HTLV-1-related adult T-cell leukemia/lymphoma: insights in early detection and management.

PURPOSE OF REVIEW: Adult T-cell leukemia-lymphoma (ATL) is an aggressive mature T-cell malignancy that arises in approximately 5% of carriers of human T-lymphotropic virus type 1 (HTLV-1), but this risk is not random among carriers. We describe recent advance in pathogenesis, risk factors and for early detection of ATL. RECENT FINDINGS: Unraveling ATL molecular genetics has shed light on pathogenesis and provides insights into novel therapeutic targets. Moreover, an important step in improving outcomes is identifying asymptomatic carriers who are at high risk of progression to ATL, which has traditionally relied on quantifying the proviral load (PVL). This can be done by quantifying oligoclonality- and in particular the expanded clone- with molecular and flow cytometric techniques, that can be applied to a clinical setting. Studies using these methods have shown that carriers with oligoclonal populations are at an increased risk of transformation, beyond that that predicted by PVL alone. SUMMARY: There is an urgent unmet need for developing novel therapies in ATL in order to improve survival. Recent advances in the molecular and epigenetic landscape of ATL, and the early detection of disease offer the potential to intervene early, before disease becomes aggressive, and to offer tailored therapeutic strategies.

Quantification of T cell clonality in human T cell leukaemia virus type-1 carriers can detect the development of adult T cell leukaemia early.

Adult T cell leukaemia/lymphoma (ATL) arises from clonally expanded T cells that are infected with human T cell leukaemia virus type-1 (HTLV-1). Here, we show that ATL can be detected early in HTLV-1-carriers through quantification of T-cell receptor (TCR)Vß subunit diversity on T-cells infected with HTLV-1 (CD3+ CCR4+ CD26- T-cells) using an 'oligoclonality index' (OCI-flow). We established a reference range for OCI-flow by analysing peripheral blood mononuclear cells (PBMCs) from HTLV-1-carriers who had not developed ATL in a median of 10.5 years follow up (n = 38) and patients with ATL (n = 30). In the third cohort of HTLV-1-carriers with no history or clinical evidence of ATL (n = 106), 19% of high proviral load (PVL, ≥4 copies of HTLV-1/100 PBMCs) carriers had an OCI-flow in the ATL range, >0.770. Carriers with an OCI-flow >0.770 (n = 14) had higher lymphocyte counts and PVLs and were more likely to have a family history of ATL than carriers with OCI-flow ≤0.770. ATL subsequently developed in two of these 14 carriers but no carriers with OCI-flow ≤0.770 (p = 0.03, cumulative follow-up 129 person-years). This method can be used to identify a subset of high-PVL HTLV-1-carriers at increased risk of developing ATL who may benefit from intervention therapy, prior to the detection of disease.

Postpartum bleeding in women with inherited bleeding disorders: a matched cohort study.

: Women with inherited bleeding disorders (IBDs) are reported to have higher rates of primary and secondary postpartum haemorrhage (PPH), even with optimal haemostatic management. We evaluated whether women with IBD have higher odds of PPH compared with those without, when controlled for mode of delivery with a control group of women without IBDs. The obstetric experiences and outcomes of all women with IBD delivering at a tertiary centre between 2008 and 2017, were compared with matched controls (1 : 1). Obstetric care was provided according to national guidelines to both women with IBD and controls. Primary PPH was defined as estimated blood loss at least 500 ml. There were 46 completed pregnancies in women with IBD: 16 haemophilia A carriers, eight haemophilia B carriers, eight factor XI deficiency patients and 14 von Willebrand disease patients (type 1 = 6; type 2 = 8). No peripartum haemostatic treatment was received by carriers of haemophilia A or B. There were 74 control pregnancies. Women with IBD had higher odds of primary PPH, in a model controlling for mode of anaesthesia (adjusted odds ratio 5.30, 95% confidence interval 1.02-27.59, P = 0.048). Carriers of haemophilia A had a higher, statistically nonsignificant, odds for primary PPH than controls (adjusted odds ratio 6.85, confidence interval 0.77-60.73, P = 0.084). An increase in primary PPH was observed in women with IBD, particularly in haemophilia A, despite management according to guidelines. These results warrant further investigation and consideration should be given as to which factor levels to target.

O significado psicológico da perda dos dentes em sujeitos adultos / The psychological meaning of losing one's teeth in adult subjects

Os instrumentos da pesquisa foram aplicados a sujeitos portadores de prótese ou de implante dentário, objetivando compreender os aspectos psicológicos envolvidos na perda dos dentes. A análise do material obtido mostrou a importância dos dentes para a identidade e para a integridade egóica das pessoas e revelou que o paciente, quando busca recursos odontológicos para substituiçäo dos dentes perdidos, está também demandando a reconstituiçäo de sua imagem pessoal e social

As idades do homem: crise e transformacoes

Este e um trabalho de reflexao sobre as crises que acompanham o processo de desenvolvimento humano. Foram enfatizadas as etapas: adolescencia e meia idade, por se constituirem pontos de passagem. Procura-se ressaltar a influencia dos aspectos socio-economicos na organizacao do comportamento.

As psicoterapias e suas praticas contemporâneas / Psychotherapies and contemporary practices

A autora propöe-se a analisar as condiçöes para realizaçäo de psicoterapias em instituiçöes públicas de saúde. Para tanto, reflete sobre a construçäo da subjetividade do cliente e sobre as relaçöes que se estabelecem entre os programas de saúde mental, os psicoterapeutas e os pacientes da instituiçäo. Ao final, sugere estudos e pesquisas que atendam à necessidade de renovaçäo da pr tica terapêutica frente a estes sujeitos

As psicoterapias e suas praticas contemporaneas

A autora propoe-se a analisar as condicoes para realizacao de psicoterapias em instituicoes publicas de saude. Para tanto, reflete sobre a construcao da subjetividade do cliente e sobre as relacoes que se estabelecem entre os programas de saude mental, os psicoterapeutas e os pacientes da instituicao. Ao final, sugere estudos e pesquisas que atendam a necessidade de renovacao da pratica terapeutica frente a estes sujeitos.