Should COVID-19 patients >75 years be Ventilated? An Outcome Study.

BACKGROUND: Elderly patients with COVID-19 disease are at increased risk for adverse outcomes. Current data regarding disease characteristics and outcomes in this population are limited. AIM: To delineate the adverse factors associated with outcomes of COVID-19 patients ≥75 years of age. DESIGN: Retrospective cohort study. METHODS: Patients were classified into mild/moderate, severe/very severe and critical disease (intubated) based on oxygen requirements. The primary outcome was in-hospital mortality. RESULTS: A total of 355 patients aged ≥75 years hospitalized with COVID-19 between 19 March and 25 April 2020 were included.Mean age was 84.3 years. One-third of the patients developed critical disease. Mean length of stay was 7.10 days. Vasopressors were required in 27%, with the highest frequency in the critical disease group (74.1%). Overall mortality was 57.2%, with a significant difference between severity groups (mild/moderate disease: 17.4%, severe/very severe disease: 71.3%, critical disease: 94.9%, P < 0.001).Increased age, dementia, and severe/very severe and critical disease groups were independently associated with increased odds for mortality while diarrhea was associated with decreased odds for mortality (OR: 0.12, 95% CI: 0.02-0.60, P < 0.05). None of the cardiovascular comorbidities were significantly associated with mortality. CONCLUSION: Age and dementia are associated with increased odds for mortality in patients ≥75 years of age hospitalized with COVID-19. Those who require intubation have the greatest odds for mortality. Diarrhea as a presenting symptom was associated with lower odds for mortality.

Maternal body mass index, smoking status and small for gestational age: an Australian retrospective cohort study.

OBJECTIVES: Both maternal body mass index (BMI) and smoking during pregnancy have been associated with a range of adverse maternal and infant birth outcomes. This study aimed to identify whether these independent variables had an interacting relationship with small for gestational age in an Australian obstetric cohort. STUDY DESIGN: A retrospective cohort design used data from the Birthing Outcomes System of a major tertiary hospital in Australia. METHODS: A total of 14,487 singleton births between January 2008 and December 2013 were included in the analysis. Chi-squared tests and one-way analysis of variance were used for the comparison of categorical and continuous variables, respectively. Adjusted odds ratios (AORs) were calculated to determine the association of smoking status with the outcome variable of interest, and these are reported for each maternal BMI category. RESULTS: Of the 14,487 women, 716 (4.9%) were underweight (BMI ≤18 kg/m2), 7268 (50.2%) had healthy weight (BMI = 19-24 kg/m2), 3658 (25.3%) were overweight (BMI = 25-29 kg/m2), 1558 (10.8%) had class I obesity (BMI = 30-34 kg/m2), 711 (4.9%) had class II obesity (BMI = 35-39 kg/m2) and 576 (3.9%) had class III obesity (BMI = 40+ kg/m2). Of all women, 10.8% reported being current smokers, 82.0% reported to have never smoked and 4.0% reported to have stopped smoking during or before pregnancy. Smokers with a BMI ≥40 kg/m2 were 4.5 (AOR = 4.508; 95% confidence interval: 2.068-9.828) times more likely to give birth to a small-for-gestational-age infant than non-smokers within the same BMI category. This increased risk was not observed in women who ceased smoking before or during pregnancy. CONCLUSIONS: Our study supports the efficacy of antismoking policies within maternal public health. In addition, greater support with respect to smoking cessation is indicated for women during pregnancy with an elevated BMI.

Outcomes in patients with severe COVID-19 disease treated with tocilizumab: a case-controlled study.

BACKGROUND: COVID-19 is an ongoing threat to society. Patients who develop the most severe forms of the disease have high mortality. The interleukin-6 inhibitor tocilizumab has the potential to improve outcomes in these patients by preventing the development of cytokine release storm. AIMS: To evaluate the outcomes of patients with severe COVID-19 disease treated with the interleukin-6 inhibitor tocilizumab. METHODS: We conducted a retrospective, case-control, single-center study in patients with severe to critical COVID-19 disease treated with tocilizumab. Disease severity was defined based on the amount of oxygen supplementation required. The primary endpoint was the overall mortality. Secondary endpoints were mortality in non-intubated patients and mortality in intubated patients. RESULTS: A total of 193 patients were included in the study. Ninety-six patients received tocilizumab, while 97 served as the control group. The mean age was 60 years. Patients over 65 years represented 43% of the population. More patients in the tocilizumab group reported fever, cough and shortness of breath (83%, 80% and 96% vs. 73%, 69% and 71%, respectively). There was a non-statistically significant lower mortality in the treatment group (52% vs. 62.1%, P = 0.09). When excluding intubated patients, there was statistically significant lower mortality in patients treated with tocilizumab (6% vs. 27%, P = 0.024). Bacteremia was more common in the control group (24% vs. 13%, P = 0.43), while fungemia was similar for both (3% vs. 4%, P = 0.72). CONCLUSION: Our study showed a non-statistically significant lower mortality in patients with severe to critical COVID-19 disease who received tocilizumab. When intubated patients were excluded, the use of tocilizumab was associated with lower mortality.

Prophylactic strategies in recurrent vulvovaginal candidiasis: a 2-year study testing a phytonutrient vs itraconazole.

The aim of the present study was to assess the clinical efficacy of a one week/month treatment with a phytocompound with antimycotic properties (K-712, with following 100 mg composition: 10 mg of oleoresin from Pseudowintera colorata at 30 percent concentration in Polygodial together with trace amounts of Olea europea) in recurrent vulvo-vaginal candidiasis (RVVC), as compared to once a week treatment with an azole drug for 24 months follow up. This prospective randomized study involving 122 women (19 to 63 years old) with a history of proven episodes of RVVC in the prior 12 months. Patients were allocated in two treatment groups of 61 patients each and given A) Itraconazole 200 mg orally once a week or B) 1 tab twice a day of K-712 for one week/month. Each treatment schedule was well tolerated with 19 patients in the azole group complaining of transient mild symptoms (nausea, abdominal discomfort, unpleasant taste), while only 3 patients on K-712 reported slight dyspepsia. The number of relapses was significantly lower in the K-712-treated group as compared to the itraconazole-group (22 vs 39, p less than 0.05). Moreover, the former group showed a significantly decreased number of cases resistant or dose-dependent susceptible as compared to group A (p less than 0.05 vs itraconazole) and the same occurred for the occurrence of non-albicans species (group A 64.1 percent vs group B 31.8 percent, p less than 0.05). The overall mycological cure at the end of the 2-year study showed a comparable benefit between the two groups. From these data it appears that the present antifungal phytonutrient is equally effective as itraconazole in the overall treatment of RVVC over a 2-year follow-up, but yielding a significantly better prophylactic effect and also maintenance benefit with lower relapse rate, antifungal susceptibility and growth of azole-resistant species.

Hypoadiponectinemia in obesity: association with insulin resistance.

Obesity is risk factor for insulin resistance, diabetes, and other chronic diseases. Adiponectin, an adipose-specific protein with antiatherogenic and antiinflammatory effects, were found to be associated with obesity, type 2 diabetes, and insulin resistance. Our aim to identify possible relationships between circulating adiponectin and obesity as well as obesity related phenotypes. A total of 642, obese and non-obese individuals were included in this cross-sectional study. Hormone and glucose levels were estimated using standard protocols. The adiponectin levels showed a significant decrease with increasing quartiles of insulin resistance index. Subjects in lowest quartile of adiponectin level had a significantly higher risk than those in the highest quartile, with higher body mass index, waist circumference, blood pressure, percentage body fat, fat mass, fasting insulin, insulin resistance index, total cholesterol (p < 0.001), low density lipoprotein-cholesterol (p = 0.001), very low density lipoprotein-cholesterol (p = 0.002), and Triglyceride (p = 0.002). The present study indicates that adiponectin is significantly associated with obesity, insulin resistance and other obesity related phenotypes.

Sensorineural deafness in patients of type 2 diabetes mellitus in uttar pradesh: a pilot study.

B/L symmetrical sensorineural hearing loss has long been associated with diabetes Mellitus. Microangiopathy associated with thickening of the basement membrane of small vessels has been implicated as a major source. This study was done to observe the predominant site of lesion whether cochlear or retrocochlear in patients of diabetic sensorineural hearing loss. This was a random study. Forty two patients with diabetic B/L symmetrical sensorineural hearing loss were selected in a tertiary referral centre. All the patients selected were of diabetic B/L symmetrical sensorineural hearing loss. The study was designed to show the predominant site of lesion whether cochlear or retrocochlear in patients of diabetes with or without noise exposure. The parameter for inferring blood sugar control was level of glycosylated haemoglobin (Hb1AC). The incidence of the classical symptoms of diabetes mellitus namely polyurea, polydypsia and polyphagia were seen in (40.8%) of patients. The present study was designed to show that even early diabetic patients without symptoms of hearing loss had mild bilaterally symmetrical purely sensorineural hearing loss (32.65%) signifying the diabetic hypoacusis is present significantly even in early aural symptomless diabetics. On follow up it was revealed that the hearing loss of these patients was irreversible. The predominant site of lesion was found to be cochlear by performing Chi Square test P < .05 and so this is applicable to the general population of Uttar Pradesh.

Association of PPAR-γ gene polymorphisms with obesity and obesity-associated phenotypes in North Indian population.

OBJECTIVES: The worldwide increasing prevalence of obesity is considered as a major health problem. Peroxisome proliferator-activated receptor gamma (PPAR-γ) controls adipocyte differentiation and regulates a number of genes associated with energy homeostasis. In this study, we investigated the association of PPAR-γ gene Pro12Ala (rs1801282) and C1431T (rs3856806) polymorphisms with morbid obesity and related phenotypes, in north Indian population. METHODS: A total of 6,42 subjects, 309, obese and 333 nonobese individuals were included in this case-control study. Insulin, adiponectin, glucose, and lipid levels were estimated using standard protocols. All subjects were genotyped by PCR restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The ProAla+AlaAla genotypes of PPAR-γ Pro12Ala were significantly associated with higher risk of obesity while C1431T polymorphism did not show any significant association. None of the haplotypes showed association with morbid obesity. However, a strong association of variant genotypes was observed with higher levels of insulin, HOMA-IR, and lower serum adiponectin concentrations. CONCLUSION: PPAR-γ gene polymorphisms influence obesity and obesity phenotype in a complex manner, probably involving insulin resistance in north Indian population.

Association of TNF-α promoter gene G-308A polymorphism with metabolic syndrome, insulin resistance, serum TNF-α and leptin levels in Indian adult women.

BACKGROUND: Tumour necrosis factor alpha is a multifunctional proinflammatory cytokine involved in the pathogenesis of metabolic syndrome, insulin resistance, and obesity. Aim of this study is to investigate in a North Indian female population the impact of the G-308A TNF-α variant on various components of the metabolic syndrome, Insulin Resistance, serum TNF-α and Leptin levels. METHODS: The G-308A TNF-α polymorphism has been studied in 269 females with metabolic syndrome (NCEP ATP III criteria) (age 31.91±6.05) and 272 healthy females without metabolic syndrome (age 30.96±7.01). The G-308A variant was detected by PCR amplification and Nco-1 digestion. RESULTS: Homozygous mutant genotype (AA) (p=<0.001: OR=3.24: 95% CI=2.15-4.89) and mutant allele (A) (p=<0.001: OR=3.04: 95% CI=2.08-4.43) of TNF-α was significantly less frequently observed in the control population as compared to study group. Furthermore, on dividing the subjects into two groups according to the absence (TNF-1 allele) or presence of the mutant A (TNF-2) allele, significant results were obtained in most of the metabolic risk factors. CONCLUSIONS: Our results suggest that the G-308A polymorphism of the TNF-α gene may be independently associated with hypertension, leptin level and hypercholesterolemia leading to metabolic syndrome independent of Insulin resistance and hyperglycemia.

Association of FTO rs17817449 SNP with obesity and associated physiological parameters in a north Indian population.

BACKGROUND: Obesity is a very common disorder directly linked with various diseases such as type-2 diabetes, hypertension and atherosclerosis. Variants in the FTO gene have been associated with Body Mass Index in Western European and North American populations. AIM: This study analysed the association between the FTO gene variant rs17817449 (G>T) and obesity and obesity-related phenotypes in a north Indian population. SUBJECTS AND METHODS: A total of 642 subjects, 309 obese and 333 non-obese individuals, were included in this case-control study. Genotyping of FTO gene (rs17817449) polymorphism for all subjects was performed by the PCR-RFLP method. RESULTS: Significant associations were found for FTO rs17817449 SNP with obesity and obesity-related phenotypes. The strongest associations were observed between the rs17817449 and fasting blood glucose, insulin, homeostasis model of assessment--insulin resistance (HOMA-IR) and fat mass under a recessive model. CONCLUSIONS: This study replicated the genetic association of SNP of FTO (rs17817449) with obesity in a north Indian population and, to the authors' knowledge; this is the first such association study in a north Indian population. This study also established that SNP in intron 1 of FTO (rs17817449) are strongly associated with several measures of adiposity and are also associated with plasma insulin, insulin resistance, percentage body fat and fat mass.

Influence of Bcl-1 Gene Polymorphism of Glucocorticoid Receptor Gene (NR3C1, rs41423247) on Blood Pressure, Glucose in Northern Indians.

Glucocorticoids and its receptor are known to be involved in the dysregulation of hormone and lipid levels. Therefore, we evaluated the association of Bcl1 gene polymorphism of glucocorticoids receptor (GCR) gene variant with hormone and lipid levels in Northern Indians obese. A total of 435 obese and non-obese age matched subjects were included in the case-control study. Lipid and hormonal levels were estimated using standard protocols. Analysis of +646 C>G NR3C1 gene polymorphism was done using PCR-RFLP. The frequencies of GR Bcl1, C>G genotypes and alleles did not differ significantly (P > 0.05) between obese and non-obese. The +646 G allele carriers had higher waist to hip ratio, blood pressure, insulin and glucose levels than non-carriers in obese subjects while diastolic blood pressure and glucose in non-obese. The NR3C1, +646 C>G polymorphism did not associate with obesity. However, the GG genotype may modulate blood pressure, blood glucose and hormonal levels in northern Indians.

Bilateral sudden sensorineural deafness with vertigo as the sole presenting symptoms of diabetes mellitus - a case report.

This Paper reports a late uncontrolled diabetic presenting to an otolaryngologist with sudden severe sensorineural hearing loss of immediate origin with vertigo and tinnitus as the symptoms. Appropriate investigative and treatment measure resulted in deterioration of hearing in the right ear and mild improvement of hearing in the left ear, with no recovery of imbalance.

A common polymorphism in the promoter of UCP2 is associated with obesity and hyperinsulenemia in northern Indians.

A polymorphism in the promoter region of uncoupling protein 2 gene -866 G/A has been associated with its expression levels, the risk of obesity, and metabolic abnormalities. We aimed to investigate the associations of uncoupling protein (UCP)2 gene variants with obesity and related traits. A total of 440 subjects, 200 obese, and 240 non-obese individuals were included in this case-control study. Hormone and glucose levels were estimated using standard protocols. Genotyping of UCP-2 gene polymorphism for all subjects was performed by the PCR-RFLP polymerase chain reaction (PCR) method. Higher Systolic blood pressure, Diastolic blood pressure, Waist to hip ratio, Leptin, Insulin, and blood glucose levels were observed in obese than non-obese (P < 0.05). The distributions of genotype (0.001) and allele (0.003) were significantly different between the non-obese and the obese groups. In the obese group, subjects with the A allele showed significant high insulin levels (<0.001) in comparison with A allele non-carriers. In conclusion, our results suggest that the -866 AA genotype and A allele of the UCP2 gene is associated with obesity and A allele associated with hyperinsulinemia in obese subjects.

Abdominal wall endometriosis.

Endometriosis of abdominal wall scar following operation on uterus and tubes is extremely rare. The late onset of symptoms after surgery is the usual cause of misdiagnosis. Scar endometriosis is a rare disease which is difficult to diagnose and should always be considered as a differential diagnosis of painful abdominal masses in women. The diagnosis is made only after excision and histopathology of the lesion. Preoperative differentials include hernia, lipoma, suture granuloma or abscess. Hence an awareness of the entity avoids delay in diagnosis, helps clinicians to a more tailored treatment and also avoids unnecessary referrals. We report a case of abdominal endometriosis. The definitive diagnosis of which was established by histopathological studies.

Association of cholesteryl ester transfer protein (TaqIB) and apolipoprotein E (HhaI) gene variants with obesity.

Background The pathophysiology of obesity is known to be influenced by alterations in lipid levels. We aimed to evaluate association of cholesteryl ester transfer protein (CETP) and apolipoprotein (APO) E gene variants with asymptomatic obesity. Methods A total of 437 subjects, 159 asymptomatic obese (BMI = 29.29 +/- 3.76) and 278 non-obese (BMI = 23.38 +/- 1.71) individuals, were included in this case-control study. Lipid levels were estimated using standard protocols. Analysis of CETP (TaqIB) and APOE (HhaI) gene polymorphisms was done using PCR-RFLP. Results We found significant difference in blood pressure (systolic, P < 0.0001 and diastolic, P < 0.0001), total cholesterol (P < 0.0001), LDL-cholesterol (P < 0.0001), and HDL-cholesterol (P < 0.0001) in obese as compared to non-obese group. Homozygous APO E4E4 genotype was only observed in 5.7% of obese individuals and none in non-obese group. APO E4 allele carriers were also susceptible for obesity (P = 0.016, OR = 1.73; 95% CI = 1.12-2.68) than non-carriers. Higher blood pressure (Systolic, P = 0.001 and Diastolic, P = 0.004) and triglyceride levels (P = 0.029) were observed in obese subjects with APO E4 allele than individuals without APO E4. However, CETP B1 variant allele carriers did not show alteration in blood pressure and lipid profile in asymptomatic obese subjects. Conclusions APO E4 genotype and allele were found to be associated with asymptomatic obesity, whereas CETP Taq1B polymorphism showed no such association in North Indian subjects.

Association of beta2-adrenergic receptor and insulin receptor substrate-1 polymorphisms with obesity in a Northern Indian population.

BACKGROUND: Imbalance in hormonal levels, regulated by host genetic factors, are known to be a major cause of obesity. Therefore, we aimed to evaluate association of genetic polymorphisms of beta(2)-adrenergic receptor (beta(2)-AR) and insulin receptor substrate-1 (IRS-1) with hormonal levels in northern Indian obese. METHODS: A total of 111 obese and 89 age matched non-obese subjects were studied after taking detailed clinical profile. Hormonal assays in serum/plasma for different hormones were done using IRMA and RIA kits. Genetic analysis of beta(2)-AR (-47 and -20, T to C) and IRS-1 (Arg972Gly) was done using PCR-RFLP. STATISTICAL ANALYSIS: Statistical analysis was performed by SPSS (version 11.5) software. All continuous variables were expressed as mean +/- SD and tested by ANOVA test. Comparisons of categorical variables were assessed using X(2) tests or Fisher's exact test. P-value <0.05 was considered as significant. RESULTS: Analysis showed that obese subjects had significantly higher value of blood pressure (systolic), WHR, leptin insulin and glucagon and lower value of GH. In beta(2)-AR (-47) T/C and IRS-1 Gly972Arg gene polymorphisms we did not found significant differences in genotype or allele frequencies. Moreover, none of the studied hormonal or metabolic parameters showed any association with the gene polymorphisms. CONCLUSIONS: Study reveals no significant association of beta(2)-AR (-47 and -20, T to C) and IRS-1 Gly 972 Arg polymorphisms with obesity in northern Indians.

Spontaneous unusual expression of frequency of chromosome aberrations and common fragile in human lymphocytes of colorectal cancer patients induced by Aphidicolin.

Chromosomal fragile sites are distributed all over the human genome. Aphidicolin mediated expression frequency of common fragile sites and other chromosomal changes were evaluated in prometaphase/metaphase chromosomes obtained from peripheral blood lymphocytes of colorectal cancer patients. The present study reveals first time high incidence i.e. 6 % of aphidicolin induced chromosome breaks / gaps designated as "common fragile sites" in cell population of clinically diagnosed patients of colorectal cancer patients in Nepalese population. These chromosomal changes including structural and numerical were compare to clinically healthy normal individual of same sex / age groups, act as controls for statistical analysis. The frequency of chromosomal aberration in cancer patients were significantly higher (p<0.001) when compare to normal individuals. The increased genetics instability probably either due to nutritional factor i.e. lack of folic acid component in diet--an essential component required for DNA synthesis or unknown environmental factor for such genetic disorder. The present study indicates aphidicolin high frequency of induced chromosome aberrations and "common fragile sites" because of late replication of DNA in mitosis in colorectal cancer patients suggesting these sites could be used as suitable marker for determining genetic predisposition in cancer patients.