In vitro and in vivo effects of JAK2 inhibition in chronic myelomonocytic leukemia

In chronic myelomonocytic leukemia (CMML), colony‐forming units granulocyte/macrophage (CFU‐GM), which grow in vitro in the absence of exogenous growth factors, arise from the abnormal clone that is responsible for the overproduction of granulomonocytic cells. Previous in vitro findings including ours suggest that divergent molecular aberrations in CMML seem to converge within the GM‐CSF signaling pathway. As JAK2 is a sentinel kinase in this pathway, JAK2 inhibition may be an attractive treatment approach in CMML. We investigated the in vitro effects of the specific JAK2 inhibitor TG101209 on the autonomous CFU‐GM formation from peripheral blood mononuclear cells of patients with CMML. TG101209 was found to either block or strongly inhibit spontaneous CFU‐GM growth in all 10 patients tested. This inhibitory effect was dose dependent and significantly more pronounced as compared to the inhibitory effect on stimulated CFU‐GM growth from normal individuals. In a CMML patient with splenomegaly, who was treated with the JAK1/2 inhibitor ruxolitinib off label, we can demonstrate a spleen response and the disappearance of constitutional symptoms which was associated with a decrease in autonomous CFU‐GM formation ex vivo. Pharmacological JAK2 inhibition may be an interesting approach to be systematically studied in patients with CMML.     

Prediction of intimate partner violence by type of substance use disorder

The present study investigated whether (combinations of) specific substance use disorders predicted any and severe perpetration and victimization in males and females entering substance abuse treatment. All patients (N = 1799) were screened for IPV perpetration and victimization; almost one third of the sample committed or experienced any IPV in the past year. For males, an alcohol use disorder in combination with a cannabis and/or cocaine use disorder significantly predicted any IPV (perpetration and/or victimization) as well as severe IPV perpetration. For females, alcohol and cocaine abuse/dependence predicted both any IPV (perpetration and/or victimization) and severe IPV perpetration. Results from the present study emphasize the importance of routinely assessing IPV in patients in substance abuse treatment and demonstrate that clinicians should be particularly alert for IPV in patients with specific substance use disorder combinations.     

Community-Based Accompaniment and Psychosocial Health Outcomes in HIV-Infected Adults in Rwanda: A Prospective Study

We examined whether the addition of community-based accompaniment to Rwanda’s national model for antiretroviral treatment (ART) was associated with greater improvements in patients’ psychosocial health outcomes during the first year of therapy. We enrolled 610 HIV-infected adults with CD4 cell counts under 350 cells/μL initiating ART in one of two programs. Both programs provided ART and required patients to identify a treatment buddy per national protocols. Patients in one program additionally received nutritional and socioeconomic supplements, and daily home-visits by a community health worker (“accompagnateur”) who provided social support and directly-observed ingestion of medication. The addition of community-based accompaniment was associated with an additional 44.3 % reduction in prevalence of depression, more than twice the gains in perceived physical and mental health quality of life, and increased perceived social support in the first year of treatment. Community-based accompaniment may represent an important intervention in HIV-infected populations with prevalent mental health morbidity.     

Novel Real-Time PCR Assays Using TaqMan Minor Groove Binder Probes for Identification of Fecal Carriage of Streptococcus bovis/Streptococcus equinus Complex from Rectal Swab Specimens

Real-time PCR based on the recN and gyrB genes was developed to detect four Streptococcus bovis/Streptococcus equinus complex (SBEC) subspecies from rectal swab specimens. The overall prevalence was 35.2%: Streptococcus gallolyticus subsp. gallolyticus (11.1%), S. gallolyticus subsp. pasteurianus (13%), Streptococcus infantarius subsp. coli (20.4%), and S. infantarius subsp. infantarius (11.1%). To conclude, these real-time PCR assays provide a reliable molecular method to detect SBEC pathogenic subspecies from rectal swab specimens.