Myxoinflammatory Fibroblastic Sarcoma of the Hand.

Myxoinflammatory fibroblastic sarcoma is an ultra-rare tumor type with a prevalence of fewer than two per 100,000 people. The tumor poses a challenge because it can be misdiagnosed as a benign lesion in clinical and radiological investigations, causing serious morbidity in patients. We present the case of a 33-year-old patient who presented with painless hand swelling that was misdiagnosed as lymphaticovenous malformation based on magnetic resonance imaging. The patient underwent surgical excision, and myxoinflammatory fibroblastic sarcoma was diagnosed postoperatively. All surgical interventions failed to achieve negative margin. A decision to start radiotherapy was made, and tissue convergence was done temporally using acellular dermal matrix and split-thickness skin graft. On patient follow-up, the graft had taken well, and the patient was undergoing radiotherapy sessions with a plan for permanent hand reconstruction after negative margins are achieved. Based on this case report, we identified that magnetic resonance imaging is not yet a reliable method to diagnose myxoinflammatory fibroblastic sarcoma. Therefore, implementing a multidisciplinary team approach, a preoperative core needle biopsy, planned surgical intervention, and early involvement of radiotherapy is recommended to minimize morbidity. We strongly urge establishing a sarcoma specialized treatment center in the region to limit patient morbidity.

A Systematic Review and Meta-analysis of Randomized Controlled Trials Comparing Surgical versus Conservative Treatments for Acute Undisplaced or Minimally-Displaced Scaphoid Fractures.

BACKGROUND: Surgical and conservative methods have been reported by various studies for high rates of fracture union and subsequent regain of function among patients with undisplaced or minimally-displaced scaphoid fractures. Hence, this study aims to analyze the best available evidence to comprehend the relative benefits and risks of these therapeutic options. METHODS: A systematic search of the literature from different databases and search engines was performed with strict eligibility criteria to obtain the highest quality of evidence. All randomized controlled trials delineating the outcomes of surgical versus conservative treatments for acute undisplaced or minimally-displaced scaphoid fractures were included and then evaluated using scoring tools: Cochrane risk of bias tool and PEDro scale. Data were pooled using random-effects models with standard mean differences for continuous outcomes and risk ratios for dichotomous variables. RESULTS: The search yielded 339 potentially related articles, further trimmed down to eight studies based on the eligibility criteria. The meta-analysis revealed that surgical treatment resulted in significantly better functional outcomes than conservative treatment. Furthermore, surgery resulted in the prevention of delayed union of fractures and reduction of time needed to return to work. CONCLUSIONS: While four studies reported advantages of surgical treatment, evidence was insufficient to provide a definitive conclusion that surgery is a better option. Due to the significant limitations with respect to certain variables, the superiority of one method to the other could not be established.

Obesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance.

Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppresses adiponectin expression through epigenetic control and, in turn, exacerbates metabolic diseases in obesity. Obesity-induced, pro-inflammatory cytokines promote DNMT1 expression and its enzymatic activity. Activated DNMT1 selectively methylates and stimulates compact chromatin structure in the adiponectin promoter, impeding adiponectin expression. Suppressing DNMT1 activity with a DNMT inhibitor resulted in the amelioration of obesity-induced glucose intolerance and insulin resistance in an adiponectin-dependent manner. These findings suggest a critical role of adiponectin gene epigenetic control by DNMT1 in governing energy homeostasis, implying that modulating DNMT1 activity represents a new strategy for the treatment of obesity-related diseases.

Mature adipocyte proteome reveals differentially altered protein abundances between lean, overweight and morbidly obese human subjects.

Overweight (OW) and obese individuals are considered to be graded parts of the scale having increasing weight as a common feature. They may not, however, be part of the same continuum and may differ metabolically. In this study we applied an untargeted proteomic approach to compare protein abundances in mature adipocytes derived from the subcutaneous adipose tissue of overweight and morbidly obese female subjects to those of lean age matched controls. Mature adipocytes were isolated from liposuction samples of abdominal subcutaneous adipose tissue collected from both lean (L; n = 7, 23.3 ± 0.4 kg/m(2); mean BMI ± SD), overweight (OW; n = 8, 27.9 ± 0.6 kg/m(2); mean BMI ± SD) and morbidly obese (MOB; n = 7, 44.8 ± 3.8 kg/m(2); mean BMI ± SD) individuals. Total protein extracts were then compared by two-dimensional difference in gel electrophoresis (2D DIGE). One hundred and ten differentially expressed protein spots (i.e., fitting the statistical criteria ANOVA test, p < 0.05; fold-change ≥1.5) were detected, and of these, 89 were identified by MALDI-TOF mass spectrometry. Of these, 66 protein spots were common to both groups whereas 23 were unique to the MOB group. Significant differences were evident in the abundances of key proteins involved in glucose and lipid metabolism, energy regulation, cytoskeletal structure and redox control signaling pathways. Differences in the abundance of some chaperones were also evident. The differentially abundant proteins were investigated using Ingenuity Pathway Analysis (IPA) to establish their associations with known biological functions. The network identified in the OW group with the highest score relates to-: cell-to-cell signaling and interaction; in contrast, in the MOB group the major interacting pathways are associated with lipid metabolism, small molecule biochemistry and cancer. The differences in abundance of the differentially regulated proteins were validated by immunoblotting. These findings provide insights into metabolic differences in OW and MOB individuals.

Differential patterns of serum concentration and adipose tissue expression of chemerin in obesity: adipose depot specificity and gender dimorphism.

Chemerin, a recognized chemoattractant, is expressed in adipose tissue and plays a role in adipocytes differentiation and metabolism. Gender- and adipose tissue-specific differences in human chemerin expression have not been well characterized. Therefore, these differences were assessed in the present study. The body mass index (BMI) and the circulating levels of chemerin and other inflammatory, adiposity and insulin resistance markers were assessed in female and male adults of varying degree of obesity. Chemerin mRNA expression was also measured in paired subcutaneous and visceral adipose tissue samples obtained from a subset of the study subjects. Serum chemerin concentrations correlated positively with BMI and serum leptin levels and negatively with high density lipoprotein (HDL)-cholesterol levels. No correlation was found between serum chemerin concentrations and fasting glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, C-reactive protein or adiponectin. Similarly, no relation was observed with the homeostasis model assessment for insulin resistance (HOMA-IR) values. Gender- and adipose tissue-specific differences were observed in chemerin mRNA expression levels, with expression significantly higher in women than men and in subcutaneous than visceral adipose tissue. Interestingly, we found a significant negative correlation between circulating chemerin levels and chemerin mRNA expression in subcutaneous fat. Among the subjects studied, circulating chemerin levels were associated with obesity markers but not with markers of insulin resistance. At the tissue level, fat depot-specific differential regulation of chemerin mRNA expression might contribute to the distinctive roles of subcutaneous vs. visceral adipose tissue in human obesity.