Improvement of Nonalcoholic Fatty Liver Disease After Bariatric Surgery in Morbidly Obese Chinese Patients

Background

Obesity is a risk factor for nonalcoholic fatty liver disease (NAFLD), which appears to improve after weight loss induced by bariatric surgery in Western countries. The present study aims to determine the alterations of clinical measurements and liver histology of NAFLD after bariatric surgery in morbidly obese Chinese patients.

Methods

Between November 2006 and December 2007, 21 morbidly obese patients receiving intra-operative liver biopsy and follow-up liver biopsy 1?year after laparoscopic Roux-en-Y gastric bypass were enrolled. NAFLD activity score (NAS) and fibrosis stage were histologically evaluated.

Results

The mean body mass index fell from 43.8?±?7.5 to 28.3?±?4.6?kg/m² (P?P?P?<?0.01), but not aspartate aminotransferase (P?=?0.66). Histological improvement was noted in NAS (P?P?P?P?=?0.02). Pre-operatively, 4 (19.0%), 11 (52.4%), and 6 (28.6%) patients were found to have NAS ?R5, 3 or 4, and ?Q2, respectively. All patients had NAS ?Q2 after surgery. Fibrosis stage also showed significant improvement (P?Conclusions Bariatric surgery can achieve a dramatic improvement of NAFLD both biochemically and histologically in morbidly obese Chinese patients.     

N-acetylcysteine attenuates ventilator-induced lung injury in an isolated and perfused rat lung model

N-acetylcysteine (NAC) suppresses the generation of reactive oxygen species (ROS) that are implicated in ventilator-induced lung injury (VILI). We thus hypothesised that NAC attenuates VILI. VILI was induced by mechanical ventilation with a tidal volume (Vt) of 15mlkg(-1) in isolated and perfused rat lung. NAC was administered in the perfusate prior to the onset of mechanical ventilation. A group ventilated with low Vt of 5mlkg(-1) served as control. Haemodynamics, lung injury indices, inflammatory responses and activation of apoptotic pathways were determined upon completion of the mechanical ventilation. There was an increase in lung permeability and lung weight gain after mechanical ventilation with high Vt, compared to low Vt. The levels of inflammatory cytokines including interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and macrophage inflammatory protein-2 (MIP-2) increased in lung lavage fluids; the concentrations of H(2)O(2) were higher in lung lavage fluids, and the expression of myeloperoxidase (MPO), JNK, P38, pAKT and caspase-3 in lung tissue was greater in the high Vt than in the low Vt group. The concentrations of glutathione (GSH) in lung tissue were higher in low Vt than those in high Vt. The administration of NAC increased GSH, attenuated ROS, cytokines, MPO, JNK, pAKT and caspase-3 and lung permeability associated with decreased activation of nuclear factor-κB. VILI is associated with inflammatory responses including the generation of ROS, cytokines and the activation of mitogen-activated protein kinase cascade. The administration of NAC attenuates the inflammatory responses, apoptosis and VILI in the isolated, perfused rat lung model.     

Association of metabolic syndrome, atherosclerosis risk factors, sex hormones in ED in aboriginal Taiwanese

The overall prevalence of metabolic syndrome (MS) in aboriginal male Taiwanese is very high. Many studies have found that those with cardiovascular disease and MS have a significantly higher risk of ED. In this study, we attempted to find the correlation among MS risk factor, atherosclerosis risk factors and low serum testosterone in relation to the development of ED. This was a cross-sectional study of 238 cases, and collected data included demographic data, lifestyle questionnaires, sexual desire scale, sexual satisfaction scale and International Index of Erectile Function (IIEF) questionnaire. Among our 238 subjects, 146 had MS (61.3%) and 114 subjects with MS had ED (85.7%). Using age-adjusted multivariate logistic regressive analysis, this study showed that aboriginal males with ED had a significantly higher prevalence of MS (OR=12.02, 95% confidence intervals (CI): 6.33-22.83, P<0.001). Among the MS components, abnormal fasting blood sugar was the most significantly independent factor for ED in aboriginal males (OR=8.94, 95% CI: 4.71-16.97, P<0.001). The presence of MS had a significant correlation with lower IIEF-5 scores, lower sexual desire scores, lower testosterone serum level (P<0.01) and abnormal interleukin-6 (IL-6) and high sensitivity C-reactive protein (HsCRP). The results of this study support the idea that MS, low serum testosterone and HsCRP may predict ED in aboriginal Taiwanese males. Further studies with population-based and longitudinal design should be conducted to confirm this finding and design to compare rates of ED in aboriginal men with MS.     

Scale‐up of MSC under hypoxic conditions for allogeneic transplantation and enhancing bony regeneration in a rabbit calvarial defect model

To realize the therapeutic potential of mesenchymal stem cells (MSCs), we aimed to develop a method for isolating and expanding New Zealand rabbit MSCs in a great scale. Rabbit MSCs expanded under hypoxic and normoxic conditions were compared in terms of replication capacity, differentiation potential, and the capacity for allogeneic transplantation in a calvarial defect model. The cells from all tested rabbits were expanded more rapidly when plated at low‐density under hypoxic conditions compared to under normoxic conditions. Moreover, cells expanded under hypoxic conditions increased in the potential of osteoblastic, adipocytic, and chondrocytic differentiation. More importantly, radiographic analysis and micro‐CT measurement of bone volume revealed the hypoxic cells when transplanted in the calvarial defects of another rabbit increased in the ability to repair bone defect compared to the normoxic cells. Six weeks after allogeneic transplantation of hypoxic MSCs, histological analysis revealed a callus spanned the length of the defect, and several bone tissues spotted in the implant. At 12 weeks, new bone had formed throughout the implant. Using BrdU labeling to track the transplanted cells, the hypoxic cells were more detected in the newly formed bone compared to the normoxic cells. For defects treated with allogeneic MSCs, no adverse host response could be detected at any time‐point. In conclusion, we have developed a robust method for isolation and expansion of rabbit MSCs by combining low‐density with hypoxic culture, which can be applied for the design of clinical trials in allogeneic transplantation of MSCs for bone healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1213–1220, 2012     

Recurrent laryngeal nerve palsy after thyroidectomy with routine identification of the recurrent laryngeal nerve

BACKGROUND: The aim of this study was to assess the risk of recurrent laryngeal nerve palsy (RLNP) after thyroidectomy with routine identification of the recurrent laryngeal nerve (RLN) during the operation. METHODS: The present study was confined to 521 patients, 348 total lobectomies and 178 total thyroidectomies, treated by the same surgeon. Temporary and permanent RLNP rates were analyzed for patient groups with stratification of primary operation for benign thyroid disease, thyroid cancer, Graves' disease, and reoperation. Measurement of the RLNP rate was based on the number of nerves at risk. Twenty-six RLNs in 20 thyroid cancer patients with intentional sacrifice were excluded from analysis. RESULTS: Forty RLNs (40 patients) developed postoperative RLNP. Complete recovery of RLN function was documented for 35 of the 37 patients (94.6%) whose RLN integrity had been ensured intraoperatively. Recovery from temporary RLNP ranged from 3 days to 4 months (mean, 30.7 days). Overall incidence of temporary and permanent RLNP was 5.1% and 0.9%, respectively. The rates of temporary/permanent RLNP were 4.0/0.2%, 2.0/0.7%, 12.0/1.1%, and 10.8/8.1% for groups classified according to benign thyroid disease, thyroid cancer, Graves' disease, and reoperation, respectively. CONCLUSIONS: Operations for thyroid cancer, Graves' disease, and recurrent goiter demonstrated significantly higher RLNP rates. Invasion of RLN was identified in 19.4% of patients with thyroid cancer. Postoperatively, the RLN recovered in most of the patients without documented nerve damage during the operation. Total lobectomy with routine RLN identification is recommended as a basic procedure in thyroid operations.     

Lanthanum carbonate (Fosrenol) efficacy and tolerability in the treatment of hyperphosphatemic patients with end-stage renal disease

AIMS: High serum phosphorus levels are a common problem in patients receiving long-term dialysis treatment. Lanthanum carbonate (Fosrenol) is a new non-aluminum, non-calcium phosphate binder developed for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). We report data from a recent trial, which, for the first time, assessed the efficacy and tolerability of lanthanum carbonate treatment, compared with placebo, in Chinese patients with ESRD. PATIENTS AND METHODS: Following a one- to three-week washout phase and a four-week, open-label lanthanum carbonate dose-titration phase, male and female hemodialysis patients were randomized (1:1) to receive either lanthanum carbonate or placebo for four weeks. The primary efficacy parameter of the study was the control of serum phosphorus levels (< or =1.8 mmol/l [< or = 5.6 mg/dl]). Secondary endpoints included the profile of serum phosphorus during titration and parathyroid hormone, calcium, and calcium x phosphorus (Ca x P) product levels. The safety and tolerability of lanthanum carbonate were assessed by monitoring adverse events throughout the study. RESULTS: Mean serum phosphorus level at the end of washout was 2.5 +/- 0.5 mmol/l (7.7 +/- 1.5 mg/dl; n=73), and there was no evidence of a difference in levels between the treatment groups pre-randomization. At the end of the study, lanthanum carbonate-treated patients had significantly lower phosphorus levels (1.6 +/- 0.5 mmol/l [5.1 +/- 1.5 mg/dl]; n=30) than those receiving placebo (2.3 +/- 0.4 mmol/l [7.2 +/- 1.3 mg/dl]; n=31; p < 0.001). In addition, a significantly higher proportion of patients receiving lanthanum carbonate had controlled serum phosphorus levels (60%) compared with the placebo group (10%; p < 0.001). Ca x P product levels were also significantly lower in the lanthanum carbonate group at the end of randomized treatment (p < 0.001). Lanthanum carbonate was well tolerated; only one serious adverse event was reported, which was unrelated to treatment. CONCLUSIONS: Lanthanum carbonate was shown to be an effective and well-tolerated phosphate binder for the treatment of hyperphosphatemia in Chinese patients with ESRD. This finding supports the results of previous US and European studies, which have also shown that lanthanum carbonate treatment effectively controls serum phosphorus levels.     

Multi‐lineage differentiation and angiogenesis potentials of pigmented villonodular synovitis derived mesenchymal stem cells ‐ pathological implication

Pigmented villonodular synovitis (PVNS) is a benign tissue proliferation characterized by its hyper‐vascularity within the lesion. The true etiology and cell source of this disease entity still remain unclear. Mesenchymal stem cells (MSCs) exist in various tissues of human body. However, it has not been clarified whether MSCs could be isolated from tissue of PVNS. Here, we isolated MSCs from PVNS (PVNS‐SCs), and by comparing to the MSCs from normal synovium (Syn‐SCs) of the same individual, we investigated whether PVNS‐SCs differed in the capacity for multi‐differentiation and inducing angiogenesis. We first demonstrated that PVNS‐SCs existed in the lesion of PVNS of three individuals. Moreover, we showed PVNS‐SCs had better osteogenic differentiation potential than Syn‐SCs, whereas Syn‐SCs had better capacity for adipogenic and chondrogenic differentiation. By genome–wide analysis of gene expression profile using a complementary DNA microarray and comparing to Syn‐SCs, we identified in PVNS‐SCs a distinct gene expression profile characterized by up‐regulation of genes involved in angiogenesis. In vitro and in vivo studies further confirmed that PVNS‐SCs had better capacities for promoting angiogenesis. In summary, the identification of PVNS‐SCs in PVNS tissue and their distinct angiogenic potential may help elucidate the underlying etiology of this disease. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:395–403, 2016.     

Extracorporeal shock wave treatment modulates skin fibroblast recruitment and leukocyte infiltration for enhancing extended skin-flap survival

Extracorporeal shock wave (ESW) treatment has a positive effect of rescuing ischemic skin flaps. This study assessed whether ESW treatment rescues the compromised flap tissue by suppressing the apoptosis of ischemic tissue and recruiting tissue remodeling. We used a random-pattern extended dorsal–skin-flap (10 × 3 cm) rodent model. Thirty-six male Sprague–Dawley rats were divided into three groups. Group I, the control group, received no treatment. Group II received one session of ESW treatment (500 impulses at 0.15 mJ/mm²) immediately after surgery. Group III received two sessions of ESW treatment, immediately and the day after the surgery. Results indicated that the necrotic area in the flaps in group II was significantly smaller than that of the flaps in group I ( p <0.01). Transferase dUTP-nick end labeling (TUNEL) analysis revealed a significant decrease in the number of apoptotic cells in group II. Hydrogen peroxide (H₂O₂) expression in circulation blood was significantly decreased in group II on the day after ESW treatment. Immunohistochemical staining indicated that compared with no treatment, ESW treatment could substantially increase proliferating cell nuclear antigen (PCNA), endothelial nitric oxide synthase, and prolyl 4-hydroxylase (rPH) expression, reduce CD45 expression, and suppress 8-hydroxyguanosine (8-OG) expression in the ischemic zone of the flap tissue. In conclusion, ESW treatment administered at an optimal dosage exerts a positive effect of rescuing ischemic extended skin flaps. The mechanisms of action of ESWs involve modulation of oxygen radicals, attenuation of leukocyte infiltration, decrease in tissue apoptosis, and recruitment of skin fibroblasts, which results in increased flap tissue survival.     

The aggressiveness of urinary tract urothelial carcinoma increases with the severity of chronic kidney disease

OBJECTIVE

To assess, in a retrospective cohort, urinary tract urothelial carcinoma (UT‐UC) in patients with various stages of chronic kidney disease (CKD) and their clinicopathological features, as patients with end‐stage renal disease (ESRD) have a higher incidence of UT‐UC, but the relationship between early stages of CKD and characteristics of UT‐UC are less well known.

PATIENTS AND METHODS

The study included 267 patients with pathologically confirmed UT‐UC from January 1994 to December 2006; all had a physical examination (blood pressure), and measurements of laboratory data (serum creatinine, serum haemoglobin) and pathological data. The glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease equation. Patients were divided into three groups by individual GFR (mL/min), i.e. >60 (no/mild CKD), 30–60 (CKD stage 3) and <30 (CKD stage 4/5).

RESULTS

The CKD stages included 81 (30.3%) patients with none/mild CKD, 121 (45.3%) with CKD stage 3 and 65 (24.3%) with CKD stage 4/5. There was a significant and parallel increase in the frequency of UT‐UC as CKD severity increased from none/mild CKD to stage 3 (11% vs 55%), and from CKD stage 3 to 4/5 (55% vs 71%; P < 0.05). Pathologically, the frequency of high‐grade and high T stage UT‐UC in patients with CKD stage 3 (90% and 35%, respectively) and CKD stage 4/5 (91% and 29%, respectively) were significantly greater than in the group with none/mild CKD (P < 0.001). Advanced age and more distant metastasis were independent risk factors for patient survival.

CONCLUSION

The aggressiveness of UT‐UC increased with the severity of CKD, and this might have important clinical consequences.