice beyond the two-regimen dichotomy. These trajectories were related to sexual behaviour and rates of sexually transmitted infection. Tailoring PrEP care according to different PrEP use patterns could be an important strategy to improve efficient PrEP delivery.     

Craniopharyngioma in Nigerian children

Between 1971 and 1986, 20 Nigerian children (less than 1 year to 15 years of age) with craniopharyngiomas were treated at the University College Hospital (UCH) in Ibadan. The children made up 71% of all patients with craniopharyngiomas seen in the hospital during the study period. The mean age of the 12 boys and 8 girls was 9.2 years. The predominant symptoms and signs were raised intracranial pressure and visual disturbance. Characteristic radiological features occurred in over 60% of cases; about two-thirds of the tumors were cystic. The advanced tumor stage upon arrival at UCH limited the amount of radical surgery that could be done; 31% died soon after surgery.     

Endovascular treatment of bifurcation intracranial aneurysms with the WEB SL/SLS: 6-month clinical and angiographic results

Background

The WEB device is a recent intrasaccular flow disruption technique developed for the treatment of wide-necked intracranial aneurysms. To date, a single report on the WEB Single-Layer (SL) treatment of intracranial aneurysms has been published with 1-months'' safety results. The aim of this study is to report our experience and 6-month clinical and angiographic follow-up of endovascular treatment of wide-neck aneurysm with the WEB SL.

Methods

Ten patients with 10 unruptured wide-necked aneurysms were prospectively enrolled in this study. Feasibility, intraoperative and postoperative complications, and outcomes were recorded. Immediate and 6-month clinical and angiographic results were evaluated.

Results

Failure of WEB SL placement occurred in two cases. Eight aneurysms were successfully treated using one WEB SL without additional treatment. Three middle cerebral artery, four anterior communicating artery, and one basilar artery aneurysms were treated. Average dome width was 7.5 mm (range 5.4–10.7 mm), and average neck size was 4.9 mm (range 2.6–6.5 mm). No periprocedural complication was observed, and morbi-mortality at discharge and 6 months was 0.0%. Angiographic follow-up at 6 months demonstrated complete aneurysm occlusion in 2/8 aneurysms, neck remnant in 5/8 aneurysms, and aneurysm remnant in 1/8 aneurysm.

Conclusions

From this preliminary study, treatment of bifurcation intracranial aneurysms using WEB SL is feasible. WEB SL treatment seems safe at 6 months; however, the rate of neck remnants is not negligible due to compression of the WEB SL. Further technical improvements may be needed in order to ameliorate the occlusion in the WEB SL treatment.     

Primary hyperparathyroidism and malignancy: "studies by nature"

The American Food and Drug Administration approval of parathyroid hormone (PTH) administration for osteoporosis as well as the possibility for its future therapeutic applications requires an examination of the suggested association between PTH and cancer, particularly osteosarcomas. The objective was to evaluate such a connection by collecting observational data from two groups of patients, designated as "studies by nature". Cohort 1: Medical records of all patients with primary hyperparathyroidism that were treated in a referral center during a 12-year period were retrospectively reviewed for malignancy before, at the time or after diagnosis. Cohort 2: Records of patients with osteosarcomas that were treated in referral centers during 15 years were retrospectively reviewed for hyperparathyroidism, as indicated by history or laboratory results. There were 582 patients with primary hyperparathyroidism. While 56 (9.6%) had malignancy, 47 (8%) developed cancer after diagnosis with hyperparathyroidism during 6.1 years of documentation. This rate did not exceed the incidence of developing cancer among the general population. Although thyroid cancer was about 4 times the incidence in the general population, this may be attributed to a high level of detection while work-up, treating and following the parathyroid disease. None had osteosarcoma. None of the 126 patients with osteosarcoma had documentation of primary hyperparathyroidism or had biochemical evidence of hyperparathyroidism. No obvious association was found between primary hyperparathyroidism and cancer. Similarly, there was no demonstrable relationship between osteosarcomas and hyperthyroidism biochemical stigmata. Since PTH may contribute to tumor invasiveness, screening for existing neoplasms, especially prostate and breast, before PTH treatment may be of importance.