The fate of aspergilloma patients after surgical treatment-experience from 22 cases

Background: Patients with pulmonary aspergillomas occasionally undergo surgery but it is somewhat unclear who of these patients benefit from surgical treatment. Methods: We retrospectively evaluated all 22 patients that underwent surgery in Helsinki University Central Hospital between 2004 and 2017. We assessed their clinical backgrounds, anti-fungal medication, indication for surgery, complications, recurrent infections and survival. Results: Of the 22 patients, 14 male and 8 female, mean age 56, an underlying pulmonary disease was present in 20. On immunosuppressive medication were 8 (36%). Most received anti-fungal medication preoperatively (n=12) and/or postoperatively (n=17), 3 patients did not receive anti-fungal medication. Length of the medication periods were diverse. Main indication for surgery was haemoptysis. One in-hospital-death occurred, and other complications included prolonged air-leak, postoperative pneumonia, pneumothorax and pneumomediastinum. No Aspergillus empyema or pleurites occurred. Five-year survival was 54%. One in-hospital-death and one other death were the result of Aspergillus disease, other deaths were unrelated to Aspergillus. Recurrent disease occurred in four cases. Three of these patients were asthma patients with allergic bronchopulmonary aspergillosis (ABPA). Conclusions: Overall results of surgery in this cohort were good and number of complications was low. Therapy with antifungals was diverse. Surgical treatment of aspergilloma can be life-saving for patients suffering of haemoptysis, and patients with restricted disease and well-preserved pulmonary capacity may benefit from surgery. Careful patient selection is crucial.Peer reviewe

Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis) by affecting vertebral body growth plates (endplate physes). A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc) wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the effects of mechanical strain on chondrocytic metabolism a possible target for novel therapeutic intervention

The interaction of Thrombospondins with extracellular matrix proteins

The thrombospondins (TSPs) are a family of five matricellular proteins that appear to function as adapter molecules to guide extracellular matrix synthesis and tissue remodeling in a variety of normal and disease settings. Various TSPs have been shown to bind to fibronectin, laminin, matrilins, collagens and other extracellular matrix (ECM) proteins. The importance of TSP-1 in this context is underscored by the fact that it is rapidly deposited at the sites of tissue damage by platelets. An association of TSPs with collagens has been known for over 25 years. The observation that the disruption of the TSP-2 gene in mice leads to collagen fibril abnormalities provided important in vivo evidence that these interactions are physiologically important. Recent biochemical studies have shown that TSP-5 promotes collagen fibril assembly and structural studies suggest that TSPs may interact with collagens through a highly conserved potential metal ion dependent adhesion site (MIDAS). These interactions are critical for normal tissue homeostasis, tumor progression and the etiology of skeletal dysplasias

Can mental health diagnoses in administrative data be used for research? A systematic review of the accuracy of routinely collected diagnoses

BACKGROUND: There is increasing availability of data derived from diagnoses made routinely in mental health care, and interest in using these for research. Such data will be subject to both diagnostic (clinical) error and administrative error, and so it is necessary to evaluate its accuracy against a reference-standard. Our aim was to review studies where this had been done to guide the use of other available data. METHODS: We searched PubMed and EMBASE for studies comparing routinely collected mental health diagnosis data to a reference standard. We produced diagnostic category-specific positive predictive values (PPV) and Cohen’s kappa for each study. RESULTS: We found 39 eligible studies. Studies were heterogeneous in design, with a wide range of outcomes. Administrative error was small compared to diagnostic error. PPV was related to base rate of the respective condition, with overall median of 76 %. Kappa results on average showed a moderate agreement between source data and reference standard for most diagnostic categories (median kappa = 0.45–0.55); anxiety disorders and schizoaffective disorder showed poorer agreement. There was no significant benefit in accuracy for diagnoses made in inpatients. CONCLUSIONS: The current evidence partly answered our questions. There was wide variation in the quality of source data, with a risk of publication bias. For some diagnoses, especially psychotic categories, administrative data were generally predictive of true diagnosis. For others, such as anxiety disorders, the data were less satisfactory. We discuss the implications of our findings, and the need for researchers to validate routine diagnostic data. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12888-016-0963-x) contains supplementary material, which is available to authorized users

New tools for the study of an old collagen:characterization of the human COL9A1, COL9A2 and COL9A3 genes and production of human type IX collagen as a recombinant protein

Abstract Type IX collagen is a quantitatively minor component of cartilage collagen fibrils. Although a few mutations have been associated with multiple epiphyseal dysplasia, recent evidence suggests involvement of type IX collagen in a wider spectrum of phenotypes. The functional role of this molecule remains undetermined, in part due to difficulties in obtaining high amounts of intact protein. To facilitate more efficient mutation screening and comparison of the genomic organization of the human genes encoding the α1(IX), α2(IX) and α3(IX) polypeptides, their genomic structures were characterized. Complete nucleotide sequences were determined for the COL9A2 and COL9A3 genes along with sequences for all the exon boundaries in the COL9A1 gene. Putative transcription control elements were identified and the alternative promoter region was characterized in the human and mouse COL9A1 genes. Mutation screening was performed for the COL9A3 gene and two apparently neutral 9-bp deletions within the COL1 domain were identified. These are the first deletions within a triple-helical domain of any collagen that are not associated with a disease phenotype. An insect cell expression system with an exogenous source of prolyl 4-hydroxylase was used to produce heterotrimeric human type IX collagen. The recombinant protein consisted of the three a chains in a 1:1:1 ratio and showed correct folding and high thermal stability. Up to 10 mg of secreted protein could be purified from a litre of culture medium. The expression system was used to analyze the chain association of type IX collagen in cellulo. Although the chains are capable of homotrimerization, a preference for heterotrimer formation was noted.The neutral deletion was characterized further using the insect cell system. Mutant α3(IX) chains carrying a deletion of one Gly-X-Y triplet were shown to form correctly folded heterotrimers with the wild-type α1(IX) and α2(IX) chains. The results suggest a function for the NC2 domain in neutralizing the effect of the deletion. This work provides a novel means for the analysis of type IX collagen mutations and their protein-level effects, and should enable future studies to be made of the structure-function relationship in type IX collagen