Medical abortion in the first trimester: the use of serum hCG and endometrial thickness as markers of completeness.

OBJECTIVE: The combination of mifepristone and misoprostol is an established method for induction of early first trimester abortion, but there is no consensus about the best evaluation of treatment outcome. We assessed endometrial thickness, determined by ultrasound and serum-human chorionic gonadotropin (s-hCG) as markers of successful management. METHODS: Prospective trial involving 255 women, with a gestation of 62 days or less, who were to undergo medical abortion. In addition to our established routines of performing clinical and ultrasound examinations, we also determined the s-hCG level prior to treatment and at follow-up. RESULTS: Of the 255 subjects treated during the study, 20 (7.8%) were lost to follow-up. The overall complete abortion rate was 94.0%. Fourteen subjects required vacuum aspiration, nine of them prior to the scheduled follow-up and five thereafter. None of the pregnancies were ongoing. A decrease of 99% in s-hCG levels was noted in 99% of the women, when levels determined prior to mifepristone intake and those measured 15-71 days post-abortion were compared. CONCLUSION: This study confirms that s-hCG levels drop sharply after medical abortion. To assess the completeness of medical abortion, we recommend that clinical examination to be combined with determination of s-hCG. Ultrasonography should be carried out only when indicated.     

Loss of fibroblast Thy-1 expression correlates with lung fibrogenesis

Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-beta in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1-/- C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-beta activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-beta activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-alpha induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis.     

Longer duration of homelessness is associated with a lower likelihood of non-detectable plasma HIV-1 RNA viral load among people who use illicit drugs in a Canadian setting

Homelessness is common among people who use drugs (PWUD) and, for those living with HIV/AIDS, an important contributor to sub-optimal HIV treatment outcomes. This study aims to investigate the relationship between the duration of homelessness and the likelihood of plasma HIV-1 RNA viral load (VL) non-detectability among a cohort of HIV-positive PWUD. We used data from the ACCESS study, a long-running prospective cohort study of HIV-positive PWUD linked to comprehensive HIV clinical records including systematic plasma HIV-1 RNA VL monitoring. We estimated the longitudinal relationship between the duration of homelessness and the likelihood of exhibiting a non-detectable VL (i.e., <500?copies/mL plasma) using generalized linear mixed-effects modelling. Between May 1996 and June 2014, 922 highly active antiretroviral therapy-exposed participants were recruited and contributed 8188 observations. Of these, 4800 (59%) were characterized by non-detectable VL. Participants reported they were homeless in 910 (11%) interviews (median: six months, interquartile range: 6–12 months). A longer duration of homelessness was associated with lower odds of VL non-detectability (adjusted odds ratio?=?0.71 per six-month period of homelessness, 95% confidence interval: 0.60–0.83) after adjustment for age, ancestry, drug use patterns, engagement in addiction treatment, and other potential confounders. Longer durations of episodes of homelessness in this cohort of HIV-positive illicit drug users were associated with a lower likelihood of plasma VL non-detectability. Our findings suggest that interventions that seek to promptly house homeless individuals, such as Housing First approaches, might assist in maximizing the clinical and public health benefits of antiretroviral therapy among people living with HIV/AIDS.     

Heart failure education in the emergency department markedly reduces readmissions in un- and under-insured patients

Background

Heart failure (HF) readmissions are a longstanding national healthcare issue for both hospitals and patients. Our purpose was to evaluate the efficacy of a structured, educational intervention targeted towards un- and under-insured emergency department (ED) HF patients.

Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals

Aspirin (ASA) is unique among current therapies because it acetylates cyclooxygenase (COX)-2 enabling the biosynthesis of R-containing precursors of endogenous antiinflammatory mediators. Here, we report that lipidomic analysis of exudates obtained in the resolution phase from mice treated with ASA and docosahexaenoic acid (DHA) (C22:6) produce a novel family of bioactive 17R-hydroxy-containing di- and tri-hydroxy-docosanoids termed resolvins. Murine brain treated with aspirin produced endogenous 17R-hydroxydocosahexaenoic acid as did human microglial cells. Human COX-2 converted DHA to 13-hydroxy-DHA that switched with ASA to 17R-HDHA that also proved a major route in hypoxic endothelial cells. Human neutrophils transformed COX-2-ASA-derived 17R-hydroxy-DHA into two sets of novel di- and trihydroxy products; one initiated via oxygenation at carbon 7 and the other at carbon 4. These compounds inhibited (IC(50) approximately 50 pM) microglial cell cytokine expression and in vivo dermal inflammation and peritonitis at ng doses, reducing 40-80% leukocytic exudates. These results indicate that exudates, vascular, leukocytes and neural cells treated with aspirin convert DHA to novel 17R-hydroxy series of docosanoids that are potent regulators. These biosynthetic pathways utilize omega-3 DHA and EPA during multicellular events in resolution to produce a family of protective compounds, i.e., resolvins, that enhance proresolution status.     

Retrospective Study of Carfilzomib-Pomalidomide-Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients in a Tertiary Care Hospital in India

Carfilzomib is a second-in class Proteosome Inhibitor and has been approved for Relapsed/Refractory Multiple Myeloma (RRMM). We retrospectively retrieved and analyzed data of KPd combination both biweekly and weekly regimens at our centre from 1 st August 2017 and 31 st May 2020. Sixty-nine patients were treated with KPd with median age of 58 years. Median prior lines of chemotherapy were 2(1-15). Twenty-eight (40.5%) patients underwent autoSCT. Median no. of cycles was 4(1-12) and 3(1-13) with median time to response of 4(2-12) and 2(2-6) months in biweekly and once weekly regimen cohorts respectively. At last follow-up, overall response rate (ORR) was 65.2%{CR-n = 10 (14.5%), VGPR-n = 19 (27.5%), PR-n = 16 (23.2%)} with n = 13(18.8%) patients had PD and relapse was observed in n = 24(34.8%). Thirty (43.4%) patients received maintenance therapy {n = 21(70%)} or autoSCT {n = 9(30%)}. Common toxicities were anemia {n = 11(15.9 %)}, thrombocytopenia (n = 15(21.7%) and neutropenia (n = 16 (23.2%)}, hypertension {n = 28(40.5%)}, peripheral neuropathy (grade1/2) {n = 15(21.7%)}, infections [n = 18(26%) {bacterial [n = 9(13%),viral n = 7(10.1%), fungal n = 8(11.6%)}]. At a median follow-up of 18 months, the estimated median PFS was 11.3 months (95%C.I. 8.3– 14.2) whereas the estimated median OS was 28 months (95%C.I. 20.4-35.5) for the entire cohort. Mortality rate of 2.5% and 10% in two cohorts respectively. Commonest cause of death was PD and sepsis. KPD is a well-tolerated regimen for RRMM, which can be a bridge to ASCT, however with significant side effects.