Medical Imaging and Analysis of Thermal Necrosis During Bone Grinding: Implementation of Non-dominated Sorting Genetic Algorithm (NSGA-III) in Healthcare.

BACKGROUND: Medical imaging plays a key role in neurosurgery; thereby, imaging and analysis of the soft and hard tissues during bone grinding is of paramount importance for neurosurgeons. Bone grinding, a minimally invasive operation in the field of neurosurgery amid osteotomy, has been used during brain cancer surgery. AIMS AND OBJECTIVES: With increasing attention to neural tissue damage in machining operations, imaging of these neural tissues becomes vital and reducing temperature is imperative. METHOD: In the present study, a novel attempt has been made to perform the imaging of bone tissues during the bone grinding procedure and further investigate the relationship between rotational speed, feed rate, depth of cut with cutting forces, and temperature. The role of cutting forces and temperature has been addressed as per the requirements of neurosurgeons. Firstly, a three-factor, three-level design was constructed with a full factorial design. Regression models were employed to construct the models between input parameters and response characteristics. Medical imaging techniques were used to perform a thorough analysis of thermal necrosis and damage to the bone. Subsequently, the non-dominated sorting genetic algorithm (NSGA-III) was used to optimize the parameters for reduction in the cutting forces and temperature during bone grinding while reducing neural tissue damage. RESULTS: The results revealed that the maximum value of tangential force was 21.32 N, thrust force was 9.25 N, grinding force ratio was 0.453, torque was 4.55 N-mm, and temperature was 59.3°C. It has been observed that maximum temperature was generated at a rotational speed of 55000 rpm, feed rate of 60 mm/min, and depth of cut of 1.0 mm. Histopathological imaging analysis revealed the presence of viable lacunas, empty lacunas, haversian canals, and osteocytes in the bone samples. Furthermore, the elemental composition of the bone highlights the presence of carbon (c) 59.49%, oxygen (O) 35.82%, sodium (Na) 0.11%, phosphorous 1.50%, sulphur 0.33%, chlorine 0.98%, and calcium 1.77%. CONCLUSION: The study revealed that compared to the initial scenario, NSGA-III can produce better results without compromising the trial results. According to a statistical study, the rise in temperature during bone grinding was significantly influenced by rotating speed. The density of osteocytes in the lacunas was higher at lower temperatures. Furthermore, the results of surface electron microscopy and energy dispersive spectroscopy revealed the presence of bone over the surface of the grinding burr, which resulted in the loading of the grinding burr. The results of the present investigation will be beneficial for researchers and clinical practitioners worldwide.

Development and Optimization of Novel Emulgel Loaded with Andrographolide-Rich Extract and Sesame Oil Using Quality by Design Approach: In Silico and In Vitro Cytotoxic Evaluation against A431 Cells.

An epidermoid carcinoma is a form of non-melanoma skin cancer that originates from the outer layer of the skin's squamous cells. Previous studies have shown that andrographis extract and andrographolide inhibit the growth and proliferation of epidermoid carcinoma cells while also inducing cell cycle arrest and apoptosis. The objective of this study was to improve the anticancer efficacy of the andrographolide-rich extract by delivering it in the form of nanoemulgel. During the formulation of emulgels, sonication, and homogenization were employed, and a 22-factorial design was used to optimize the formulations through the quality by design (QbD) approach. The optimized formulation (AEE8) was subjected to preliminary evaluations along with particle size, drug release, and scanning electron microscopy (SEM) studies. The potential of the optimized emulgel against A431 cell lines was also investigated using MTT assay followed by flow cytometric analysis. The SEM results reveal that the optimized emulgel had a well-defined spherical shape, with a droplet size of 226 ± 1.8 nm, a negative surface charge of -30.1 ± 1.6 mV, and a PDI of 0.157. The cellular data indicate that AEE8 reduced the viability of the A431 cells with an IC50 of 16.56 µg/mL, as determined by MTT assay when compared to cells treated with the extract alone. Furthermore, the flow cytometric analysis of the optimized emulgel formulation demonstrated a marked G2/M phase arrest. This finding further supports the effectiveness of the gel in disrupting the cell cycle at the critical G2 and M phases, which are pivotal for cell division and proliferation. This disruption in cell cycle progression can impede the growth and spread of cancer cells, making the gel a promising candidate for anti-skin-cancer therapy. The safety of emulgels (AEE8) was validated through rigorous biocompatibility testing conducted on HDF (human dermal fibroblast) cell lines, ensuring their suitability for use. Considering the potential of the nanoemulgel, particularly AEE8, as demonstrated by its favorable properties and its ability to disrupt the cell cycle, it holds great promise as an innovative approach to treating skin cancer.

Comparative statement for diametric delamination in drilling of cortical bone with conventional and ultrasonic assisted drilling techniques.

Drilled hole quality is a significant parameter for successful orthopedic surgery. The present investigation is an effort to reduce the delamination produced drilling with state-of-the-art hybrid drilling i.e. ultrasonically-assisted drilling. A comparative analysis has carried out as per experimental design to assess the ultrasonic drilling with conventional drilling. The novelty of the work is the use of coordinate measuring machine (CMM) for characterization of the delamination during bone drilling. The results revealed that ultrasonically-assisted drilling caused lesser delamination than conventional drilling. The maximum percentage delamination during conventional drilling was found to be 9.153% and 8.541% during ultrasonically-assisted drilling.

Histological evaluation of thermal damage to Osteocytes: A comparative study of conventional and ultrasonic-assisted bone grinding.

This paper addresses an important issue faced by neurosurgeons during surgical skull bone grinding, a common process used to remove bone in skull base tumour removal surgery to enable the neurosurgeon to reach the target region. The heat generated during bone grinding could harm the soft tissues and can lead to osteonecrosis and cell death. In the present study, a novel process of rotary ultrasonic bone grinding (RUBG) was proposed for osteotomy to limit the temperature to a safe level. A systematic investigation was conducted to determine the effect of varying process parameters on osteonecrosis at the cut surface. Three input parameters - rotational speed, feed rate and frequency - were investigated (at three levels) in terms of change in temperature and thermal biological damage. A sterile solution was used as a coolant to irrigate the grinding zone. Viable lacunae (filled osteocytes), non-viable lacunae (empty lacunae), necrosed tissues, and Haversian canal were found during the histological examination. Statistical analysis revealed that feed rate (45.43%) had the highest contribution towards temperature rise during grinding, followed by ultrasonic frequency (23.87%), and rotational speed (12.85%). The optimal machining parameters to avoid osteonecrosis and thermal trauma were rotational speed 35,000 rpm, feed rate 20 mm/min and ultrasonic frequency 20 kHz. Furthermore, histograms revealed that ultrasonic skull bone grinding was associated with greater cell viability and reduced temperature compared with conventional bone grinding.

Finite element simulation and integration of CEM43 °C and Arrhenius Models for ultrasonic-assisted skull bone grinding: A thermal dose model.

The aim of the study was to develop a novel automated setup for bone grinding to limit the temperature to below 43 °C. The feasibility of using ultrasonic actuation during bone osteotomy was explored with different machining variables, such as rotational speed, feed rate and ultrasonic frequency, in terms of the criterion variable (i.e., temperature). A thermal dose model based on the CEM43 °C and the Arrhenius model was developed for the prediction of tissue damage during bone grinding. CEM43 °C is a normalizing method to convert the time-temperature relationship into an equivalent number of minutes at 43 °C. For every degree rise in temperature above 43 °C, the cell viability significantly increased. The temperature generated during bone grinding was measured with an infrared thermography technique. The increase in temperature above threshold levels of 43 °C and 47 °C may harm the bone tissues and cause thermogenesis and osteonecrosis, respectively. A finite-element simulation was conducted to visualise the spatial and temporal distribution of temperature on the bone surface after bone grinding. Furthermore, simulation results were used to measure the depth of thermogenesis and osteonecrosis at the grinding site. Evaluation of the optimised set of bone grinding process parameters was supported with analysis of variance at the 95% confidence level.

In vivo evaluation of machining forces, torque, and bone quality during skull bone grinding.

This study investigates neurosurgical bone grinding with varying parameters on skull bone using a miniature grinding burr. Three process parameters, namely, rotational speed, feed rate, and depth of cut, have been investigated at three different levels in the terms of tangential force, thrust force, and torque generated during grinding. The results revealed that as the rotational speed is increased, the cutting forces and torque showed a decreasing trend. Nevertheless, the increase in feed rate and depth of cut leads to the escalation in response characteristics. The best parametric combination for minimum cutting forces and torque is as follows: rotational speed = 55,000 r/min, feed rate = 20 mm/min, and depth of cut = 0.50 mm. Morphological analysis reveals cracks in the bone's surface at a higher feed rate. Furthermore, delamination and cutting streaks are also visible on the surface of the bone after grinding. Energy-dispersive spectroscopy and elemental mapping of the tool after bone grinding indicate the accumulation of the bone chips in the successive diamond abrasives. The outcomes of the study will be beneficial for the neurosurgeons in understanding the effect of various process parameters on cutting force, toque, microcracks, and bone's regeneration ability during surgical bone grinding.

Parametric effect of vibrational drilling on osteonecrosis and comparative histopathology study with conventional drilling of cortical bone.

Drilling to the bones is required to re-fix them at their appropriate location using the implants. During drilling some thermal and mechanical losses may be faced by the bone and surrounding tissues which may lead to the serious issue in terms of osteonecrosis. Osteonecrosis is one of the reasons for impaired healing process for the fractured bone and causes further complications like low pullout strength of cortical screws and bone crush. In order to maintain the low temperature during bone drilling, this study focused the thermal damages observed by the bone and its surrounding during bone drilling and compared the results of conventional and vibrational drilling techniques. Parametric optimization under the influence of vibrations was also studied. Drilling has been done with the both drilling technique, and results were recorded in terms of temperature raise. Optimal solution for drilling the bone has been accessed using Taguchi optimization technique. The morphological comparison has been done for conventional and vibrational drilled holes using histopathology of drilled bones sections. From Taguchi optimization, it was observed that R1F1A1 is the parametric combination which gives minimum thermal injury to the bone in case of vibrational bone drilling. Analysis of variance cleared that the all parameters involved significantly affect the results (P ≤ 0.05). Rotational speed was found to be the most influential factor among the all with 80.53%. Histopathology studies of bone specimens help to understand how heat generation affects the bone morphology during drilling. The specimens drilled with vibrational drilling show less damage in terms of osteonecrosis near the drill site which shows the significance of vibrational drilling in case of orthopedic surgeries. The raise in temperature during drilling is collective result of different drilling parameters. Vibrational drilling was observed a helping tool to control the thermal damage in bone drilling.

Multi-objective performance investigation of orthopaedic bone drilling using Taguchi membership function.

Orthopaedic bone drilling attacks the surrounded bone cells and tissues in terms of thermal and mechanical in such a way that these cells can get damaged permanently. This damage to the surrounding of drill point upsurges the rehabilitation time of injury and in some cases leads to the failure of the bone screw joint. This study is based on the optimization of multiple response characteristics to minimize the damage during the bone drilling. All real-life problems, including bone drilling, require the multiple response optimization for getting a combined optimization result for all countable response characteristics. The Taguchi optimization technique is observed as a highly recommended tool for single response optimization. This article uses the Taguchi technique with little modification of membership function that will help to convert the multiple response characteristics into single response and further optimize it as a single function of performance. Rotational speed, feed rate of tool at three different levels with three different kinds of drilling tools are the drilling parameters selected for the study. The objective of this study is to minimize the surface roughness and thrust force simultaneously. Analysis of variance helps to find the percentage contribution and significance of each parameter on the performance.

Does awareness of diagnosis influence health related quality of life in north Indian patients with lung cancer ?

BACKGROUND & OBJECTIVES: Several patients with cancer in India are not aware of their diagnosis. We evaluated the impact of awareness of cancer diagnosis on health-related quality of life (HRQL) in newly diagnosed patients with lung cancer. METHODS: A total of 391 treatment-naïve patients with lung cancer, seen at the Lung Cancer Clinic of a tertiary care hospital in north India, were categorized into those aware of their diagnosis (group A) and those not aware (group B). All patients answered Hindi versions of abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-Bref) and European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30), and its lung cancer module, EORTC QLQ-LC13. Various domain scores were computed and compared between the two groups. Analysis of covariance was used to determine significance of differences after adjustment for potential confounding factors. RESULTS: Only 117 (29.9%) patients were aware of their diagnosis. Of all, 302 (77.2%) patients had non-small cell lung cancer, and 301 (77.0%) had advanced disease. All HRQL domain scores were similar between the two groups, except that group B patients had significantly poorer median (interquartile range) Physical [39.3 (28.6-50.0) vs 46.4 (28.6-57.1)] and Environment [46.9 (40.6-56.3) vs 53.1 (0.6-65.6)] domain scores of WHOQOL-Bref, and p0 hysical function [60.0 (40.0-73.3) vs 66.7 (46.7-80.0)] and Fatigue [66.7 (55.6-77.8) vs 66.7 (44.4-66.7)] scores of QLQ-C30. After adjusting for gender, age, education, family income, and tumour extent, these differences were not significant. INTERPRETATION & CONCLUSIONS: Disclosure of cancer diagnosis, or lack of it, had no significant impact on HRQL in patients with lung cancer after adjustment of potential confounders.

Disseminated Skeletal Muscle and Cardiac Metastasis from Squamous Cell Carcinoma of the Lung Detected with FDG and FLT PET/CT.

Lung cancer is one of the leading cancers all over the world. Positron emission tomography (PET) using 18F fluorodeoxyglucose (18F FDG) is useful for staging of the disease and decide the appropriate management. 3'-deoxy-3'-18 F-fluorothymidine (18F FLT) is a tracer being extensively evaluated currently and is said to represent tumor proliferation. Common sites of metastases from lung cancer include adrenal glands, bone, and brain. Muscle metastasis and cardiac metastasis are uncommon findings. We report a case of squamous cell carcinoma of the lung with metastases to multiple skeletal muscles and myocardium detected with both FDG and FLT PET/computed tomography (CT).

Fatigue and health-related quality of life in patients with pulmonary sarcoidosis treated by oral Corticosteroids.

BACKGROUND: It is not clear how well sarcoidosis-associated fatigue improves with definitive therapy. OBJECTIVE: To evaluate improvement in fatigue in patients of sarcoidosis receiving oral corticosteroid therapy, and correlate it with clinical recovery and change in health-related quality of life (HRQL). METHODS: We studied 51 newly diagnosed adult patients of pulmonary sarcoidosis. Sarcoidosis Health questionnaire (SHQ) was used to assess HRQL. Fatigue was evaluated using Fatigue Assessment Scale (FAS). All patients received six month treatment with oral prednisolone, and SHQ and FAS were administered before initiation and after completion of treatment. Baseline and post-treatment scores were compared and a 4-point change in FAS scores considered clinically significant. RESULTS: All patients improved clinically and radiologically with therapy. Body aches, however, persisted in 12 of 28 (42.9%) patients having this symptom at baseline. 33 patients (64.7%) had pre-treatment fatigue (FAS >=22), of which seven (13.7%) were severely fatigued (FAS score >=35). Of them 21 (63.6%) and 4 (12.1%) patients respectively showed improvement and deterioration in FAS score by >4 points. Only five of 18 patients with baseline FAS score <22 also showed >4 point score increment after treatment, and four of them developed fatigue during therapy. All patients with baseline severe fatigue improved. Overall, FAS scores, and all SHQ domain scores, significantly improved with treatment. CONCLUSIONS: Both fatigue as well as HRQL improved significantly, and largely parallelly, with treatment for sarcoidosis. Persistence of fatigue, or new onset fatigue, may be encountered during treatment, possibly as an adverse effect of corticosteroid therapy.

Optimization of process parameters for drilled hole quality characteristics during cortical bone drilling using Taguchi method.

Orthopaedic surgery involves drilling of bones to get them fixed at their original position. The drilling process used in orthopaedic surgery is most likely to the mechanical drilling process and there is all likelihood that it may harm the already damaged bone, the surrounding bone tissue and nerves, and the peril is not limited at that. It is very much feared that the recovery of that part may be impeded so that it may not be able to sustain life long. To achieve sustainable orthopaedic surgery, a surgeon must try to control the drilling damage at the time of bone drilling. The area around the holes decides the life of bone joint and so, the contiguous area of drilled hole must be intact and retain its properties even after drilling. This study mainly focuses on optimization of drilling parameters like rotational speed, feed rate and the type of tool at three levels each used by Taguchi optimization for surface roughness and material removal rate. The confirmation experiments were also carried out and results found with the confidence interval. Scanning electrode microscopy (SEM) images assisted in getting the micro level information of bone damage.

Role of serial F-18 FDG PET/CT scans in assessing treatment response and predicting relapses in patients with symptomatic sarcoidosis.

ackground: Monitoring disease activity in sarcoidosis remains a clinical challenge as there is no gold standard. Positron emission tomography (PET) imaging is a novel tool to assess the metabolic activity. There is limited data on the role of serial PET scans in monitoring the disease activity. METHODS: This is a prospective study of 27 sarcoidosis patients treated with systemic corticosteroids. Patients underwent two serial PET/CT scans: one before initiating therapy and the follow up scan at end of therapy. The metabolic response on PET scan was classified as: (a) complete metabolic response (CMR); (b) partial metabolic response (PMR); (c) stable metabolic disease (SMD); and, (d) progressive metabolic disease (PMD). Patients with either CMR or PMR were classified as PET responders while those with SMD or PMD were considered as PET non-responders. All patients were followed at 3, 6 and 12 months after completion of therapy. Relapse rates and relapse-free survival was compared between the various groups. RESULTS: There was significant decline in the median SUVmax of the mediastinal lymph nodes, peripheral lymph nodes and the lung parenchyma in the follow up PET scan. Eight patients achieved CMR, 6 patients achieved PMR while 13 patients were PET non-responders. There was no difference in the clinical remission rates between the responders and non-responders. However, the relapse rate was significantly higher in non-responders vs. responders (61.5% vs. 14.2%, p=0.018). None of the patients who achieved a CMR relapsed during the study period. CONCLUSIONS: Patients with metabolic response on PET scan have significantly fewer relapses as compared to those with no response on PET scan.

(18)F-FDG and (18)F-FLT PET/CT imaging in the characterization of mediastinal lymph nodes.

PURPOSE: There is currently no single modality for accurate characterization of enlarged mediastinal lymph nodes into benign or malignant. Recently (18)F-fluorothymidine (FLT) has been used as a proliferation marker. In this prospective study, we examined the role of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) and (18)F-FLT PET/CT in categorizing mediastinal lymph nodes as benign or malignant. MATERIALS AND METHODS: A total of 70 consecutive patients with mediastinal lymphadenopathy detected on computed tomography (CT) or chest radiograph underwent whole body (18)F-FLT PET/CT and (18)F-FDG PET/CT (within 1 week of each other). Lymph nodal tracer uptake was determined by calculation of standardized uptake value (SUV) with both the tracers. Results of PET/CT were compared with histopathology of the lymph nodes. RESULTS: Histopathology results showed thirty-seven patients with sarcoidosis, seven patients with tuberculosis, nine patients with non-small cell lung cancer, five patients with Hodgkin's lymphoma and twelve patients with non-Hodgkin's lymphoma. The mean FDG SUVmax of sarcoidosis, tuberculosis, Hodgkin's and non-Hodgkin's lymphoma was 12.7, 13.4, 8.2, and 8.8, respectively, and the mean FLT SUVmax was 6.0, 5.4, 4.4, and 3.8, respectively. It was not possible to characterize mediastinal lymphadenopathy as benign or malignant solely based on FDG SUVmax values (p > 0.05) or FLT SUVmax values (p > 0.05). There was no significant difference in FDG uptake (p > 0.9) or FLT uptake (p > 0.9) between sarcoidosis and tuberculosis. In lung cancer patients, the FDG SUVmax and FLT SUVmax of those lymph nodes with tumor infiltration on biopsy was 6.7 and 3.9, respectively, and those without nodal infiltration was 6.4 and 3.7, respectively, and both the tracers were not able to characterize the nodal status as malignant or benign (p > 0.05). CONCLUSION: Though (18)F-FLT PET/CT and (18)F-FDG PET/CT reflect different aspects of biology, i.e., proliferation and metabolism, respectively, neither tracer could provide satisfactory categorization of benign and malignant lymph nodes. The results of this study clearly suggest that differentiation of mediastinal nodes into benign and malignant solely based on SUVmax values cannot be relied upon, especially in settings where tuberculosis and sarcoidosis are common.

Is There Any Role of Inhalational Corticosteroids in the Prophylaxis of Post-Traumatic Fat Embolism Syndrome?

Fat embolism syndrome (FES) is primarily a lung parenchymal disorder resulting from interstitial and alveolar inflammation triggered by the lipid metabolites in blood circulation. The 'low-dose' corticosteroid is supposed to have a prophylactic effect on the incidence of the FES and arterial hypoxemia by reducing this inflammatory response. It is expected that inhaled corticosteroids (ciclesonide aerosol) may prevent the development of hypoxemia or fat embolism syndrome in high-risk patients by reducing this inflammatory response. Metered-dose inhaler (MDI) steroid preparations can reach the lung parenchyma with minimal systemic effect. Sixty cases of polytrauma patients presenting within eight hours of injury were randomly allocated into one of the two groups. In Group 1 (n1=30) ciclesonide, 640 mcg, was given with a metered dose inhaler and repeated once again after 24 hours, whereas Group 2 (n2=30) was taken as control and observed for 72 hours for any episode of hypoxia. The outcome was assessed using Schonfeld's criteria for the eventual outcome of subclinical or clinical FES. Out of 30 patients in each group, six patients developed subclinical FES, whereas three from ciclesonide prophylaxis group and eight from controls developed clinical FES. There is no statistical significance found between the eventual outcomes of subclinical or clinical FES between the ciclesonide prophylaxis and control group. Although there was a trend seen in the possible preventive efficacy of inhalational steroid in the present study, it did not reach the statistically significant level. The prophylactic role of inhalational steroid in post-traumatic subclinical and clinical FES is statistically insignificant in the present study.

Role of digital tomosynthesis and dual energy subtraction digital radiography in detection of parenchymal lesions in active pulmonary tuberculosis.

OBJECTIVE: To assess the role of digital tomosynthesis (DTS) and dual energy subtraction digital radiography (DES-DR) in detection of parenchymal lesions in active pulmonary tuberculosis (TB) and to compare them with digital radiography (DR). MATERIALS AND METHODS: This prospective study was approved by our institutional review committee. DTS and DES-DR were performed in 62 patients with active pulmonary TB within one week of multidetector computed tomography (MDCT) study. Findings of active pulmonary TB, that is consolidation, cavitation and nodules were noted on digital radiography (DR), DTS and DES-DR in all patients. Sensitivity, specificity, positive and negative predictive values of all 3 modalities was calculated with MDCT as reference standard. In addition presence of centrilobular nodules was also noted on DTS. RESULTS: Our study comprised of 62 patients (33 males, 29 females with age range 18-82 years). Sensitivity and specificity of DTS for detection of nodules and cavitation was better than DR and DES-DR. Sensitivity and specificity of DTS for detection of consolidation was comparable to DR and DES-DR. DES-DR performed better than DR in detection of nodules and cavitation. DTS was also able to detect centrilobular nodules with sensitivity and specificity of 57.4% and 86.5% respectively. CONCLUSION: DTS and DES-DR perform better than DR in detection of nodules, consolidation and cavitation in pulmonary TB. DTS gives better results than DES-DR, particularly in detection of cavitation and has moderate sensitivity for detection of centrilobular nodules. Thus DTS can be used for evaluation of patients of suspected pulmonary TB, thereby giving a more confident diagnosis of active disease and also in follow up.

Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a Systematic Review and Meta-Analysis.

The role of interferon gamma release assays (IGRAs), although established for identifying latent tuberculosis, is still evolving in the diagnosis of active extrapulmonary tuberculosis. We systematically evaluated the diagnostic performance of blood- and pleural fluid-based IGRAs in tuberculous pleural effusion (TPE). We searched the PubMed and Embase databases for studies evaluating the use of commercially available IGRAs on blood and/or pleural fluid samples for diagnosing TPE. The quality of the studies included was assessed through the QUADAS-2 tool. The pooled estimates of sensitivity and specificity with 95% confidence intervals (95% CI) were generated using a bivariate random-effects model and examined using forest plots and hierarchical summary receiver operating characteristic (HSROC) curves. Indeterminate IGRA results were included for sensitivity calculations. Heterogeneity was explored through subgroup analysis and meta-regression based on prespecified covariates. We identified 19 studies assessing the T.SPOT.TB and/or QuantiFERON assays. There were 20 and 14 evaluations, respectively, of whole-blood and pleural fluid assays, involving 1,085 and 727 subjects, respectively. There was only one good-quality study, and five studies used nonstandard assay thresholds. The pooled sensitivity and specificity for the blood assays were 0.77 (95% CI, 0.71 to 0.83) and 0.71 (95% CI, 0.65 to 0.76), respectively. The pooled sensitivity and specificity for the pleural fluid assays were 0.72 (95% CI, 0.55 to 0.84) and 0.78 (95% CI, 0.65 to 0.87), respectively. There was considerable heterogeneity; however, multivariate meta-regression did not identify any covariate with significant influence. There was no publication bias for blood assays. We conclude that commercial IGRAs, performed either on whole-blood or pleural fluid samples, have poor diagnostic accuracy in patients suspected to have TPE.

Indications for performing flexible bronchoscopy: Trends over 34 years at a tertiary care hospital.

BACKGROUND AND AIM: Due to its easy maneuverability, patient comfort and documented safety as an outpatient procedure, flexible bronchoscopy (FB) has replaced rigid bronchoscopy for routine diagnostic use. Herein, we report our 34-year experience with outpatient performance of FB. MATERIALS AND METHODS: This was a retrospective analysis of all FB procedures performed between September 1979 and November 2013 (period I: 1979-1990; period II: 1991-2000; period III: 2001-2013) in a tertiary care hospital. Demographic profile of patients, indications for performing FB, and annual and seasonal trends were noted from the records. RESULTS: A total of 24,814 bronchoscopies were performed during the study period. The mean (SD) age of patients (71.6% males) was 48.4 (15.5) years. The number of procedures performed per decade showed an absolute increase by 322%. The most common indication for FB was suspected bronchogenic carcinoma (32.2%) followed by pulmonary infections (18.6%) and interstitial lung diseases (13%). The proportion of annual cases due to interstitial lung diseases (3.9% in period I to 16.2% in period III) increased over the years, whereas disorders such as hemoptysis and pleural effusion showed a declining trend as an indication for FB. A seasonal trend was observed for diseases such as sarcoidosis, bronchogenic carcinoma and pulmonary infections. Six deaths were encountered during the study period in patients undergoing FB. CONCLUSION: FB is increasingly being performed in the diagnosis of respiratory disorders and is a safe outpatient procedure. Although bronchogenic carcinoma remains a common indication for performing FB, benign conditions such as pulmonary infections and sarcoidosis constitute important indications in the Indian scenario.