Thyroid Cancer Screening Using Tumor-Associated DN T Cells as Immunogenomic Markers.

Background: Thyroid nodules are an extremely common entity, and surgery is considered the ultimate diagnostic strategy in those with unclear malignant potential. Unfortunately, strategies aiming to predict the risk of malignancy have inadequate specificity. Our group recently found that the microenvironment of thyroid cancer is characterized by an enhanced immune invasion and activated immune response mediated by double-negative T lymphocytes (DN T) (CD3+CD4-CD8-), which are believed to enable or promote tumorigenesis. In the present work, we try to use the DN T cells' proportion in thyroid fine-needle aspiration (FNA) material as a predictor of the risk of malignancy. Methods: We recruited 127 patients and obtained ultrasound-guided FNA samples from subjects with cytology-positive or suspicious for malignancy and from those with benign nodular goiter associated with compressive symptoms (such as dysphagia, shortness of breath, or hoarseness), Hashimoto thyroiditis, and Graves' disease. Out of 127, we investigated 46 FNA samples of patients who underwent total thyroidectomy and for which postoperative histological diagnosis by the academic pathologists was available. We specifically measured the number of cells expressing CD3+CD4-CD8- (DN T) as a function of total CD3+ cells in FNA samples using flow cytometry. We correlated their FNA DN T-cell proportions with the pathological findings. Results: The DN T cells were significantly more abundant in lymphocytic infiltrates of thyroid cancer cases compared to benign nodule controls (p < 0.0001). When the DN T-cell population exceeded a threshold of 9.14%, of total CD3+ cells, the negative likelihood ratio of being cancer-free was 0.034 (96.6% sensitivity, 95% CI, 0.915-1.000, p < 0.0001). DN T cells at <9.14% were not found in any subject with benign disease (specificity 100%). The high specificity of the test is promising, since it abolishes a false-positive diagnosis and in turn unnecessary surgical procedures. Conclusion: The present study proposes DN T cells' proportion as a preoperative diagnostic signature for thyroid cancer that with integration of RNA transcriptomics can provide a simplified technology based on the PCR assay for the ease of operation.

Hyponatraemia: Epidemiology and aetiology in a tertiary care centre in Pakistan.

OBJECTIVE: To determine the incidence, aetiology and epidemiology of hospitalized patients with hyponatraemia. METHODS: Subjects were identified through hospital information system for two consecutive low sodium values (< 130 mEq/L) and charts were reviewed retrospectively. Possible etiologic factors were identified and co-morbidities documented. Management plans were also noted. RESULTS: Among the hospitalized patients the incidence of hyponatraemia was 6.72%. The mean age was 54.8±14.8 years and there were 50% males. The mean serum sodium at presentation was 122 mEq/L. Most common causes were volume depletion (30.6%) and chronic kidney disease (22.6%). Most of the patients had two or more co morbidities. Hyponatraemia at presentation and improvement or worsening during hospital stay did not affect survival of patients. CONCLUSIONS: Hypervolaemic hyponatraemia was the most common presentation in our study.

IgG4-related retroperitoneal fibrosis: A case report and review of literature.

Idiopathic Retroperitoneal fibrosis is a rare clinical condition recently identified as an autoimmune process related to Immunoglobulin G4 (IgG4) deposition. Herein we report a case of a 46 year old male presenting with 4 months history of backache, fever, flank pain and leg swelling for 2 weeks. Investigations revealed acute kidney injury diagnosed as a result of bilateral ureteric obstruction. This was later confirmed to be retroperitoneal fibrosis on CT scan and biopsy. Histopathology was consistent with IgG4 related disease. Treatment with immunosuppressive agents showed reduction in the fibrosis and normalization of the kidney functions. We discuss the IgG4 related retroperitoneal fibrosis in detail along with its varied presentations.