Demographic and clinical characteristics of primary lung cancer patients in Kerala: Analysis of data from six teaching centers.

Background: Lung cancer continues to be the leading cause of cancer-related deaths in men and women. A breakdown by level of economic development shows no differences in cancer deaths in men but a higher rate of lung cancer deaths in women in industrialized countries as compared with developing nations. The risk factors for lung cancer most commonly include lifestyle, environmental, and occupational exposures. The role these factors play varies depending on geographic location, sex and race characteristics, genetic predisposition, as well as their synergistic interactions. Materials and Methods: It was a hospital-based registry, wherein hospitals were selected from three zones-north, central, and south zones of Kerala. The study was registered with clinical trial registry of India with Registration No. CTRI/2021/02/031299. Registry of lung cancer patients was prepared at all sites and institutional ethical clearance was received from all sites. All patients with primary lung cancer, histologically proven of all age groups were included in the study. Results: A total of 761 patients were registered from six teaching hospitals in Kerala who were diagnosed with primary lung cancer during the period 2017-2019. The mean age of the study population was 65.1 ± 10.2 years. Of all, 81.1% of them were males and 18.9% were females. Histologically, 56.4% had adenocarcinoma and 25.6% had squamous cell carcinoma. Conclusion: It was observed that the proportion of females diagnosed with primary lung cancer is increasing. Patients get diagnosed at a later stage of the disease, which calls for screening and early detection of lung cancer. As it accounts for the highest mortality among all other cancers, there is high scope for prevention and screening strategies.

Breast screening practices of 35-65 years old women - A cross-sectional survey in Alappuzha, Kerala, India.

BACKGROUND: Enhancing cancer literacy, promoting early detection, and avoiding treatment delays are essential for reducing breast cancer mortality and ensuring a good quality of life among women in less developed countries. The present paper describes the breast screening practices of women in the Alappuzha district of Kerala state, India. MATERIALS AND METHODS: A multi-stage cluster sampling method was used to select study participants. Data were collected using a structured questionnaire, entered using Kobo Toolbox, and analyzed using IBM SPSS Statistics-25 for Windows. The proportions of women who practiced breast examinations were estimated with 95% confidence intervals. The Chi-square test was used to test the associations, and binary logistic regression was used to estimate odds ratios. RESULTS: Among 320 women, 55% were less than 50 years old, 45% had higher secondary education or above, and six were already diagnosed with breast cancer (1.9%, 95% CI: 0.4%-3.4%). Of the 314 women, 73.2% were practicing breast self-examination (95% CI: 68.4%-78.1%), and 25.2% ever attended clinical breast examination (95% CI: 20.4%-30.0%). Working/retired/self-employed women with higher secondary education and above had almost 10 times higher odds (OR = 10, 95% CI: 3.35-29.86) of practicing breast self-examination (BSE) compared to homemakers or women working under rural employment schemes with a low level of education. CONCLUSION: A higher percentage of women practicing BSE and clinical breast examination (CBE) in the present study indicates that women in this population are more concerned about breast cancer. Women should be educated more on the symptoms and risk factors, the proper ways of practicing BSE, and the importance of consulting a health practitioner for CBE. Also, it is crucial to ensure that awareness and screening programs reach marginalized women.

The Impact of Time to Reperfusion on Recanalization Rates and Outcome After Mechanical Thrombectomy: A Single Center Experience.

Background: Timely and effective recanalization to salvage the penumbra is the main determinant of outcome in acute ischemic strokes. Randomized controlled trials on late window mechanical thrombectomy (MT) have proved its safety and efficacy upto 24 h after stroke onset. We looked at the impact of time to reperfusion on vessel recanalization rates and short-term outcome in patients undergoing MT for large vessel occlusion. Methods: The clinical, imaging, and outcome of all patients undergoing MT upto 24 h from last seen normal was extracted from a prospectively maintained ischemic stroke database from January 2012 till September 2019. Results: There were 145 patients with a mean (SD) age of 58.2 (±14) years. Of them, 28 had wake up/unknown time of onset stroke and 9 presented beyond >360 min. There were 23 vertebrobasilar strokes. Median National Institute of Health Stroke scale score (NIHSS) at admission was 16.4 (Inter quartile range (IQR) 12-21). CT-Alberta Stroke program early CT score (CT-ASPECTS) was excellent (8-10) in 39 (31.6%) and fair (5-7) in 77 (63.6%) patients in anterior circulation strokes. About 25% underwent bridging therapy. Recanalization rates did not differ between those presenting early (<6 h) versus wake up strokes and late presenting patients (81.79% vs 71.9%). Symptomatic Intracerebral hemorrhage (ICH) occurred in 5%. At 3 months, excellent outcome (modified rankin scale <2) was observed in 28.9%. While Admission NIHSS remained strong predictor of poor outcome at 3 months, delay in presentation did not impact MT outcome (37.5% vs 45.79% and P = 0.460). Conclusions: The recanalization rates were similar in patients irrespective of the time to reperfusion from stroke onset. The functional outcome was not inferior in late presenters selected by advanced imaging.

Status of cancer screening in India: An alarm signal from the National Family Health Survey (NFHS-5).

Background: Cancer is often detected much later to its onset, resulting in poor prognosis. This makes cancer the second most common cause of death globally. Looking for cancers much before any symptoms occur is termed "cancer screening" and is a powerful strategy for prevention, early diagnosis, and better management of several cancers. This paper examines the status of cancer screening in India from the National Family Health Survey (NFHS)-5 report for the period of 2019-2021. Methods: Secondary data on participation in screening for cervical, breast, and oral cancer were extracted from the NFHS-5 report. Participation status for all the above cancer types is represented as percentages and compared across 28 states and eight union territories in India. Results: The percentages of women who have ever undergone cervical, breast, and oral cavity screening were 1.9%, 0.9%, and 0.9%, respectively. About 1.2% of men participated in oral cavity screening. The highest percentage of cervical and breast cancer screening participation was reported in Tamil Nadu (9.8% and 5.6%, respectively), followed by Puducherry (7.4% and 4.2%) and Mizoram (6.9% and 2.7%). Andaman and Nicobar Islands reported the highest oral cancer screening among women (10.1%) while Andhra Pradesh (6.3%) reported the highest participation among men. Conclusion: Cancer screening participation in India is extremely inadequate and calls for the immediate attention of national and state governments. Additional efforts are warranted to improve public awareness of cancer screening, and appropriate measures should be implemented to conduct well-organized screening programs across the country to ensure maximum participation.

Consumption of fruits, vegetables and salt in the context of control of type 2 diabetes and hypertension in Kerala, India.

BACKGROUND: Proper diet is necessary to control hypertension and diabetes. This paper describes the combined fruit and vegetable, and salt intake of adults (>=18 years) who were detected to have hypertension or diabetes. METHODS: We analysed the data from a state-wide survey of 12012 adults using the World Health Organization STEPs for NCD risk factor surveillance. We evaluated the recommended intake of fruit and vegetable (>=5 servings/day) and salt (<5 gm/day) across participants divided into four strata, and the probabilities were also estimated using the fitted multiple binary logistic regression models. RESULTS: Overall, 13.9% (95%CI: 12.2%-15.9%) and 29.4% (95%CI: 28%-30.8%) of participants consumed the recommended level of fruit and vegetable, and salt, respectively. Adjusted odds ratios were not significantly different across the four strata based on the status of treatment and control of diabetes or hypertension. The likelihood of following the recommended fruit and vegetable intake was highest for 50-69-year-old females with above high school education, obese, under treatment for diabetes or hypertension, and had normal values of FBS and BP (0.28). The likelihood for recommended salt intake was highest for 50-69-year-old males with above high school education and had normal BMI, under treatment for diabetes or hypertension, and had normal values of FBS and BP (0.69). CONCLUSION: The status of diabetes or hypertension did not show considerable influence in the fruit, vegetable, and salt intake of adults in general. A detailed exploration of the accessibility and acceptability of such recommended intakes in the Kerala context is warranted.

Regulation of CNKSR2 protein stability by the HECT E3 ubiquitin ligase Smurf2, and its role in breast cancer progression.

BACKGROUND: Smurf2 E3 ubiquitin ligase physically associates with and regulate the stability of distinct cellular protein substrates. The multi-functional scaffold protein Connector enhancer of kinase suppressor of ras 2 (CNKSR2) plays a key role in regulating cell proliferation, and differentiation through multiple receptor tyrosine kinase pathways. The aim of this study was to investigate whether the interaction between Smurf2 and CNKSR2 has any significant role in the post transcriptional regulation of CNKSR2 expression in breast cancer. METHODS: Here we demonstrate a novel interaction of CNKSR2 with Smurf2 by co-immunoprecipitation, indirect immunofluorescence studies, and surface plasmon resonance (SPR) analysis, which can ubiquitinate, but stabilize CNKSR2 by protecting it from proteasome mediated degradation. RESULTS: CNKSR2 protein levels were significantly increased upon forced overexpression of Smurf2, indicating the role of Smurf2 in regulating the stability of CNKSR2. Conversely, Smurf2 knockdown resulted in a marked decrease in the protein level expression of CNKSR2 by facilitating enhanced polyubiquitination and proteasomal degradation and reduced the proliferation and clonogenic survival of MDA-MB-231 breast cancer cell lines. Tissue microarray data from 84 patients with various stages of mammary carcinoma, including (in order of increasing malignant potential) normal, usual hyperplasia, fibrocystic changes, fibroadenoma, carcinoma-in-situ, and invasive ductal carcinoma showed a statistically significant association between Smurf2 and CNKSR2 expression, which is also well correlated with the ER, PR, and HER2 status of the tissue samples. A comparatively high expression of Smurf2 and CNKSR2 was observed when the expression of ER and PR was low, and HER2 was high. Consistently, both Smurf2 and CNKSR2 showed an integrated expression in MCF10 breast progression model cell lines. CONCLUSIONS: Altogether, our findings reveal that Smurf2 is a novel positive regulator of CNKSR2 and suggest that Smurf2-CNKSR2 interaction may serve as a common strategy to control proliferation of human breast cancer cells by modulating CNKSR2 protein stability.

Circulating Thrombotic Risk Factors in Young Patients with Coronary Artery Disease Who Are on Statins and Anti-platelet Drugs.

Thrombotic risk factors may contribute to premature coronary artery disease (CAD), in addition to the conventional risk factors. There is paucity of data on studies evaluating the role of thrombotic factors in premature CAD in Indian patients. Thus a case-control study was performed to evaluate the role of thrombotic and atherogenic factors in young patients with angiographically proven CAD who are on treatment with statins and anti-platelet drugs. 152 patients (≤55 years) with angiographically proven CAD and 102 asymptomatic controls were recruited. Clinical and biochemical data were obtained in both groups. Blood levels of thrombotic factors-fibrinogen, antithrombin-III, tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von-Willebrand factor (v-WF), lipoprotein(a) [Lp(a)] and homocysteine were analyzed. Patients had high levels of conventional CAD risk factors (diabetes mellitus, smoking, hypertension, dyslipidemia and positive family history) compared to controls. Logistic regression analysis revealed that low antithrombin-III (odds ratio/OR 11.2; 95 % confidence interval/CI 2.29-54.01), high fibrinogen (OR 6.04; 95 % CI 1.09-33.21) and high Lp(a) (OR 4.54; 95 % CI 0.92-22.56), as important, independent risk factors in patients. PAI-1(OR 0.15; 95 % CI 0.03-0.69) levels were significantly lower in patients. But other thrombotic risk factors studied (t-PA, v-WF and homocysteine) were comparable among patients and controls. The treatment using statins and anti-platelet drugs might be contributing to the control of some of the thrombotic risk factors. The strategies aiming at lowering the levels of thrombotic risk factors along with conventional risk factors may be useful in primary and secondary prevention of CAD.

Risk of invasive cancer among women visually screened and colposcopy triaged by trained nurses in rural South India.

OBJECTIVE: To estimate the long-term risk of cervical cancer among women screened by visual inspection with acetic acid (VIA) and to evaluate the benefit of additional colposcopy triage in rural south India. METHODS: A retrospective analysis was conducted among 31 343 women who had undergone VIA at Dindigul district, India between January 1, 2000, and August 5, 2003, as part of a randomized screening trial. Women with positive VIA test results were offered colposcopy triage by trained nurses. Cervical cancer incidence data during follow-up (January 1, 2000, to December 31, 2012) were obtained from a regional cancer registry. RESULTS: Among 3021 screen-positive women free of cancer at baseline, 2974 women underwent colposcopy; colposcopic abnormalities suggestive of precancerous lesions were detected among 2792 of these women (93.9%). Compared with the women with negative VIA screening results, the hazard ratio (HR) of cervical cancer during follow-up among the VIA-positive women without colposcopic abnormalities was 6.5 (95% confidence interval [CI], 1.6-27.1). The risk was similar among VIA-positive women with colposcopic abnormalities but without histological confirmation (HR5.2; 95% CI, 1.9-14.6). CONCLUSION: The high risk of cancer among women without colposcopic abnormalities who tested positive by VIA suggested that screening without triage is potentially effective.

Forkhead box C2 promoter variant c.-512C>T is associated with increased susceptibility to chronic venous diseases.

Chronic venous disease (CVD) is one of the most prevalent yet underrated disorders worldwide. High heritability estimates of CVD indicate prominent genetic components in its etiology and pathology. Mutations in human forkhead box C2 (FoxC2) gene are strongly associated with valve failure in saphenous and deep veins of lower extremities. We explored the association of genetic variants of FoxC2 as well as FoxC2 mRNA and protein expression levels with CVD of lower limbs. We systematically sequenced the single coding exon, 5' and 3' flanking regions of FoxC2 gene in 754 study subjects which includes 382 patients with CVD and 372 healthy subjects. Four novel and three reported polymorphisms were identified in our cohort. Three variants in 5' flanking region and one in 3' flanking region of FoxC2 gene were significantly associated with CVD risk. FoxC2 mRNA in vein tissues from 22 patients was 4±1.42 fold increased compared to saphenous veins from 20 normal subjects (p<0.01). FoxC2 protein was also significantly upregulated in varicose veins compared to control samples. The c.-512C>T (rs34221221: C>T) variant which is located in the FoxC2 putative promoter region was further analyzed. Functional analysis of c.-512C>T revealed increased mRNA and protein expression in patients with homozygous TT genotype compared to heterozygous CT and wild CC genotypes. Luciferase assay indicated higher transcriptional activity of mutant compared to wild genotype of this variant. These findings suggested that c.-512C>T variant of FoxC2 was strongly associated with susceptibility to CVD and also that this variant resulted in FoxC2 overexpression. To obtain a mechanistic insight into the role of upregulated FoxC2 in varicosities, we overexpressed FoxC2 in venous endothelial cells and observed elevated expression of arterial markers Dll4 and Hey2 and downregulation of venous marker COUP-TFII. Our study indicates altered FoxC2-Notch signaling in saphenous vein wall remodeling in patients with varicose veins.

Transesophageal echocardiographic evaluation of left ventricular systolic and diastolic function in response to 20% mannitol and 3% hypertonic saline infusion in neurosurgical patients undergoing craniotomy.

BACKGROUND: Mannitol and hypertonic saline (HS) are routinely used during craniotomy. Both increase myocardial preload and reduce afterload, and may improve cardiac output. It is not currently known whether this results in an improvement in the global myocardial function. Thus, the aim of this study was to compare the effects of a single equiosmolar bolus of 20% mannitol (5 mL/kg) or 3% HS (5 mL/kg) on the global myocardial function by tissue Doppler-derived myocardial performance index (TD-MPI) in patients undergoing craniotomy. METHODS: Fifty adult patients were included and randomized to receive either mannitol or 3% HS. Transesophageal echocardiography was performed in all patients. Early (E) and late (A) peak mitral inflow velocity, early diastolic mitral annular velocity (E prime), isovolumetric relaxation time (IVRT), ejection time (ET), and isovolumetric contraction time (IVCT) were recorded at baseline and at 15, 30, 60, and 120 minutes after administration of the hyperosmolar solutions. TD-MPI was calculated as IVRT+IVCT/ET. RESULTS: There were no significant differences in the TD-MPI (HS vs. mannitol: 0.43 vs. 0.44 [baseline], 0.45 vs. 0.43 [15 min], 0.44 vs. 0.45 [30 min], 0.47 vs. 0.45 [60 min], 0.45 vs. 0.46 [120 min]), E/A ratio, IVCT, and E/E' either within or between the 2 groups at any time point. IVRT was prolonged in HS group as compared with baseline at 15, 30, and 60 minutes postinfusion. ET was decreased in both the groups at 120 minutes postinfusion. Neither of these altered the TD-MPI. CONCLUSIONS: Equiosmolar administration of 20% mannitol and 3% HS did not show any difference in global myocardial performance as measured by TD MPI.

Socio demographic and reproductive risk factors for cervical cancer - a large prospective cohort study from rural India.

BACKGROUND: India shows some of the highest rates of cervical cancer worldwide, and more than 70% of the population is living in rural villages. Prospective cohort studies to determine the risk factors for cervical cancer are very rare from low and medium resource countries. The aim of this study was to quantify the effect of risk factors related to cervical cancer in a rural setting in South India. MATERIAL AND METHODS: Sociodemographic and reproductive potential risk factors for cervical cancer were studied using the data from a cohort of 30,958 women who constituted the unscreened control group in a randomised screening trial in Dindigul district, Tamilnadu, India. The analysis was accomplished with the Cox proportional hazard regression model. RESULTS: Women of increasing age (HR=2.4; 95% CI: 1.6, 3.8 in 50-59 vs 30-39), having many pregnancies (HR=7.1; 1.0, 52 in 4+ vs 0) and no education (HR=0.6; 0.2, 0.7 in high vs none) were found to be at significantly increased risk of cervical cancer. CONCLUSION: This cohort study gives very strong evidence to say that education is the fundamental factor among the sociodemographic and reproductive determinants of cervical cancer in low resource settings. Public awareness through education and improvements in living standards can play an important role in reducing the high incidence of cervical cancer in India. These findings further stress the importance of formulating public health policies aimed at increasing awareness and implementation of cervical cancer screening programmes.

A case-control nutrigenomic study on the synergistic activity of folate and vitamin B12 in cervical cancer progression.

The present study was designed to identify the role of folate, B12, homocysteine, and polymorphisms of methylene tetrahydrofolatereductase (MTHFR) gene in cervical carcinogenesis among 322 women from Kerala, South India. Serum folate, vitamin B12 (chemiluminescence assay), and homocysteine (EIA) along with genetic polymorphisms of MTHFR gene (polymerase chain reaction/restriction fragment length polymorphism) were analyzed for 136 control subjects, 92 low-grade squamous intraepithelial lesions (LSIL) subjects, and 94 invasive cervical cancer cases (ICC). Statistically significant associations between MTHFR polymorphisms, serum homocysteine, and folate levels with cervical carcinogenesis were not evident, but we found that these parameters acted as effect modifiers of serum vitamin B12. The risk estimates observed for B12 became prominent only when there was a deficiency in serum folate levels [LSIL-odds ratio (OR): 14.9 (95% CI: 2.65 to 84.4); ICC-OR = 8.72 (95% CI = 1.55 to 48.8)] or when MTHFR A1298C polymorphic variant was present [LSIL-OR = 9.8 (95% CI = 2.61 to 36.7); ICC-OR = 10.0 (95%CI = 2.5 to 39.3)]. The statistical significance of this effect modification was further studied using an interaction model, where only folate was observed to have an influence on B12 levels as suggested by the odds ratio of 7.11 (95% CI = 0.45 to 111.9) obtained for ICC group, implicating a synergistic role of these 2 vitamins in invasive cervical cancer.

Prognostic significance of STAT3 and phosphorylated STAT3 in human soft tissue tumors - a clinicopathological analysis.

BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is a key signaling molecule and a central cytoplasmic transcription factor, implicated in the regulation of growth. Its aberrant activation has been demonstrated to correlate with many types of human malignancy. However, whether constitutive STAT3 signaling plays a key role in the survival and growth of soft-tissue tumors is still unclear and hence needs to be elucidated further. In our study we examined the expression levels of STAT3 and pSTAT3 in different grades of soft tissue tumors and correlated with its clinicopathological characteristics. METHODS: Expression levels of STAT3 and pSTAT3 in soft tissue tumors were studied using Immunohistochemistry, Western blotting and Reverse transcriptase- PCR and correlated with its clinicopathological characteristics using Chi squared or Fisher's exact test and by logistic regression analysis. Statistical analysis was done using Intercooled Stata software (Intercooled Stata 8.2 version). RESULTS: Of the 82 soft tissue tumor samples, fifty four (65.8%) showed immunoreactivity for STAT3 and twenty eight (34.1%) for pSTAT3. Expression of STAT3 and pSTAT3 was significantly associated with tumor grade (P < 0.001; P < 0.001), tumor location (P = 0.025; P = 0.027), plane of tumor (P = 0.011; P = 0.006), and tumor necrosis (P = 0.001; P = 0.002). Western blotting and RT-PCR analysis showed increased expression of STAT3 and p-STAT3 as grade of malignancy increased. CONCLUSION: These findings suggest that constitutive activation of STAT3 is an important factor related to carcinogenesis of human soft tissue tumors and is significantly associated with its clinicopathological parameters which may possibly have potential diagnostic implications.