Reducing Peg-IFN doses causes later virologic response or no response in HCV genotype 1 patients treated with Peg-IFN alfa-2b plus ribavirin

Background

The timing to the first undetectable hepatitis C virus (HCV) RNA level is strongly associated with sustained virologic response in pegylated interferon (Peg-IFN) plus ribavirin combination therapy for patients with chronic hepatitis C (CH-C) with genotype 1. This study was conducted to clarify the impact of drug exposure to Peg-IFN on the timing of HCV RNA negativity in Peg-IFN plus ribavirin combination therapy for CH-C patients with genotype 1.

Methods

A total of 1409 patients treated with Peg-IFN alfa-2b plus ribavirin were enrolled and classified into four categories according to the Peg-IFN dosage. Furthermore, 100 patients were extracted from each Peg-IFN dosage category to adjust for characteristic factors, using the propensity score method.

Results

Peg-IFN exposure was dose-dependently associated with the timing of HCV RNA negativity (p????0.001). The HCV RNA negative rate at week 4 decreased from 12% with a Peg-IFN dose of >1.5???g/kg/week to 1?C3% with a dose of <1.5???g/kg/week (p????0.001), and at week 12 the rate had decreased from 44% with a dose of ??1.2???g/kg/week to 18% with a dose of <1.2???g/kg/week (p?=?0.001). Treatment failure (patients without a 1-log decrease of HCV RNA at week 4 or a 2-log decrease of HCV RNA at week 12, or positive at week 24) was found in 54?C66% of patients given <1.2???g/kg/week (p????0.001), and these patients accounted for 64% of the non-responders.

Conclusions

The timing of HCV RNA negativity depends significantly on the Peg-IFN dose. Reducing the Peg-IFN dose can induce a later virologic response or non-response in HCV genotype 1 patients treated with Peg-IFN plus ribavirin.     

Synchronous double cancers of primary hepatic adenosquamous carcinoma and hepatocellular carcinoma: report of a case

A 76-year-old male was referred for the treatment of liver tumors detected by abdominal computed tomography (CT). Dynamic CT revealed a low-density tumor with an irregularly enhanced rim in the left lateral sector, and a highly enhanced, well-circumscribed tumor in the caudate lobe, accompanied by dilation of the intrahepatic biliary ducts in the left lobe. Preoperative imaging studies led to the diagnosis of double cancers consisting of intrahepatic cholangiocarcinoma and hepatocellular carcinoma (HCC). Left hemihepatectomy with caudate lobectomy was performed. The postoperative course was uneventful. Microscopic evaluation revealed that the tumor in the left lateral sector was adenosquamous carcinoma (ASC), whereas that in the caudate lobe was HCC. This report presents the first case describing the resection of synchronous double cancers of primary hepatic ASC and HCC.     

Definitions of the physical properties of pressure ulcers and characterisation of their regional variance

A pressure ulcer is a localised injury of the skin and underlying tissue that usually develops over a bony prominence. A decrease in the pressure over the bony prominence effectively prevents pressure ulcers; however, no studies have systematically assessed the physical properties of existing pressure ulcers. To characterise pressure ulcers, we established new terminology that clarifies the physical properties of pressure ulcers: wound mobility was defined as movement using the bony prominence as a predefined specific marker, and wound deformity was defined as a change in the three‐dimensional shape of the wound. Observational studies using this terminology showed that the distinct physical properties of pressure ulcers depend on the site of development and the wound depth according to the National Pressure Ulcer Advisory Panel criteria. Most grade IV sacrum pressure ulcers exhibited mobility and deformity. Superficial sacrum pressure ulcers below grade II showed only mobility. In contrast, foot pressure ulcers did not exhibit mobility or deformity. We propose a new concept, ‘wound physical property’, for understanding the unique pathogenesis of pressure ulcers.     

Correction to: Association of initial prednisolone dose with remission,relapse, and infectious complications in adult‑onset minimal change disease

Clinical and Experimental Nephrology - In the original publication, the author has found few errors. The corrections are given below.     

The feasibility of detecting cerebral blood flow direction using the indocyanine green video angiography

The intraoperative confirmation of blood flow direction is necessary in cerebral vascular surgery. Using indocyanine green video angiography (ICG-VAG) with the FLOW 800 system, we examined the transit time of the blood vessel of interest and semiquantitatively evaluated the delay time (T1/2max) from indocyanine green (ICG) injection into the donor artery in reconstructive surgery and the middle cerebral artery (MCA) in aneurysmal surgery. The direction of cerebral blood flow (CBF), which can often be confirmed by ICG-VAG, may be more difficult to determine with faster blood flow. Here, we report our findings regarding the feasibility of detecting CBF direction using the FLOW 800 system. Twenty patients undergoing superficial temporal artery (STA) to MCA anastomosis for carotid occlusive disease and 13 patients with a small MCA aneurysm clipping were evaluated using the T1/2max, semiquantitative method with the FLOW 800 system. In STA–MCA anastomosis cases, the regions of interest (ROIs) included: the proximal donor STA and a region more than 10 mm on the distal side of the donor STA near the anastomosis site. In MCA aneurysms, the ROIs included the proximal M1 and distal M2 sides of the MCA aneurysm. T1/2max was significantly shorter for the proximal sites compared to the distal sites for all subjects (ps?<?0.01). T1/2max was shorter for all subjects in the proximal sites. The direction of CBF can be determined using the FLOW 800 system.     

Pulmonary leiomyosarcoma presenting as a pancoast tumor

A patient presenting with Pancoast syndrome was definitely diagnosed to have pulmonary leiomyosarcoma. The patient underwent a right upper lobectomy combined with resection of the chest wall, including the 1st to 3rd ribs. The disease recurred rapidly at the local and distant sites. No previous reports about pulmonary sarcoma presenting as a Pancoast tumor were found in the literature. The possibility of primary pulmonary leiomyosarcoma should be considered, and early detection and surgical resection are necessary when a round or oval tumor with necrosis is observed in the apex of the lung.     

Very Short-Term Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin on the Secretion of Insulin,Glucagon, and Incretin Hormones in Japanese Patients with Type?2 Diabetes Mellitus: Analysis of Meal Tolerance Test Data

Background

Sitagliptin inhibits dipeptidyl peptidase-4, which inactivates the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. To assess its antidiabetic potency, we used meal tolerance tests (MTTs) to determine the very short-term effects of sitagliptin on plasma concentrations of insulin and glucagon.

Methods

On day 1, patients with newly diagnosed or uncontrolled type 2 diabetes mellitus started a calorie-restricted diet. On day 2, the first MTT was performed, before treatment with sitagliptin 50 mg/day started later the same day. On day 5, a second MTT was performed. Area under the concentration–time curves (AUCs) of relevant laboratory values were calculated [AUC from time zero to 2 h (AUC_0–2h) and from time zero to 4 h (AUC_0–4h)].

Results

Fifteen patients were enrolled. AUCs for postprandial plasma glucose were decreased after 3 days of sitagliptin treatment [AUC_0–2h 457 ± 115 mg/dL·h (25.4 ± 6.4 mmol/L·h) to 369 ± 108 mg/dL·h (20.5 ± 6.0 mmol/L·h); AUC_0–4h 896 ± 248 mg/dL·h (49.7 ± 13.8 mmol/L·h) to 701 ± 246 mg/dL·h (38.9 ± 13.7 mmol/L·h); both p < 0.001]. AUC_0–2h and AUC_0–4h for postprandial plasma glucagon also decreased: 195 ± 57 to 180 ± 57 pg/mL·h (p < 0.05) and 376 ± 105 to 349 ± 105 pg/mL·h (p < 0.01), respectively. The AUC_0–2h [median with quartile values (25 %, 75 %)] for active GLP-1 increased: 10.5 (8.5, 15.2) to 26.4 (16.7, 32.4) pmol/L·h (p = 0.03).

Conclusions

Very short-term (3-day) treatment with sitagliptin decreases postprandial plasma glucose significantly. This early reduction in glucose may result partly from suppression of excessive glucagon secretion, through a direct effect on active GLP-1. Improvement in postprandial plasma glucose, through suppression of glucagon secretion, is believed to be an advantage of sitagliptin for the treatment of patients with type 2 diabetes.