Health-related quality of life after oncological resection and reconstruction of the chest wall

Objectives: There is limited information of the health-related quality of life (HRQoL) after surgical treatment of chest wall tumors. This cross-sectional study aimed to assess long-term HRQoL after chest wall reconstruction following oncological resection. Methods: Seventy-eight patients having undergone chest wall tumor resection and reconstruction during 1997-2015 were invited to complete the 15D and QLQ-C30 HRQoL instruments. Results: Altogether, 55 patients (17 men and 38 women), with a mean (SD) age of 68 (14) years, completed the questionnaires (response rate 71%). Patients had been operated due to soft tissue sarcoma (n=16), advanced breast cancer (n=15), osteo- or chondrosarcoma (n=14), or other tumor (n=10). Median time after primary surgery was 66 (IQR 38, 141) months. The resection was full thickness in 29/55 cases and partial thickness in 26/55 cases. Chest wall reconstruction was required for 47/55 cases (85%). Reconstruction was performed using soft-tissue flap in eight cases, skeletal stabilizations with mesh or mesh-cement-mesh (sandwich method) in 15 cases, and skeletal stabilizations and soft-tissue flap in 24 cases. Patients' mean 15D score (0.878, SD 0.111) was comparable to that of the age- and gender-standardized general population (0.891, SD 0.041). Limitations in breathing and usual activities were noted. The QLQ-C30 cancer-specific HRQoL was 72 points (maximum 100). Scores in the QLQ-C30 Functional scales ranged from 78 (Physical) to 91 (Social). Conclusions: Long-term HRQoL in patients after chest wall reconstruction following oncological resection is fair and comparable to that of the general population. Limitations in breathing and usual activities can occur. (C) 2019 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Treatment of compound tibia fracture with microvascular latissimus dorsi flap and the Ilizarov technique : A cross-sectional study of long-term outcomes

Background: Extensive compound tibial fractures present reconstructive challenges. The present study aimed to assess the outcomes of microvascular latissimus dorsi (LD) flap combined with the Ilizarov technique for extensive compound tibial fractures with bone loss and bone healing complications. Methods: Patient records were reviewed retrospectively. The Lower Extremity Functional Scale (LEFS), the Disabilities of the Arm, Hand and Shoulder (DASH), and the 15D health-related quality of life (HRQoL) instrument were applied. Results: Between 1989 and 2014, 16 patients underwent reconstruction with a microvascular LD flap and bone transport (11/16) or late bone lengthening (5/16). The mean clinical follow-up time was 6.6 (standard deviation (SD): 6.5) years. Three patients had minor complications requiring reoperation. Partial necrosis of one flap required late flap reconstruction in one case. Late bone grafting was used to enhance union in eight of 16 cases. The mean new bone gain was 3.8 cm (SD: 2.5). Overall, 11 patients completed the questionnaires in a mean of 22.3 years (SD: 2.4) after surgery. The main findings revealed a relatively good function of the reconstructed limb and good shoulder function. The mean HRQoL was comparable to that of an age-standardized sample of the general population. Conclusion: Segmental tibia transport and lengthening to correct limb length discrepancy do not compromise the microvascular muscle flap. Combined microvascular LD flap reconstruction and the Ilizarov technique can be used in treating acute compound tibial defects, pseudoarthrosis, and osteitis, all associated with significant amputation risk. Fair long-term functional outcomes and HRQoL are achieved when these combined techniques are used. (C) 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Pretreatment resistin levels are associated with erosive disease in early rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs and infliximab

Objective: Resistin is an adipocytokine related to insulin resistance and inflammation. We investigated whether resistin is associated with disease activity and inflammation in disease-modifying anti-rheumatic drug (DMARD)-naive rheumatoid arthritis (RA) patients, whether it has predictive value for radiological disease progression, and whether tumour necrosis factor-alpha (TNF-alpha) is involved in these effects. Method: Ninety-nine patients with early, DMARD-naive RA participated in the NEO-RACo study. Patients were treated for the first 4 weeks with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone (FIN-RACo treatment). Thereafter, they were randomized to receive either infliximab or placebo added to the combination for 6 months. Patients were followed for 5 years. Disease activity was evaluated using the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate, radiographs were scored with the modified Sharp-van der Heijde method, and plasma resistin concentrations were measured by immunoassay. Human THP-1 macrophages were used in the in vitro studies. Results: A high resistin level at baseline was associated with active inflammatory disease and predicted more rapid radiological progression during 5 year follow-up. Adding infliximab to the DMARD combination delayed radiological progression and overcame the poor predictive value of resistin. Resistin increased TNF-alpha production in human macrophages, indicating a possible connection between resistin and TNF-alpha. Conclusion: The results suggest that high resistin concentration may be a useful marker to distinguish patients with an increased risk of erosive disease in early active RA, and that adding TNF-alpha antagonist to the traditional DMARD combination may delay radiological progression of the disease in these patients.Peer reviewe

Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia.

Schizophrenia is a severe psychiatric disorder with strong heritability and marked heterogeneity in symptoms, course, and treatment response. There is strong interest in identifying genetic risk factors that can help to elucidate the pathophysiology and that might result in the development of improved treatments. Linkage and genome-wide association studies (GWASs) suggest that the genetic basis of schizophrenia is heterogeneous. However, it remains unclear whether the underlying genetic variants are mostly moderately rare and can be identified by the genotyping of variants observed in sequenced cases in large follow-up cohorts or whether they will typically be much rarer and therefore more effectively identified by gene-based methods that seek to combine candidate variants. Here, we consider 166 persons who have schizophrenia or schizoaffective disorder and who have had either their genomes or their exomes sequenced to high coverage. From these data, we selected 5,155 variants that were further evaluated in an independent cohort of 2,617 cases and 1,800 controls. No single variant showed a study-wide significant association in the initial or follow-up cohorts. However, we identified a number of case-specific variants, some of which might be real risk factors for schizophrenia, and these can be readily interrogated in other data sets. Our results indicate that schizophrenia risk is unlikely to be predominantly influenced by variants just outside the range detectable by GWASs. Rather, multiple rarer genetic variants must contribute substantially to the predisposition to schizophrenia, suggesting that both very large sample sizes and gene-based association tests will be required for securely identifying genetic risk factors. © 2012 The American Society of Human Genetics

GPR37 is processed in the N‐terminal ectodomain by ADAM10 and furin

GPR37 is an orphan G protein-coupled receptor (GPCR) implicated in several neurological diseases and important physiological pathways in the brain. We previously reported that its long N-terminal ectodomain undergoes constitutive metalloprotease-mediated cleavage and shedding, which have been rarely described for class A GPCRs. Here, we demonstrate that the protease that cleaves GPR37 at Glu167↓Gln168 is a disintegrin and metalloprotease 10 (ADAM10). This was achieved by employing selective inhibition, RNAi-mediated downregulation, and genetic depletion of ADAM10 in cultured cells as well as in vitro cleavage of the purified receptor with recombinant ADAM10. In addition, the cleavage was restored in ADAM10 knockout cells by overexpression of the wild type but not the inactive mutant ADAM10. Finally, postnatal conditional depletion of ADAM10 in mouse neuronal cells was found to reduce cleavage of the endogenous receptor in the brain cortex and hippocampus, confirming the physiological relevance of ADAM10 as a GPR37 sheddase. Additionally, we discovered that the receptor is subject to another cleavage step in cultured cells. Using site-directed mutagenesis, the site (Arg54↓Asp55) was localized to a highly conserved region at the distal end of the ectodomain that contains a recognition site for the proprotein convertase furin. The cleavage by furin was confirmed by using furin-deficient human colon carcinoma LoVo cells and proprotein convertase inhibitors. GPR37 is thus the first multispanning membrane protein that has been validated as an ADAM10 substrate and the first GPCR that is processed by both furin and ADAM10. The unconventional N-terminal processing may represent an important regulatory element for GPR37

The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis

Peer reviewe

The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis

Peer reviewe

Impact testing to determine the mechanical properties of articular cartilage in isolation and on bone

The original publication is available at www.springerlink.comNon peer reviewedPostprin