Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH

Plasma levels of natriuretic peptide type B and A in children with heart disease with different types of cardiac load or systolic dysfunction

Natriuretic peptide levels B (BNP) and A (ANP) have been described in children with different diagnose of congenital heart defects (CHD). However, the impact of the type of cardiac load per se on natriuretic peptide levels, irrespective of diagnosis, has not been reported. The aim of the present study was to evaluate the levels of BNP and ANP in children with congenital and acquired heart disease according to different types of cardiac load. Plasma BNP and ANP were analysed in 137 children with CHD/heart disease, median age 2.9 (0.3-16.7) years. Haemodynamic load was classified as: no overload, pressure overload, volume overload of right and/or left ventricle and systolic ventricular dysfunction. Twenty-three children without heart disease served as controls for the natriuretic peptide measurements. The highest BNP and ANP values were observed in the systolic dysfunction, 613 ng l(-1) (81.8-3910) and 431 (43.8-1990), and volume groups, 29.8 (5.5-352) and 93.0 (15.9-346), respectively, whereas the values in the pressure, 17.9 (0.7-315) and 51.9 (8.7-210), and no overload groups, 10.3 (0.2-28.1) and 28.6 (8.6-105), respectively, were only slightly higher than those in the controls 4.7 (0.0-17.7) and 32.9 (11.7-212.2), respectively. The highest BNP and ANP values were seen in children with systolic dysfunction, while volume overload in the absence of heart failure resulted in higher levels than pressure overload

Abstract PD4-08: Efficacy of compression therapy using surgical gloves for nanoparticle albumin-bound-paclitaxel-induced peripheral neuropathy: A phase II multicenter study by the Kamigata breast cancer study group

Abstract PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse effect of many commonly used chemotherapeutic agents, including taxanes. However, there is currently no established effective prophylactic management for CIPN. Thus, we investigated the efficacy of using surgical glove (SG) compression therapy to prevent nanoparticle albumin-bound-paclitaxel (nab-PTX)-induced peripheral neuropathy. PATIENTS AND METHODS: Patients with primary and recurrent breast cancer who received 260 mg/m2 of nab-PTX were eligible for this case-control study. The patients wore two SGs of the same size, that is, one size smaller than the size that fit, on their dominant hand for 90 minutes. They did not wear SGs on the non-dominant hand, which served as the control hand. Peripheral neuropathy was evaluated at each treatment cycle using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and the Patient Neurotoxicity Questionnaire (PNQ). The temperatures of each fingertip of the compression SG-protected and control hands were measured by using thermography. RESULTS: Between August 2013 and January 2016, 43 patients were enrolled, and 42 were evaluated. As shown in Table 1, the overall occurrence of ≥grade 2 sensory and motor peripheral neuropathy according to the CTCAE was significantly lower in the SG-protected hands than in the control hands (76.1% vs. 21.4% and 57.1% vs. 26.2%, respectively, p &amp;lt; 0.0001). The PNQ results showed that the incidence of ≥grade 4 neuropathy was significantly higher in the control hands than in the SG-protected hands in terms of both sensory and motor neurotoxicity (p &amp;lt; 0.0001, Table 2). As the treatment cycles of nab-PTX increased, the mean CTCAE and PNQ grades of the control hands gradually increased. However, the SG-protected hands maintained significantly lower mean grades than the control hands over time (p &amp;lt; 0.0001). No patients withdrew from this study because they could not tolerate the compression from the SGs. The mean temperature of each fingertip significantly decreased (1.42–2.60 °C) in the SG-protected hands compared to in the control hands. CONCLUSIONS: SG compression therapy appears effective for reducing nab-PTX-induced peripheral neuropathy. The nab-PTX exposure to the peripheral nerve may be decreased because the SG decreases microvascular flow to the fingertip. Table 1: Comparison of the overall occurrences of the different grades of peripheral neuropathy according to CTCAE version 4.0 between the compression surgical glove-protected hands and control handsCTCAE v.4.0SensoryMotorGradeSurgical GloveControlSurgical GloveControl012418712161311292411163080840000 Table 2: Changes in the overall occurrence of the Patient Neurotoxicity Questionnaire (PNQ) grade with surgical glove compression therapyPNQSensoryMotorGradeSurgical gloveControlSurgical gloveControl194209223512113717912431611050000 Citation Format: Tsuyuki S, Senda N, Kanng Y, Yamaguchi A, Yoshibayashi H, Kikawa Y, Katakami N, Kato H, Hashimoto T, Okuno T, Yamauchi A, Inamoto T. Efficacy of compression therapy using surgical gloves for nanoparticle albumin-bound-paclitaxel-induced peripheral neuropathy: A phase II multicenter study by the Kamigata breast cancer study group [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD4-08.</jats:p

Bosentan for the treatment of pulmonary arterial hypertension associated with congenital heart defects

Bosentan is an effective first-line therapy in New York Heart Association (NYHA) III patients with idiopathic pulmonary arterial hypertension (PAH). Pre-clinical data support the rationale for the potential benefit of bosentan in PAH associated with congenital heart disease (CHD)

Abstract P3-13-04: Skeletal related Events and Bone Metastasis Patients with Breast Cancer in Japan. A Retrospective Study

Abstract Objective: Since skeletal related events (SRE) worsen QOL, the information relating to the SRE is important in the patient's care. We have examined the incidences of bone metastasis (BM) and SRE in Japan and explored the prognostic factors which may affect the BM or SRE free period or survival. Patients and Methods: A retrospective, multicenter (21 institutes) study was performed. Patients with node positive or node negative with moderate to severe recurrence risk primary breast cancer were included. The primary endpoint was SRE-free period, and the secondary endpoints were BM-free period and the over-all survival period. By using a proportional hazard model (Cox regression), factors which affect these endpoints were examined in the population excluding stage IV patients. Results: 1,779 patients were registered and 1,708 patients' data were used for analysis. The median follow-up duration was 5.71 years. SRE occurred in 133 (68.9%) of 193 patients who developed BM. The median SRE-free period from the initial treatment was 1,006 days. The SRE-free rate and SRE-free survival rate at 5-years were 92.6% and 85.4%, respectively. The median period from the initial SRE to the second one was 112 days, and the second to the third one was 147 days. The median BM-free period was 767 days. The BM-free and BM-free survival rates at 5-years were 89.2% and 83.7%, respectively. The over-all survival rate at 5-years was 89.4%. The SRE-free period was significantly affected by the number of lymph node metastasis (LN mets) (Hazard Ratio; HR [95%CI]; 1.09 [1.042–1.143], p = 0.0002) and clinical stage (when stage I was assumed as reference, HR in stage II; 4.54 [1.296–15.933], stage III; 7.36 [1.171–31.539], p = 0.0262). SRE-free survival period was affected by the number of LN mets (HR; 1.10 [1.066–1.131], p &amp;lt; 0.0001), stage (stage I as reference, HR in stage II: 2.93 [1.349–6.349], and stage III: 4.28 [1.694–10.815], p = 0.008), and tumor phenotype (Luminal [L] A as reference, HR in LB; 1.89 [0.868–4.117], L-HER2: 2.81 [1.334–5.923], HER2: 2.68 [1.266–5.659], Triple negative (TN); 5.38 [3.031–9.537], p &amp;lt; 0.0001). The BM-free period was affected by the number of LN mets (HR; 1.09 [1.048–1.125], p &amp;lt; 0.0001), stage (stage I as reference, HR in stage II; 3.24 [1.219–8.619], stage III; 6.37 [2.080–19.485], p = 0.0045), and BMI (HR; 0.92 [0.854–0.987], p = 0.0213). BM free-survival period was affected by the number of LN mets (HR;1.10 [1.067–1.129], p &amp;lt; 0.0001), stage (stage I as reference, HR in stage II; 2.80 [1.344–5.825], stage III; 4.43 [1.853–10.609], p = 0.0037), phenotype (LA as reference, HR in LB; 2.23 [1.097–4.534], L-HER2; 3.10 [1.557–6.191], HER2; 2.57 [1.344–5.324], TN; 5.02 [2.887–8.738], p &amp;lt; 0.0001), and BMI (HR; 0.92 [0.872–0.981], p = 0.0090). Over-all survival period was affected by the number of LN mets (HR; 1.11 [1.075–1.147], p &amp;lt; 0.0001), stage (stage I as reference, HR in stage II; 2.32 [1.000–5.381], stage III; 4.24 [1.551–11.573], p = 0.01777), and phenotype (LA as reference, HR in LB; 2.26 [0.850–6.013], L-HER2; 3.58 [1.393–9.184], HER2; 4.22 [1.719–10.347], TN; 10.05 [4.810–21.004], p &amp;lt; 0.0001). Conclusion: Tumor phenotype appears to have an impact on SRE-free, BM-free and overall survival period, but not on SRE-free and BM-free period. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-13-04.</jats:p