Mortality and burden of post-COVID-19 syndrome have reduced with time across SARS-CoV-2 variants in haematology patients.

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.

Coronavirus disease 2019: achieving good mental health during social isolation.

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.

Regional outcomes of severe acute respiratory syndrome coronavirus 2 infection in hospitalised patients with haematological malignancy.

OBJECTIVES: We sought to characterise the outcomes of patients with haematological malignancy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hospital in our regional network of 7 hospitals. METHODS: Consecutive hospitalised patients with haematological malignancy and SARS-CoV-2 infection were identified from 01/03/2020 to 06/05/2020. Outcomes were categorised as death, resolved or ongoing. The primary outcome was preliminary case fatality rate (pCFR), defined as the number of cases resulting in death as a proportion of all diagnosed cases. Analysis was primarily descriptive. RESULTS: 66 Patients were included, overall pCFR was 51.5%. Patients ≥ 70 years accounted for the majority of hospitalised cases (42, 63%) and fatalities (25, 74%). Mortality was similar between females (52%) and males (51%). Immunosuppressive or cytotoxic treatment within 3 months of the diagnosis of SARS-CoV-2 infection was associated with a significantly higher pCFR of 70%, compared with 28% in those not on active treatment (P = .0013, 2 proportions z test). CONCLUSIONS: Mortality rates in patients with haematological malignancy and SARS-CoV-2 infection in hospital are high supporting measures to minimise the risk of infection in this population.

The use of artificial neural network analysis can improve the risk-stratification of patients presenting with suspected deep vein thrombosis.

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.

Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination.

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.

Fractures are common within 18 months following first-line R-CHOP in older patients with diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) and osteoporotic fracture are both more common in older patients. Exposure to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) is likely to increase the risk of fracture, but evidence is lacking to define fracture incidence in this group. Data on consecutive patients with DLBCL aged ≥70 years treated with 1 to 8 cycles of full or attenuated R-CHOP were retrospectively collected across 10 UK centers (2009-2019). Patients were followed up from starting R-CHOP for a minimum of 6 months and censored at 18 months; at last follow-up if <18 months; or at progression or death. Of 877 patients identified, 148 were excluded: 121 had progression or died before 6 months; 23 had follow-up <6 months. Across 729 remaining patients, the median age was 77 years, and 68% had an Eastern Cooperative Oncology Group performance status of 0 to 1. Eighty-one fractures occurred within 18 months of follow-up; 42 were symptomatic, including 30 requiring hospital attendance or admission. The cumulative fracture incidence was 6.2% (95% confidence interval [CI], 4.7-8.2) at 6 months; 9.7% (95% CI, 7.8-12.1) at 12 months; and 11.4% (95% CI, 9.3-14.0) at 18 months. Multivariate analysis identified a predisposing history (osteoporosis, osteopenia, prior fracture, and rheumatoid arthritis [RhA]), DLBCL bone involvement at baseline, and receipt of prephase steroids as independent risk factors for fracture. There is a clinically relevant fracture risk and significant associated morbidity in older patients receiving R-CHOP. Careful attention to bone health is warranted in older patients receiving R-CHOP. Randomized studies are required to better define the most effective strategies to reduce fracture risk.

Multiple myeloma in the very elderly patient: challenges and solutions.

Diagnosis and management of myeloma in the very elderly patient is challenging. Treatment options have vastly improved for elderly myeloma patients but still require the clinician to personalize therapy. In this paper, we offer evidence-based, pragmatic advice on how to overcome six of the main challenges likely to arise: 1) diagnosis of myeloma in this age group, 2) assessment of the need for treatment, and the fitness for combination chemotherapy, 3) provision of the best quality of supportive care, 4) choice of combination chemotherapy in those fit enough for it, 5) treatment of relapsed myeloma, and 6) provision of end of life care. With an increased burden of comorbidities and a reduced resilience to treatment and its associated toxicities, the management of myeloma in this age group requires a different approach to that in younger patients to maximize both quality and length of life.