Bassekidd5466

OBJECTIVE Standard treatment in locally-advanced cervical cancer is external beam radiotherapy concomitant with platinum-based chemotherapy, followed by brachytherapy. The goal of our study was to determine whether an intensity modulated radiation therapy (IMRT) boost is feasible in patients unfit for brachytherapy. METHODS We retrospectively analyzed data of 25 patients unfit for brachytherapy with median age 55 years (range, 30-82) with locally-advanced/metastatic cervical cancer who underwent external beam radiotherapy to pelvis ±para-aortic lymph nodes and sequential IMRT boost between July 2014 and December 2017. Total dose of 45-50.4 Gy in 25-28 fractions (1.8 Gy/fraction) was administered to the cervix, uterus, parametria, ovaries, vaginal tissues (based on vaginal extension), involved lymph nodes, or relevant draining lymph-nodal groups. Para-aortic nodes were included if involved at radiological staging or if common iliac nodes were positive. The IMRT boost included all residual tumor after external , 10 patients experienced gastrointestinal and/or genitourinary grade G1-2 acute toxicity. G2 rectal late toxicity requiring laser-coagulation was registered in two patients, there were no gastrointestinal and/or genitourinary acute or late toxicities≥G3. CONCLUSION The combination of external beam radiotherapy and brachytherapy remains the standard of care, however our preliminary data show the feasibility of IMRT boost in terms of toxicity with promising results in terms of local control and overall survival. © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES von Willebrand factor (vWF) has prognostic value in patients with heart failure (HF) and in those with liver disease. Liver congestion, due to right-sided HF (RHF), is one of the major clinical pathophysiologic manifestations in adults with congenital heart disease (ACHD). The present study's purpose was to clarify the prognostic value of plasma levels of vWF antigen (vWFAg) in ACHD. METHODS We measured vWFAg (%) in 382 consecutive patients (20 unrepaired cyanotic ACHD, 172 Fontan patients and 190 ACHD after biventricular repair) and compared the results with the clinical profiles and prognosis. RESULTS The plasma vWFAg level was 130±53 (normal range 55%-190%), and 48 patients (13%) showed high levels of vWFAg (≥190%). Older age, Fontan circulation, higher central venous pressure, lower arterial oxygen saturation and lower plasma levels of albumin were independently associated with high log (vWFAg) (p less then 0.05-0.0001). During the follow-up of 2.4±1.4 years, 15 patients died. High log (vWFAg) predicted the all-cause mortality (HR 1.63 per 0.1, 95% CI 1.40 to 1.96, p less then 0.0001). Specifically, patients with high vWFAg (≥165%) had a substantially higher risk of all-cause mortality (HR 56.4, 95% CI 11.4 to 1020, p less then 0.0001), and this prognostic value was independent of plasma levels of brain-type natriuretic peptide. CONCLUSIONS High vWFAg may reflect RHF severity and related liver dysfunction with a strong prognostic value of all-cause mortality in ACHD. Thus, vWFAg might be an excellent biomarker for monitoring ACHD with RHF. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Metastatic cancer involving spread to the peritoneal cavity is referred to as peritoneal carcinomatosis and has a very poor prognosis. Our previous study demonstrated a toll-like receptor (TLR) and C-type lectin receptor (CLR) agonist pairing of monophosphoryl lipid A (MPL) and trehalose-6,6'-dicorynomycolate (TDCM) effectively inhibits tumor growth and ascites development following TA3-Ha and EL4 challenge through a mechanism dependent upon B-1a cell-produced natural IgM and complement. In the current study, we investigated additional players in the MPL/TDCM-elicited response. MPL/TDCM treatment rapidly increased type I IFN levels in the peritoneal cavity along with myeloid cell numbers, including macrophages and Ly6Chi monocytes. Type I IFN receptor (IFNAR1-/-) mice produced tumor-reactive IgM following MPL/TDCM treatment, but failed to recruit Ly6C+ monocytes and were not afforded protection during tumor challenges. Clodronate liposome depletion of phagocytic cells, as well as targeted depletion of Ly6C+ cells, also ablated MPL/TDCM-induced protection. Cytotoxic mediators known to be produced by these cells were required for effects. TNFa was required for effective TA3-Ha killing and nitric oxide was required for EL4 killing. Collectively, these data reveal a model whereby MPL/TDCM-elicited anti-tumor effects strongly depend on innate cell responses, with B-1a cell-produced tumor-reactive IgM and complement pairing with myeloid cell-produced cytotoxic mediators to effectively eradicate tumors in the peritoneal cavity. Copyright ©2020, American Association for Cancer Research.The mechanisms responsible for persistent and lethal coronary spasm remain incompletely understood. Our group treated a patient with non-ST-elevation myocardial infarction (MI) caused by a spontaneously persistent spasm associated with high-grade macrophage accumulation. A 48-year-old man was transferred to an emergency room because of persisted chest tightness. Selleckchem TR-107 The patient's chest pain subsided without ST elevation when he arrived at the hospital, but he tested positive for fatty acid-binding protein. Emergent coronary angiography revealed a subtotal occlusion in the middle of the right coronary artery. The occluded lesion was released immediately after an injection of isosorbide dinitrate. No disruption, ulceration or erosion was observed at the culprit lesion segment on optical coherence tomography. The only finding was high-grade macrophage accumulation in the segment of the persistent focal coronary spasm. The present case suggests that the early stage of atherosclerosis with high-grade macrophage accumulation was associated with persistent coronary spasm resulting in acute MI. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.