Comparison of indocyanine green angiography vs intraoperative parathyroid hormone in early prediction of risk of post-thyroidectomy hypocalcemia: a prospective cohort study.

Introduction: Indocyanine green (ICG) angiography is the 'real-time intraoperative imaging' technique used to reduce the chances of hypoparathyroidism in post-thyroidectomy patients. In our study, the authors predicted the risk of early post-thyroidectomy hypocalcemia by intraoperative evaluation of parathyroid gland perfusion by ICG angiography. Materials and methods: In patients who underwent total thyroidectomy, ICG angiography was done using the SPY PHI imaging system (Stryker). Post-thyroid specimen removal, scoring of parathyroids was done in spy contrast mode. All 4 or <4 visualized parathyroids were scored for vascularity with the highest score of 8. Serum ionized calcium was done 6 h postsurgery and on the morning and evening of postoperative days 1 and 2. Calcium supplements were given to only those who developed clinical or severe biochemical hypocalcemia. Results: Out of 60, postoperative hypocalcemia was noted in 41 patients. Total ICG score ≤5 was seen in 34 patients, out of which 28 developed postoperative hypocalcemia showing PPV 82.3% and diagnostic accuracy of 68.3% while iPTH (4.28 pmol/l) showed PPV 76.7 and diagnostic accuracy 70 %. In eight patients, none of the glands was scored as 2 (White) and all these patients developed hypocalcemia requiring calcium infusion. Conclusion: The absence of visualization of at least 1 well-perfused (score 2) gland on ICG angiography is highly predictive of hypocalcemia and the majority of patients with total ICG score ≤5 developed hypocalcemia in the immediate postoperative period. ICG is a good predictor of the absence of hypoparathyroidism after thyroidectomy and is comparable to iPTH in the prediction of post-thyroidectomy hypocalcemia.

Making the Cut: Parathyroidectomy Before or After Kidney Transplantation?

BACKGROUND: Hyperparathyroidism is common in patients with end-stage kidney disease and may persist after kidney transplantation (KT). Parathyroidectomy (PTx) is curative, but whether PTx should be performed before or after KT remains controversial. There is concern that PTx can adversely affect renal allograft function if performed post-KT and result in persistent hypocalcemia. This study evaluated outcomes and postoperative complications of PTx before and after KT at our institution. METHODS: We performed a retrospective review of patients at our center (1/2012-2/2019) who had PTx either pre-KT or post-KT. Data on patient demographics, surgical outcomes, and postoperative complications of PTx were collected. RESULTS: Ninety-eight patients were included in this study, with 23 patients undergoing PTx before KT and 75 after KT. The length of follow-up after KT was 67.7 ± 25.5 months. In post-KT PTx patients, 30-day allograft function was unchanged after PTx. Calcium oxalate and phosphate crystals were less common on allograft biopsies in pre-KT PTx patients (10.0% vs. 34.8%, p = 0.038). Patients in the pre-KT group required more calcium supplementation after PTx than the post-KT group (p < 0.001). At one-year post-PTx, 17 (19.1%) patients required > 1000 mg elemental calcium per day and 7 (7.9%) patients required > 2000 mg/day. There was no difference in surgical success or postoperative complications between the two groups. CONCLUSIONS: Parathyroidectomy before or after kidney transplantation does not adversely affect allograft function. The incidence of persistent hypocalcemia was low. Parathyroidectomy is safe and effective either before or after kidney transplantation.

Ergocalciferol treatment does Not improve erythropoietin utilization and hospitalization rate in hemodialysis patients.

BACKGROUND: Vitamin D (25-hydroxyvitamin D; 25[OH]D) deficiency (VDD) is highly prevalent in chronic kidney disease. The aim of this study was to evaluate the effect of oral ergocalciferol supplementation on requirement of erythropoietin (EPO) and active vitamin D analogues, and hospitalization rate in maintenance hemodialysis (HD) patients. METHODS: This retrospective cohort study included 186 patients who were on HD for 3 months and had 25(OH)D levels < 30 ng/ml. Over 1-year period, 107 patients were supplemented with protocol-based ergocalciferol (D2 group) and 79 were not (control). Parameters of erythropoiesis and bone-mineral metabolism, and monthly doses of EPO and paricalcitol were assessed at 6- and 12- months of ergocalciferol supplementation. Total hospitalizations were recorded for the same year. RESULTS: Baseline characteristics were similar across two arms except higher serum ferritin, transferrin saturation and prevalence of stroke in D2 and higher coronary artery disease in control group with overall mean ± SD 25(OH)D level of 16.8 ± 7 ng/ml. At 12 months, 25(OH)D levels increased significantly in D2 group compared to control (30.5 ± 11.7 vs. 14.2 ± 9.3 ng/ml; p < 0.001). The EPO dose remained same with no difference in hemoglobin values between the two groups during the intervention period. On multivariate regression which included above variables there was no effect of ergocalciferol treatment on EPO dose (p = ns). Hospitalization rate was similar in two arms; however, ergocalciferol treatment inversely associated with paricalcitol dose (ß ± SE = -10.4 ± 2.8; p < 0.001). CONCLUSIONS: One-year of ergocalciferol supplementation was not associated with reduction in EPO requirement or hospitalization rate in HD patients with VDD. Further studies are warranted to determine definitive role of nutritional vitamin D in these patients.

Prospective evaluation of intra-operative quick parathyroid hormone assay as an early predictor of post thyroidectomy hypocalcaemia.

BACKGROUND: Hypocalcaemia following total thyroidectomy is a major contributing factor in delayed hospital discharge and dissuading surgeons from day care thyroidectomy. We prospectively evaluated the utility of Intra-operative serum quick parathyroid hormone level measurement twenty minutes after total thyroidectomy in predicting post-operative hypocalcemia. MATERIAL AND METHODS: Prospective longitudinal study which included patients undergoing total thyroidectomy for benign or malignant thyroid disorders at SGPGIMS, Lucknow, India from November 2013 to February 2015. Patients who received calcium prophylaxis were excluded from the study. Intraoperative serum quick PTH level measurements were done twenty minutes after resection of thyroid. Serum calcium levels were estimated preoperatively and on three consecutive post operative days. Calcium supplementation was started in patients with symptomatic hypocalcemia. RESULTS: The study included 100 patients with a mean age of 41 years, range 17-72 years. 48 patients had Euthyroid multinodular goitre, 10 patients grave's disease and 42 patients had differentiated thyroid cancer. Total thyroidectomy was performed in 88 patients, total thyroidectomy with lymph node dissection in 12 patients. Post-operatively 23% patients experienced symptomatic hypocalcemia. The IOPTH level of 9 pmol/L, twenty minutes after total thyroidectomy, had the highest sensitivity and specificity of 92% and 83% respectively in predicting post-operative hypocalcemia. CONCLUSION: Parathyroid hormone assay twenty minutes after thyroidectomy is an accurate and reliable means of predicting clinically relevant hypocalcemia. Patients with PTH values greater than 9 pmol/L twenty minutes after thyroidectomy, can be safely discharged on the same postoperative day as the probability of life threatening hypocalcemia is unlikely.

Draft genome of the peanut A-genome progenitor (Arachis duranensis) provides insights into geocarpy, oil biosynthesis, and allergens.

Peanut or groundnut (Arachis hypogaea L.), a legume of South American origin, has high seed oil content (45-56%) and is a staple crop in semiarid tropical and subtropical regions, partially because of drought tolerance conferred by its geocarpic reproductive strategy. We present a draft genome of the peanut A-genome progenitor, Arachis duranensis, and 50,324 protein-coding gene models. Patterns of gene duplication suggest the peanut lineage has been affected by at least three polyploidizations since the origin of eudicots. Resequencing of synthetic Arachis tetraploids reveals extensive gene conversion in only three seed-to-seed generations since their formation by human hands, indicating that this process begins virtually immediately following polyploid formation. Expansion of some specific gene families suggests roles in the unusual subterranean fructification of Arachis For example, the S1Fa-like transcription factor family has 126 Arachis members, in contrast to no more than five members in other examined plant species, and is more highly expressed in roots and etiolated seedlings than green leaves. The A. duranensis genome provides a major source of candidate genes for fructification, oil biosynthesis, and allergens, expanding knowledge of understudied areas of plant biology and human health impacts of plants, informing peanut genetic improvement and aiding deeper sequencing of Arachis diversity.

Zoledronate and Molecular Iodine Cause Synergistic Cell Death in Triple Negative Breast Cancer through Endoplasmic Reticulum Stress.

Women consuming molecular iodine (I2) through seaweeds suffer the least from breast cancers. Zoledronate (Zol) is in clinical use for alleviation of bone pain in cancer patients. Triple negative breast cancers exhibit high mortality due to lack of neoadjuvant chemotherapy. I2 and Zol independently cause weak antiproliferative and apoptotic effect. So far, their combined effects have not been tested. We analyzed the effect of combination of I2 with Zol as a potent adjuvant therapeutic agent for triple negative breast cancer cells (MDA-MBA-231) and in the mice model of breast cancer. Cell viability, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, Western blotting, real-time PCR, flow cytometry, and other assays were performed for assessing cell death, calcium levels, and migration potential, respectively, in treated cells. The increased caspase 8, increased [Ca(2+)]c levels, and endoplasmic reticulum (ER) stress resulted in apoptosis. Real time and fluorescence-based analysis demonstrated that the combination treatment targets ER Ca(2+) homeostasis chaperons leading to apoptosis. Combination therapy reduces metalloproteinases 2 and 9, inhibits invasion/migration of cells, and prevents growth of tumor in mice. I2 + Zol combination treatment induces synergistic increase in ER-mediated apoptosis, reduces invasion/migration potential of MDA-MB-231 cells, and exhibits antiproliferative property in vivo demonstrating its potential as combination therapy.

Relationship of MTHFR and NQO1 Pharmacogenetics and Chemotherapy Clinical Outcomes in Breast Cancer Patients.

The study aimed at evaluating the influence of MTHFR 677C>T and NQO1 609C>T polymorphisms in toxicity and response to chemotherapy in breast cancer patients. These two genes are involved in the folate homeostasis and bioactivation of chemotherapeutic drugs, respectively. In this study, 243 patients treated with FEC/FAC/methotrexate chemotherapy regimen were recruited and followed up for toxicity (NCI-CTCAE ver. 3). While out of 243 patients, 115 patients who received neo-adjuvant chemotherapy (NACT) were followed for treatment response. Genetic analysis of MTHFR 677C>T and NQO1 609C>T was done by PCR-restriction fragment length polymorphism. We found significant association of variant genotype (TT) of NQO1 609C>T with grade 2-4 toxicity [OR 0.33 (0.13-0.88), P = 0.027] and with grade 2-4 anemia [OR 0.34 (0.12-0.95), P = 0.041]. However, no association of MTHFR 677C>T was seen with either response to NACT or drug-induced toxicity. The study provides useful information for prediction of clinical outcomes in breast cancer patients in terms of NQO1 609C>T by evaluating its association with chemotherapy-induced toxicity.

Long-term outcome of differentiated thyroid carcinoma: experience in a developing country.

BACKGROUND: The presentation and outcome of differentiated thyroid carcinoma (DTC) in developing countries are different from the developed nations. We report the clinicopathologic profile and long-term outcome of DTC in an iodine-deficient area (IDA) in a developing country. METHODS: This retrospective study included 302 patients with DTC operated between 1989 and 2002. These patients had been followed up for a minimum period of 5 years after surgery. Clinicopathological profile, intervention, and follow-up details were noted. RESULTS: Mean age of the patients was 42 +/- 14 years. Mean follow-up period was 80 +/- 34 (24-196) months. Papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and poorly differentiated thyroid carcinoma (PDTC) was present in 62, 30, and 8% patients, respectively. Mean tumor size was 3.5 cm. Tumor multicentricity was noted in 40% of PTC, 22.2% of FTC, and 25% of PDTC patients. Lymphadenopathy was observed in 45, 10, and 67% patients with PTC, FTC, and PDTC, respectively. Extrathyroidal invasion and distant metastasis were observed in 36.8% (PTC 33%; FTC 36%; PDTC 71%) and 27% (PTC 17%; FTC 44%; PDTC 42%) of cases, respectively. Twenty percent of patients had synchronous metastases. Risk stratification ratio was 1:1.8 (high-risk vs. low-risk). Initial operative procedure was total thyroidectomy in 86.5% cases, and therapeutic lymph node dissection was performed in 37% cases. A total of 77.2% patients received adjuvant radioiodine therapy. Disease recurred in 26.6% of patients (thyroid bed recurrence 1.7%), and 21.2% patients died during follow-up. Overall survival (OS) rate at 10 years in both low-risk and high-risk groups of FTC (80 and 54%) was inferior to PTC (94 and 62%). Five-year OS for PDTC was 50%. Tumor multicentricity was a significant risk factor for OS in the low-risk group, whereas the presence of skeletal metastases and extrathyroidal invasion were significant factors for OS in the high-risk group. CONCLUSIONS: Advance stage at presentation and proportionately high rates of FTC and PDTC contribute to poor outcome of DTC in developing countries. Despite dismal outcome, total thyroidectomy seems to prevent thyroid bed recurrence in surviving patients.

The role of a more extensive surgical approach in the initial multimodality management of papillary thyroid cancer in children.

PURPOSE: Papillary thyroid cancer (PTC) in children is rare. The optimal initial surgical treatment remains controversial, given the generally favorable overall prognosis but high rate of cervical metastasis and local recurrence. Our objective was to examine the surgical outcomes of a policy of total thyroidectomy and routine selective lymph node dissection (SLND) as the initial surgical approach to children with PTC. METHODS: This is a retrospective cohort study comprising 14 children (age, < or =17 years) with PTC referred for thyroid surgery during the past 15 years. Clinical presentation, the surgical procedure, final pathology, lymph node involvement, complications, and recurrence rates are reported. RESULTS: There were 9 females and 5 males, with an average age of 12.5 years. Seven patients (50%) had clinically apparent cervical lymphadenopathy at the time of surgical referral. All subjects underwent total thyroidectomy, and 12 (86%) had SLND. Of the 12 who underwent SLND, 10 (83%) had nodal metastases. Temporary hypocalcemia was noted in 3 of the patients (21%), and 1 patient has required ongoing intermittent calcium supplementation. All patients are alive and well at follow-up with no clinical, biochemical, or radiological evidence of local recurrence. CONCLUSIONS: Total thyroidectomy with initial SLND is an appropriate surgical approach in children with PTC. It can be done without a significantly increased risk for permanent complications and may reduce the requirement for subsequent surgical intervention for local recurrence in this young population.

Recovery pattern of patients with osteitis fibrosa cystica in primary hyperparathyroidism after successful parathyroidectomy.

BACKGROUND: After parathyroidectomy, recovery of osteitis fibrosa cystica, which continues to dominate presentation of primary hyperparathyroidism in India has not been documented objectively. METHODS: We followed up clinical recovery, biochemic markers of bone turnover, bone mineral density, and skeletal radiology in 51 patients with primary hyperparathyroidism and osteitis fibrosa cystica for 9 to 124 months (median, 32 months). RESULTS: After parathyroidectomy, 46 patients had hypocalcemia. During postoperative week 1, bone pain improved in 71%. During 3 months, appendicular fractures healed in all 33 such patients, and 6 of 7 patients who were bedridden could walk. Mean bone mineral density increments (percent change/y) seen at various sites at 1 week, 3, 6, and 12 months were distal forearm--37, 28, 23, 21; lumbar spine--165, 104, 101, 106; and total hip--168, 157, 166, 133. Follow-up radiographs demonstrated prompt recovery though disorderly remineralization. Brown tumors and fractures showed hyperdensities within 3 months. Brown tumors regressed partially in 6 of 27 patients after 6 months. CONCLUSIONS: After parathyroidectomy, patients with primary hyperparathyroidism have early, marked, and sustained recovery of osteitis fibrosa cystica. Early (1 week) bone mineral density increments of > 100%/y hint at the skeleton's ability to promptly restore itself. Densitometric recovery is prompt at cancellous (lumbar spine), but not at cortical (forearm) bone sites. Contour defects and bony tumors persist, and may need corrective osteotomies.