Plastic Surgery After Gastric Bypass Improves Long-Term Quality of Life

Background: Excess skin after massive weight loss impairs patient's health-related quality of life (HRQoL). Therefore, body-contouring surgeries can be proposed. However, few data exist concerning the effect of body contouring after bariatric surgery on HRQoL, including control group with a long-term follow-up. Methods: In a prospective study, 98 consecutive patients who had body contouring after gastric bypass for obesity (BMI > 40) were included (group A). A matched control-group containing 102 patients who had only gastric bypass was selected (group B). HRQoL was measured by Moorehead-Ardelt questionnaire before (group A1) and after (A2) body contouring, and at different time points for group B until 8years post-gastric bypass. To evaluate the effect of body contouring by two parallel methods, HRQoL was compared between groups A1 and A2, and between A2 and B. Results: We found that body contouring procedures improved significantly patients' HRQoL, in comparison to those who had only gastric bypass. Of the patients who had body contouring (group A2), 57% evaluated their HRQoL "much better” in comparison to only 22% of patients before body contouring (group A1) or those who never had body contouring (group B) (p < 0.001). The improvement was significant in all sub-domains of HRQoL: self-esteem, social life, work ability, sexual activity and physical activity (p < 0.001), and remained stable over time. Conclusions: Our study confirms the important role of plastic surgery in treatment of patients after massive weight loss. We demonstrated that body contouring, despite important scars, significantly improves satisfaction and HRQoL of patients after gastric bypass. Therefore, the treatment of morbid obesity should not be deemed achieved unless plastic surgery has been considere

Upregulation of circulating cancer stem cell marker, DCLK1 but not Lgr5, in chemoradiotherapy-treated colorectal cancer patients

Cancer stem cell (CSC) markers have attracted considerable attention in tumor diagnostic, prognostic, and therapeutic implications. Detection of cancer stem cells in circulating blood using cancer stem cell markers has received remarkable attention recently. In this study, we aimed to investigate the messenger RNA (mRNA) expression level of Lgr5 and DCLK1 as most proposed colorectal CSC markers in blood circulation also determine the subsequent association to patients� clinical and pathological findings. Peripheral blood mononuclear cells (PBMCs) of 58 patients with colorectal cancer at stage I�IV with 33 out of 58 patients undergoing preoperative chemoradiotherapy (CRT), as well as 58 healthy controls have been isolated and the extracted RNAs were analyzed using real-time PCR. The mRNA expression pattern of CSC markers of patients and controls was compared using ��Ct method. The expression level of Lgr5 was significantly higher in colorectal cancer (CRC) patients comparing to healthy group (4.8-fold change, p < 0.001). Also there was a significant increase in expression level of Lgr5 in patients at stages III and IV comparing to stages I and II (p = 0.031) and higher grades (p = 0.039) of CRC. The expression of DCLK1 was also elevated in patients significantly (2.7-fold change, p < 0.001) and the related expression was increased by increasing disease stage (p = 0.025). Combination of DCLK1 and Lgr5 markers was analyzed by logistic regression and proved to be a slightly better marker compared to each marker alone. Interestingly the DCLK1 expression level was significantly higher in patients undergoing preoperative CRT (p = 0.041); however, no association to neoadjuvant CRT was observed for Lgr5. Considering the over-expression of DCLK1 and Lgr5 in circulating blood of CRC patients comparing to controls, our results might emphasize on the presence of CSCs in blood of these patients which might be attributed to their clinical and pathological characteristics and may lead to apply in future clinical implications. Moreover, the higher expression level of DCLK1 in patients undergoing CRT can propose it as a more relevant candidate among CSC markers comparing to Lgr5 for CRC patients. © 2015, International Society of Oncology and BioMarkers (ISOBM)

Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b)

Background: Glycogen storage disease (GSD) is a rare inborn error of the synthesis or degradation of glycogen metabolism. GSD1, the most common type of GSD, is categorized into GSD1a and GSD1b which caused by the deficiency of glucose-6-phosphatase (G6PC) and glucose-6-phosphate transporter (SLC37A4), respectively. The high rates of consanguineous marriages in Iran provide a desirable context to facilitate finding the homozygous pathogenic mutations. This study designates to evaluate the clinical and genetic characteristics of patients with GSD1b to assess the possible genotype-phenotype correlation. Results: Autozygosity mapping was performed on nineteen GSD suspected families to suggest the causative loci. The mapping was done using two panels of short tandem repeat (STR) markers linked to the corresponding genes. The patients with autozygous haplotype block for the markers flanking the genes were selected for direct sequencing. Six patients showed autozygosity in the candidate markers for SLC37A4. Three causative variants were detected. The recurrent mutation of c.10421043delCT (p.Leu348Valfs*53) and a novel missense mutation of c.365G > A (p.G122E) in the homozygous state were identified in the SLC37A4. In silico analysis was performed to predict the pathogenicity of the variants. A novel whole SLC37A4 gene deletion using long-range PCR and sequencing was confirmed as well. Severe and moderate neutropenia was observed in patients with frameshift and missense variants, respectively. The sibling with the whole gene deletion has shown both severe neutropenia and leukopenia. Conclusions: The results showed that the hematological findings may have an appropriate correlation with the genotype findings. However, for a definite genotype-phenotype correlation, specifically for the clinical and biochemical phenotype, further studies with larger sample sizes are needed. © 2020 The Author(s)

IL-25 participates in keratinocyte-driven dermal matrix turnover and is reduced in systemic sclerosis epidermis

OBJECTIVES: Evidence shows that dysfunctional SSc keratinocytes contribute to fibrosis by altering dermal homeostasis. Whether IL-25, an IL-17 family member regulating many epidermal functions, takes part in skin fibrosis is unknown. Here we address the role of IL-25 in skin fibrosis. METHODS: The expression of IL-25 was evaluated by immunofluorescence and in situ hybridization in 10 SSc and seven healthy donor (HD) skin biopsies. Epidermal equivalents (EE) reconstituted by primary HD keratinocytes were used as a model to study transcriptomic changes induced by IL-25 in the epidermis. RNA expression profile in EEs was characterized by RNAseq. The conditioned medium (CM) from primary SSc and HD keratinocytes primed with IL-25 was used to stimulate fibroblasts. IL-6, IL-8, MMP-1, type-I collagen (Col-I), and fibronectin production by fibroblasts was assessed by ELISA. RESULTS: SSc epidermis expressed lower levels of IL-25 compared with HDs. In EEs, IL-25 regulated several molecular pathways related to wound healing and extracellular matrix remodelling. Compared with control CM, the CM from IL-25-primed keratinocytes enhanced the fibroblast production of MMP-1, IL-6 and IL-8, but not of Col-I nor fibronectin. However, IL-25 significantly reduced the production of Col-I when applied directly to fibroblasts. The activation of keratinocytes by IL-25 was receptor-dependent and evident after a very short incubation time (10 min), largely mediated by IL-1, suggesting enhanced and specific release of preformed mediators. CONCLUSIONS: These results show that IL-25 participates in skin homeostasis, and its decreased expression in SSc may contribute to skin fibrosis by favouring extracellular matrix deposition over degradation

Forehead biconvexity enhancement with fat grafting

Background: Frontal biconvexity is a key criterion for an attractive forehead. Fat injection as an effective, safe and reliable method for soft tissue augmentation could be used to enhance forehead contour. We report our experience with combined platelet-rich plasma (PRP) and fat grafting to create or restore frontal biconvexity and to reduce wrinkles. Methods: Fifty-seven females and 4 males (mean age, 40.2 years) underwent the combined PRP and fat injection. Fat mixed with PRP on the ratio of 5:1 was injected in small aliquots in the space between the dermis and underlying frontalis muscle. Patient satisfaction with the cosmetic result was evaluated by a questionnaire using pre- and postoperative photos and a four-point grading scale. Results: All patients who underwent three injection sessions (n = 5) evaluated the esthetic result as excellent. In patients who had two injection sessions (n = 36), 36 evaluated the result as excellent, 50 as good, and the remaining 5 as moderate. In patients who had a single injection session (n = 15), 27 evaluated the result as excellent, 40 as good, and the remaining 5 as moderate. Concerning frontal wrinkles, 25 of 34 (73.5) patients reported good improvement and the remaining 9 (26.5) reported moderate improvement. Conclusion: Fat injection combined with PRP should be considered as an effective tool to improve forehead biconvexity. Level of evidence: Level IV, therapeutic study. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature

Weekly Multi-agent Chemotherapy (CMF-b) for Advanced Non-melanoma Skin Cancer.

Advanced unresectable and metastatic non-melanoma skin cancers (NMSC) are rare, but often arise in elderly patients. When surgery or irradiation are no longer feasible, chemotherapy is often precluded by the patient's age and comorbidities. Whether low-dose multi-agent chemotherapy could be an alternative for this vulnerable population in an outpatient setting was the issue examined in this retrospective analysis. Twenty-six patients with advanced unresectable or metastatic NMSC received weekly multi-agent chemotherapy with carboplatin at an area under the curve of 2 or 40 mg total dose of cisplatin, with 15 IU total dose of bleomycin, 40 mg total dose of methotrexate, and 500 mg total dose of 5-fluorouracil (CMF-b) until best response, toxicity, or progression of their disease. Twenty-four patients were treated as outpatients; two were hospitalized. Twenty-three patients were previously treated with surgery or radiotherapy. The median age was 68 years (range=44-100 years). The median number of cycles was 6 (range=1 to 17). The overall response rate was 61.5% (seven complete remissions, nine partial remissions) for the entire cohort and 63.6% (two complete remissions and five partial remissions) for patients &gt;80 years. The median duration of response was 6.1 months (range=1.6-63 months). Responses longer than 6 months were obtained in 11/26 (42.3%) of the entire cohort and in 4/11 (36.3%) patients &gt;80 years. Symptom improvement was observed in 17 patients (65.3%). Toxicity was acceptable, with grade 3 renal failure (n=1) and grade 3 or 4 myelotoxicity (n=2). CMF-b is a safe, weekly low-dose multi-agent regimen that offers palliation for vulnerable patients with NMSC

In vitro effects of glutathione on Transforming Growth Factor beta and epidermal Growth Factor Receptor genes expression in the protoscoleces and strobilated worms of Echinococcus granulosus

Cystic Echinococcosis (CE) caused by the small taeniid cestode Echinococcus granulosus, is a globally distributed zoonosis. Administration of some chemicals or natural compounds could lead to significant effects on the expression of some developmentally important genes including Transforming Growth Factor beta (TGF-β) and Epidermal Growth Factor Receptor (EGFR) in other parasitic organisms. The main purpose of this study was to describe the effect of glutathione (GSH) on the expression of TGF-β and EGFR genes in different developmental stages of E. granulosus. Protoscoleces of hydatid cysts collected from naturally infected sheep liver were cultured in diphasic CMRL1066 medium. Glutathione Mono-ethyl Ester (GME) at 250 μg/ml concentration was applied on the invaginated protoscoleces (PSCi), evaginated protoscoleces (PSCe) and strobilated worms (SW3) in vitro. TGF-β and EGFR genes expression were evaluated by using Real Time qPCR analysis compared to the controls. In response to GME treatment TGF-β expression was affected, however no significant effect was observed in EGFR expression. The results indicate a significant difference of TGF-β expression in the intact protoscoleces and the strobilated worms comparing to the controls. In intact invaginated protoscoleces TGF-β expression was significantly increased (p < 0.01) while in the strobilated worms a significant decrease was observed comparing to no-treatment controls (p < 0.001). None of the three developmental stages of E. granulosus demonstrated significant changes in EGFR expression. The results indicated that administration of GSH modified TGF-β expression in the protoscoleces and strobilar stages of E. granulosus. To improve our understanding of the physiology and biochemistry of the parasite more in depth in vitro and in vivo studies on the morphological and molecular effects of glutathione on the parasite is recommended. Further investigation on the gene profiles in other stages including microcysts and germinal layer cells is also suggested. This paves the way for the effective treatment and control of cystic echinococcosis. © 2020 Elsevier Inc