ABSTRACT
PURPOSE: To perform an extensive exploratory analysis to build a deeper insight into clinically relevant molecular biomarkers in Papillary, Follicular, and Anaplastic thyroid carcinomas (PTC, FTC, ATC). METHODS: Thirteen Thyroid Cancer (THCA) datasets incorporating PTC, FTC, and ATC were derived from the Gene Expression Omnibus. Genes differentially expressed (DEGs) between THCA and normal were identified and subjected to GO and KEGG analyses. Multiple topological properties were harnessed and protein-protein interaction (PPI) networks were constructed to identify the hub genes followed by survival analysis and validation. RESULTS: There were 70, 87, and 377 DEGs, and 23, 27, and 53 hub genes for PTC, FTC, and ATC samples, respectively. Survival analysis detected 39 overall and 49 relapse-free survival-relevant hub genes. Six hub genes, BCL2, FN1, ITPR1, LYVE1, NTRK2, TBC1D4, were found common to more than one THCA type. The most significant hub genes found in the study were: BCL2, CD44, DCN, FN1, IRS1, ITPR1, MFAP4, MKI67, NTRK2, PCLO, TGFA. The most enriched and significant GO terms were Melanocyte differentiation for PTC, Extracellular region for FTC, and Extracellular exosome for ATC. Prostate cancer for PTC was the most significantly enriched KEGG pathway. The results were validated using TCGA data. CONCLUSIONS: The findings unravel potential biomarkers and therapeutic targets of thyroid carcinomas.
ABSTRACT
Background and objective Chronic kidney disease (CKD) is a clinical syndrome characterized by the irreversible loss of kidney function. It is a widespread condition affecting populations worldwide. The kidneys play a crucial role in the metabolism, breakdown, and elimination of thyroid hormone and thyroid-stimulating hormone (TSH). Consequently, thyroid dysfunction can occur as an endocrine manifestation in CKD patients. Previous studies investigating thyroid abnormalities and the severity of CKD have yielded diverse outcomes. In light of this, this study aimed to determine the prevalence of thyroid dysfunction in CKD patients and explore the association between different thyroid dysfunctions and markers of kidney function. Methods A total of 140 CKD patients who met the inclusion criteria were recruited, and their demographic details and routine investigations were recorded. Blood samples were collected for kidney function tests and thyroid function tests. The primary outcome measures included markers of kidney function [urea, creatinine, and estimated glomerular filtration rate (e-GFR)] and thyroid profile [TSH, free thyroxine (FT4), and free triiodothyronine (FT3)]. Mean and standard deviation (SD) were calculated for continuous variables, while frequencies were calculated for categorical data. Fisher's exact test was employed to evaluate the association between two categorical variables, and p-values below 0.05 were considered statistically significant. Results The mean (± SD) urea, creatinine, and e-GFR were found to be 139 (± 81.1) mg/dL, 5.33 (± 4.1) mg/dL, and 20.1 (± 15) ml/min/1.73 m2, respectively. Of note, 133 (95%) patients had elevated urea levels, with the majority (n = 109, 77.8%) having urea levels between 40 and 199 mg/dL; 70 (50%) patients had creatinine levels less than 4 mg/dL, and 107 (76.4%) had e-GFR of less than 30 ml/min/1.73 m2. The mean (± SD) TSH, FT4, and FT3 levels were found to be 6.64 (± 11.2) mIU/ml, 13.6 (± 4.54) pmol/L, and 2.65 (± 1.89) pmol/L, respectively. It was observed that 18 (12.9%, 95% CI: 8.29-19.4%) of the CKD patients had hypothyroidism and 21 (15%, 95% CI: 10.02-21.8%) had subclinical hypothyroidism (SCH), while only two (1.4%, 95% CI: 0.39-5.05%) and five (3.6%, 95% CI: 1.5-8.08%) had hyperthyroidism and subclinical hyperthyroidism, respectively. Thirty-nine (27.9%, 95% CI: 21.1-35.8%) patients had low FT4 levels, whereas a considerable majority (n = 123, 87.9%, 95% CI: 81.41-92.28%) of the patients suffering from CKD were found to have low FT3 levels. The associations of urea levels with SCH, low FT4, and FT3 status were found to be statistically significant with p-values of 0.002, 0.033, and <0.001, respectively. The association between e-GFR and low FT3 status was also statistically significant, with a p-value of 0.014. Conclusion Nine out of 10 patients with CKD were discovered to have low FT3 levels, whereas one in four patients had low FT4 levels. The study participants also exhibited a significant presence of SCH and hypothyroidism, with prevalence rates of 15% and 12.9%, respectively. Urea levels and e-GFR, indicating the severity of CKD, showed a significant association with the presence of various thyroid abnormalities. Hypothyroidism in CKD patients can complicate disease progression, impact mortality rates, and affect overall quality of life. Therefore, routine screening for thyroid abnormalities should be conducted in all CKD patients.
ABSTRACT
BACKGROUND: There has been a growing interest in ivermectin ever since it was reported to have an in-vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This trial was conducted to test the efficacy of ivermectin in mild and moderate coronavirus disease 19 (COVID-19). METHODS: A double blind, parallel, randomised, placebo-controlled trial conducted among adult COVID-19 patients with mild to moderate disease severity on admission in a COVID dedicated tertiary healthcare of eastern India. Enrolment was done between 1st August and 31st October 2020. On day 1 and 2 post enrolment, patients in the intervention arm received ivermectin 12 mg while the patients in the non-interventional arm received placebo tablets. RESULTS: About one-fourth (23.6%) of the patients in the intervention arm and one-third (31.6%) in the placebo arm were tested reverse transcriptase polymerase chain reaction (RTPCR) negative for SARS-CoV-2 on 6th day. Although this difference was found to be statistically insignificant [rate ratio (RR): 0.8; 95% confidence interval (CI): 0.4-1.4; p=0.348]. All patients in the ivermectin group were successfully discharged. In comparison the same for the placebo group was observed to be 93%. This difference was found to be statistically significant (RR: 1.1; 95% CI; 1.0-1.2; p=0.045). CONCLUSIONS: Inclusion of ivermectin in treatment regimen of mild to moderate COVID-19 patients could not be said with certainty based on our study results as it had shown only marginal benefit in successful discharge from the hospital with no other observed benefits.
