This large, multicentre study identifies contemporary challenges related to the diagnosis and prognostication of CPVT patients. Structural modelling of RyR2 can improve our understanding severe CPVT phenotypes. Wakeful rest, rather than exertion, often precipitated life-threatening cardiac events.

Our systematic review of worldwide literature consistently identified gaps in gout knowledge among providers, which is likely to contribute to patients' lack of appropriate education about the fundamental causes of and essential treatment approaches for gout. Furthermore, system barriers among providers and day-to-day challenges of taking long-term medications among patients are considerable. These factors provide key targets to improve the widespread suboptimal gout care.

BackgroundThe indication, composition and timing of administration of non-resuscitation fluid in septic shock have so far received little attention and accordingly the potential to reduce this source of fluid is unknown. The objective of the study was to quantify and characterize non-resuscitation fluid administered to patients with septic shock.MethodsThis prospective observational study was performed in eight intensive care units in Sweden and Canada during 4 months in 2018. Adult patients with septic shock within 24 h of admission to the intensive care unit were eligible for inclusion. Non-resuscitation fluids were defined as fluids other than colloids, blood products and crystalloids at a rate ≥ 5 ml/kg/h. Indication, volume and type of fluid were recorded during the first 5 days after admission. A maximum of 30 patients could be included per centre. To estimate the potential to reduce administration of non-resuscitation fluid, a pragmatic “restrictive” protocol for administration of non-resuscitation fluids was devised based on the most restrictive practice already in place for non-resuscitation fluids at any of the participating centres. Data are presented as median (interquartile range [IQR]).ResultsA total of 200 patients were included in the study and the 30-day mortality was 35%. Patients received a total of 7870 (4060–12,340) ml of non-resuscitation fluids and 2820 (1430–4580) of resuscitation fluids during the observation period. Median volumes of non-resuscitation and resuscitation fluids were similar at day 1 (1620 [710–2320] and 1590 [520–3000]) ml, respectively) and non-resuscitation fluids represented the largest source of fluid from day 2 and onwards after admission to the ICU. Vehicles for drugs such as vasoactive drugs and antibiotics constituted the largest fraction of non-resuscitation fluids (2400 [1270–4030] ml) during the 5-day observation period. Modelling suggested that volume of non-resuscitation fluids could be reduced by 2840 (1270–4900) ml during the first 5 days of admission to the ICU, mainly through reducing maintenance fluids.ConclusionsNon-resuscitation fluids constitute the major fraction of fluids administered in the ICU to patients suffering from septic shock and may represent the largest modifiable target to reduce fluid overload.

Rare CD4 T cells that contain HIV under antiretroviral therapy represent an important barrier to HIV cure1–3, but the infeasibility of isolating and characterizing these cells in their natural state has led to uncertainty about whether they possess distinctive attributes that HIV cure-directed therapies might exploit. Here we address this challenge using a microfluidic technology that isolates the transcriptomes of HIV-infected cells based solely on the detection of HIV DNA. HIV-DNA+ memory CD4 T cells in the blood from people receiving antiretroviral therapy showed inhibition of six transcriptomic pathways, including death receptor signalling, necroptosis signalling and antiproliferative Gα12/13 signalling. Moreover, two groups of genes identified by network co-expression analysis were significantly associated with HIV-DNA+ cells. These genes (n = 145) accounted for just 0.81% of the measured transcriptome and included negative regulators of HIV transcription that were higher in HIV-DNA+ cells, positive regulators of HIV transcription that were lower in HIV-DNA+ cells, and other genes involved in RNA processing, negative regulation of mRNA translation, and regulation of cell state and fate. These findings reveal that HIV-infected memory CD4 T cells under antiretroviral therapy are a distinctive population with host gene expression patterns that favour HIV silencing, cell survival and cell proliferation, with important implications for the development of HIV cure strategies.