A structural and metabolic framework for classifying pre-clinical tuberculosis infection phenotypes using 18F-FDG PET-CT: a prospective cohort analysis following M. tuberculosis exposure.

Tuberculosis (TB) control efforts are limited by ineffective characterisation of tuberculosis infection (TBI) -a heterogeneous spectrum of pre-clinical infection states, invisible to tools of routine clinical screening, that are associated with variable risk of progression to TB disease. In this prospective study, we use positron emission tomography-CT (PET-CT) as a high-resolution imaging modality to characterise and classify structural and metabolic features observed in 16 asymptomatic household TB contacts with normal chest radiographs. We identify four feature patterns that associate with distinct clinical and microbiological outcomes, supporting potential utility of PET-CT for objective classification of TBI phenotypes.

Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19.

BACKGROUND: Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19. METHODS: For this prospective outcomes validation study, we developed a radiotranscriptomic platform that uses RNA sequencing data from human internal mammary artery biopsies to develop novel radiomic signatures of vascular inflammation from CT angiography images. We then used this platform to train a radiotranscriptomic signature (C19-RS), derived from the perivascular space around the aorta and the internal mammary artery, to best describe cytokine-driven vascular inflammation. The prognostic value of C19-RS was validated externally in 435 patients (331 from study arm 3 and 104 from study arm 4) admitted to hospital with or without COVID-19, undergoing clinically indicated pulmonary CT angiography, in three UK National Health Service (NHS) trusts (Oxford, Leicester, and Bath). We evaluated the diagnostic and prognostic value of C19-RS for death in hospital due to COVID-19, did sensitivity analyses based on dexamethasone treatment, and investigated the correlation of C19-RS with systemic transcriptomic changes. FINDINGS: Patients with COVID-19 had higher C19-RS than those without (adjusted odds ratio [OR] 2·97 [95% CI 1·43-6·27], p=0·0038), and those infected with the B.1.1.7 (alpha) SARS-CoV-2 variant had higher C19-RS values than those infected with the wild-type SARS-CoV-2 variant (adjusted OR 1·89 [95% CI 1·17-3·20] per SD, p=0·012). C19-RS had prognostic value for in-hospital mortality in COVID-19 in two testing cohorts (high [≥6·99] vs low [<6·99] C19-RS; hazard ratio [HR] 3·31 [95% CI 1·49-7·33], p=0·0033; and 2·58 [1·10-6·05], p=0·028), adjusted for clinical factors, biochemical biomarkers of inflammation and myocardial injury, and technical parameters. The adjusted HR for in-hospital mortality was 8·24 (95% CI 2·16-31·36, p=0·0019) in patients who received no dexamethasone treatment, but 2·27 (0·69-7·55, p=0·18) in those who received dexamethasone after the scan, suggesting that vascular inflammation might have been a therapeutic target of dexamethasone in COVID-19. Finally, C19-RS was strongly associated (r=0·61, p=0·00031) with a whole blood transcriptional module representing dysregulation of coagulation and platelet aggregation pathways. INTERPRETATION: Radiotranscriptomic analysis of CT angiography scans introduces a potentially powerful new platform for the development of non-invasive imaging biomarkers. Application of this platform in routine CT pulmonary angiography scans done in patients with COVID-19 produced the radiotranscriptomic signature C19-RS, a marker of cytokine-driven inflammation driving systemic activation of coagulation and responsible for adverse clinical outcomes, which predicts in-hospital mortality and might allow targeted therapy. FUNDING: Engineering and Physical Sciences Research Council, British Heart Foundation, Oxford BHF Centre of Research Excellence, Innovate UK, NIHR Oxford Biomedical Research Centre, Wellcome Trust, Onassis Foundation.

Abemaciclib in patients with p16ink4A-deficient mesothelioma (MiST2): a single-arm, open-label, phase 2 trial.

BACKGROUND: Genetically stratified therapy for malignant mesothelioma is unavailable. Mesotheliomas frequently harbour loss of the chromosome 9p21.3 locus (CDKN2A-MTAP), which is associated with shorter overall survival due to loss of the tumour suppressor p16ink4A, an endogenous suppressor of cyclin-dependent kinase (CDK)4 and CDK6. Genetic restoration of p16ink4A suppresses mesothelioma in preclinical models, underpinning the rationale for targeting CDK4 and CDK6 in p16ink4A-negative mesothelioma. We developed a multicentre, stratified, phase 2 trial to test this hypothesis. METHODS: The MiST2 study was a single-arm, open-label, phase 2 clinical trial done two UK centres. Patients older than 18 years with any histologically confirmed subtype of mesothelioma (pleural or peritoneal) with radiological progression after at least one course of platinum-based chemotherapy were molecularly screened by immunohistochemistry for p16ink4A. Patients with p16ink4A-negative mesothelioma were eligible for inclusion in the study. Patients were required to have measurable disease by modified Response Evaluation Criteria in Solid Tumours version 1.1 for malignant mesothelioma, a predicted life expectancy of at least 12 weeks, and an Eastern Cooperative Oncology Group performance status score of 0-1. Patients received oral abemaciclib 200 mg twice daily, administered in 28-day cycles for 24 weeks. The primary endpoint was the disease control rate (patients with complete responses, partial responses, or stable disease) at 12 weeks. The null hypothesis could be rejected if at least 11 patients had disease control. The efficacy and safety populations were defined as all patients who received at least one dose of the study drug. The study is registered with ClinicalTrials.gov, NCT03654833, and is ongoing (but MiST2 is now closed). FINDINGS: Between Sept 31, 2019, and March 2, 2020, 27 eligible patients consented to molecular screening. The median follow-up was 18·4 weeks (IQR 6·7-23·9). One patient was excluded before treatment because of a serious adverse event before study drug allocation. 26 (100%) of 26 treated patients were p16ink4A deficient and received at least one dose of abemaciclib. Disease control at 12 weeks was reported in 14 (54%) of 26 patients (95% CI 36-71). Grade 3 or worse treatment-related adverse events (of any cause) occurred in eight (27%) of 26 patients (diarrhoea, dyspnoea, thrombocytopenia, vomiting, urinary tract infection, increased alanine aminotransferase, ascites, chest infection or suspected chest infection, neutropenic sepsis, alopecia, blood clot left calf, fall [broken neck and collar bone], haemoptysis, lower respiratory tract infection, and pulmonary embolism). Grade 3 or worse treatment-related adverse events occurred in three (12%) of 26 patients (diarrhoea, thrombocytopenia, vomiting, increased alanine aminotransferase, and pulmonary embolism). Serious adverse events occurred in six (23%) of 26 patients, leading to treatment discontinuation in one (4%) patient (diarrhoea, urinary tract infection, chest infection, neutropenic sepsis, fall [broken neck and collar bone], haemoptysis, lower respiratory tract infection, and pulmonary embolism). One patient had a serious adverse event related to abemaciclib (diarrhoea). One (4%) of 26 patients died from an adverse event (neutropenic sepsis). INTERPRETATION: This study met its primary endpoint, showing promising clinical activity of abemaciclib in patients with p16ink4A-negative mesothelioma who were previously treated with chemotherapy, and warrants its further investigation in a randomised study as a targeted stratified therapy. FUNDING: University of Leicester, Asthma UK and British Lung Foundation Partnership, and the Victor Dahdaleh Foundation.

True thymic hyperplasia causing pure red cell aplasia: a case report.

Pure red cell aplasia caused by true thymic hyperplasia is extremely rare. We report the case of a 25-year-old female diagnosed with pure red cell aplasia. Following a thymectomy confirming true thymic hyperplasia and corticosteroid therapy, complete response was achieved. Patients diagnosed with pure red cell aplasia should be investigated with a computerized tomographic scan to assess for thymic pathology and if present, this should be resected. Follow-up is essential to monitor for recurrence.

Diagnostic dilemma of Hodgkin's lymphoma versus tuberculosis: a case report and review of the literature.

BACKGROUND: Hodgkin's Lymphoma (HL) is a rare malignancy characterised histologically by the presence of Reed-Sternberg cells. Diagnosis of lymphomas can be difficult due to broad, non-specific presentations of disease, which can be similar to several other conditions ranging from infective, inflammatory or malignant causes, with one of the most common differentials being tuberculosis (TB). We aim to highlight the diagnostic dilemma of TB versus lymphoma with an atypical presentation of HL and explored areas for further research and improvement with a non-systematic literature review using MEDLINE database and Google Scholar. Written consent was obtained from the patient in compliance with ethical guidelines. CASE PRESENTATION: A 23-year-old Asian female initially presented to rheumatology with over a one-year history of neuropathic pain, alongside abnormal white cell count and inflammatory markers. This was investigated with magnetic resonance imaging resulting in an incidental finding of mediastinal mass and pulmonary infiltrates. An initial diagnosis of TB was made despite testing negative for acid-fast bacilli and anti-tubercular treatment was commenced. Four months later, following clinical deterioration and further investigations, a mediastinal biopsy assisted in diagnosing Stage IV HL. CONCLUSIONS: Lymphoma is often misdiagnosed as TB, prolonging time to treatment and may adversely impact patient prognosis due to disease progression. Existing TB guidelines for smear-negative cases are not clear when to consider alternative diagnoses. In smear-negative TB, lymphoma should be considered as a differential and definitive diagnostic tests such as molecular testing and histological examination of biopsies should be considered earlier in the diagnostic work-up to prevent diagnostic delay.

Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment.

Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20-50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/-3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/-22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evolutionary clusters dictate MPM inflammation and immune evasion. These results reveal potentially drugable evolutionary bottlenecking in MPM, and an impact of clonal architecture on shaping the immune landscape, with potential to dictate the clinical response to immune checkpoint inhibition.

Haemodynamic effects of pharmacologic stress with adenosine in patients with left ventricular systolic dysfunction.

BACKGROUND: In patients with heart failure, downregulation of adenosine receptor gene expression and impaired adenosine-related signal transduction may result in a diminished response to adenosine. This may have implications for cardiac stress testing. We evaluated the haemodynamic response to intravenous adenosine in patients with left ventricular systolic dysfunction (LVSD) undergoing stress cardiovascular magnetic resonance imaging (CMR). METHODS AND RESULTS: We retrospectively examined 497 consecutive patients referred for clinical stress CMR. Blood pressure and heart rate responses with intravenous adenosine were compared in patients with normal, mild-moderately impaired and severely impaired LV systolic function (ejection fraction [EF] > 55%, 36-55% and < 35%, respectively). Following 2 min of adenosine infusion, there was a significant difference between the groups in the heart rate change from baseline, with a diminished heart rate response in patients with LVSD (p < 0.001). An increase in the dose of adenosine (up to 210 µg/kg/min) was required to achieve a sufficient haemodynamic response in more patients with severe LVSD (41%) than those with mild-moderately impaired and normal LV systolic function (24% and 19%, respectively, p < 0.001). Even with increased doses of adenosine in subjects with severe LVSD, peak haemodynamic response remained blunted. With multivariate analysis age (p < 0.001) and LVEF (p = 0.031) were independent predictors of heart rate response to adenosine. CONCLUSION: Patients with reduced LVEF referred for stress CMR may have a blunted heart rate response to adenosine. Further study is warranted to determine whether this may be associated with reduced diagnostic accuracy and also the potential utility of further dose increases or alternative stressors.

Pharmacokinetics and pharmacodynamics of intranasally administered selegiline nanoparticles with improved brain delivery in Parkinson's disease.

Selegiline, a well-known anti-Parkinson agent, is reported to be associated with poor oral bioavailability and safety. Therefore, we formulated selegiline as chitosan nanoparticles and evaluated its pharmacokinetics and pharmacodynamics after intranasal administration to rats relative to those after oral administration. The optimized formulation exhibited spherical nanoparticles with more than 90% drug loading and steady in vitro and ex vivo drug release. Selegiline concentrations in the brain and plasma were 20- and 12-fold higher, respectively, after intranasal administration than after oral administration. Treatment with intranasal nanoparticles was also associated with better performance in locomotor activity, catalepsy, and stride length tests and significantly increased dopamine, catalase activity, and glutathione content in the brain. Therefore, intranasally administered selegiline nanoparticles holds superior therapeutic value compared to oral administration and can be a promising approach for the treatment of Parkinson's disease.

Brain targeted delivery of mucoadhesive thermosensitive nasal gel of selegiline hydrochloride for treatment of Parkinson's disease.

Selegiline hydrochloride (SL), is an anti-Parkinson's agent, has low-oral bioavailability due to its high first pass metabolism and scarce oral absorption. In the present study, SL mucoadhesive nasal thermosensitive gel (SNT-gel) was prepared to enhance the bioavailability and subsequently, its concentration in the brain. The SNT-gel was prepared using Poloxamer 407-Chitosan combination and optimised formulation was further evaluated for physicochemical parameters. The comparative pharmacodynamic studies including behavioural studies, biochemical testing and histopathology of the brain was carried out in rats for SNT-gel, SL-nasal solution and SL Marketed Tablets. The optimised SNT-gel formulation (SNT-V) revealed sol-gel transition at 33-34°C. In-vitro diffusion study of SNT-V showed 102.37 ± 2.1% diffusion at 12 h which reduced to 89.64 ± 1.2% in Ex-vivo diffusion. Comparative results of behavioural studies indicated an improved score of photoactometer and reduced motor deficit (catalepsy score) in SNT-gel treatment group as compared with other groups. Similarly, a significant increase in brain dopamine, reduction in monoamine oxidase B level, increase in catalase activity and level of reduced glutathione upon treatment with SNT-gel indicated its effectiveness which was also supported by histopathology results. Therefore, nasal thermosensitive gel holds better potential for brain targeting in Parkinson's disease over the conventional nasal or oral formulations.

Fabrication of topical metered dose film forming sprays for pain management.

Topical film-forming metered dose spray formulations were designed for management of pain. Ropivacaine, a local anesthetic is explored for its topical efficacy in alleviating pain. Metered dose spray containers, organic solvents, film forming polymers and permeation enhancers were utilized to fabricate the Metered Dose topical spray. Factors like viscosity, spray pattern, spray angle, volume of actuation, droplet size distribution of the metered dose spray formulation and drying time, flexibility and wash-ability of the film formed after spraying were assessed. Permeation of the drug into the porcine skin was observed based on ex-vivo diffusion studies and confocal microscopy. The results indicated a high level of drug concentration in the skin layers. Anti-nociceptive efficacy of the formulations was assessed on Wistar rats by hot plate and tail flick tests, based on the response to pain perception. The results were comparable to the conventional lidocaine gel. Topical film forming sprays have the ability to provide an accurate, long lasting and patient compliant delivery of drugs on the skin as compared to conventional gels.

Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route.

Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors.

A Study on Mortality Profile among Fifty Plus- (50+-) Population (FPP) of India: A 5-Year Retrospective Study at New Delhi District.

Objectives. To find out the mortality profile vis-a-vis different epidemiological factors at the time of autopsy among the 50+-Population. Material and Method. A five-year retrospective evaluation of medicolegal records between 2006 and 2010 was done at Lady Hardinge Medical College, New Delhi. Results. A total of 493 (17.78%) cases belonged to 50+-Population age group out of total 2773 autopsies performed. The proportion of unidentified/unknown persons among this age group was 36.51%. The unnatural and natural causes constituted 44.62% and 55.38% cases, respectively. The unspecified pneumonitis (50.18%) was reported as the commonest cause followed by coronary artery disease and respiratory tuberculosis among natural ones and the transport accident (57.27%) followed by accidental and intentional self-poisoning and exposure to noxious substances and falls among the unnatural ones. Conclusion. The findings reveal that this age group most commonly dies of natural causes rather than the unnatural ones even in autopsy cases. They have definite cure with timely interventions. The study also points out the need to devise the road and home safety measures to reduce mortality among the study population.

Surface-coated PLA nanoparticles loaded with temozolomide for improved brain deposition and potential treatment of gliomas: development, characterization and in vivo studies.

Hydrophobicity of PLA nanoparticles makes them a good substrate for macrophageal and reticulo-endothelial system uptake. Long-circulating properties can be imparted to these particles by coating them with hydrophilic stabilizers. Surface-modified PLA nanoparticles loaded with anti-cancer agent temozolomide were fabricated by solvent evaporation method and coated with surface modifiers. Selection of the surface modifier was based upon uptake of nanoparticles by K9 cells (liver cells). The particles were prepared and characterized for various physicochemical properties using transmission electron microscopy, differential scanning calorimetry, powder X-ray diffraction and in vitro dissolution studies. In vitro BBB permeation studies were performed using the co-culture model developed by using Madin-Darby canine kidney and C6 glioma cells as endothelial and glial cells, respectively. In vitro C6 glioma cell cytotoxicity, cellular proliferation, cellular migration and cellular uptake studies due to developed nanoparticles was assessed. In vivo studies such as pharmacokinetics, qualitative and quantitative biodistribution studies were performed for the developed nanoparticles. Drug-loaded nanoparticles with entrapment efficiency of 50% were developed. PEG-1000 and polysorbate-80 coated nanoparticles were least taken up by the liver cells. Characterization of the nanoparticles revealed formation of spherical shape nanoparticles, with no drug and excipient interaction. In vivo pharmacokinetics of developed nanoparticles depicted enhancement of half-life, area under the curve and mean residence time of the drug. Qualitative and quantitative biodistribution studies confirmed enhanced permeation of the drug into the brain upon loading into nanoparticles with less deposition in the highly perfused organs like lung, liver, spleen, heart and kidney.

A Simple and Safe Technique for CT Guided Lung Nodule Marking prior to Video Assisted Thoracoscopic Surgical Resection Revisited.

Aim. We describe our experience of a simple, safe, and reproducible technique for lung nodule marking prethoracoscopic metastasectomy. Thoracoscopic lung nodule resection reduces patient discomfort, complications, higher level of care, hospital stay, and cost; however, small deeply placed lung nodules are difficult to locate and resect thoracoscopically. Materials and Methods. We describe and review the success of our novel technique, where nodules are identified on a low dose CT and marked with methylene blue using CT fluoroscopy guidance immediately prior to surgery. Results. 30 nodules were marked with a mean size of 8 mm (4-18 mm) located at a mean depth of 17 mm, distributed through both lungs. Dye was detected at the pleural surface in 97% of the patients and at the nodule in 93%. There were no major complications. Thoracoscopic resection was possible in 90%. Conclusion. This is a simple and safe method of lung nodule marking to facilitate thoracoscopic resection in cases where this may not be technically possible due to nodule location.

Evaluation of anti-metastatic potential of Cisplatin polymeric nanocarriers on B16F10 melanoma cells.

Nanoparticles are being increasingly used in the field of cancer treatment due to their unique properties and advantages. The aim of the present research work was to prepare and characterize a polymeric albumin nanosystem for Cisplatin and evaluate its in-vitro efficacy against B16F10 melanoma. The developed nanoparticles were almost spherical in shape with a particle size in the range of 150-300 nm, low polydispersity values and about 80% drug entrapment efficiency. Albumin nanocarriers sustained the release of Cisplatin for more than 48 h, suggesting the reduction in dosing schedule for this drug. The results from in-vitro cell line studies indicated the dose dependent cytotoxic potential of drug loaded albumin nanoparticles, their potential to inhibit cell proliferation and induce morphological changes. In addition, these nanoparticles exhibited superiority to Cisplatin in hampering the cell migration. Developed nanoparticles caused cell cycle arrest along with time and concentration dependent cellular uptake in B16F10 cell line. These results signify that the prepared Cisplatin albumin nanoparticles could serve as a promising approach for B16F10 melanoma treatment.

Double-salting out assisted liquid-liquid extraction (SALLE) HPLC method for estimation of temozolomide from biological samples.

The role of temozolomide (TMZ) in treatment of high grade gliomas, melanomas and other malignancies is being defined by the current clinical developmental trials. Temozolomide belongs to the group of alkylating agents and is prescribed to patients suffering from most aggressive forms of brain tumors. The estimation techniques for temozolomide from the extracted plasma or biological samples includes high-performance liquid chromatography with UV detection (HPLC-UV), micellar electrokinetic capillary chromatography (MKEC) and liquid chromatography coupled to mass spectroscopy (LC-MS). These methods suffer from disadvantages like low resolution, low sensitivity, low recovery or cost involvement. An analytical method possessing capacity to estimate low quantities of TMZ in plasma samples with high extraction efficiency (%) and high resolution with cost effectiveness needs to be developed. Cost effective, robust and low plasma component interfering HPLC method using salting out liquid-liquid extraction (SALLE) technique was developed and validated for estimation of drug from plasma samples. The extraction efficiency (%) with conventional LLE technique with methanol, ethyl acetate, dichloromethane and acetonitrile was found to be 5.99±2.45, 45.39±4.56, 46.04±1.14 and 46.23±3.67 respectively. Extraction efficiency (%) improved with SALLE where sodium chloride was used as an electrolyte and was found to be 6.80±5.56, 52.01±3.13, 62.69±2.11 and 69.20±1.18 with methanol, ethyl acetate, dichloromethane and acetonitrile as organic solvent. Upon utilization of two salts for extraction (double salting liquid-liquid extraction) the extraction efficiency (%) was further improved and was twice of LLE. It was found that double salting liquid-liquid extraction technique yielded extraction efficiency (%) of 11.71±5.66, 55.62±3.44, 77.28±2.89 and 87.75±0.89. Hence a method based on double SALLE was developed for quantification of TMZ demonstrating linearity in the range of 0.47-20 µg/ml. The LOQ and LOD for the developed method were 0.4 µg/ml and 0.1 µg/ml, respectively. Thus, plasma non-interfering SALLE-HPLC method that is precise, robust, accurate, specific and cost effective for estimation of temozolomide from plasma samples was developed and validated.

Unraveling the cytotoxic potential of Temozolomide loaded into PLGA nanoparticles.

BACKGROUND: Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells.Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry. RESULTS: PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility. CONCLUSION: PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity.

Subcutaneous drain insertion in patients with post-operative extensive subcutaneous surgical emphysema: a single centre experience.

OBJECTIVE: Extensive surgical subcutaneous emphysema (ESE) albeit a benign condition could cause patients distress and in many cases temporary vision impairment. We describe the role and value of early subcutaneous drain insertion (SCD) in the management of ESE and patients' experience in this cohort study. METHODS: Extensive surgical subcutaneous emphysema is that which extends to the neck and/or the peri-orbital region. A cohort study of a prospectively collected data was conducted between December 2009 and January 2012. All patients with extensive post-operative surgical emphysema who had SCD (size ≥24 French gauge) were included. RESULTS: 1069 thoracic procedures were performed. 21 patients (1.96 %) were diagnosed with extensive surgical emphysema, there were 16 males, median age was 65 (54-82 years). There were 16 VATS and 5 open procedures. All patients had chest surgical emphysema, 16 patients had peri-orbital and neck swelling and 5 had neck swelling. Surgical emphysema occurred within a median of 3 days post-operatively. 14 (67 %) patients had 1 subcutaneous drain inserted, and 7 (33 %) had bilateral SCD insertion (1 drain each side). 19 (90 %) patients experienced improvement of their symptoms with resolution of neck and peri-orbital swelling within 1 day of SCD insertion, 2 patients had their symptoms improved within 2 days. All patients were satisfied with the outcome following insertion of SCD. CONCLUSIONS: ESE should always be investigated and treated promptly. Early SCD insertion has a valuable role in the management of ESE with improvement of patients' experience.