Adipokine Chemerin Bridges Metabolic Dyslipidemia and Alveolar Bone Loss in Mice

Chemerin is an adipokine that regulates adipogenesis and metabolic functions of mature adipocytes mainly through the activation of chemokine‐like receptor 1 (CMKLR1). Elevated levels of chemerin have been found in individuals with obesity, type 2 diabetes, and osteoporosis. This adipokine was identified as an inflammatory and metabolic syndrome marker. Considering that the association between metabolic syndrome and bone health remains unclear, the present study aimed to clarify the role of chemerin in the pathophysiology of bone loss induced by dyslipidemia, particularly modulating osteoclastogenesis. In vitro analyses showed a downregulation of CMKLR1 at the early stage of differentiation and a gradual increase at late stages. Strikingly, chemerin did not modify osteoclast differentiation markers or osteoclast formation; however, it increased the actin‐ring formation and bone resorption activity in mature osteoclasts. The increased bone resorption activity induced by chemerin was effectively inhibited by CMKLR1 antagonist (CCX832). Chemerin boosting mature osteoclast activity involves ERK5 phosphorylation. Moreover, two models of dyslipidemia (high‐fat diet [HFD]‐treated C57/BL6 and db/db mice) exhibited significantly increased level of chemerin in the serum and gingival tissue. Morphometric analysis showed that HFD‐treated and db/db mice exhibited increased alveolar bone loss compared to respective control mice, which was associated with an up‐regulation of chemerin, CMKLR1 and cathepsin K mRNA expression in the gingival tissue. The treatment of db/db mice with CCX832 effectively inhibited bone loss. Antagonism of chemerin receptor also inhibited the expression of cathepsin K in the gingival tissue. Our results show that chemerin not only increases osteoclasts activity in vitro, but also that increased level of chemerin in dyslipidemic mice plays a critical role in bone homeostasis. © 2016 American Society for Bone and Mineral Research.     

Hearing Improvement after Resection of a Large Jugular Foramen Schwannoma: Case Report

Although hearing improvement after surgery for small tumors of the cerebellopontine angle has been reported, the mechanism by which surgery leads to the improvement in hearing remains controversial. We report a patient who sought treatment for progressive tinnitus and hearing loss. Magnetic resonance imaging showed a large (5-cm) schwannoma in the cerebellopontine angle. At surgery the lesion was found to originate from rootlets of cranial nerve X at the jugular foramen. The patient underwent gross total resection of the tumor. Immediately after surgery, his hearing improved dramatically. We believe that our patient represents an example of hearing impairment at least in part referable to direct compression of the brainstem. Importantly, the patient''s hearing deficit was completely reversible. Some authors claim that surgery to preserve hearing may be contraindicated in patients with speech discrimination scores below 50%. However, when extrinsic brainstem compression may contribute to the cause of such a hearing decrement, postoperative improvement in hearing may be a reasonable expectation.     

Reduction in Fracture Rate and Back Pain and Increased Quality of Life in Postmenopausal Women Treated with Teriparatide: 18-Month Data from the European Forsteo Observational Study (EFOS)

The European Forsteo Observational Study was designed to examine the effectiveness of teriparatide in postmenopausal women with osteoporosis treated for up to 18 months in normal clinical practice in eight European countries. The incidence of clinical vertebral and nonvertebral fragility fractures, back pain, and health-related quality of life (HRQoL, EQ-5D) were assessed. Spontaneous reports of adverse events were collected. All 1,648 enrolled women were teriparatide treatment-naive, 91.0% of them had previously received other anti-osteoporosis drugs, and 72.8% completed the 18-month study. A total of 168 incident clinical fractures were sustained by 138 (8.8%) women (821 fractures/10,000 patient-years). A 47% decrease in the odds of fracture in the last 6-month period compared to the first 6-month period was observed (P < 0.005). Mean back pain VAS was reduced by 25.8 mm at end point (P < 0.001). Mean change from baseline in EQ-VAS was 13 mm by 18 months. The largest improvements were reported in the EQ-5D subdomains of usual activities and pain/discomfort. There were 365 adverse events spontaneously reported, of which 48.0% were considered related to teriparatide; adverse events were the reason for discontinuation for 79 (5.8%) patients. In conclusion, postmenopausal women with severe osteoporosis who were prescribed teriparatide in standard clinical practice had a significant reduction in the incidence of fragility fractures and a reduction in back pain over an 18-month treatment period. This was associated with a clinically significant improvement in HRQoL. Safety was consistent with current prescribing information. These results should be interpreted in the context of the open-label, noncontrolled design of the study.     

Non-alcoholic Steatohepatitis (NASH) and Hepatocellular Carcinoma

Non-alcoholic fatty liver disease (NAFLD) is characterized by an excessive accumulation of fatty acids and triglycerides within the cytoplasm of the hepatocytes of non-alcohol users. The natural history varies according to the initial histological diagnosis. A current consideration is that cryptogenic cirrhosis may be representative of a late stage of non-alcoholic steatohepatitis (NASH), which has lost its features of necroinflammatory activity and steatosis in up to 80% of patients. Since NASH is able to progress to cirrhosis, hepatocellular carcinoma (HCC) development may be an end-stage of this disease. We report below two clinical cases of patients diagnosed with NASH who developed HCC. The relationship between NAFLD and HCC is reviewed.     

Results of gastric bypass plus resection of the distal excluded gastric segment in patients with morbid obesity

Surgical treatment is the procedure of choice for morbidly obese patients. Gastric bypass with a long limb Roux-en-Y anastomosis is the "gold standard" technique for these patients. We sought to determine the early and late results of open gastric bypass with resection of the distal excluded stomach in patients with morbid obesity. We included in this prospective study 400 patients who were seen from September 1999 through August 2003 (311 women and 89 men; mean age, 38.5 years). The mean body mass index of the patients was 46 kg/m2. All underwent 95% distal gastrectomy, with resection of the bypassed stomach, leaving a small gastric pouch of 15 to 20 ml. An end-to-side gastrojejunostomy was performed with circular stapler No. 25. The length of the Roux-en-Y loop was 125 to 150 cm. In all patients, a biopsy was taken from the liver and routine cholecystectomy was performed. Follow-up was as long as 36 months. A barium study was performed in all patients at 5 days after surgery. Mortality and postoperative morbidity rates were 0.5% and 4.75%, respectively, mainly due to anastomotic leak in 10 patients (2.5%). Hospital length of stay was 7 days for 95% of the patients. Follow-up data for longer than 12 months were available in 184 patients. There was excess body weight loss of 70% at 24 and 36 months, and there was an inverse correlation among preoperative body mass index and the loss of weight. Anemia was present in 10%, and incisional hernia was present in 10.2%. At 1 year after surgery, the BAROS index demonstrated very good or excellent index in 96.6% of the patients. Gastric bypass with resection of the distal excluded segment has results very similar to those of gastric bypass alone but eliminates the potential risks of gastric bypass such as anastomotic ulcer, gastrogastric fistula, postoperative bleeding due to peptic ulcer and gastritis, and the eventual future development of gastric cancer. It is also possible to perform via laparoscopy, as we started to do recently.     

Extravulvar subcutaneous cellular angiofibroma

Cellular angiofibroma is a rare distinctive mesenchymal neoplasm of the vulva or perineal region. We report here one unique extravulvar case. A 43-year-old woman presented with an asymptomatic tumor, 7 cm in diameter, located in the subcutaneous tissue of the chest below the left submammary sulcus. Histologically, the lesion was composed of uniform spindled stroma cells, numerous thick-walled vessels, and scarce mature adipocytes. An additional feature was the presence of prominent perivascular lymphoid aggregates. The stromal cells were positive for vimentin and negative for CD34 and muscle, epithelial, myoepithelial, or neural markers. Although nasopharyngeal angiofibroma or the group of acral angiofibromas have a concurrent heading, cellular angiofibroma should not be mistaken with them. Differential diagnosis of this distinctive tumor especially includes aggressive angiomyxoma, angiomyofibroblastoma, superficial angiomyxoma, vascular myxolipoma, and other tumors with spindle cells reminiscent of those in angiofibroma.