Historically, it was often associated with chronic Syphilis infection and patients would experience paroxysms of hemolysis on exposure to cold; however, nowadays, it almost always occurs as acute ...transient anemia in children after some form of viral illness. ...bouts of hemolysis on exposure to cold are now rarely demonstrated 2. CONFLICT OF INTEREST The authors declare they have no conflicts of interest.
Investigations of humans with disorders of sex development (DSDs) resulted in the discovery of many of the now-known mammalian sex-determining genes, including
SRY, RSPO1, SOX9,
NR5A1,
WT1,
NR0B1, ...and
WNT4. Here, the locus for an autosomal sex-determining gene was mapped via linkage analysis in two families with 46,XY DSD to the long arm of chromosome 5 with a combined, multipoint parametric LOD score of 6.21. A splice-acceptor mutation (c.634-8T>A) in
MAP3K1 segregated with the phenotype in the first family and disrupted RNA splicing. Mutations were demonstrated in the second family (p.Gly616Arg) and in two of 11 sporadic cases (p.Leu189Pro, p.Leu189Arg)—18% prevalence in this cohort of sporadic cases. In cultured primary lymphoblastoid cells from family 1 and the two sporadic cases, these mutations altered the phosphorylation of the downstream targets, p38 and ERK1/2, and enhanced binding of RHOA to the MAP3K1 complex.
Map3k1 within the syntenic region was expressed in the embryonic mouse gonad prior to, and after, sex determination. Thus, mutations in
MAP3K1 that result in 46,XY DSD with partial or complete gonadal dysgenesis implicate this pathway in normal human sex determination.
The coronavirus disease 2019 pandemic has led to unprecedented disruption to the normal way of life for people around the globe. Social distancing, self-isolation or shielding have been strongly ...advised or mandated in most countries. We suggest evidence-based ways that people can maintain or even strengthen their mental health during this crisis.
Summary
Haematology patients contracting SARS‐CoV‐2 were identified at the start of the pandemic to be at higher risk of death or of persistent symptoms (post‐COVID‐19 syndrome). As variants with ...altered pathogenicity have emerged, uncertainty remains around how that risk has changed. We prospectively set up a dedicated post‐COVID‐19 clinic to monitor haematology patients infected with COVID‐19 from the start of the pandemic. In total, 128 patients were identified and telephone interviews were conducted with 94 of 95 survivors. Ninety‐day mortality attributed to COVID‐19 has fallen sequentially from 42% for the Original and Alpha strains to 9% and to 2% for the Delta and Omicron variants respectively. Furthermore, the risk of post‐COVID‐19 syndrome in survivors has fallen from 46% for the Original or Alpha strains to 35% for Delta and 14% for the Omicron strain. Since vaccine uptake has been nearly universal in haematology patients, it is not possible to determine whether improved outcomes reflect the reduced pathogenicity of the virus, or widespread vaccine deployment. Whilst mortality and morbidity remain higher in haematology patients than in the general population, our data suggest that the absolute risks are now significantly lower. Given this trend, we believe clinicians should initiate conversations about risk with their patients on whether to maintain any self‐imposed social isolation.
Summary
Artificial neural networks are machine‐learning algorithms designed to analyse data without a pre‐existing hypothesis as to any associations that may exist. This technique has not previously ...been applied to the risk stratification of patients referred with suspected deep vein thrombosis (DVT). Current assessment is usually with a points‐based clinical score, which may be combined with a D‐dimer blood test. A neural network was trained to risk‐stratify patients presenting with suspected DVT and its performance compared with existing tools. Data from 11 490 cases of suspected DVT presenting consecutively between 1 January 2011 and 31 December 2017 were analysed, and 7080 for whom all components of the Wells’ score, a D‐dimer and an ultrasound result were available were included in the analysis. The data were broken into a training set of 5270 patients, used to develop the algorithm, and a testing set of 1810 patients to assess performance of the trained algorithm. This network was able to exclude DVT without the need for ultrasound in significantly more patients than existing risk assessment scores, whilst retaining very low false negatives rates. More generally, this approach may improve the analysis of complex data to support decision‐making in other areas of clinical medicine.
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