Standalone epicardial left atrial appendage exclusion for thromboembolism prevention in atrial fibrillation

Open in a separate window OBJECTIVESMost strokes associated with atrial fibrillation (AF) result from left atrial appendage thrombi. Oral anticoagulation can reduce stroke risk but is limited by complication risk and non-compliance. Left atrial appendage exclusion (LAAE) is a new surgical option to reduce stroke risk in AF. The study objective was to evaluate the safety and feasibility of standalone thoracoscopic LAAE in high stroke risk AF patients.METHODSThis was a retrospective, multicentre study of high stroke risk AF patients who had oral anticoagulation contraindications and were not candidates for ablation nor other cardiac surgery. Standalone thoracoscopic LAAE was performed using 3 unilateral ports access and epicardial clip. Periprocedural adverse events, long-term observational clinical outcomes and stroke rate were evaluated.RESULTSProcedural success was 99.4% (174/175 patients). Pleural effusion occurred in 4 (2.3%) patients; other periprocedural complications were <1% each. One perioperative haemorrhagic stroke occurred (0.6%). No phrenic nerve palsy or cardiac tamponade occurred. Predicted annual ischaemic stroke rate of 4.8/100 patient-years (based on median CHA₂DS₂-VASc score of 4.0) was significantly higher than stroke risk observed in follow-up after LAAE. No ischaemic strokes occurred (median follow-up: 12.5 months), resulting in observed rate of 0 (95% CI 0–2.0)/100 patient-years (P < 0.001 versus predicted). Six all-cause (non-device-related) deaths occurred during follow-up.CONCLUSIONSStudy proved that a new surgical option, standalone thoracoscopic LAAE, is feasible and safe. With this method, long-term stroke rate may be reduced compared to predicted for high-risk AF population.     

Articular cartilage collagen and proteoglycans their functional interdependency

By use of an in vitro experimental system which permits the observation at high resolution of articular cartilage in a physiologic condition, its biomechanical response to compression was investigated before and after enzymatic digestion of the proteoglycan components with testicular hyaluronidase. The study provides further insight into the functional interplay between the collagen network and the hydrated proteoglycans. Certain structural features associated with age-related and osteoarthritic changes occurring in vivo in human articular cartilage were mimicked in the compressive response of the enzymatically digested tissue.     

The HIV-1 proviral landscape reveals that Nef contributes to HIV-1 persistence in effector memory CD4+ T cells

Despite long-term antiretroviral therapy (ART), HIV-1 persists within a reservoir of CD4⁺ T cells that contribute to viral rebound if treatment is interrupted. Identifying the cellular populations that contribute to the HIV-1 reservoir and understanding the mechanisms of viral persistence are necessary to achieve an effective cure. In this regard, through Full-Length Individual Proviral Sequencing, we observed that the HIV-1 proviral landscape was different and changed with time on ART across naive and memory CD4⁺ T cell subsets isolated from 24 participants. We found that the proportion of genetically intact HIV-1 proviruses was higher and persisted over time in effector memory CD4⁺ T cells when compared with naive, central, and transitional memory CD4⁺ T cells. Interestingly, we found that escape mutations remained stable over time within effector memory T cells during therapy. Finally, we provided evidence that Nef plays a role in the persistence of genetically intact HIV-1. These findings posit effector memory T cells as a key component of the HIV-1 reservoir and suggest Nef as an attractive therapeutic target.     

Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer

Background Excess adiposity at diagnosis and weight gain during chemotherapy is associated with tumour recurrence and chemotherapy toxicity. We assessed the efficacy of intermittent energy restriction (IER) vs continuous energy restriction (CER) for weight control and toxicity reduction during chemotherapy.Methods One hundred and seventy-two women were randomised to follow IER or CER throughout adjuvant/neoadjuvant chemotherapy. Primary endpoints were weight and body fat change. Secondary endpoints included chemotherapy toxicity, cardiovascular risk markers, and correlative markers of metabolism, inflammation and oxidative stress.Results Primary analyses showed non-significant reductions in weight (−1.1 (−2.4 to +0.2) kg, p = 0.11) and body fat (−1.0 (−2.1 to +0.1) kg, p = 0.086) in IER compared with CER. Predefined secondary analyses adjusted for body water showed significantly greater reductions in weight (−1.4 (−2.5 to −0.2) kg, p = 0.024) and body fat (−1.1 (−2.1 to −0.2) kg, p = 0.046) in IER compared with CER. Incidence of grade 3/4 toxicities were comparable overall (IER 31.0 vs CER 36.5%, p = 0.45) with a trend to fewer grade 3/4 toxicities with IER (18%) vs CER (31%) during cycles 4–6 of primarily taxane therapy (p = 0.063).Conclusions IER is feasible during chemotherapy. The potential efficacy for weight control and reducing toxicity needs to be tested in future larger trials.Clinical trial registration ISRCTN04156504.Subject terms: Randomized controlled trials, Breast cancer, Nutrition, Weight management, Breast cancer     

Vogt Koyanagi Harada disease following a recent COVID-19 infection

A 23-year-old female presented with a 3-day history of bilateral (OU) diminution of vision 3 weeks after COVID-19 infection. Best corrected visual acuity (BCVA) was 20/30 in right eye and 20/40 in left eye. Anterior segment showed OU 1+ cells in anterior chamber and anterior vitreous face. Fundus OU showed disc hyperemia and multiple pockets of subretinal fluid (SRF), confirmed on optical coherence tomography. Fundus fluorescein angiography showed multiple pin point leaks suggestive of Vogt Koyanagi Harada disease. Oral corticosteroids 1 mg/kg/day were started. At 2-months’ follow-up, her BCVA improved to 20/25 OU with complete resolution of SRF.     

The Impact of the Universal Infant Free School Meal Policy on Dietary Quality in English and Scottish Primary School Children: Evaluation of a Natural Experiment

The Universal Infant Free School Meal (UIFSM) policy was introduced in September 2014 in England and January 2015 in Scotland and offered all infant schoolchildren (ages 4–7 years) a free school lunch, regardless of income. Yet, impacts of UIFSM on dietary intakes or social inequalities are not known. A difference-in-differences study using the National Diet and Nutrition Survey assessed pooled pre-UIFSM (2010–2014) and post-UIFSM (2014–2017) dietary data. English or Scottish infant schoolchildren (4–7 years; n = 458) were the intervention group, with junior schoolchildren (8–11 years; n = 401) as controls. We found that implementation of UIFSM led to an increase in infant schoolchildren having a school meal. Impacts on key food groups such as fruit and vegetables or sweetened beverages were not seen. However, there was evidence that the UIFSM policy lowered consumption of foods associated with packed lunches, such as crisps, and some nutrients, such as total fat and sodium. Policy impacts differed by income group, with larger effect sizes in low-income children. In conclusion, evaluation of UIFSM demonstrated some improvements in dietary quality but the findings suggest school meal quality needs to be improved to fully realise the benefits of UIFSM.     

Ophthalmologic safety of long-term hydroxychloroquine treatment

Ocular toxicity of long-term hydroxychloroquine treatment was assessed by regular ophthalmologic examinations in 99 patients. No patient developed significant loss of vision or visual field constriction to a white test object. Three patients had evidence of toxicity, but the medication had to be permanently discontinued in only one who subsequently had regression of all abnormalities except visual field constriction to a red test object. Neither duration of treatment nor the diagnosis of systemic lupus erythematosus predisposed patients to toxicity.