Blood pressure after treatment with sodium–glucose cotransporter 2 inhibitors influences renal composite outcome: Analysis using propensity score-matched models

Aims/IntroductionSodium–glucose cotransporter 2 inhibitors (SGLT2i) improve renal outcome in patients with type 2 diabetes mellitus, but the mechanism is not fully understood. The aim of this retrospective study was to assess the association of achieved blood pressure with renal outcomes in Japanese type 2 diabetes mellitus patients with chronic kidney disease.Materials and MethodsWe assessed 624 Japanese type 2 diabetes mellitus patients with chronic kidney disease taking SGLT2i for >1 year. The patients were classified as those with post‐treatment mean arterial pressure (MAP) of ≥92 mmHg (n = 344) and those with MAP of <92 mmHg (n = 280) for propensity score matching (1:1 nearest neighbor match with 0.04 of caliper value and no replacement). The end‐point was a composite of progression of albuminuria or a decrease in the estimated glomerular filtration rate by ≥15% per year.ResultsBy propensity score matching, a matched cohort model was constructed, including 201 patients in each group. The incidence of renal composite outcome was significantly lower among patients with MAP of <92 mmHg than among patients with MAP of ≥92 mmHg (n = 11 [6%] vs n = 26 [13%], respectively, P = 0.001). The change in estimated glomerular filtration rate was similar in the two groups; however, the change in the albumin‐to‐creatinine ratio was significantly larger in patients with MAP of <92 mmHg.ConclusionsIn Japanese type 2 diabetes mellitus patients with chronic kidney disease, blood pressure after SGLT2i administration influences the renal composite outcome. Blood pressure management is important, even during treatment with SGLT2i.     

A synthetic peptide vaccine involving the product of the pre-S(2) region of hepatitis B virus DNA: protective efficacy in chimpanzees.

The S gene encoding the major surface polypeptide of hepatitis B virus is preceded by the region pre-S(2) with a capacity to code for 55 amino acid residues. In the product of region pre-S(2), the sequence of 19 amino acid residues (amino acids 14-32 from the N terminus) representing an area of high local hydrophilicity is shared by viral strains of subtypes adr, ayw, and ayr; residue 22, phenylalanine, is replaced by leucine in a strain of the other subtype, adw. A synthetic peptide vaccine involving these 19 amino acid residues, when given to two chimpanzees, raised antibodies that bound to viral particles and protected the animals from challenge with 10(6) chimpanzee infectious doses of hepatitis B virus.     

Usefulness of helical computed tomography for diagnosis of cystic lesions of the pancreas

Using helical computed tomography (CT), we evaluated cystic pancreatic lesions in 11 patients and compared the imaging and the histopathologic findings. Helical CT allowed us to assess the tumor vasculature. Contrastenhanced images showed satisfactory details of the cysts, cyst walls, and intracystic structures. Helical CT is extremely useful for the evaluation of cystic pancreatic lesions.     

Analysis of risk factors for hepatocellular carcinoma that is negative for hepatitis B surface antigen (HBsAg)

OBJECTIVE: To clarify risk factors for hepatocellular carcinoma (HCC) other than hepatitis B surface antigen (HBsAg). PATIENTS AND METHODS: We investigated serum HBV-DNA and other factors in 146 patients with liver cirrhosis (LC) or HCC who were HBsAg negative. We analyzed the clinical background of the patients, status of hepatitis B (HBV) viral markers and platelet count as well as the presence of an HBV-DNA fragment by PCR and elucidated risk factors for HCC generation using a logistic regression model. RESULTS: Among ten factors, we determined that four represented a significant risk for HBsAg negative HCC: male gender, total alcohol consumption, total cigarettes smoked, and the presence of an HBV-DNA fragment. Multivariate analysis showed that among the four factors, the HBV-DNA fragment was an independent factor associated with HCC. CONCLUSION: The presence of an HBV-DNA fragment irrespective of the status of antibodies to either HBsAg (anti-HBs) or hepatitis B core antigen (anti-HBc) is a pivotal factor associated with the development of HCC.     

Excretion into bile of a novel unenveloped DNA virus (TT virus) associated with acute and chronic non-A-G hepatitis

Recently, an unenveloped, single-stranded DNA virus named TT virus (TTV) has been reported in association with hepatitis of non-A-G etiology. Five patients with TTV viremia, who received bile drainage or cholecystectomy, were tested for TTV DNA in bile by polymerase chain reaction with heminested primers. TTV DNA was detected in bile from all patients; titers were 10-100 times higher than in serum in 4 and at a comparable level in the remaining 1 patient. TTV DNA was detected in feces, also, in 1 of the 2 patients tested. The buoyant density of TTV in bile from 1 tested patient (1.33-1.35 g/cm3) was the same as that in feces (1.32-1.35 g/cm3). TTV may be secreted via bile into feces in a transmissible form and would spread by a fecal-oral route for deep and wide penetration into the general population.     

Applicability of the linear–quadratic model to single and fractionated radiotherapy schedules: an experimental study

The aim of this study was to examine the applicability of the linear-quadratic (LQ) model to single and fractionated irradiation in EMT6 cells. First, the α/β ratio of the cells was determined from single-dose experiments, and a biologically effective dose (BED) for 20 Gy in 10 fractions (fr) was calculated. Fractional doses yielding the same BED were calculated for 1-, 2-, 3-, 4-, 5-, 7-, 15- and 20-fraction irradiation using LQ formalism, and then irradiation with these schedules was actually given. Cell survival was determined by a standard colony assay. Differences in cell survival between pairs of groups were compared by t-test. The α/β ratio of the cells was 3.18 Gy, and 20 Gy in 10 fr corresponded to a BED_3.18 of 32.6 Gy. The effects of 7-, 15- and 20-fraction irradiation with a BED_3.18 of 32.6 Gy were similar to those of the 10-fraction irradiation, while the effects of 1- to 5-fraction irradiation were lower. In this cell line, the LQ model was considered applicable to 7- to 20-fraction irradiation or doses per fraction of 2.57 Gy or smaller. The LQ model might be applicable in the dose range below the α/β ratio.     

Higher cardiorespiratory fitness attenuates the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism

Purpose

β3-Adrenergic receptor (ADRB3) Trp64Arg polymorphism is associated with atherogenic risk factors that include weight gain, insulin resistance, and diabetes. Habitual exercise brings higher cardiorespiratory fitness and results in the amelioration of atherosclerotic risk factors. However, the effects of cardiorespiratory fitness level and ADRB3 Trp64Arg polymorphism on the risk of cardiovascular disease remain unclear. A cross-sectional investigation of 877 Japanese men and women (18–75 years old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between ADRB3 Trp64Arg polymorphism and risk of cardiovascular disease.

Method

Common carotid intima-media thickness (ccIMT) and blood lipid profiles were assessed as surrogate markers of atherosclerosis. We measured peak oxygen uptake ( \(\dot V\) O_2peak) during incremental cycle ergometer exercise testing. Subjects were divided into groups with high (High-Fit) and low (Low-Fit) levels of cardiorespiratory fitness based on the median value of \(\dot V\) O_2peak for sex and decade.

Results

Levels of body fat, triglycerides, and plasma glucose were lower and high-density lipoprotein cholesterol levels and \(\dot V\) O_2peak were higher in High-Fit subjects than Low-Fit subjects. ADRB3 Trp64Arg polymorphism did not significantly affect ccIMT or blood lipid profiles. In Low-Fit subjects, ccIMT was higher in individuals with the Arg/Arg genotype compared to the Trp/Trp and Trp/Arg genotypes (each P < 0.0001); however, ADRB3 polymorphism had no effect in High-Fit subjects.

Conclusion

Higher levels of cardiorespiratory fitness may attenuate the risk of atherosclerosis associated with ADRB3 Trp64Arg polymorphism.     

Infection with GB virus C in leprous patients in Japan

The detection of hepatitis C virus (HCV) in blood donors and patients with acute and chronic hepatitis has brought to the fore another virus or viruses which can be transmitted parenterally and induce liver disease. The RNA of a candidate virus designated GB virus C (GBV-C) was determined by the polymerase chain reaction with primers deduced from a helicase-like region in 229 leprous patients in Japan. GBV-C RNA was detected in 12 (5.2%) patients, and HCV RNA in 41 (18%). Three patients were coinfected with GBV-C and HCV. The nine patients infected with GBV-C alone had aminotransferase levels lower than the three patients with the mixed infection or the 38 patients infected with HCV only (P < 0.001). Sequence comparison within 100 base pairs in the helicase-like region suggested that two, three and three patients, respectively, would have been infected with three distinct strains of GBV-C. These results indicate that patients with leprosy are at increased risk for infection not only with HCV, but also with GBV-C, and that the infection with GBV-C alone would not induce hepatic injuries as severe as HCV infection. © 1996 Wiley-Liss, Inc.