Exploratory study on the relationship between urinary sodium/potassium ratio, salt intake, and the antihypertensive effect of esaxerenone: the ENaK Study.

Excessive salt intake is one of the causes of hypertension, and reducing salt intake is important for managing the risk of hypertension and subsequent cardiovascular events. Esaxerenone, a mineralocorticoid receptor blocker, has the potential to exert an antihypertensive effect in hypertensive patients with excessive salt intake, but evidence is still lacking, especially in clinical settings. We aimed to determine if baseline sodium/potassium ratio and baseline estimated 24-h urinary sodium excretion can predict the antihypertensive effect of esaxerenone in patients with essential hypertension inadequately controlled with an angiotensin receptor blocker (ARB) or a calcium channel blocker (CCB). This was an exploratory, open-label, interventional study with a 4-week observation period and a 12-week treatment period. Esaxerenone was orally administered once daily in accordance with the Japanese package insert. In total, 126 patients met the eligibility criteria and were enrolled (ARB subcohort, 67; CCB subcohort, 59); all were included in the full analysis set (FAS) and safety analysis. In the FAS, morning home systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from baseline to end of treatment (primary efficacy endpoint) (-11.9 ± 10.9/ - 6.4 ± 6.8 mmHg, both p < 0.001); a similar trend was observed in both subcohorts. Significant reductions were also shown in bedtime home and office SBP/DBP (all p < 0.001). Each BP change was consistent regardless of the urinary sodium/potassium ratio or estimated 24-h urinary sodium excretion at baseline. The urinary albumin-creatinine ratio (UACR) and N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly decreased from baseline to Week 12 in the total population and both subcohorts. No new safety concerns were raised. Esaxerenone significantly decreased morning home, bedtime home, and office BP; UACR; and NT-proBNP in this patient population, regardless of concomitant ARB or CCB use. The antihypertensive effect of esaxerenone was independent of the urinary sodium/potassium ratio and estimated 24-h urinary sodium excretion at baseline.

X-ray analysis of bilirubin oxidase from Myrothecium verrucaria at 2.3 A resolution using a twinned crystal.

Bilirubin oxidase (BOD), a multicopper oxidase found in Myrothecium verrucaria, catalyzes the oxidation of bilirubin to biliverdin. Oxygen is the electron acceptor and is reduced to water. BOD is used for diagnostic analysis of bilirubin in serum and has attracted considerable attention as an enzymatic catalyst for the cathode of biofuel cells that work under neutral conditions. Here, the crystal structure of BOD is reported for the first time. Blue bipyramid-shaped crystals of BOD obtained in 2-methyl-2,4-pentanediol (MPD) and ammonium sulfate solution were merohedrally twinned in space group P6(3). Structure determination was achieved by the single anomalous diffraction (SAD) method using the anomalous diffraction of Cu atoms and synchrotron radiation and twin refinement was performed in the resolution range 33-2.3 A. The overall organization of BOD is almost the same as that of other multicopper oxidases: the protein is folded into three domains and a total of four copper-binding sites are found in domains 1 and 3. Although the four copper-binding sites were almost identical to those of other multicopper oxidases, the hydrophilic Asn residue (at the same position as a hydrophobic residue such as Leu in other multicopper oxidases) very close to the type I copper might contribute to the characteristically high redox potential of BOD.

Repeated instillation of a limited volume of ethanol for the treatment of symptomatic hepatic cysts.

BACKGROUND/AIMS: In the past, various treatments for symptomatic hepatic cysts have been reported. In recent years, sclerosis therapy seems to be most common. In the present study, repeated instillation of a limited volume of ethanol was evaluated. METHODOLOGY: Six patients who had one or more hepatic cysts underwent percutaneous alcohol sclerosis therapy. Of the six patients, five had epigastric discomfort, and one had back pain. A 7.0-French pigtail polyethylene catheter was inserted into the cyst. The fluid was aspirated and it was demonstrated by radiograph that there were no communications between the cysts and the intrahepatic duct or hepatic vessels. Six hepatic cysts were instilled with 99% sterile ethanol, which was allowed to remain in place for 5 minutes, and then removed. Ethanol instillation was repeated every day or every other day in all patients. It was performed two to five. Ethanol volume of a single instillation varied from 10mL to 100mL. In all cases, the ethanol volume of first instil lation was limited to 20mL or less to prevent severe complications. RESULTS: The diameters of the initial cysts ranged from 7.8 to 13.2cm (mean, 10.4cm) and aspirated fluid volume varied from 70 to 1000mL (mean, 455mL). All patients had slight alcohol intoxication for a few hours after alcohol instillation, two had moderate abdominal pain at the time of alcohol instillation. In five of six patients, subtotal or total regression of the hepatic cysts was observed within eight months following treatment. In one case, the hepatic cyst was reduced from 13x11 to 7.8x7.5cm in size after seven months, but further regression was not obtained thereafter. All patients became symptom-free. CONCLUSIONS: It is concluded that repeated instillation of a limited volume of ethanol is effective for the treatment of symptomatic hepatic cysts and potentially reduces the incidence of complications.

Clinical features of patients with chronic pancreatitis complicated by bile duct strictures.

BACKGROUND/AIMS: Distal bile duct stenosis is relatively rare in patients with non-alcoholic chronic pancreatitis. METHODOLOGY: The clinical features of eight patients who had chronic pancreatitis complicated by bile duct strictures who underwent surgical treatments were reviewed. RESULTS: Ages ranged from 38 to 80 years, with a mean of 53.4 years. All but one patient were male. Six patients had moderate or slight epigastric pain. Five patients had obstructive jaundice and underwent biliary drainage. All patients had liver dysfunction due to biliary obstruction. Although four of the eight patients were heavy or moderate drinkers, none of the patients had a history of chronic pancreatitis. Stricture shapes of the common bile ducts were smooth and tapering in five patients, funnel-shaped in two, and rat-tail in one. Four patients underwent a pancreatoduodenectomy and one patient underwent a pylorus-preserving pancreatoduodenectomy for clinically suspected pancreatic malignancy that was later proven histopathologically to be chronic pancreatitis. The other three patients underwent a choledochoduodenostomy. There were no postoperative complications or deaths. During the follow-up period, all patients were asymptomatic. CONCLUSIONS: In conclusion, bile duct stricture potentially occurs not only in patients with alcoholic chronic pancreatitis but also in patients with nonalcoholic chronic pancreatitis. Furthermore, in some cases, it is impossible to differentiate chronic pancreatitis from pancreatic or periampullary malignancy.

Sepsis delays gastric emptying following pylorus-preserving pancreaticoduodenectomy.

BACKGROUND/AIMS: The mechanism of delayed gastric emptying following pylorus-preserving pancreaticoduodenectomy is not completely understood. METHODOLOGY: The records of 25 patients who underwent pylorus-preserving pancreaticoduodenectomy were reviewed. Correlations of postoperative delayed gastric emptying defined as the need for postoperative nasogastric decompression for > 10 days, with perioperative parameters and clinical outcome were analyzed. RESULTS: Delayed gastric emptying occurred in 13 patients. Age, gender, presence of pancreatic carcinoma, operating time, estimated blood loss, and preservation of right gastric artery did not affect the incidence of delayed gastric emptying. Patients with pancreatic fibrosis (n = 13) had a significantly lower incidence of delayed gastric emptying than in those without fibrosis (n = 12) (23% vs. 83%, P = 0.0048). Ten patients developed postoperative septic complications, including anastomotic leakage (n = 7), pneumonia (n = 2), and severe wound infection (n = 1). The incidence of postoperative delayed gastric emptying was significantly higher in patients with septic complications than in those without septic complications (100% vs. 20%, P = 0.0001). Also, patients with intraabdominal sepsis had a significantly higher incidence of delayed gastric emptying (P = 0.0052). CONCLUSIONS: Delayed gastric emptying following pylorus-preserving pancreaticoduodenectomy is related to the presence of non-fibrotic pancreas and postoperative septic complications.

Evaluation of total hepatic vascular exclusion and pringle maneuver in liver resection.

BACKGROUND/AIMS: The effects of total hepatic vascular exclusion and Pringle maneuver on intraoperative course and postoperative recovery were retrospectively studied. METHODOLOGY: Records of 42 patients who underwent a major hepatectomy and six who had a minor hepatectomy were reviewed. Patients with chronic liver disease or obstructive jaundice were excluded. Hepatic vascular exclusion was used in 5 patients who were at high risk for back flow bleeding from the hepatic veins. Pedicular clamping was used in the other 43 patients. Intergroup differences in intraoperative blood loss, postoperative liver function, the serum interleukin-6 concentrations, and clinical outcome were compared. RESULTS: In four patients of the hepatic vascular exclusion group (n = 5), intraoperative blood loss was less than 2000 mL, and 6000 mL in the remaining patient. However the hepatic vascular exclusion group had longer hepatic ischemia time (45.2 +/- 10.3 min vs. 30.6 +/- 10.9 min), a greater blood loss (2304 +/- 2106 L vs. 913 +/- 1130 mL), a higher serum interleukin-6 concentration (347 +/- 320 pg/mL vs. 93 +/- 58 pg/mL), and a higher morbidity rate (80 vs. 7.1%) compared with the pedicular clamping group (n = 43) (P < 0.05). Postoperative liver function tests were comparable, and no patient developed postoperative hepatic failure. In the pedicular clamping group, intermittent pedicular clamping with periods of 15 minutes (n = 12) increased blood loss (662 +/- 421 mL vs. 1427 +/- 1890 mL), but did not reduce serum interleukin-6 concentration, liver cell damage, or morbidity rate postoperatively, compared with continuous or intermittent clamping of longer periods. CONCLUSIONS: Hepatic vascular exclusion is an effective way to limit blood loss in hepatic resection without causing sever liver injury. However, the interleukin-6 production is increased and the morbidity rate is high. Paradoxically, periodic release of pedicular clamping increases the blood loss but does not reduce liver cell injury or interleukin-6 production.