Study of outcome of displaced calcaneal fractures by closed reduction and percutaneous internal fixation with multiple k wires and screws

Background: Calcaneum is the largest of the tarsal bones and the largest bone of the foot. Calcaneum fracture account for 2% of all fracture of the body and 60% of all tarsal fractures. Many calcaneal fractures are work related as they result from a fall from height, especially in male age 35-45 years. In our study we treated the displaced calcaneal fracture with closed reduction and percutaneous fixation using multiple percutaneous K-wires and screw to evaluate their functional outcome. Methods: The study was conducted as a prospective study at the department of Orthopaedics, Dr. Shankarrao chavan Government Medical College, Nanded, India during the period January 2019 to June 2020. Thirty patients of 20 to 60 years, who underwent surgical fixation for displaced calcaneal fracture using multiple K wires and screws were followed up. Functional outcomes at six month follow up were assessed. Results: In this study we selected 30 patients with displaced calcaneal fracture admitting in our institute. All patients underwent operative procedure in the form of multiple k wire and cc .screws by percutaneous approach Out of all 30 patients treated with this method had shown excellent results with minimal postoperative complications. Conclusions: The study with percutaneous K wires and screws for displaced calcaneal fractures showed very good functional outcome. Although it was not free of complications, our study has shown very good results. Technique involve in our study is less invasive, with minimum blood loss, less operative time without soft tissue stripping

Biological clustering supports both "Dutch'' and "British'' hypotheses of asthma and chronic obstructive pulmonary disease

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases. OBJECTIVE: We sought to determine, in terms of their sputum cellular and mediator profiles, the extent to which they represent distinct or overlapping conditions supporting either the "British" or "Dutch" hypotheses of airway disease pathogenesis. METHODS: We compared the clinical and physiological characteristics and sputum mediators between 86 subjects with severe asthma and 75 with moderate-to-severe COPD. Biological subgroups were determined using factor and cluster analyses on 18 sputum cytokines. The subgroups were validated on independent severe asthma (n = 166) and COPD (n = 58) cohorts. Two techniques were used to assign the validation subjects to subgroups: linear discriminant analysis, or the best identified discriminator (single cytokine) in combination with subject disease status (asthma or COPD). RESULTS: Discriminant analysis distinguished severe asthma from COPD completely using a combination of clinical and biological variables. Factor and cluster analyses of the sputum cytokine profiles revealed 3 biological clusters: cluster 1: asthma predominant, eosinophilic, high TH2 cytokines; cluster 2: asthma and COPD overlap, neutrophilic; cluster 3: COPD predominant, mixed eosinophilic and neutrophilic. Validation subjects were classified into 3 subgroups using discriminant analysis, or disease status with a binary assessment of sputum IL-1β expression. Sputum cellular and cytokine profiles of the validation subgroups were similar to the subgroups from the test study. CONCLUSIONS: Sputum cytokine profiling can determine distinct and overlapping groups of subjects with asthma and COPD, supporting both the British and Dutch hypotheses. These findings may contribute to improved patient classification to enable stratified medicine

Expression of the T Helper 17-Associated Cytokines IL-17A and IL-17F in Asthma and COPD

BACKGROUND: Asthma and COPD are characterized by airway dysfunction and inflammation. Neutrophilic airway inflammation is a common feature of COPD and is recognized in asthma, particularly in severe disease. The T helper (Th) 17 cytokines IL-17A and IL-17F have been implicated in the development of neutrophilic airway inflammation, but their expression in asthma and COPD is uncertain. METHODS: We assessed IL-17A and IL-17F expression in the bronchial submucosa from 30 subjects with asthma, 10 ex-smokers with mild to moderate COPD, and 27 nonsmoking and 14 smoking control subjects. Sputum IL-17 concentration was measured in 165 subjects with asthma and 27 with COPD. RESULTS: The median (interquartile range) IL-17A cells/mm² submucosa was increased in mild to moderate asthma (2.1 [2.4]) compared with healthy control subjects (0.4 [2.8]) but not in severe asthma (P = .04). In COPD, IL-17A(+) cells/mm² submucosa were increased (0.5 [3.7]) compared with nonsmoking control subjects (0 [0]) but not compared with smoking control subjects (P = .046). IL-17F(+) cells/mm² submucosa were increased in severe asthma (2.7 [3.6]) and mild to moderate asthma (1.6 [1.0]) compared with healthy controls subjects (0.7 [1.4]) (P = .001) but was not increased in subjects with COPD. IL-17A and IL-17F were not associated with increased neutrophilic inflammation, but IL-17F was correlated with the submucosal eosinophil count (rs = 0.5, P = .005). The sputum IL-17 concentration in COPD was increased compared with asthma (2 [0-7] pg/mL vs 0 [0-2] pg/mL, P < .0001) and was correlated with post-bronchodilator FEV₁% predicted (r = -0.5, P = .008) and FEV(1)/FVC (r = -0.4, P = .04). CONCLUSIONS: Our findings support a potential role for the Th17 cytokines IL-17A and IL-17F in asthma and COPD, but do not demonstrate a relationship with neutrophilic inflammation

Sputum mediator profiling in severe asthma: relationships with clinical phenotypes, airway inflammation and morphometry in stable disease and at exacerbations

Asthma is characterised by typical symptoms or cough, breathlessness and wheeze with variable airflow obstruction. It is severe in about 10% of asthmatics with persistent symptoms and frequent exacerbations. There is increasing recognition that asthma, and to a greater extent severe asthma, is a heterogeneous disease with respect to its aetiology, inflammatory profile, and clinical expression and treatment responses. However, our understanding of the relationship between cellular and cytokine profiles in severe asthma with symptoms, physiology, airway morphometry and environmental exposure to pathogens in stable disease and at exacerbations is poorly understood. I hypothesized that sputum mediator profiling in severe asthma would identify clinically important biological phenotypes in stable disease and provide insights into relationships with airway remodelling and reveal key dynamic changes in airway inflammation at exacerbation. I undertook a multivariate analysis of sputum mediators from severe asthmatics in stable state and found distinct biological phenotypes associated with clinical features and moreover differential sputum cell counts. Interestingly, in obese asthmatics sputum IL-5 was elevated in spite of a low sputum eosinophil count whereas bronchial submucosal eosinophils were increased suggesting eosinophil trafficking is altered in obese asthmatics. Sputum mediator profiles were weakly associated with airway morphometry. At exacerbation there were marked differences in sputum mediator profiles with upregulation of Th1 cytokines, TNF-R1 and IL-1β in those with evidence of bacterial colonisation and with IL-6R most strongly associated with severe exacerbations of asthma. In summary, this thesis has explored sputum mediator profiles in severe asthma; informed our understanding of the mechanisms underpinning the heterogeneity of disease and identified biomarkers of exacerbations

Formulation and Evaluation of Floating In-Situ Gel of Nicardipine Hydrochloride

The present research work aimed to formulate and evaluate a gastro retentive in situ gelling system of Nicardipine Hydrochloride using Sodium Alginate as gelling polymer, HPMC K100M as release retard polymer, calcium carbonate as a cross-linking agent, and tri-sodium citrate as fluidity enhancer agent to treat hypertension. The mechanism for the floatation was based on ionic cross-linking. Several evaluation tests were carried out for pre and final formulation evaluation. Based on the outcomes white-colored, viscous solution of uniform consistency was obtained. Batch B1 was very well prepared for the ability to control long-term drug release. The drug content was found to be > 97 %, the viscosities were in the acceptable range suitable for swallowing, and pH was found to be in the range of 7.33 – 7.68 which was compatible with oral digestion. Design expert 13 Software was used to derive results of interaction and responses based on the concentration of polymer and statistical analysis. The optimized formulation i.e., Batch B1 (0.6 % w/v and 0.5 % w/v HPMC K100M) showed a slow drug release of 96.44 % up to 12 hours. The best fit model for the drug release followed the Higuchi model which explained that the drug release occurred by the Fiskian mechanism i.e., a combination of both diffusion and erosion. The in-situ gel prepared can ultimately provide prolonged release, enhance the bioavailability of the drug and increase patient compliance. Keywords: - In situ gel, Ionic cross linking, Sodium alginate, HPMC K100M, Nicardipine Hydrochloride

Fibrocyte localisation to the ASM bundle in asthma: bidirectional effects on cell phenotype and behaviour.

Objectives Airway hyper-responsiveness and persistent airflow obstruction contribute to asthma pathogenesis and symptoms, due in part to airway smooth muscle (ASM) hypercontractility and increased ASM mass. Fibrocytes have been shown to localise to the ASM in asthma however it is not known whether fibrocytes localise to the ASM in nonasthmatic eosinophilic bronchitis (NAEB) and chronic obstructive pulmonary disease (COPD). In addition, the potential consequences of fibrocyte localisation to ASM as regards asthma pathophysiology has not been widely studied. Methods Fibrocytes and proliferating cells were enumerated in ASM in bronchial tissue using immunohistochemistry. The effects of primary ASM and fibrocytes upon each other in terms of phenotype and behaviour following co-culture were investigated by assessing cell number, size, apoptotic status, phenotype and contractility in cell-based assays. Results Increased fibrocyte number in the ASM was observed in asthma versus NAEB, but not NAEB and COPD versus controls, and confirmed in asthma versus controls. ASM proliferation was not detectably different in asthmatics versus healthy controls . No difference in proliferation, apoptotic status or size of ASM was seen following culture with/without fibrocytes. Following co-culture with ASM from asthmatics versus nonasthmatics, fibrocyte smooth muscle marker expression and collagen gel contraction were greater. Following co-culture, fibrocyte CD14 expression was restored with the potential to contribute to asthma pathogenesis via monocyte-mediated processes dependent on the inflammatory milieu. Conclusion Further understanding of mechanisms of fibrocyte recruitment to and/or differentiation within the ASM may identify novel therapeutic targets to modulate ASM dysfunction in asthma

Sputum mediator profiling and relationship to airway wall geometry imaging in severe asthma

Background: Severe asthma is a heterogeneous disease and the relationship between airway inflammation and airway remodelling is poorly understood. We sought to define sputum mediator profiles in severe asthmatics categorised by CT-determined airway geometry and sputum differential cell counts. Methods: In a single centre cross-sectional observational study we recruited 59 subjects with severe asthma that underwent sputum induction and thoracic CT. Quantitative CT analysis of the apical segment of the right upper lobe (RB1) was performed. Forty-one mediators in sputum samples were measured of which 21 mediators that were assessable in >50% of samples were included in the analyses. Results: Independent of airway geometry, sputum MMP9 and IL-1β were elevated in those groups with a high sputum neutrophil count while sputum ICAM was elevated in those subjects with a low sputum neutrophil count. In contrast, sputum CCL11, IL-1α and fibrinogen were different in groups stratified by both sputum neutrophil count and airway geometry. Sputum CCL11 concentration was elevated in subjects with a low sputum neutrophil count and high luminal and total RB1 area, whereas sputum IL1α was increased in subjects with a high sputum neutrophil count and low total RB1 area. Sputum fibrinogen was elevated in those subjects with RB1 luminal narrowing and in those subjects with neutrophilic inflammation without luminal narrowing. Conclusions: We have demonstrated that sputum mediator profiling reveals a number of associations with airway geometry. Whether these findings reflect important biological phenotypes that might inform stratified medicine approaches requires further investigation