Acylated ghrelin level in patients with OSA before and after nasal CPAP treatment

Background and objective: Patients with newly diagnosed OSA have been reported to have recent weight gain prior to diagnosis. Ghrelin stimulates food intake and increases weight gain. Plasma ghrelin is decreased in obese and increased in lean individuals. Of the two circulating forms of ghrelin, acylated and unacylated, the former is thought to be essential for the biological activity of ghrelin. Methods: The plasma levels of the two forms of ghrelin were measured in 21 OSA patients (with a mean of 46.2 sleep‐disordered events/h) before and after 1 month of nasal CPAP (nCPAP) treatment, and were compared with those in 14 untreated OSA patients and 13 individuals without OSA. Results: The BMI was significantly higher in the 21 OSA patients than in the non‐OSA group as were the baseline acylated (11.4 ± 5.86 vs 7.19 ± 3.80 fmol/mL, P = 0.03) and unacylated (84.2 ± 50.6 vs 48.3 ± 23.2 fmol/mL, P = 0.02) ghrelin levels. The total ghrelin level was positively correlated with the number of sleep‐disordered breathings (P = 0.002). After 1 month of nCPAP treatment, the acylated ghrelin level significantly decreased (P = 0.02) while the unacylated ghrelin level did not (P = 0.09). Conclusions: Treatment of OSA may play an important role in the management of obesity in these patients by reducing the acylated ghrelin level.     

Inhibitory effect of angiotensin Ⅱ receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis

AIM: To investigate the efficacy of angiotensin II receptor antagonist on hepatic stellate cells (HSCs) activation in the patients with non-alcoholic steatohepatitis (NASH). METHODS: Seven patients with NASH were prescribed losartan, a selective angiotensin II type 1 receptor antagonist (50 mg/d) for 48 wk. Liver biopsies were performed both at the entry and end of the study in all patients. Quiescent and activated HSCs were identified by double immunostaining using anti-p75 and -smooth muscle actin antibodies, and the number of each phenotype was counted. Similarly, the liver specimens obtained from the eight patients with non-alcoholic fatty liver (NAFL) were also examined as controls. RESULTS: In NASH hepatic tissues, activated HSCs were dominantly distributed as compared with those in NAFL. The 48-wk losartan treatment induced a remarkable decrease in activated HSCs and a mild increase in quiescent phenotypes. CONCLUSION: Our data suggest the crucial involvement of HSCs in anti-fibrotic effect of angiotensin II receptor antagonist on patients with NASH.     

Myeloablative unrelated cord blood transplantation for acute leukemia patients between 50 and 55?years of age: single institutional retrospective comparison with patients younger than 50?years of age

Increasing recipient age is a well-known risk factor for graft-versus-host disease (GVHD) and treatment-related mortality (TRM) and has a negative impact on allogeneic hematopoietic stem cell transplantation. Since the incidence of severe GVHD after cord blood transplantation (CBT) is lower than that after transplants using bone marrow or mobilized peripheral blood grafts from adult cells, we should expect better outcomes from CBT in older patients. To evaluate the feasibility and efficacy of myeloablative unrelated CBT in patients aged between 50 and 55 years, we performed a retrospective comparison of 100 patients with acute leukemia who received cord blood grafts at our institution. Nineteen older patients (median age, 52; range, 50–55) and 81 younger patients (median, 36; range, 16–49) received a myeloablative conditioning regimen including 12 Gy of total body irradiation and chemotherapy. GVHD prophylaxis included cyclosporine with (n = 96) or without (n = 4) methotrexate. There were no significant differences in the incidences of grades II to IV acute GVHD, extensive-type chronic GVHD, TRM, and the probability of overall and disease-free survival between these groups. These results suggest that, in patients with acute leukemia, myeloablative CBT might be as safe and effective in patients aged between 50 and 55 years as in younger patients.     

Tips for anatomical hepatectomy for hepatocellular carcinoma by the Glissonean pedicle approach (with videos)

Couinaud described three fundamental approaches at the hepatic hilus in liver surgery. The Glissonean pedicle approach at the hepatic hilus is one of these procedures and provides anatomical hepatectomy for hepatocellular carcinoma (HCC). The Glissonean pedicle approach was introduced by Couinaud and Takasaki in the early 1980s. The key of the Glissonean pedicle approach is clamping the pedicle first, secondly confirming the territory, which includes the HCC, and finally dissecting the liver parenchyma. This procedure prevents intrahepatic metastasis of HCC, which spreads along the portal vein and improves the overall survival after surgery. Another key feature is that we do not have to consider any variations of the vascular elements in the hepatoduodenal ligament under the hilar plate. This procedure allows an approach to the tertiary branches, which feed a smaller anatomical area than Couinaud's segment. We refer to this area as a cone unit of the liver. The procedure is also available in laparoscopic hepatectomy and provides new knowledge of the surgical anatomy, especially for small anatomical liver resection in the cirrhotic liver.     

Loss of Amino Acids Into Dialysate During Hemodialysis Using Hydrophilic and Nonhydrophilic Polyester–Polymer Alloy and Polyacrylonitrile Membrane Dialyzers

During hemodialysis, amino acid loss through the dialysate remained a significant problem and was not clear in some dialyzers; therefore, we investigated amino acid loss with hydrophilic and nonhydrophilic polyester–polymer alloy membranes and polyacrylonitrile membranes. Nine maintenance hemodialysis patients were studied to assess amino acid loss during hemodialysis with the three membranes. Total amino acid losses were 85.7 ± 27.2 mg/L, 83.3 ± 16.1 mg/L, and 72.1 ± 22.5 mg/L with the hydrophilic, nonhydrophilic polyester–polymer alloy, and polyacrylonitrile membranes, respectively. Amino acid losses were greater with the hydrophilic membrane compared with the polyacrylonitrile membrane for ornithine (2.0 ± 0.6 vs. 1.4 ± 0.4 mg/L, P = 0.025), phenylalanine (2.4 ± 0.9 vs. 1.8 ± 0.8 mg/L, P = 0.012), and tryptophan (0.6 ± 0.2 vs. 0.4 ± 0.2 mg/L, P = 0.023). Amino acid losses were greater with the nonhydrophilic membrane than with the polyacrylonitrile membrane for ornithine (2.0 ± 0.4 vs. 1.4 ± 0.4 mg/L, P = 0.017), phenylalanine (2.3 ± 0.5 vs. 1.8 ± 0.8 mg/L, P = 0.018), tryptophan (0.7 ± 0.2 vs. 0.4 ± 0.2 mg/L, P = 0.003), and cystine (3.2 ± 0.7 vs. 2.0 ± 0.7 mg/L, P = 0.005). In conclusion, greater losses of ornithine, phenylalanine, tryptophan, and cystine were observed with polyester–polymer alloy than with polyacrylonitrile membranes during hemodialysis. Constant attention should be paid to the amino acid loss profile to improve nutritional control in hemodialysis patients.     

Early cytotoxic lymphocyte expansion contributes to a deep molecular response to dasatinib in patients with newly diagnosed chronic myeloid leukemia in the chronic phase: results of the D‐first study

Dasatinib is one of the key treatment options for chronic myeloid leukemia (CML) patients. Increase in lymphocyte counts has been known to be predictive of a good treatment response under dasatinib treatment as a second line therapy. However, clinical significance of lymphocyte dynamics in the upfront setting has yet to be clarified. To investigate the significance of lymphocyte dynamics in newly diagnosed chronic phase (CP)‐CML, patient data of D‐First study ( ClinicalTrials.gov NCT01464411) were analyzed. Fifty‐two CML‐CP patients enrolled to this study were treated with dasatinib (100 mg day^?1) and all were followed‐up for 18 months. The incidence of lymphocyosis was observed in 14 (27%), but it was not associated with deep molecular response achievement. However, natural killer (NK) cell or cytotoxic T lymphocyte (CTL) counts at 1 month were significantly higher in patients with deep molecular response (DMR) by 18 months compared to those without DMR. When the patients were divided into two groups according to those calculated thresholds by receiver operating characteristic curve (407/μL for NK cells and 347/μL for CTLs), the cumulative DMR rates by 18 months were significantly better in higher value group compared to lower value group. In contrast, regulatory T cell counts were significantly lower at 12 and 15 months in patients achieved DMR. These results suggest the presence of dual effects of dasatinib on immune system through the cytotoxic lymphocytes activation and Treg deregulation in different periods in newly diagnosed CML‐CP. Am. J. Hematol. 90:819–824, 2015. © 2015 Wiley Periodicals, Inc.     

Eosinophilic cholangitis coexisted with idiopathic thrombocytopenic purpura: Report of a case

Eosinophilic cholangitis is a rare disease of which only 31 cases have been reported. Eosinophilic infiltration causes stricture of the bile duct diffusely or locally, and the imaging of eosinophilic cholangitis resembles primary sclerosing cholangitis or cancer of the bile tract. For eosinophilic cholangitis, treatment with steroid is effective and the prognosis is good. Therefore, its accurate diagnosis is very important. Here, we describe a patient with eosinophilic cholangitis who was also diagnosed with idiopathic thrombocytopenic purpura (ITP). He was treated for ITP using prednisolone, the unexpected sudden interruption of which caused severe deterioration of eosinophilic cholangitis and acute cholecystitis. Cholecystectomy and choledochojejunostomy were performed, and the addition of treatment by prednisolone resulted in a good clinical course. This is the first report on eosinophilic cholangitis coexisting with ITP.