Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Scedosporium apiospermum mediastinitis in an orthotopic heart transplant recipient.

Scedosporiosis is an opportunistic mycosis that may cause disseminated disease in transplant recipients. This article reports a case of recurrent Scedosporium apiospermum mediastinitis without pneumonia in an orthotopic heart transplant recipient, with durable control achieved by long-term antifungal therapy and serial debridement. This case highlights the importance of an opportunistic scedosporium infection in immunocompromised hosts, given the challenges in microbiological identification and limited treatment options.

Risk Factors for COVID-19 Associated Mucormycosis: The Ophthalmologist's Perspective.

The COVID-19 pandemic has led to a dramatic rise in the incidence of rhino-orbito-cerebral mucormycosis (ROCM) in India. The purpose of our report is to describe the prevalence of ROCM in the context of SARS-CoV-2 infection during the second Indian COVID-19 wave, as well as its diagnostics proceeding, and to discuss the challenges met in the time frame from the suspected diagnosis to the therapeutic decision in such patients. We conducted a retrospective multicentre case series study at six centres of Sudhalkar and Raghudeep group of hospitals in India. ROCM was confirmed in 38 (2.5%) of the 1546 patients admitted with SARS-CoV-2 infection. The average time to establish a diagnosis was 16 days. In total, 19 (50%) patients suffered from type 2 diabetes and were mostly treated with hypoglycaemic agents (in 90% of cases). The standard of care for SARS-CoV-2 management included systemic steroids therapy, intravenous remdesivir for 5 days, and concomitant prophylactic antibiotic therapy following admission. The median (IQR) blood glucose levels in all patients during the course of hospitalisation was 320 (250.5-375) mg/dl. A total of 16% of patients had an irreparable functional loss, and the mortality was 5%. We may hypothesise that excessive administration of antibiotics that profoundly affects human microbiota, coupled with poorly controlled glycaemia and unprotocolised haphazard steroid administration, contribute to a favourable setting for mucormycosis infections.

Correlation of density of microvessels and myofibroblasts with the aggressiveness of central giant cell granulomas of jaws: A preliminary study.

Objectives: Central giant cell granuloma (CGCG) is a fairly common lesion involving the jaw bones. CGCG can show relatively innocuous biological behaviour or it may show clinicoradiological features suggestive of aggressive biological behaviour. To date, there are no histological parameters which can be used to predict the behaviour of these lesions. This study was conducted to assess the utility of parameters of angiogenesis, i.e., total vascular area (TVA), mean vascular area (MVA) and microvessel density (MVD), and density of myofibroblasts in aggressive and non-aggressive CGCGs. Materials and Methods: The study was undertaken as a retrospective study. A total of 20 previously diagnosed cases (10 non-aggressive and 10 aggressive) of CGCGs were included in the study. The sections were subjected to immunohistochemistry using the markers CD34 and α-SMA. For the assessment of vascular parameters, image J software was used. The density of myofibroblasts was determined in each case ranging from score-1 to 4, using the criteria given by Sridhara et al. The correlation between mean values of vascular parameters and density of myofibroblasts with aggressiveness of CGCG was assessed using Mann-Whitney U test. Results: The result of Mann-Whitney U test suggested that the differences between the values of TVA (P < 0.001), MVA (P < 0.003) and density of myofibroblasts, i.e., SMA mean (P < 0.001) and SMA score (P < 0.001), in two groups are statistically significant. The formula for the assessment of aggressiveness was obtained using discriminant analysis. Conclusions: Angiogenesis and density of myofibroblasts significantly differ in aggressive and non-aggressive cases of CGCGs. The aggressiveness of CGCG case can be predicted using the obtained formula by entering the values of vascular parameters and myofibroblasts.

Sequential dosing of convalescent COVID-19 plasma with significant temporal clinical improvements in a persistently SARS-COV-2 positive patient.

The current global pandemic, SARS-CoV-2 infection, is still extending across the world affecting millions of lives to the date. While new successful vaccines are available with promising outcomes to minimize the spread and to reduce the severity of the disease, optimal therapeutic options still remain elusive. COVID-19 convalescent plasma (CCP) is an investigational treatment option which studies suggesting signals of efficacy and favorable outcomes only for patients treated very early in course of the disease. Benefits of the use of CCP later in the disease remain highly debated and therefore are not common practice. We hereby report a case of severe SARS-CoV-2 infection in a young male patient with prolonged COVID-19 positivity who received repeat doses of CCP treatments later in the disease with temporal clinical improvement. This patient's case highlights the need of further studies evaluating efficacy of repeated dosing of CCP. This also suggests a potential of successful use of CCP later in the disease in selected COVID-19 patients.

Bronchiectasis in India: results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry.

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients (≥18 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0·0001]) and more likely to be men (1249 [56·9%] of 2195). Previous tuberculosis (780 [35·5%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13·7%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1·17, 95% CI 1·03-1·32; p=0·015), P aeruginosa infection (1·29, 1·10-1·50; p=0·001), a history of pulmonary tuberculosis (1·20, 1·07-1·34; p=0·002), modified Medical Research Council Dyspnoea score (1·32, 1·25-1·39; p<0·0001), daily sputum production (1·16, 1·03-1·30; p=0·013), and radiological severity of disease (1·03, 1·01-1·04; p<0·0001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation.

Paralytics, Sedation, and Steroids in Acute Respiratory Distress Syndrome.

In this article, we discuss the literature behind the use of paralytics, sedation, and steroids in acute respiratory distress syndrome. We explore the controversies and discuss the recommendations for the use of these agents.

Acute Respiratory Distress Syndrome From an Infectious Disease Perspective.

Acute respiratory distress syndrome (ARDS) is an inflammatory form of lung injury in response to various clinical entities or inciting events, quite frequently due to an underlying infection. Morbidity and mortality associated with ARDS are significant. Hence, early recognition and targeted treatment are crucial to improve clinical outcomes. This article encompasses the most common infectious etiologies of ARDS and their clinical presentations and management, along with commonly encountered infectious complications in such patients.

Neutrophil: Lymphocyte ratio and oral squamous cell carcinoma: A preliminary study.

INTRODUCTION/BACKGROUND: It is well-established that host response plays a vital role in the determination of biological behavior of tumors. Inflammatory response against tumors has been a focus of research in recent years. There has been extensive research regarding inflammatory reaction in oral squamous cell carcinoma (OSCC) in tissue specimens. However, there is no much data regarding systemic inflammatory response in OSCC. It was recently reported that an elevated neutrophil:lymphocyte ratio (NLR) may correlate with aggressive biological behavior in various malignancies including head-and-neck tumors. Thus, the study was undertaken with the aim of evaluation of NLR in peripheral blood of patients suffering from OSCC. MATERIALS AND METHODS: The research was a prospective, case-control study. Hundred patients suffering from OSCC and 100 healthy individuals were included in the study, after obtaining informed consent. NLR was determined from the differential leukocyte count obtained from complete blood count in each case. Comparison of NLR was made among two groups. RESULTS: The mean value of absolute neutrophil count was found to be significantly higher in OSCC cases than in controls (P < 0.01). The mean value of NLR in OSCC was found to be 2.84, and in controls, it was 1.95. This difference was found to be statistically significant (P < 0.001). CONCLUSION: NLR and other hematological parameters may serve as surrogate marker for potential aggressive behavior of OSCC and may help in prognostic prediction of these cases.

Quantitative assessment of tumor-associated tissue eosinophilia and mast cells in tumor proper and lymph nodes of oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is the most common cancer of the oral cavity. Tumor stage, thickness, lymph node metastasis (LNM), extranodal spread, perineural invasion, tumor differentiation, mutations, human papillomavirus infection and tumor microenvironment are independent prognostic indicators of OSCC. However, clinically, among all factors, LNM is considered an important prognostic factor in OSCC as it not only determines the stage of disease but also the strongest independent factor which predicts recurrence of disease. Further research proves that there are several biologically important factors in tumor tissue and LNs which promote or defend LNM. While it is proposed that tumor-associated tissue eosinophils (TATE) and mast cells (MCs) have "immuno-protective" effect, this remains unproven and various researchers have conflicting opinion. Aim: The aim is to determine the presence of TATE and MCs in OSCC and to evaluate if any association exists between them and LNM. Study Design: It is a comparative retrospective study between two groups including 35 OSCC cases positive and 35 negative for LNM. Materials and Methodology: Quantification of cells was done by counting total number of cells in 10 high-power fields under ×40 objective lens using "zigzag" method and dividing it by total number of fields. Eosinophils stained bright red with carbol chromotrope and MCs purple-violet with toluidine blue. Statistics: Independent t-test and Pearson's correlation were done using STATA IC 0.2 software. The level of significance was at 5%. Comparison of eosinophil and MC infiltration was done based on gender, metastatic, nonmetastatic LN and in tumor proper. Results and Conclusion: Our study showed weak positive correlation between mean eosinophils count in tumor and LNs which implies a definite association between the microenvironment of tumor, its progression and LNM. There was a significant association between MC density and decreased LNM also. We conclude that an increased number of immunological cells (TATE and MCs) are a favorable prognostic indicator in OSCC. There is evidence of reduction in LNM with increasing density of these immunological cells. Recognition of TATE and MCs as integral to tumor biology opens an avenue for novel approaches to cancer therapies.

Postoperative pathologic assessment of surgical margins in oral cancer: A contemporary review.

Adequacy of resection margins is of utmost importance for decisions regarding postoperative treatment and prediction of prognosis in patients with oral squamous cell carcinoma. However, there are differences in opinions about various basic concepts of surgical margins in oral and maxillofacial pathology. Fundamental issues such as concepts of positive or negative surgical margins and impact of epithelial dysplasia at margin require clarification to standardize the practice of postoperative margin surveillance. The issue of postresection tissue shrinkage must be considered and addressed while reporting the status of surgical margin. The current status of "molecular assessment" of resection margins is far from mature and it may expand the horizons of postoperative margin surveillance in future. The present review summarizes the fundamental concepts and methods involved in postoperative assessment of surgical margins in oral and maxillofacial pathology. This will help in understating the rationale of current approach for the assessment of resection margins. Understanding the limitations of the existing approach will also help to improve our practice of postoperative margin surveillance.

Quantitative assessment of tumor-associated tissue eosinophilia and mast cells in tumor proper and lymph nodes of oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common cancer of oral cavity. Tumor stage, thickness, lymph node metastasis (LNM), extranodal spread, perineural invasion, tumor differentiation, mutations, human papillomavirus infection, and tumor microenvironment are independent prognostic indicators of OSCC. However, clinically, among all factors, LNM is considered an important prognostic factor in OSCC as it not only determines the stage of disease but also the strongest independent factor which predicts recurrence of disease. Further research proves that there are several biologically important factors in tumor tissue and LNs which promote or defend LNM. While it is proposed that tumor-associated tissue eosinophils (TATE) and mast cells (MCs) have "immuno-protective" effect, this remains unproven and various researchers have conflicting opinion. AIM: The aim is to determine the presence of TATE and MCs in OSCC and to evaluate if any association exists between them and LNM. STUDY DESIGN: It is a comparative-retrospective study between 2 groups including 35 OSCC cases positive and 35 negative for LNM. MATERIALS AND METHODOLOGY: Quantification of cells was done by counting total number of cells in 10 high-power fields under ×40 objective lens using "zigzag" method and dividing it by total number of fields. Eosinophils stained bright red with carbol chromotrope and MCs purple-violet with toluidine blue. STATISTICS: Independent t-test and Pearson's correlation were done using STATA IC 0.2 software. Level of significance was at 5%. Comparison of eosinophil and MC infiltration was done based on gender, metastatic, nonmetastatic LN, and in tumor proper. RESULTS AND CONCLUSION: This study showed weak positive correlation between mean eosinophils count in tumor and LNs. Recognition of TATE and MCs as integral to tumor biology opens an avenue for novel approaches to cancer therapies. We conclude that an increased number of immunological cells are a favorable prognostic indicator in OSCC.

Cutaneous horn: A mask to underlying malignancy.

Cutaneous horns (cornu cutaneum) are uncommon lesions consisting of keratotic material resembling that of an animal horn. It is a conical- or cylindrical-shaped excessive hyperkeratosis of variable size ranging from few millimeters to several centimeters with a variable in size and shape, such as cylindrical, conical, pointed, transversely or longitudinally corrugated, or curved like a ram's horn. The lesions typically occur in sun-exposed areas, particularly the face, ear, nose, forearms and dorsum of hands. Even though 60% of the cutaneous horns are benign in nature, the possibility of skin cancer should always be kept in mind. The clinical diagnosis includes various benign and malignant lesions at its base. Lesions associated with cutaneous horn are keratosis, sebaceous molluscum, verruca, trichilemmal, Bowen's disease, epidermoid carcinoma, malignant melanoma and basal cell carcinoma. Herewith, we report a case of cutaneous horn on the upper lip vermillion masking the underlying malignancy at its base.

Plunging Ranula Occurring Without its Oral Counterpart: A Case Report.

A ranula is a lesion that arises from mucin spillage from the sublingual or submandibular gland ducts, beneath the mucosa of the oral floor. A plunging or cervical ranula dissects the mylohyoid muscle and appears as a submandibular swelling. Rarely, a plunging ranula is encountered without its oral counterpart. Here, we report a rare case of a plunging ranula that occurred without its oral counterpart in a 11-year-old male patient. We have also discussed the pathogenesis and treatment options for the ranula.

Denture labels: Various types and their abilities to resist different assaults.

INTRODUCTION: The use of denture labels for the purpose of identification has been well documented. A number of labels for marking the denture are documented till date demonstrating the ease of fabrication and its potential value in identification. Therefore, it becomes essential that these denture labels fulfill the requisites of an ideal denture label and thus should be able to sustain the various assaults to which they might be subjected simulating a crime scene. AIM: The aim of this study was to determine the ability of various denture labels to withstand different types of assaults thereby evaluating the performance of routinely used denture labels. MATERIALS AND METHODS: Four polymethylmethacrylate blocks were fabricated where the inclusion labels were incorporated on one side, and the surface labels were marked on the other side. Each of the blocks was then placed in different containers to be subjected to different assaults such as acid, alkali, water, and heat of increasing temperature. RESULTS: Inclusion labels performed better as compared to surface marking labels. Among the inclusion labels, the metallic labels performed the best. CONCLUSION: The metallic inclusion labels were able to withstand most assaults than any other inclusion labels or surface marking labels. Due to easy availability, cost-effectiveness, ease of incorporation and inertness, metallic labels are best suited as denture labels for personal identification.