Is a composite score of physical performance measures more useful than usual gait speed alone in assessing functional status?

Overall physical performance can be represented by a composite score that is derived from upper and lower extremity performance measures. We aimed to identify whether composite scores of performance measures, particularly the lower extremity performance (LEP) score, upper extremity performance (UEP) score, and an overall score, are more accurate than usual gait speed (UGS) for assessing a wide range of functional status. We conducted a cross-sectional analysis on data from 701 community-dwelling older women (mean age 74.3 years). Trained testers measured UGS and the seven tests included in the composite scores. Using self-reported questionnaires, we assessed multiphasic functional status: physical function, higher-level functional capacity, mobility limitation, activities of daily living (ADLs), and falls. We compared the areas under the receiver operating characteristic curves (AUCs) of UGS with LEP, UEP, and overall scores for each status. We found no significant differences between the AUCs of UGS and LEP score for each status. The UEP score had significantly smaller AUCs for low physical function (0.73) and mobility limitation (0.78) than UGS alone (0.81 and 0.85, respectively), and the differences were substantial. Although the overall score had significantly greater AUCs for low higher-level functional capacity (0.83) and ADLs disability (0.83) than UGS alone (0.78 and 0.80, respectively), the differences were only 3-5%. The UGS should not be regarded solely as a measure of lower extremity function; this single test may represent overall physical performance. The UGS alone, which can be measured quickly and easily, suffice for assessing a wide range of functional status in older women.     

Severe liver injury associated with simeprevir plus pegylated interferon/ribavirin therapy in a patient with treatment-naïve genotype 1b hepatitis C virus: a case report

A second-generation direct-acting antiviral agent, simeprevir, now provides a new treatment option for hepatitis C virus (HCV) infection with good safety profile in combination with pegylated interferon and ribavirin. We herein report a rare case of severe liver injury under simeprevir plus pegylated interferon/ribavirin therapy. We initiated this therapy in a 65-year-old male with treatment-naïve genotype 1b HCV. On day 28, the patient’s HCV-RNA was successfully eliminated, and his liver function was fully restored. However, on day 49, the serum alanine aminotransferase level was elevated at 700 IU/L. The HCV-RNA titer was still undetectable and the involvement of other possible viruses was negligible. A liver biopsy performed on day 60 showed an acute hepatitis pattern. The discontinuation of therapy alone successfully improved his liver damage on day 84. No other treatments such as steroids were required. According to the diagnostic criteria for drug-induced liver injury in Japan (DDW-J2004), the liver injury observed in this case can be associated with the administration of simeprevir plus pegylated interferon/ribavirin therapy. In conclusion, simeprevir plus pegylated interferon/ribavirin should be used with caution, as these agents may cause unreported serious adverse events including severe liver injury, despite their clinical safety profile.     

Sustained improvement in cardiac function with persistent amyloid deposition in a patient with multiple myeloma-associated cardiac amyloidosis treated with bortezomib

We describe the case of a 62-year-old man with biopsy-proven cardiac involvement of multiple myeloma-associated immunoglobulin light-chain amyloidosis, whose cardiac function improved after bortezomib therapy. Angiotensin-converting enzyme inhibitors and diuretics were initially administered, resulting in improvement of heart failure symptoms and disappearance of nonsustained ventricular tachycardia. To reduce production of amyloidogenic precursor proteins, bortezomib therapy combined with dexamethasone was subsequently started. Hematological responses were rapid and adverse events were manageable. At present, 15 months after the treatment, cardiac function of the patient showed sustained improvement, although follow-up biopsy specimens showed persistent amyloid deposition in the myocardium corresponding to echocardiogram results demonstrating no reduction in ventricular wall thickness.     

Spironolactone inhibits production of proinflammatory mediators in response to lipopolysaccharide via inactivation of nuclear factor-κB

The effect of spironolactone (SPIR) on lipopolysaccharide (LPS)-induced production of proinflammatory mediators was examined using RAW 264.7 macrophage-like cells and mouse peritoneal macrophages. SPIR significantly inhibited LPS-induced production of nitric oxide (NO), tumor necrosis factor-α and prostaglandin E2. The inhibition was not mediated by cell death. SPIR reduced the expression of an inducible NO synthase mRNA in response to LPS. SPIR significantly inhibited phosphorylation of p65 nuclear factor (NF)-κB in response to LPS. Furthermore, SPIR inhibited phosphorylation of IκB kinase (IKK) as an upstream molecule of NF-κB in response to LPS. LPS did not induce the production of aldosterone in RAW 264.7 cells. Taken together, SPIR is suggested to inhibit LPS-induced proinflammatory mediators via inactivation of IKK/NF-κB in LPS signaling.     

Blockade of histamine H2 receptors protects the heart against ischemia and reperfusion injury in dogs

We have previously reported that histamine H(2) blockers may be cardioprotective in patients with chronic heart failure. Since both endogenous histamine and histamine H(2) receptors are present in heart tissue, we tested the hypothesis that the blockade of histamine H(2) receptors mediates protection against reversible or irreversible ischemia and reperfusion injury. In open-chest dogs, the left anterior descending coronary artery was occluded for 90 minutes, followed by reperfusion for 6 hours. Administration of famotidine and cimetidine from 10 minutes before occlusion until after 1 hour of reperfusion reduced infarct size (17.0 +/- 4.1% and 17.8 +/- 2.9% vs. 36.9 +/- 5.9% of the solvent group, respectively) Famotidine administration only during the reperfusion period for 1 hour also attenuated infarct size (22.5 +/- 3.5%). There were no differences in either area at risk or collateral flow among the groups. In another set of experiments, we decreased coronary perfusion pressure in dogs so that the coronary blood flow decreased to 50% of the non-ischemic level. In such conditions, we observed the increases in histamine release compared with non-ischemic conditions (0.04 +/- 0.03 to 0.28 +/- 0.13 ng/ml, p < 0.05). Famotidine improved anaerobic myocardial metabolism gauged by both lactate extraction ratio and myocardial oxygen consumption. We conclude that the blockade of histamine H(2) receptors mediates improvements in the anaerobic myocardial metabolism, and thus protects against ischemia and reperfusion injury.     

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.