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Purpose: To assess the technical and clinical success rates of superior rectal artery embolization in the treatment of symptomatic Grades 2 and 3 hemorrhoidal disease., Materials and Methods: Since March 2019, 43 patients (24 men and 19 women; mean age, 52 years [18-77 years]) with symptomatic hemorrhoidal disease have been treated and completed the 6-month follow-up with anamnestic questionnaire and disease scores, including French bleeding, Goligher prolapse, visual analog scale for pain, and quality of life. Clinical success was assessed at 7 days, 1 month, and 6 months of follow-up by updating the clinical scores. Statistical analysis was performed using SPSS 25.0., Results: In all, 25 patients had Grade 2 prolapse and 18 patients had Grade 3 prolapse, with 96% and 77%, respectively, having bleeding as a symptom. All patients were discharged within 24 hours. The reduction in the French bleeding score (global and single entity) in Grade 3 prolapse was statistically significant (P = .001). Improvement in the quality of life was significant in both groups (P < .05). No serious complications were registered., Conclusions: Hemorrhoidal embolization was a safe and effective technique in the treatment of symptomatic hemorrhoidal disease with minimal hospitalization, pain, and disruption of daily activities. It can be offered to patients unwilling to undergo a surgical procedure but can also be indicated in the emergency setting for patients on anticoagulant therapy or those unfit for surgery., (Copyright © 2021 SIR. Published by Elsevier Inc. All rights reserved.)

Acromegaly, when left untreated, is associated with premature mortality which is chiefly related to cardiovascular complications. We report on a 50-year-old acromegalic woman, resistant to therapy, who died suddenly because of thoracic aortic rupture and massive bleeding into the left pleural space. The postmortem examination disclosed, nearby the point of rupture, a pulmonary abscess as well as extensive intrinsic alteration of arteries originating from the aortic arch and aorta itself, which featured microscopic cystic medial necrosis. We discussed how these aspects could be related to long-term exposition to growth hormone excess. In particular, this case gives further evidence of vascular system frailty in acromegaly.

Objective: To investigate pharmacokinetic and pharmacodynamic factors associated with population differences in warfarin doses needed to achieve anticoagulation, in particular the possible involvement of genetic variability in vitamin K epoxide reductase (VKOR) and CYP2C9., Methods: Warfarin maintenance dose, unbound plasma S-warfarin concentration [Cu(S)] and INR were determined in 157 Caucasians, 172 Japanese, and 36 African-Americans stably anticoagulated patients. In a subset (n = 166), fully carboxylated plasma normal prothrombin levels (NPT) were also measured. Genotyping for seven CYP2C9 (CYP2C9*1 through 6 and *11) and seven VKORC1 variants were performed in 115 Caucasians and 64 Japanese patients and 66 healthy African-Americans. Multivariate analysis was performed to identify covariates associated with warfarin requirement., Results: The relationship between NPT and Cu(S) indicated Japanese are more susceptible to inhibition of NPT production by S-warfarin than the other two populations. VKORC1 1173 C > T had a greater frequency in Japanese (89.1%) than Caucasians (42.2%) and African-Americans (8.6%). CYP2C9 variants with reduced metabolizing ability were less frequent in Japanese compared to the other two populations. The median warfarin dose was significantly higher in Caucasians than Japanese patients (5.5 versus 3.5 mg/day), however, when matched for CYP2C9*1 homozygosity, no difference in dose was observed between VKORC1 genotype-matched groups. Furthermore, VKORC1 1173C > T and CYP2C9 (*2/*3/*11) genotypes, age and weight were identified as independent covariates contributing to interpatient variability in warfarin dosage., Conclusions: Both VKORC1 and CYP2C9 polymorphisms contribute to inter-population difference in warfarin doses among the three populations, but their contribution to intra-population variability may differ within each population.

Autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) at Thr286 generates Ca2+-independent activity. As an initial step toward understanding CaMKII inactivation, protein phosphatase classes (PP1, PP2A, PP2B, or PP2C) responsible for dephosphorylation of Thr286 in rat forebrain subcellular fractions were identified using phosphatase inhibitors/activators, by fractionation using ion exchange chromatography and by immunoblotting. PP2A-like enzymes account for >70% of activity toward exogenous soluble Thr286-autophosphorylated CaMKII in crude cytosol, membrane, and cytoskeletal extracts; PP1 and PP2C account for the remaining activity. CaMKII is present in particulate fractions, specifically associated with postsynaptic densities (PSDs); each protein phosphatase is also present in isolated PSDs, but only PP1 is enriched during PSD isolation. When isolated PSDs dephosphorylated exogenous soluble Thr286-autophosphorylated CaMKII, PP2A again made the major contribution. However, CaMKII endogenous to PSDs (32P autophosphorylated in the presence of Ca2+/calmodulin) was predominantly dephosphorylated by PP1. In addition, dephosphorylation of soluble and PSD-associated CaMKII in whole forebrain extracts was catalyzed predominantly by PP2A and PP1, respectively. Thus, soluble and PSD-associated forms of CaMKII appear to be dephosphorylated by distinct enzymes, suggesting that Ca2+-independent activity of CaMKII is differentially regulated by protein phosphatases in distinct subcellular compartments.