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.

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.

Predominance of PR3 specific immune response and skewed TH17 vs. T-regulatory milieu in active granulomatosis with polyangiitis.

OBJECTIVE: We compared levels of Th1/Th2/Th17 cytokines and T-regulatory cells in active and remitting granulomatosis with polyangiitis (GPA). METHODOLOGY: Twenty-one cases of GPA in active state as well as in remitting state and 20 healthy controls (HC) were enrolled in the study. Cytokines were detected in culture supernatants of PBMCs after stimulation with proteinase-3 (PR3) and phytohemagglutinin antigen (PHA). Serum IL-17 cytokine was studied by ELISA. T-regulatory cells (Tregs) were analyzed by flow cytometry. Gene expression of FOXP3 and ROR-γt was compared by Real Time PCR. RESULTS: We observed significantly increased level of IL-17 in serum as well in culture supernatants of PBMCs after PR3 stimulation along with ROR-γt gene expression in active disease state of GPA as compared to HC. Importantly, remitting state showed low levels of serum IL-17 with decreased ROR-γt gene expression and increased FOXP3 expression. Using PR3 as an immunostimulant, we could demonstrate the generation of IL-17 and TNF-α secreting effector memory cells during remission. Reduced FOXP3 expression with reduced IL-10 levels in active disease indicated the reduced function of Tregs in active disease. CONCLUSION: We observed Th17 dominant environment in peripheral blood of patients in active state of disease, with "hyporesponsiveness", in, in vitro stimulated PBMC-in their ability to secrete TNF-α and IL-6. Treg numbers were unaltered but function was compromised. Targeting PR3 specific effector memory cells, to prevent relapse, and instituting anti IL-17 therapy, or modulating Tregs could be newer forms of therapy for this serious autoimmune disease.

Guidelines for Diagnosis and Management of Bronchial Asthma: Joint Recommendations of National College of Chest Physicians (India) and Indian Chest Society.

Bronchial asthma is an important public health problem in India with significant morbidity. Several international guidelines for diagnosis and management of asthma are available, however there is a need for country-specific guidelines due to vast differences in availability and affordability of health-care facilities across the globe. The Indian Chest Society (ICS) and the National College of Chest Physicians (NCCP) of India have collaborated to develop evidence-based guidelines with an aim to assist physicians at all levels of health-care in diagnosis and management of asthma in a scientific manner. Besides a systematic review of the literature, Indian studies were specifically analysed to arrive at simple and practical recommendations. The evidence is presented under these five headings: (1) definitions, epidemiology and impact, (2) diagnosis, (3) pharmacologic management of stable disease, (4) management of acute exacerbations, and (5) non-pharmacologic management and special situations. The modified grade system was used for classifying the quality of evidence as 1, 2, 3, or usual practice point (UPP). The strength of recommendation was graded as A or B depending upon the level of evidence.

Interaction of alveolar epithelial cells with CFP21, a mycobacterial cutinase-like enzyme.

Mycobacterium tuberculosis (M. tb), an intracellular pathogen, has the ability to infect alveolar epithelial cells (AEC) also in addition to alveolar macrophages. The virulence of M. tb is attributed to proteins encoded by genomic regions of deletion (RD) and till date 16 such regions (RD1-RD16) have been identified. Culture filtrate protein 21 (CFP21), a RD2 secretory protein, is a cutinase-like enzyme that possesses esterase and lipolytic activity. It is hypothesized that CFP21 could be playing a role in M. tb virulence by disrupting the host cell integrity. In this study, recombinant CFP21 was expressed and purified. The in vitro exposure of type I (WI26) and type II (A549) AEC to CFP21 resulted in a significant decline in their cellular viability by inducing cell apoptosis. However, the cytotoxic effects were more pronounced in WI26 cells than in A549 cells. The analysis of immune responses in CFP21-treated AEC exhibited significant production of reactive oxygen species and anti-inflammatory cytokine TGF-ß which indicated oxidative stress-mediated cell death. These results show that CFP21 could play an important role in M. tb pathogenesis by disrupting the host alveolar barrier and thereby facilitating mycobacterial dissemination.

Prospective comparison of quality-of-life outcomes between ileal conduit urinary diversion and orthotopic neobladder reconstruction after radical cystectomy: a statistical model.

OBJECTIVE: To conduct a prospective comparison of quality-of-life (QoL) outcomes in patients who underwent ileal conduit (IC) urinary diversion with those who underwent orthotopic neobladder (ONB) reconstruction after radical cystectomy for invasive bladder cancers. PATIENTS AND METHODS: Between January 2007 and December 2012, 227 patients underwent radical cystectomy and either IC urinary diversion or ONB (sigmoid or ileal) reconstruction. Contraindications for ON were impaired renal function (serum creatinine >2 mg/dL), chronic inflammatory bowel disease, previous bowel resection and tumour involvement at the bladder neck/prostatic urethra. Patients who did not have these contraindications chose to undergo either IC or ONB reconstruction, after impartial counselling. Baseline characteristics, including demographic profile, body mass index, comorbidities, histopathology of the cystoprostatectomy (with lymph nodes) specimen, pathological tumour stage, postoperative complications, adjuvant therapy and relapse, were recorded and compared. The European Organization for Research and Treatment of Cancer QoL questionnaire C30 version 3 was used to analyse QoL before surgery and 6, 12 and 18 months after surgery. RESULTS: Of the 227 patients, 28 patients in the IC group and 35 in the ONB group were excluded. The final analysis included 80 patients in the IC and 84 in the ONB group. None of the baseline characteristics were significantly different between the groups, except for age, but none of the baseline QoL variables were found to be correlated with age. In the preoperative phase, there were no significant differences in any of the QoL domains between the IC or the ONB groups. At 6, 12 and 18 months in the postoperative period, physical functioning (P < 0.001, P < 0.001 and P = 0.001, respectively), role functioning (P = 0.01, P = 0.01 and P = 0.003, respectively), social functioning (P = 0.01, P = 0.01 and P = 0.01, respectively) and global health status/QoL (P < 0.001, P < 0.001 and P = 0.002, respectively) were better in patients in the ONB group than in those in the IC group and the differences were significant. The financial burden related to bladder cancer treatment was significantly lower in the ONB group than in the IC group at 6, 12 and 18 months of follow-up (P = 0.05, P = 0.05 and P = 0.005, respectively) CONCLUSIONS: ONB is better than IC in terms of physical functioning, role functioning, social functioning, global health status/QoL and financial expenditure. ONB reconstruction provides better QoL outcomes than does IC urinary diversion.

Prospective randomized comparison of retroperitoneoscopic pyelolithotomy versus percutaneous nephrolithotomy for solitary large pelvic kidney stones.

OBJECTIVES: We performed a prospective randomized comparison of retroperitoneoscopic pyelolithotomy (RP) versus percutaneous nephrolithotomy (PNL) for solitary pelvic stones >3 cm and assessed the outcome results. METHODS: From 2010 to 2012, 44 patients with a solitary pelvic stone >3 cm without any anatomical abnormality were randomized to either RP or PNL on a 1:1 ratio. Stone-free rate, number of procedures per patient and complications were recorded. RESULTS: The stone-free rate on the first postoperative day was 95.5% in the RP group versus 72.7% in the PNL group (p = 0.04). The stone-free rates at 3 months were similar between the two groups. Blood loss, visual pain analog score and analgesic requirement on the first postoperative day were significantly higher in the PNL group whereas the mean operative time and overall complications were similar between the two groups. CONCLUSION: In patients with solitary large pelvic stones, RP is associated with lesser blood loss, postoperative pain and analgesia as well as with a higher stone-free rate in the immediate postoperative period in comparison to PNL. However, the stone clearance rate remains the same at 3 months in both groups.

Guidelines for diagnosis and management of chronic obstructive pulmonary disease: joint recommendations of Indian Chest Society and National College of Chest Physicians (India).

Chronic obstructive pulmonary disease (COPD) is a major public health problem in India. Although several International guidelines for diagnosis and management of COPD are available, yet there are lot of gaps in recognition and management of COPD in India due to vast differences in availability and affordability of healthcare facilities across the country. The Indian Chest Society and the National College of Chest Physicians (India) have joined hands to come out with these evidence-based guidelines to help the physicians at all levels of healthcare to diagnose and manage COPD in a scientific manner. Besides the International literature, the Indian studies were specifically analysed to arrive at simple and practical recommendations. The evidence is presented under these five headings: (a) definition, epidemiology and disease burden, (b) disease assessment and diagnosis, (c) pharmacologic management of stable COPD, (d) management of acute exacerbations; and (e) non-pharmacologic and preventive measures.

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.

Uroflowmetry nomograms for healthy children 5 to 15 years old.

PURPOSE: We determined flow rates and generated flow rate-voided volume nomograms based on healthy children 5 to 15 years old voiding spontaneously in their natural environment. MATERIALS AND METHODS: A total of 824 healthy school children of both genders were enrolled. A single uroflow record from each child was evaluated. A total of 103 children with a voided volume of less than 50 ml and/or a staccato/interrupted uroflow pattern were excluded, and 721 records were analyzed. Data were evaluated using several mathematical formulas and goodness of fit was determined. Linear regression analysis was used to generate nomograms. RESULTS: Flow rates and voided volumes increased with increasing age, with the effect being more pronounced in girls. No significant difference was noted in uroflow rates from 5 to 10 years, but significant differences (p <0.001) started appearing at 11 to 15 years. Also no significant difference was noted in uroflow rates among children 11 to 15 years. Therefore, 2 age groups were designated, with group 1 consisting of patients 5 to 10 years old and group 2 consisting of patients 11 to 15 years old. There were 222 boys and 122 girls in group 1 and 240 boys and 137 girls in group 2. In group 1 the maximum and average ± SD flow rates were 15.26 ± 4.54 ml per second and 7.68 ± 3.26 ml per second, respectively, for boys and 17.98 ± 6.06 ml per second and 9.19 ± 4.23 ml per second, respectively, for girls. In group 2 these rates were 22.50 ± 7.24 ml per second and 10.78 ± 4.03 ml per second, respectively, for boys and 27.16 ± 9.37 ml per second and 13.48 ± 5.21 ml per second, respectively, for girls. CONCLUSIONS: This large study, which expands the scant existing literature on uroflow parameters in healthy children, will hopefully promote wider application of uroflowmetry testing in the pediatric population.

Transperitoneal versus retroperitoneal laparoscopic ureterolithotomy: a prospective randomized comparison study.

PURPOSE: We compared laparoscopic transperitoneal and retroperitoneal ureterolithotomy approaches, and determined whether one technique is superior to the other. MATERIALS AND METHODS: In this prospective randomized study from January 2009 to May 2012, 48 patients with proximal or mid ureteral stones underwent transperitoneal laparoscopic ureterolithotomy or retroperitoneal laparoscopic ureterolithotomy. The randomization occurred on a 1:1 basis. Groups 1 and 2 consisted of patients who underwent transperitoneal laparoscopic ureterolithotomy and retroperitoneal laparoscopic ureterolithotomy, respectively. Demographic and clinical characteristics as well as postoperative data were collected and analyzed. Statistical analysis was performed with SPSS® version 15.0 using the Fisher exact and Mann-Whitney U tests with p <0.05 considered statistically significant. RESULTS: The difference in visual pain analog score and mean tramadol requirement on days 1 and 2 between the 2 groups was statistically significant, and was higher in group 1 (p <0.05). Postoperative hospital stay and paralytic ileus rates were significantly higher in group 1 (p <0.05). The differences in total operative time and intracorporeal suturing time between the 2 groups were not statistically significant. However, successful stone removal was equal in the 2 groups. CONCLUSIONS: For proximal or mid ureteral large and impacted stones, transperitoneal laparoscopic ureterolithotomy is significantly associated with pain, greater tramadol requirement, ileus and longer hospital stay than retroperitoneal laparoscopic ureterolithotomy. However, successful stone removal remains the same in both groups.

Prevalence of multidrug resistance in Mycobacterium tuberculosis isolates from HIV seropositive and seronegative patients with pulmonary tuberculosis in north India.

BACKGROUND: Multidrug resistant (MDR) and extensively-drug resistant (XDR) tuberculosis (TB) are a serious threat to the national TB control programs of developing countries, and the situation is further worsened by the human immunodeficiency virus (HIV) pandemic. The literature regarding MDR/XDR-TB is, however, scanty from most parts of India. We carried out this study to assess the prevalence of MDR/XDR-TB in new and previously treated cases of pulmonary TB and in HIV seropositive and seronegative patients. METHODS: Sputum and blood specimens were obtained from 2100 patients suspected of pulmonary tuberculosis and subjected to sputum microscopy and culture for TB, and HIV serology at our tertiary care centre in north India. The culture positive Mycobacterium tuberculosis isolates were subjected to drug susceptibility testing (DST) for first line anti-tuberculosis drugs, and the MDR isolates were further subjected to second line DST. Various parameters of the patients' were analyzed viz. clinical presentation, radiology, previous treatment history, demographic and socioeconomic data and microbiology results. RESULTS: Of the 2100 patients, sputum specimens of 256 were smear positive for acid-fast bacilli (AFB), 271 (12.9%) grew Mycobacterium spp., and M. tuberculosis was isolated in 219 (10.42%). Of the 219 patients infected with M. tuberculosis, 20.1% (44/219) were found to be seropositive for HIV. Overall, MDR-TB was observed in 17.4% (39/219) isolates. There were 121 newly diagnosed and 98 previously treated patients, of which MDR-TB was found to be associated with 9.9% (12/121) and 27.6% (27/98) cases respectively. There was significantly higher association of MDR-TB (12/44, 27.3%) with HIV seropositive patients as compared to HIV seronegative patients (27/175, 15.4%) after controlling previous treatment status, age, and sex (odd's ratio, 2.3 [95% CI, 1.000-5.350]; p-value, 0.05). No XDR-TB was found among the MDR-TB isolates. CONCLUSION: The present study demonstrated a high prevalence of drug resistance amongst pulmonary TB isolates of M. tuberculosis from north India as compared to the WHO estimates for India in 2010, though this could possibly be attributed to the clustering of more serious or referred cases at our tertiary care centre. The prevalence of MDR-TB in HIV seropositive patients was significantly higher than seronegative individuals. The study emphasizes the need to monitor the trends of drug resistance in TB in various populations in order to timely implement appropriate interventions to curb the menace of MDR-TB.

Adaptive support ventilation for complete ventilatory support in acute respiratory distress syndrome: a pilot, randomized controlled trial.

BACKGROUND AND OBJECTIVE: Low tidal volume ventilation has been shown to improve survival in acute respiratory distress syndrome (ARDS). Adaptive support ventilation (ASV), a closed-loop ventilatory mode, can minimize the work of breathing, and thus potentially improve the outcomes in ARDS. The aim of this pilot, randomized clinical trial was to compare the outcomes of ASV versus volume-cycled ventilation (VCV) in ARDS. METHODS: Patients with ARDS were randomly allocated to either ASV or VCV. The primary outcomes were duration of mechanical ventilation, new-onset organ dysfunction and hospital length of stay. The secondary outcomes were ease of use of the ventilator mode (assessed using the visual analogue scale (VAS)), number of daily arterial blood gas analyses, daily requirements of sedative and neuromuscular blockers, and mortality. RESULTS: Forty-eight patients (28 males, 20 females) with ARDS were randomized to receive either ASV (n = 23) or VCV (n = 25) during the study period. The baseline characteristics were almost similar in the two groups. The duration of mechanical ventilation, delta sequential organ failure assessment scores, intensive care unit and hospital stay were comparable in the two groups. The mortality (VCV-36% vs ASV-34.7%), ease of use of mechanical ventilation, daily midazolam and vecuronium doses, and the number of arterial blood gas analyses performed were also similar in the two groups. CONCLUSIONS: There was no significant difference in the outcomes of patients with ARDS ventilated with either VCV or ASV in this study.

Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): lessons learnt & challenges ahead.

Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of 'new smear-positives' diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement.

Itraconazole in chronic cavitary pulmonary aspergillosis: a randomised controlled trial and systematic review of literature.

Patients with aspergilloma can be safely managed with supportive therapy in absence of massive haemoptysis. We hypothesised that chronic cavitary pulmonary aspergillosis (CCPA) could also be managed on similar grounds. The aim of this prospective, randomised controlled trial was to evaluate the efficacy and safety of itraconazole in CCPA. Consecutive patients of CCPA with presence of chronic pulmonary/systemic symptoms; and pulmonary cavities; and presence of Aspergillus (immunological or microbiological) were randomised to receive either supportive treatment alone or itraconazole 400 mg daily for 6 months plus supportive therapy. Response was assessed clinically, radiologically and overall after 6 months therapy. A total of 31 patients (mean age, 37 years) were randomised to itraconazole (n = 17) or the control (n = 14) group. The number of patients showing overall response was significantly higher in the itraconazole group (76.5%) vs. the control (35.7%) group (P = 0.02). The numbers of patients demonstrating clinical or radiological response were also significantly higher in the itraconazole group (P = 0.016 and 0.01 respectively). Adverse events were noted in eight patients in the itraconazole group, however, none was serious or led to discontinuation of the study drug. Itraconazole was found to be superior to standard supportive treatment alone in stabilising cases of CCPA. (clinicaltrials.gov; NCT01259336).

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.

Sarcoidosis and tuberculosis: the same disease with different manifestations or similar manifestations of different disorders.

PURPOSE OF REVIEW: Ever since sarcoidosis was first described, its relationship with tuberculosis has been debated. Whereas some consider sarcoidosis and tuberculosis as two extremes of the same disease process, other researchers have negated the role of mycobacteria in causation of sarcoidosis. Whether or not linked causally, there are obvious clinical similarities that make differential diagnosis of the two conditions very challenging, particularly in countries with high burden of tuberculosis. Herein we analyze the relationship between sarcoidosis and tuberculosis and its implications in clinical practice. RECENT FINDINGS: Initial studies had focused on finding an epidemiological link between the two conditions or demonstration of mycobacteria in sarcoid lesions on histology. Results from these studies were at best suggestive. Recent molecular and immunological studies suggest mycobacterial antigens are the inciting agents in a proportion of sarcoidosis patients. Evidence is stronger from countries with high burden of tuberculosis. Tuberculosis can manifest as a complication of treatment in sarcoidosis and the two conditions can rarely co-exist. SUMMARY: The balance of evidence favors mycobacteria or their products as a trigger for inciting immune responses leading to sarcoidosis in a proportion of patients, which is likely to be higher in countries with high tuberculosis burden. This evidence also highlights the limitations of molecular or serological studies to discriminate between the two conditions.

Efficacy & safety of iodopovidone pleurodesis: a systematic review & meta-analysis.

BACKGROUND & OBJECTIVES: Chemical pleurodesis is an accepted therapy for patients with recurrent pleural effusions and pneumothorax. Iodopovidone has been shown to be safe and effective for chemical pleurodesis in several studies. The aim of this systematic review was to update a previously reported meta-analysis on the efficacy and safety of iodopovidone pleurodesis. METHODS: Two databases MEDLINE and EMBASE were searched for a period (1952-2010), and studies that have reported success rates with iodopovidone pleurodesis were selected. The proportions with 95 per cent confidence interval (CI) were calculated to assess the outcomes in the individual studies and the results were pooled using a random effects model. RESULTS: Thirteen eligible studies with 499 patients were included in the mata-analysis. The success rates varied from 70 to 100 per cent in different studies with the pooled success rate being 88.7 per cent (95% CI, 84.1 to 92.1). The success rate was not affected by the method (tube thoracostomy vs. thoracoscopy, 89.6 vs. 94.2%) or the indication of pleurodesis (pleural effusion vs. pneumothorax, 89.2 vs. 94.9%). The only significant complication reported was chest pain of varying degree. Systemic hypotension was reported in six patients across the studies. There were no deaths associated with iodopovidone pleurodesis. Statistical heterogeneity and publication bias were found. INTERPRETATION & CONCLUSIONS: Iodopovidone may be considered a safe and effective agent for chemical pleurodesis in patients with pleural effusions and recurrent pneumothoraces.

Link between CFTR mutations and ABPA: a systematic review and meta-analysis.

Summary There is a biological plausibility on the link between cystic fibrosis transmembrane conductance regulator (CFTR) mutations and allergic bronchopulmonary aspergillosis (ABPA). The aim of the systematic review was to investigate this link by determining the frequency of CFTR mutations in ABPA. We searched the PubMed and EmBase databases for studies reporting CFTR mutations in ABPA. We pooled the odds ratio (OR) and 95% confidence intervals (CI) from individual studies using both fixed and random effects model. Statistical heterogeneity was evaluated using the I(2) test and the Cochran-Q statistic. Publication bias was assessed using both graphical and statistical methods. Our search yielded four studies (79 ABPA, 268 controls). The odds of encountering CFTR mutation was higher in ABPA compared with the control group (OR 10.39; 95% CI, 4.35-24.79) or the asthma population (OR 5.53; 95% CI 1.62-18.82). There was no evidence of statistical heterogeneity or publication bias. There is a possible pathogenetic link between CFTR mutations and ABPA. However, because of the small numbers of patients, further studies are required to confirm this finding. Future studies should adopt a uniform methodology and should screen for the entire genetic sequence of the CFTR gene.

Bronchoscopic lung biopsy using noninvasive ventilatory support: case series and review of literature of NIV-assisted bronchoscopy.

BACKGROUND: Fiberoptic bronchoscopy and lung biopsy are important diagnostic tools in patients with diffuse pulmonary infiltrates. However, these patients often have hypoxemic respiratory failure that makes this procedure hazardous. Noninvasive ventilation (NIV) has been shown to improve oxygenation in hypoxemic patients. OBJECTIVE: To report the efficacy and safety of an innovative technique of NIV-assisted bronchoscopic lung biopsy in a small case-series of hypoxemic subjects with diffuse parenchymal infiltrates; also to systematically review the literature on NIV-assisted bronchoscopy. METHODS: Subjects with bilateral diffuse parenchymal infiltrates and P(aO(2))/F(IO(2)) < 200 mm Hg underwent bronchoscopic lung biopsy under NIV support. NIV was initiated 10 min before the procedure and continued for 30 min after the procedure. The primary outcomes were performance of successful procedure and episodes of decline in S(pO(2)) < 90%. Secondary end points were the change in the respiratory and hemodynamic parameters during the procedure and occurrence of complications such as pneumothorax, hemorrhage, and endotracheal intubation. RESULTS: Six subjects, with a mean ± SD age of 44.5 ± 11.6 years, were included in the study. The median (interquartile range [IQR]) P(aO(2))/F(IO(2)) prior to lung biopsy was 164.5 mm Hg (146.3-176.3 mm Hg), and the median (IQR) inspiratory and expiratory positive airway pressures were 14 cm H(2)O (12-15 cm H(2)O) and 5 cm H(2)O. Fiberoptic bronchoscopy was well tolerated and all subjects maintained S(pO(2)) > 92% during the procedure. One subject required endotracheal intubation due to hemoptysis. A definite diagnosis was obtained in 5 of the 6 subjects. A repeat procedure was performed in one subject, which again yielded no diagnosis. No other periprocedural complications were encountered. CONCLUSIONS: NIV-assisted bronchoscopic lung biopsy is a novel method for obtaining diagnosis in hypoxemic patients with diffuse lung infiltrates. However, this approach should be reserved for centers with extensive experience in NIV. More studies are required to define the utility of this approach.