Determining the effect of climate and profession on dry eye disease: A prevalence study among young males in north, north-west and central India.

Background: Ocular tear film and the ocular surface together represent a dynamic playground of various protective factors against environmental influencers. Surrounding environment and geoclimatic milieu are the pertinent and continuous influencing factors. Prevalence study of Dry eye disease (DED) in various climatic conditions and professions provides an insight into this peculiar aspect of DED and human geography. Methods: This was a hospital based, cross-sectional, comparative, analytical observational study. 1840 young soldiers between 25 and 45 years of age were studied. Divided in five climate groups based on Köppen-Geiger climate classification system the subjects were sub-grouped into professions exposed to known aggravating environmental factors. The ocular surface was examined for signs and symptoms of DED and its prevalence and risk ratio for different climates and professions were calculated. Results: Highest prevalence of DED was found in cold desert climate and among visual display unit (VDU) users. Least prevalence was seen in highland type of climate and among people involved in professional exposed to high temperature. Prevalence of DED based upon the signs and ocular surface disease index (OSDI) was calculated and stratified with risk ratio for climatic conditions and professions. Conclusion: Different climatic conditions and professions had different prevalence of signs, symptoms of OSD and DED which indicated its influence on prevalence of the disease.

Test concordance and diagnostic accuracy of three serological assays for detection of anti-SARS-CoV-2 antibody: result from a population-based sero-epidemiological study in Delhi.

BACKGROUND: Several methodological tests are available to detect SARS-CoV-2 antibody. Tests are mostly used in the aid of diagnosis or for serological assessment. No tests are fully confirmatory and have variable level of diagnostic ability. We aimed at assessing agreement with three serological tests: quantitative anti receptor binding domain ELISA (Q-RBD), qualitative ELISA (WANTAI SARS-CoV-2 Ab) and qualitative chemiluminescence assay (CLIA). METHODS: This study was a part of a large population based sero-epidemiological cohort study. Participants aged 1 year or older were included from 25 randomly selected clusters each in Delhi urban (urban resettlement colony of South Delhi district) and Delhi rural (villages in Faridabad district, Haryana). Three type of tests were applied to all the baseline blood samples. Result of the three tests were evaluated by estimating the total agreement and kappa value. RESULTS: Total 3491 blood samples collected from March to September, 2021, out of which 1700 (48.7%) from urban and 1791 (51.3%) from rural. Overall 44.1% of participants were male. The proportion of sero-positivity were 78.1%, 75.2% and 31.8% by Wantai, QRBD and CLIA tests respectively. The total agreement between Wantai and QRBD was 94.5%, 53.1% between Wantai and CLIA, and 56.8% between QRBD and CLIA. The kappa value between these three tests were 0.84 (95% CI 0.80-0.87), 0.22 (95% CI 0.19-0.24) and 0.26 (95% CI 0.23-0.28). CONCLUSIONS: There was strong concordance between Wantai and QRBD test. Agreement between CLIA with other two tests was low. Wantai and QRBD tests measuring the antibody to same S protein can be used with high agreement based on the relevant scenario.

Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study.

Introduction: The objective of the study was to evaluate the clinical profile and outcome of patients with secondary hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. Materials and methods: A prospective observational study was conducted where critically ill adult patients presenting with fever and bicytopenia were evaluated according to the HLH-2004 diagnostic criteria for the presence of secondary HLH. The underlying trigger, clinical profile, treatment, and outcome of patients with HLH were analyzed. Results: Of the 76 critically ill patients with fever and bicytopenia, 33 (43%) patients were diagnosed with HLH. The following triggers for HLH were identified: bacterial infections (23%), fungal infections (10%), viral infections (10%), parasitic infections (10%), autoimmune diseases (13%), and malignancy (8%). A total of 78% of the HLH cases received steroids, but the use of steroids was not associated with improvement in mortality. Conclusion: There is a high prevalence of HLH in patients presenting with fever and bicytopenia in critically ill adult patients. Infections were identified as the most common trigger of HLH. How to cite this article: Fazal F, Gupta N, Soneja M, Mitra DK, Satpathy G, Panda SK, et al. Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2022;26(5):564-567.

The spectrum of clinical and subclinical endocrinopathies in treatment-naïve patients with celiac disease.

INTRODUCTION: Strong association exists between celiac disease and autoimmune endocrinopathies such as type I diabetes and hypothyroidism; there is a lack of data on the involvement of other endocrine organs such as pituitary-gonadal axis. Furthermore, there is lack of data on the spectrum of involvement of endocrine organs varying from organ autoimmunity to subclinical and clinical disease. We evaluated consecutive treatment-naïve patients with celiac disease (CeD) for clinical and subclinical endocrinopathies. METHODS: Of 154 screened, 74 treatment-naïve patients with CeD were recruited. They underwent hormonal and/or functional assessment of beta cell of pancreas, thyroid gland, pituitary-gonadal axis, and parathyroid glands. RESULTS: Of the 74 patients with CeD, 31 (41.9%) had at least one clinical or subclinical endocrinopathy and 9 (12.2%) had multiple endocrinopathies. Most common of them were clinical or subclinical type I diabetes and autoimmune thyroid disease. Interestingly, 8 (10.8%) patients also were found to have functional hypopituitarism and 7/54 (12.9%) having isolated hypogonadotropic hypogonadism. CONCLUSIONS: Patients with CeD have high percentages of not only clinical endocrinopathy including pituitary-gonadal axis dysfunction but also subclinical endocrinopathy. Whether commencement of gluten-free diet will lead to reversal of subclinical endocrinopathies requires further follow up studies.

Taxane-based Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma: Prospective Results from a Non-endemic Cohort.

AIMS: To report the outcomes of induction chemotherapy (ICT) followed by chemoradiotherapy (CTRT) for a large cohort of locoregionally advanced nasopharyngeal cancer (LA-NPC) from a non-endemic region. MATERIALS AND METHODS: Between January 2008 and July 2015, 201 patients with histologically proven, non-metastatic NPC were treated with ICT followed by CTRT at our institute. All the patients received two to three cycles of a taxane-based ICT regimen. Radiotherapy was delivered using an intensity-modulated radiotherapy (IMRT) technique in all patients. RESULTS: After a median follow-up of 37 months (range: 7-110 months), the 3-year disease-free survival (DFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival of the entire cohort was 72, 85, 83 and 87.4%, respectively. On multivariate analysis, histology was an independent predictor of DFS, LRFS and overall survival, with keratinising squamous cell carcinoma histologies predicting a worse outcome. The nodal stage was an independent predictor of DFS, DMFS and overall survival. Age, gender, ethnicity, tumour stage and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 19% of patients at last follow-up and grade 2 or worse xerostomia was seen in 24% of patients. Thirty-nine per cent of patients developed clinical hypothyroidism at last follow-up. CONCLUSION: ICT followed by concurrent CTRT in the IMRT era provides excellent locoregional control, distant control and overall survival rates in patients with LA-NPC. However, distant failure continues to be a problem and may require further systemic intensification.

Prevalence and reproductive manifestations of macroprolactinemia.

PURPOSE: Macroprolactinemia is characterized by predominance of macroprolactin molecules in circulation and generally has extra-pituitary origin. Macroprolactin is viewed as biologically inactive, therefore asymptomatic, and thus may not require any treatment or prolonged follow-up. In addition, data on prevalence of macroprolactinemia and its clinical manifestation are also rare. Therefore, the present study was aimed to find out prevalence of macroprolactinemia and its association, if any, with reproductive manifestations. MATERIAL AND METHODS: Macroprolactin was measured in 102 hyperprolactinemia cases (>100 ng/ml prolactin level), 135 physiological hyperprolactinemia cases (50 pregnant and 85 lactating females; >100 ng/ml prolactin level) and 24 controls. Poly ethylene glycol (PEG) precipitation method was carried out to screen macroprolactin. Prolactin recovery of <25% was considered overt macroprolactinemia. Detailed clinical data was recorded which included complete medical history, physical examination and hormone measurements besides CT/MRI for pituitary abnormalities. RESULTS: Prevalence of macroprolactinemia was 21.57% (22/102) in hyperprolactinemia (prolactin >100 ng/ml). There was no case of macroprolactinemia in physiological hyperprolactinemia, or healthy control females. Reproductive manifestations were present in 72.73% (16/22) macroprolactinemia cases, out of which macroprolactinemia was the sole cause of associated reproductive manifestations in 68.7% (11/16) cases. Reversal of reproductive dysfunction/s was observed in five cases with appropriate treatment for high macroprolactin. CONCLUSION: Macroprolactinemia prevalence was found to be 21.5%, out of which 72.73% cases had associated reproductive dysfunctions.

Serum Cortisol Level in Indian Patients with Severe Sepsis/Septic Shock.

BACKGROUND: The relationship between cortisol level and sepsis is not known in Indian patients of severe sepsis/septic shock. AIMS: The study was done to determine the optimal range of cortisol levels, defining the adrenocortical response, and predicting the mortality, if possible, in the above type of patients. SETTINGS AND DESIGNS: The study was a single-centered prospective cohort study, conducted in a tertiary referral center, North India. MATERIALS AND METHODS: Sixty patients with severe sepsis (n = 30) and septic shock (n = 30) were recruited. Basal and postcosyntropin (1 µg)-stimulated cortisol levels were measured, and all patients were closely monitored with daily assessments of clinical and laboratory variables. Western diagnostic criteria were followed for defining adrenal insufficiency (AI). The end point was the survival assessed at day 28 or death, whichever came earlier. RESULTS: The mean basal (T0) and poststimulation (T30) cortisol levels were 31.77 ± 15.9 µg/dL and 37.58 ± 17.31 µg/dL, respectively. In all sepsis patients, 48.33% qualified as AI at T0 ≤ 24 µg/dL, 61.67% at delta cortisol (Δ = T30-T0) ≤7 µg/dL, and 78.33% at Δ ≤9 µg/dL. Using receiver operating characteristic curve, the area under the curve (AUC) was 0.4954, signifying poor prediction to death. CONCLUSIONS: Indians have completely different characteristics of cortisol levels in sepsis patients, in comparison to the Western data. They have higher range of basal cortisol levels, higher percentage of AI, and an inability to predict mortality with the cortisol levels. Hence, there is requirement of an international study to confirm the dichotomy of the results.

Identification of Osr2 Transcriptional Target Genes in Palate Development.

Previous studies have identified the odd-skipped related 2 (Osr2) transcription factor as a key intrinsic regulator of palatal shelf growth and morphogenesis. However, little is known about the molecular program acting downstream of Osr2 in the regulation of palatogenesis. In this study, we isolated palatal mesenchyme cells from embryonic day 12.5 (E12.5) and E13.5 Osr2RFP/+ and Osr2RFP/- mutant mouse embryos and performed whole transcriptome RNA sequencing analyses. Differential expression analysis of the RNA sequencing datasets revealed that expression of 70 genes was upregulated and expression of 61 genes was downregulated by >1.5-fold at both E12.5 and E13.5 in the Osr2RFP/- palatal mesenchyme cells, in comparison with Osr2RFP/+ littermates. Gene ontology analysis revealed enrichment of signaling molecules and transcription factors crucial for skeletal development and osteoblast differentiation among those significantly upregulated in the Osr2 mutant palatal mesenchyme. Using quantitative real-time polymerase chain reaction (RT-PCR)and in situ hybridization assays, we validated that the Osr2-/- embryos exhibit significantly increased and expanded expression of many osteogenic pathway genes, including Bmp3, Bmp5, Bmp7, Mef2c, Sox6, and Sp7 in the developing palatal mesenchyme. Furthermore, we demonstrate that expression of Sema3a, Sema3d, and Sema3e, is ectopically activated in the developing palatal mesenchyme in Osr2-/- embryos. Through chromatin immunoprecipitation, followed by RT-PCR analysis, we demonstrate that endogenous Osr2 protein binds to the promoter regions of the Sema3a and Sema3d genes in the embryonic palatal mesenchyme. Moreover, Osr2 expression repressed the transcription from the Sema3a and Sema3d promoters in cotransfected cells. Since the Sema3 subfamily of signaling molecules plays diverse roles in the regulation of cell proliferation, migration, and differentiation, these data reveal a novel role for Osr2 in regulation of palatal morphogenesis through preventing aberrant activation of Sema3 signaling. Together, these data indicate that Osr2 controls multiple molecular pathways, including BMP and Sema3 signaling, in palate development.

Role of microscopic spread beyond gross disease as an adverse prognostic factor in oral squamous cell carcinoma.

INTRODUCTION: Despite meticulous surgery and proper adjuvant treatment, outcome of oral squamous cell carcinoma remains unpredictable. This shows that there may be other factors which should be considered while prognosticating these patients. Many a times there is spread of disease beyond the gross margin which can alter the margin status. We hypothesized that microscopic spread beyond gross disease may portend a poor prognosis. METHOD: This is a retrospective study of prospectively collected data of 1025 treatment naïve oral squamous cell carcinoma patients. All patients underwent surgery from January 2012 to October 2013, this was followed by appropriate adjuvant treatment. Demographic and histopathological details were noted from the electronic medical records. RESULTS: Microscopic spread beyond gross disease (MSGD) is associated with higher incidence of nodal positivity (p < 0.046), peri-neural invasion (p < 0.001), thicker tumours (p < 0.024) and poor differentiation (p < 0.060). The overall survival in patients with MSGD was 32.45 months vs. 37.5 months in patients without MSGD (p < 0.002). CONCLUSION: Tumours with MSGD tend to have a higher incidence of nodal metastasis, PNI and thicker tumours. Presence of MSGD was associated with lower overall survival as compared to those without.

Role of the pectoralis major myofascial flap in preventing pharyngocutaneous fistula following salvage laryngectomy.

OBJECTIVE: This study aimed to assess the utility of onlay pectoralis major myofascial flap in preventing pharyngocutaneous fistula following salvage total laryngectomy. METHODS: A retrospective analysis was performed of 172 patients who underwent salvage laryngectomy for recurrent carcinoma of the larynx or hypopharynx between 1999 and 2014. One hundred and ten patients underwent primary closure and 62 patients had pectoralis major myofascial flap onlay. RESULTS: The overall pharyngocutaneous fistula rate was 43 per cent, and was similar in both groups (primary closure group, 43.6 per cent; onlay flap group, 41.9 per cent; p = 0.8). Fistulae in the onlay flap group healed faster: the median and mean fistula duration were 37 and 55 days, respectively, in the primary closure group and 20 and 25 days, respectively, in the onlay flap group (p = 0.008). CONCLUSION: Use of an onlay pectoralis major myofascial flap did not decrease the pharyngocutaneous fistula rate, although fistula duration was shortened. A well-designed randomised-controlled trial is needed to establish parameters for its routine use in clinical practice.

Squamous cell carcinoma of the upper aerodigestive tract in exclusive smokers, chewers, and those with no habits.

BACKGROUND: Tobacco consumption is the major risk factor for developing head and neck squamous cell cancer (SCC). The site of development of HNSCC may depend on the way the tobacco is consumed. While laryngeal cancers are more common among smokers, oral cancers are more common among tobacco chewers. Since the use of smokeless tobacco is increasing, it is important to know whether this difference is restricted only to site wise distribution or it has other clinical and pathological implications. PATIENTS AND METHODS: We analyzed a prospectively collected dataset of HNSCC patients other than nasopharyngeal cancers attending our outpatient department at a single unit of the head and neck services at Tata Memorial Hospital, Mumbai, India, between January 2010 and September 2011. There were 747 eligible patients and were divided into three groups: Those with chewing as the only habit (chewers), those with smoking as the only habit (smokers), and those with no habits. Patients with regular use of alcohol were excluded from the study. The clinical and pathological parameters were analyzed. RESULTS: Of the 747 patients, the tobacco chewers formed 69.3% followed by smokers (19.5%) and patients with no habits (11.1%). Majority of smokers were men (98%). Site distribution revealed patients with chewing as the only habit had oral cancers (most commonly gingivobuccal complex cancers) as the most common site and those with smoking as the only habit had larynx as the most common site. In patients with no habits, oral tongue was found to be the most common site. No statistically significant pathological differences were observed in between these groups in patients who underwent surgery (n = 366) at the initial modality of treatment. CONCLUSIONS: There is a direct relationship between the form of tobacco use and site of appearance of HNSCC. However, there are no differences in clinical or pathological parameters between HNSCC caused by tobacco chewing or tobacco smoking.

Skin involvement and ipsilateral nodal metastasis as a predictor of contralateral nodal metastasis in buccal mucosa cancers.

CONTEXT: In view of low incidence of contralateral nodal metastasis and increase in the morbidity, the opposite neck is not routinely addressed. However, contralateral nodal metastasis is seen frequently in a certain group of patients. Identifying those factors associated with higher chances of contralateral nodal metastasis may help in optimizing the treatment. AIMS: The aim of this study was to identify prognostic factors associated with contralateral nodal metastasis in cases of buccal mucosa cancers. SETTINGS AND DESIGN: A retrospective audit of 125 patients with squamous cell carcinoma of buccal mucosa at a tertiary cancer center. SUBJECTS AND METHODS: Those cases in which lesions were reaching or crossing midline were included in this study. All cases underwent surgery as primary modality of treatment and had bilateral neck dissection. STATISTICAL ANALYSIS USED: Chi-square test is used for evaluating the variables predicting contralateral nodal metastasis. Finally, a multivariate analysis was performed using binomial logistic regression to identify those variables that were independently associated with the risk of contralateral nodal metastasis. RESULTS: Among 125 patients, 53 cases were node negative. Ipsilateral nodal metastasis was seen in 44/125 (35.2%) patients, 26/125 (20.8%) had bilateral neck node metastasis, and 2/125 (1.6%) had isolated contralateral nodal metastasis. Among these 28 patients with contralateral nodal metastasis, 26 patients had ipsilateral nodal metastasis. Ipsilateral nodal metastasis and skin involvement were independently predictive of contralateral nodal metastasis. CONCLUSIONS: Contralateral nodal metastasis in the absence of ipsilateral nodal metastasis is very rare and frozen section of ipsilateral neck dissection specimen can be an important pointer for addressing contralateral neck.

Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1). OBJECTIVE: The aim of this study was to evaluate prognostic heterogeneity in the stage III category. METHODS AND PATIENTS: An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011. RESULTS: Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2). CONCLUSIONS: The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.

A review on harmful effects of pan masala.

Pan masala (PM) is a mixture of areca nut with slaked lime, catechu and other flavoring agents. It is widely available and used by all the sections of the Indian society. It is genotoxic as it increases sister chromatin exchange and chromatin aberrations. Among humans, it is a leading cause of oral submucous fibrosis that often progresses to oral cancer. Among experimental animals, it leads to neoplastic lesions in lung, liver and stomach. It is hepatotoxic leading to increased level of enzymes, deranged carbohydrate and lipid metabolism. It is harmful to kidneys and testes leading to increased creatinine and sperm deformities respectively. PM is a very harmful substance affecting almost all organ systems, and there is immediate need for a national policy on complete ban on the production, storage, sale and marketing of PM.

Correlation between lead and cadmium concentration and semen quality.

There are contrary reports of association of lead and cadmium with the decline in semen quality. This study evaluates whether seminal lead (Pb) and cadmium (Cd) at environmental concentration are associated with altered semen quality. We conducted a study of healthy fertile and infertile men 20-43 years of age attending the Andrology Laboratory of Reproductive Biology Department for semen analysis. The semen analysis was carried out according to the WHO 2010 guidelines. Seminal lead and cadmium were estimated by ICP-AES. The lead and cadmium values were significantly higher in infertile subjects. A negative association between seminal lead or cadmium concentration and sperm concentration, sperm motility and per cent abnormal spermatozoa was found. This study shows that exposure to Pb (5.29-7.25 µg dl(-1) ) and cadmium (4.07-5.92 µg dl(-1) ) might affect semen profile in men. Age, diet, smoking and tobacco chewing habits may have an influence on the increase in exposure to Pb and Cd in the individual subjects.

Is taxane/platinum/5 fluorouracil superior to taxane/platinum alone and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers?

BACKGROUND: Cisplatin and 5 fluorouracil drug combination is inferior to the combination of taxane with these 2 drugs. However, often in clinical practice at our center giving TPF (docetaxel, cisplatin, 5 fluorouracil) is difficult in view of logistics and tolerance issues. In such a scenario, we prefer to use the 2 drugs combination of platinum and taxane. However, no study has addressed whether a 2 drugs combination, which includes taxane is inferior to the 3 drugs combination and which the taxane of choice is in the 2 drugs combination of taxane and platinum. METHODS: This is a retrospective analysis of prospectively collected data of patients undergoing induction chemotherapy (IC) in oral cavity cancers from 2010 to 2012. We chose for analysis those patients who had a baseline scan done within 4 weeks of starting therapy and a follow-up scan done within 2 weeks of completion of the second cycle of IC. Response was scored in accordance with RECIST version 1.1. Chi-square analysis was done to compare response rates (RRs) between regimens. RESULTS: Two hundred and forty-five patients were identified. The median age was 45 years (24-70 years), 208 (84.9%) were male patients, and 154 patients (62.9%) had primary in the Buccal mucosa. The regimens received were TPF 22 (9%), docetaxel + cisplatin 97 (39.6%), paclitaxel + cisplatin 89 (36.3%), docetaxel + carboplatin 16 (6.5%) and paclitaxel + carboplatin 21 (8.6%). The overall RRs were complete response, partial response, stable disease and progressive disease in 4 (1.6%), 56 (22.9%), 145 (59.2%) and 40 (16.3%). The 3 drugs regimen (TPF) had 50% RR as compared to 22% RR with 2 drugs regimen (P = 0.004). Docetaxel containing regimens had 30.3% RR as compared to 17.2% RR with paclitaxel containing regimens (P = 0.094). CONCLUSIONS: TPF has better RR than a 2 drugs taxane-containing regimen and docetaxel leads to a better RR than paclitaxel for IC in locally advanced oral cavity cancers.