Communication with Families in the Last Days of a Patient’s Life and Optimal Delivery of a Death Pronouncement

Communicating with family members is critically important when a severely ill patient is experiencing their last few days of life. However, healthcare professionals (HCPs) have limited opportunities to learn effective and respectful ways to perform this communication. In recent decades, significant effort has been put forth to identify the phenomena that indicate the last hours and days of life and the optimal methods to deliver a death pronouncement, which will potentially help HCPs communicate compassionately with family members throughout the dying process. In this chapter, we will review the literature regarding the phenomena that indicate the last hours and days of life and the death pronouncement. Furthermore, we will discuss clinical implications derived from those articles and future research perspectives

Adenocarcinoma in bladder diverticulum, metastatic from gastric cancer

BACKGROUND: Metastasis to the urinary bladder from gastric cancer is rare. Metastasis to a diverticulum of the bladder from gastric cancer is extremely rare. We report a case of isolated bladder metastasis from gastric cancer and invasion localized to the muscularis propria of the primary site (stomach). CASE PRESENTATION: A 90-year-old female presented with nausea and vomiting that was diagnosed as gastric cancer, the patient also had intermittent hematuria. Pelvic computed tomography identified an abnormally thickened area in the bladder wall that was diagnosed as a diverticulum of the bladder. A biopsy of the bladder wall revealed well differentiated tubular adenocarcinoma metastatic from gastric carcinoma. CONCLUSION: Almost all cases of bladder metastasis from gastric cancer had peritoneal dissemination. This particular presentation of bladder metastasis from gastric cancer, to the best of our knowledge, has not been previously reported

Amyloid Beta Annular Protofibrils in Cell Processes and Synapses Accumulate with Aging and Alzheimer-Associated Genetic Modification

Amyloid β (Aβ) annular protofibrils (APFs) have been described where the structure is related to that of β barrel pore-forming bacterial toxins and exhibits cellular toxicity. To investigate the relationship of Aβ APFs to disease and their ultrastructural localization in brain tissue, we conducted a pre-embedding immunoelectron microscopic study using anti-annular protofibril antiserum. We examined brain tissues of young- and old-aged amyloid precursor protein transgenic mice (APP23), neprilysin knockout APP23 mice, and nontransgenic littermates. αAPF-immunoreactions tended to be found (1) on plasma membranes and vesicles inside of cell processes, but not on amyloid fibrils, (2) with higher density due to aging, APP transgene, and neprilysin deficiency, and (3) with higher positive rate at synaptic compartments in aged APP23, especially in neprilysin knockout APP23 mice. These findings imply that APFs are distinct from amyloid fibrils, interact with biological membranes, and might be related to synaptic dysfunction in Alzheimer model mouse brains

Effects of Statin versus the Combination of Ezetimibe plus Statin on Serum Lipid Absorption Markers in Patients with Acute Coronary Syndrome

Background. The use of statins is essential for aggressive lipid-lowering treatment in acute coronary syndrome (ACS) patients with dyslipidemia. Recently, elevation of sitosterol, a lipid absorption marker, was reported to be associated with premature atherosclerosis. The purpose of the present study was to examine the impact of ezetimibe, a selective intestinal cholesterol transporter inhibitor, in ACS patients. Methods. A total of 197 ACS patients were randomized to pitavastatin + ezetimibe (n=100) or pitavastatin (n=97). Low-density lipoprotein cholesterol (LDL-C) and sitosterol levels were evaluated on admission and after 12 weeks. Results. After 12 weeks, the pitavastatin + ezetimibe group showed a significantly greater decrease of sitosterol (baseline versus after 12 weeks; 2.9 ± 2.5 versus 1.7 ± 1.0 ng/mL, P<0.001) than the pitavastatin group (2.7 ± 1.5 versus 3.0 ± 1.4 ng/mL). The baseline sitosterol level was significantly higher in patients with achieved LDL-C levels ≥ 70 mg/dL than in patients with levels < 70 mg/dL (3.2 ± 2.5 versus 2.4 ± 1.3 ng/mL, P=0.006). Conclusions. Ezetimibe plus statin therapy in ACS patients with dyslipidemia decreased LDL-C and sitosterol levels more than statin therapy solo. Sitosterol Elevation was a predictor of poor response to aggressive lipid-lowering treatment in ACS patients

キュウセイキ ノウコウソク ニ タイシ t‐PA リョウホウ ガ ムコウ デ アッタ ショウレイ ニ タイスル ケイドウミャクテキ ケッセン ハサイ キュウイン ジュツ ノ ユウヨウセイ

Endovascular thrombectomy have emerged as crucial treatment options for patients with acute ischemic stroke who are ineligible for intravenous tissue plasminogen activator（tPA）or in whom such therapy has failed. We assessed the efficacy of mechanical thrombectomy for acute ischemic stroke patients who failed intravenous tPA. Five of６patients achieved recanalization by means of endovascular technique and showed favorable outcome. Endovascular thrombectomy after intravenous tPA can be safe and effective for the ischemic stroke with major artery occlusion

Long-term prognosis of diabetic patients with acute myocardial infarction in the era of acute revascularization

Abstract Background The long-term prognosis of diabetic patients with acute myocardial infarction (AMI) treated by acute revascularization is uncertain, and the optimal pharmacotherapy for such cases has not been fully evaluated. Methods To elucidate the long-term prognosis and prognostic factors in diabetic patients with AMI, a prospective, cohort study involving 3021 consecutive AMI patients was conducted. All patients discharged alive from hospital were followed to monitor their prognosis every year. The primary endpoint of the study was all-cause mortality, and the secondary endpoint was the occurrence of major cardiovascular events. To elucidate the effect of various factors on the long-term prognosis of AMI patients with diabetes, the patients were divided into two groups matched by propensity scores and analyzed retrospectively. Results Diabetes was diagnosed in 1102 patients (36.5%). During the index hospitalization, coronary angioplasty and coronary thrombolysis were performed in 58.1% and 16.3% of patients, respectively. In-hospital mortality of diabetic patients with AMI was comparable to that of non-diabetic AMI patients (9.2% and 9.3%, respectively). In total, 2736 patients (90.6%) were discharged alive and followed for a median of 4.2 years (follow-up rate, 96.0%). The long-term survival rate was worse in the diabetic group than in the non-diabetic group, but not significantly different (hazard ratio, 1.20 [0.97-1.49], p = 0.09). On the other hand, AMI patients with diabetes showed a significantly higher incidence of cardiovascular events than the non-diabetic group (1.40 [1.20-1.64], p Conclusions Although diabetic patients with AMI have more frequent adverse events than non-diabetic patients with AMI, the present results suggest that acute revascularization and standard therapy with aspirin and RAS inhibitors may improve their prognosis.</p

MEDICAL TREATMENT OF UNRUPTURED CEREBRAL ANEURYSMS

Background: Currently there are no pharmacological therapies for patients with unruptured cerebral aneurysms. Elsewhere we showed that the mineralocorticoid receptor antagonist eplerenone prevented the formation of cerebral aneurysms in our ovariectomized hypertensive aneurysm rat model. The current pilot study evaluated whether it can be used to prevent the growth and rupture of cerebral aneurysms in hypertensive patients. Methods: Between August 2011 and May 2014, we enrolled 82 patients with 90 aneurysms in an open-label uncontrolled clinical trial. All provided prior informed consent for inclusion in this study, and all were treated with eplerenone (25-100 mg/d). The primary end points of our study were the rupture and enlargement of the cerebral aneurysms. Results: Of the 82 patients, 80 (88 unruptured aneurysms) were followed for a mean of 21.3 months (153.4 aneurysm-years); 12 patients (15.0%) permanently discontinued taking the drug. One month after the start of eplerenone administration and throughout the follow-up period, eplerenone kept the blood pressure within the normal range. Most notably, no aneurysms smaller than 9 mm ruptured or enlarged. However, of 2 large thrombosed aneurysms, 1 enlarged and the other ruptured. The overall annual rupture rate was .65%; it was 13.16% for aneurysms larger than 10 mm; the overall annual rate for reaching the primary end points was 1.30%. Conclusion: Our observations suggest that eplerenone may help to prevent the growth and rupture of unruptured cerebral aneurysms smaller than 9 mm. To assess its potential long-term clinical benefits, large clinical trials are needed

An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer\u27s disease

The β-site amyloid precursor protein cleaving enzyme-1 (BACE1), an essential protease for the generation of amyloid-β (Aβ) peptide, is a major drug target for Alzheimer\u27s disease (AD). However, there is a concern that inhibiting BACE1 could also affect several physiological functions. Here, we show that BACE1 is modified with bisecting N-acetylglucosamine (GlcNAc), a sugar modification highly expressed in brain, and demonstrate that AD patients have higher levels of bisecting GlcNAc on BACE1. Analysis of knockout mice lacking the biosynthetic enzyme for bisecting GlcNAc, GnT-III (Mgat3), revealed that cleavage of Aβ-precursor protein (APP) by BACE1 is reduced in these mice, resulting in a decrease in Aβ plaques and improved cognitive function. The lack of this modification directs BACE1 to late endosomes/lysosomes where it is less colocalized with APP, leading to accelerated lysosomal degradation. Notably, other BACE1 substrates, CHL1 and contactin-2, are normally cleaved in GnT-III-deficient mice, suggesting that the effect of bisecting GlcNAc on BACE1 is selective to APP. Considering that GnT-III-deficient mice remain healthy, GnT-III may be a novel and promising drug target for AD therapeutics