Safety and Early Results for Off-Label Use of Intranasal Calcitonin for Treatment of Nondisplaced Acromial and Scapular Spine Stress Fractures After Reverse Total Shoulder Arthroplasty.

Immobilization for acromial and scapular spine stress AU4fractures (AF/SSF) after reverse total shoulder arthroplasty (RSA) is associated with patient dissatisfaction. Our study reports the effects and safety of intranasal calcitonin alongside sling immobilization on pain and function in the treatment of AF/SSF after RSA. The treatment was regimented calcitonin (salmon) 200 unit/actuation nasal spray (1 spray/day) for 6 weeks with sling immobilization for 4 weeks. Each patient was monitored through blood work. Visual analog scale, American Shoulder and Elbow Surgeons score, and active range of motion were collected preoperatively, postoperatively, at presentation of AF/SSF, and after completion of calcitonin treatment. Two hundred eighty-two RSAs were performed by two board-certified orthopaedic surgeons, of which 18 patients sustained AF/SSF (6.4%). Ten patients met inclusion criteria (nine AFs and one SSF). After calcitonin treatment, patients demonstrated an average improvement of visual analog scale of 5.8 points, active range of motion of 46_, and American Shoulder and Elbow Surgeons score of 43.6 points at average 7.53 months after RSA. No medical complications were reported at 6-month follow-up after calcitonin treatment. The use of intranasal calcitonin was not associated withadverse events including no aberrations/signs of cancer at 6-month follow-up after administration. Calcitonin with sling immobilization markedly improved clinical and functional outcomes of patients with nondisplaced AF/SSF and may be considered by orthopaedic surgeons for symptom management.

Preoperative identification of low-risk medullary thyroid carcinoma: potential application to reduce total thyroidectomy.

Current guidelines recommend total thyroidectomy with central lymph node dissection (CND) for patients with medullary thyroid carcinoma (MTC). This study aimed to identify low-risk MTC patients who may be candidates for lobectomy. We retrospectively reviewed MTC patients who underwent primary surgery at a tertiary referral center from 1998 to 2019. Eighty-five MTC patients were enrolled, excluding patients with primary tumor size > 2.0 cm. Among them, one (1.2%) patient had bilateral tumors. During a median follow-up of 84 months, 12 of the 85 patients experienced structural recurrence. 13 patients had occult lymph node metastasis, and structural recurrence occurred in 2 patients. Factors that significantly affected disease-free survival were clinical N stage (cN0 vs. cN1, log-rank P < 0.001), pathological N stage (pN0 vs. pN1, P < 0.001), and preoperative calcitonin levels (≤ 250 vs. > 250 pg/mL, P = 0.017). After categorizing patients into four groups, patients with preoperative calcitonin levels > 250 pg/mL and cN1 or pN1 had a significantly worse prognosis. Patients with a primary tumor size of 2 cm or less, cN0, and preoperative calcitonin of 250 pg/mL or less can be classified as low-risk MTC patients. We used preoperative clinical information to identify low-risk MTC patients. Lobectomy with prophylactic CND may be a potential therapeutic approach.

Dual amylin and calcitonin receptor agonist treatment improves insulin sensitivity and increases muscle-specific glucose uptake independent of weight loss.

Dual amylin and calcitonin receptor agonists (DACRAs) are known to induce significant weight loss as well as improve glucose tolerance, glucose control, and insulin action in rats. However, to what extent DACRAs affect insulin sensitivity beyond that induced by weight loss and if DACRAs affect glucose turnover including tissue-specific glucose uptake is still unknown. Hyperinsulinemic glucose clamp studies were carried out in pre-diabetic ZDSD and diabetic ZDF rats treated with either the DACRA KBP or the long-acting DACRA KBP-A for 12 days. The glucose rate of disappearance was assessed using 3-3H glucose and tissue-specific glucose uptake was evaluated using 14C-2-deoxy-D-glucose (14C-2DG). In diabetic ZDF rats, KBP treatment significantly reduced fasting blood glucose and improved insulin sensitivity independent of weight loss. Furthermore, KBP increased the rate of glucose clearance, likely by increasing glucose storage, but without altering the endogenous glucose production. This was confirmed in pre-diabetic ZDSD rats. Direct assessment of tissue-specific glucose uptake showed, that both KBP and KBP-A significantly increased glucose uptake in muscles. In summary, KBP treatment significantly improved insulin sensitivity in diabetic rats and markedly increased glucose uptake in muscles. Importantly, in addition to their well-established weight loss potential, the KBPs have an insulin-sensitizing effect independent of weight loss, highlighting DACRAs as promising agents for the treatment of type 2 diabetes and obesity.

Calcium-stimulated calcitonin test for the diagnosis of medullary thyroid cancer: results of a multicenter study and comparison between different assays.

BACKGROUND: A basal serum calcitonin (Ct) increase >100 pg/mL in patients with a thyroid nodule is consistent with the diagnosis of medullary thyroid cancer (MTC). In cases where the CT test have a slight to moderate increase, the calcium gluconate stimulation test is helpful to increase diagnostic accuracy. However, reliable cut-offs for calcium-stimulated Ct are still lacking. The aim of this study was to evaluate the sex-specific calcium-stimulated Ct cutoffs for the diagnosis of MTC in a multicenter series. A comparison between different Ct assays has been also performed. METHODS: 90 subjects undergone calcium-stimulated Ct for a suspected MTC in 5 Endocrine Units between 2010-2021 were retrospectively analyzed. Serum Ct concentrations were assessed by immunoradiometric (IRMA) or chemiluminescence (CLIA) assays. RESULTS: MTC was diagnosed in 37 (41.1%) and excluded in 53 (58.9%) patients. The best calcium-stimulated Ct cut-off to identify MTC was 611 pg/mL in males (AUC =0.90, 95% CI (0.76;1) and 445 pg/mL in females (AUC=0.79, 95% CI (0.66;0.91). Logistic regression analysis showed that both basal (OR 1.01, P=0.003) and peak Ct after stimulation (OR 1.07, P=0.007) were significantly associated with MTC, together with sex (OR=0.06, P<0.001). The "Ct assay" variable was also considered in the logistic regression model, but it was not significantly associated with MTC (OR=0.93, P=0.919). CONCLUSIONS: This study indicates that calcium test could be helpful to identify patients with early-stage MTC and those without MTC. A Ct value of 611 pg/mL in males and 445 pg/mL in females are proposed as the optimal Ct cut-offs at the stimulation test.

Natural History and Predictive Factors of Outcome in Medullary Thyroid Microcarcinoma.

CONTEXT: Management of sporadic medullary thyroid microcarcinoma smaller than 1 cm (micro-MTC) is controversial because of conflicting reports of prognosis. As these cancers are often diagnosed incidentally, they pose a management challenge when deciding on further treatment and follow-up. OBJECTIVE: We report the outcomes of surgically managed sporadic micro-MTC in a specialist endocrine surgery and endocrinology unit and identify associations for recurrence and disease-specific survival in this population. METHODS: Micro-MTCs were identified from a prospectively maintained surgery database, and slides were reviewed to determine pathological grade. The primary end points were recurrence, time to recurrence and disease-specific survival. Prognostic factors assessed included size, grade, lymph node metastasis (LNM), and postoperative calcitonin. RESULTS: From 1995 to 2022, 64 patients were diagnosed with micro-MTC with 22 excluded because of hereditary disease. The included patients had a median age of 60 years, tumor size of 4 mm, and 28 (67%) were female. The diagnosis was incidental in 36 (86%) with 4 (10%) being high grade, 5 (12%) having LNM and 9 (21%) having elevated postoperative calcitonin. Over a 6.6-year median follow-up, 5 (12%) developed recurrence and 3 (7%) died of MTC. High grade and LNM were associated with 10-year survival estimates of 75% vs 100% for low grade and no LNM (hazard ratio = 831; P < .01). High grade, LNM, and increased calcitonin were associated with recurrence (P < .01). Tumor size and type of surgery were not statistically significantly associated with recurrence or survival. No patients with low grade micro-MTC and normal postoperative calcitonin developed recurrence. CONCLUSION: Most sporadic micro-MTCs are detected incidentally and are generally associated with good outcomes. Size is not significantly associated with outcomes. Using grade, LNM, and postoperative calcitonin allows for the identification of patients at risk of recurrence to personalize management.

Diagnostic value and cost-effectiveness of FNA-CT versus FNAC for medullary thyroid carcinoma.

OBJECTIVE: To evaluate the diagnostic performance and cost-effectiveness of calcitonin assays in fine-needle aspiration washout fluid (FNA-CT) compared to fine-needle aspiration cytology (FNAC) for medullary thyroid carcinoma (MTC). METHODS: A total of 27,404 patients from three medical centres between January 2020 and May 2022 were screened for serum calcitonin (sCT). Of whom, 223 patients met endpoints and were enroled for analyses. Based on sCT levels, patients were divided into two groups (group 1: 10 pg/ml< sCT ≤100 pg/ml and group 2: sCT > 100 pg/ml). The diagnostic performance and cost-effectiveness of FNA-CT and FNAC were compared. RESULTS: Most patients (N = 25,228; 92.1%) with thyroid nodules had normal sCT levels. In group 1, 24 and 167 nodules were diagnosed as MTC and non-MTC lesions, respectively. FNA-CT showed better performance in diagnosing MTC than FNAC in terms of sensitivity (100.0% vs. 58.3%), negative predictive value (100.0% vs. 94.3%), and overall accuracy (100.0% vs. 94.7%). In group 2, 67 and 7 nodules were diagnosed as MTC and non-MTC lesions, respectively. The diagnostic performance of FNA-CT was superior to FNAC in terms of sensitivity (100.0% vs. 64.2%), negative predictive value (100.0% vs. 22.6%), and overall accuracy (100.0% vs. 67.6%). Furthermore, analysis from the decision tree model showed that FNA-CT was a cost-effective tool for diagnosing MTC lesions. CONCLUSIONS: FNA-CT can serve as an auxiliary and cost-effective approach for patients with indeterminate sCT levels to detect occult MTC lesions. FNA-CT can be recommended for patients with sCT >100 pg/ml to overcome the high false-negative rate of FNAC.

The role of procalcitonin in the follow-up of medullary thyroid cancer.

Objective: Calcitonin (Ct) represents the most important biochemical marker of medullary thyroid cancer (MTC), but has certain limits. We analyzed the performance of procalcitonin (ProCt) in follow-up MTC patients. Methods: In this monocentric and retrospective study, we consecutively obtained ProCt and Ct values from all MTC patients that we visited during the period from April 2021 to May 2022. Patients were defined as having structural evidence of disease (29/90, 32.2%) irrespective of Ct values or, in its absence, as not evident disease (NED) if Ct was ≤10 ng/L (47/90, 52.2%), or minimal residual disease if Ct was >10 ng/L (14/90, 15.6%). Results: Ct and ProCt values were highly correlated (r = 0.883, P < 0.01). Median ProCt values differed between NED, minimal residual disease, and structural disease, being 0.04 ng/mL, 0.26 ng/mL, and 1.98 ng/mL, respectively (P < 0.01). ProCt was undetectable (<0.04 ng/mL) in 40/47 (85.1%) of NED patients, in 3/14 (21.4%) patients with minimal residual disease and in none of the patients with a structural disease (P < 0.01). Among the 11 patients with detectable but ≤10 ng/L Ct and undetectable ProCt values, none had a structural disease. The most accurate cut-off of ProCt to distinguish between the presence or absence of a structural disease was >0.12 ng/mL (P < 0.01, area under the curve: 0.963), with the following sensitivity, specificity, positive predictive value, and negative predictive value (NPV): 100%, 83.61%, 74.4%, and 100.0%. Conclusions: ProCt and Ct have a high correlation in MTC follow-up. ProCt may be useful as an adjunct to Ct, especially for its NPV concerning the structural disease.

Oncologic outcomes of calcitonin-negative medullary thyroid carcinoma.

Objective: Calcitonin (Ct)-negative medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor. This study aimed to clarify its incidence, clinicopathologic characteristics, management, and treatment outcome. Methods: We retrospectively analyzed data of patients with primary MTC. Patients were divided into two groups according to the preoperative serum Ct level (Ct-negative and Ct-positive). The demographic, pathologic, and molecular characteristics, and treatment outcomes were compared between the two groups. In the Ct-negative group, we analyzed the association between the operation type and treatment outcome. Results: Of the total 312 patients, 24 were diagnosed with Ct-negative MTC. The rate of lymph node metastasis was significantly higher in the Ct-positive than in the Ct-negative group (47.9% vs. 0%, p<0.001). The proportion of patients with Ki-67 ≤10% was significantly higher in the Ct-negative than in the Ct-positive group (87.5% vs. 38.2%, p<0.001). Excellent response was achieved by 91.7% and 34.7% of patients in the Ct-negative and Ct-positive groups, respectively (p<0.001). In the Ct-negative group, excellent response was achieved by all female patients, but only 50% of male patients. Conclusions: Ct-negative MTC is rare and unlikely to develop lymph node metastasis. Unilateral lobectomy tends to provide a satisfactory chance of excellent response; however, this requires further validation.

Suplementación efectiva de vitamina D en pacientes con fractura tibial / Effective vitamin D supplementation in patients with tibial fracture

OBJETIVOS Determinar la prevalencia de déficit de vitamina D, así como evaluar la seguridad y efectividad de un nuevo método de carga con colecalciferol en pacientes adultos con fractura de tibia. MATERIALES Y MÉTODOS Se reclutaron a 56 pacientes consecutivos con edades entre 18 y 65 años con fractura de tibia ingresados en nuestro hospital durante 1 año. Se determinó el nivel de 25-hidroxivitamina D ([25(OH)-D]) al ingreso y tras suplementación con 100.000 UI semanales de colecalciferol, durante 3 o 5 semanas, en casos de insuficiencia ([25(OH)-D] entre 20 ng/mL y 29,9 ng/mL) o deficiencia ([25(OH)-D] < 20 ng/mL), respectivamente. Se determinó la prevalencia de hipovitaminosis D, el porcentaje de normalización de [25(OH)-D], y los efectos adversos. RESULTADOS Se evaluaron 56 pacientes; 98,2% presentó hipovitaminosis D, y 28 (73,7%) y 10 (26,3%) presentaron déficit e insuficiencia, respectivamente. Tras la suplementación, 92,1% alcanzaron niveles [25(OH)-D] normales. Ningún paciente presentó efectos adversos. DISCUSIÓN La prevalencia de deficiencia de vitamina D en nuestra población fue mayor a la reportada en la literatura. Comprobamos que un esquema de suplementación en altas dosis de vitamina D es seguro, y más efectivo que los previamente recomendados. Este esquema de suplementación puede ser implementado en futuros estudios randomizados. CONCLUSIÓN La prevalencia de hipovitaminosis D en pacientes adultos chilenos con fractura de tibia fue alta (98,2%). El esquema de suplementación con vitamina D propuesto fue efectivo y seguro.

OBJETIVOS Determinar la prevalencia de déficit de vitamina D, así como evaluar la seguridad y efectividad de un nuevo método de carga con colecalciferol en pacientes adultos con fractura de tibia. MATERIALES Y MÉTODOS Se reclutaron a 56 pacientes consecutivos con edades entre 18 y 65 años con fractura de tibia ingresados en nuestro hospital durante 1 año. Se determinó el nivel de 25-hidroxivitamina D ([25(OH)-D]) al ingreso y tras suplementación con 100.000 UI semanales de colecalciferol, durante 3 o 5 semanas, en casos de insuficiencia ([25(OH)-D] entre 20 ng/mL y 29,9 ng/mL) o deficiencia ([25(OH)-D] < 20 ng/mL), respectivamente. Se determinó la prevalencia de hipovitaminosis D, el porcentaje de normalización de [25(OH)-D], y los efectos adversos. RESULTADOS Se evaluaron 56 pacientes; 98,2% presentó hipovitaminosis D, y 28 (73,7%) y 10 (26,3%) presentaron déficit e insuficiencia, respectivamente. Tras la suplementación, 92,1% alcanzaron niveles [25(OH)-D] normales. Ningún paciente presentó efectos adversos. DISCUSIÓN La prevalencia de deficiencia de vitamina D en nuestra población fue mayor a la reportada en la literatura. Comprobamos que un esquema de suplementación en altas dosis de vitamina D es seguro, y más efectivo que los previamente recomendados. Este esquema de suplementación puede ser implementado en futuros estudios randomizados. CONCLUSIÓN La prevalencia de hipovitaminosis D en pacientes adultos chilenos con fractura de tibia fue alta (98,2%). El esquema de suplementación con vitamina D propuesto fue efectivo y seguro.

Hypercalcaemia secondary to acute rhinovirus infection.

Hypercalcaemia-induced rhinovirus has only been reported in a single study in children. Here, we report a case of hypercalcaemia in an adult who tested positive for rhinovirus. This patient underwent an extensive evaluation of hypercalcaemia, and it was found to be mediated by an increase in 1,25 hydroxy-vitamin D that could not be attributed to a cause. Their hypercalcaemia responded to standard treatment with intravascular expansion, bisphosphonates and calcitonin. Serum 1,25 OH vitamin D levels returned to normal with recovery from rhinovirus infection.

Stimulation of osteoclast formation and bone resorption by glucocorticoids: Synergistic interactions with the calcium regulating hormones parathyroid hormone and 1,25(OH)2-vitamin D3.

Osteoporosis is a significant health problem, with skeletal fractures increasing morbidity and mortality. Excess glucocorticoids (GC) represents the leading cause of secondary osteoporosis. The first phase of glucocorticoid-induced osteoporosis is increased bone resorption. In this Chapter, in vitro studies of the direct glucocorticoid receptor (GR) mediated cellular effects of GC on osteoclasts to affect bone resorption and indirect effects on osteoblast lineage cells to increase the RANKL/OPG ratio and stimulate osteoclastogenesis and bone resorption are reviewed in detail, together with detailed descriptions of in vivo effects of GC in different portions of the skeleton in research animals and humans. Brief sections are devoted to contrasting functions of GC in osteonecrosis, vitamin D formation, in vitro and in vivo bone resorptive actions dependent on vitamin D receptor and vitamin D toxicity, as well as the molecular basis of GR action. Included are also more detailed assessments of the interactions of GC with the major calcium regulating hormones, 1,25(OH)2-vitamin D3 and parathyroid hormone, describing the in vitro increases in RANKL/OPG ratios, osteoclastogenesis and synergistic bone resorption that occurs when GC is combined with either 1,25(OH)2-vitamin D3 or parathyroid hormone. Additionally, a molecular basic for the synergistic interaction of GC with 1,25(OH)2-vitamin D3 is provided along with a suggested molecular basic for the interaction between GC and parathyroid hormone.

The dilemma of routine testing for calcitonin thyroid nodule's patients to detect or exclude medullary carcinoma: one single negative test should be valuable as rule-out strategy to avoid further calcitonin measurements over time.

PURPOSE: While calcitonin (CT) measurement is recognized as the most accurate tool to diagnose medullary thyroid carcinoma (MTC), its routine use in patients with thyroid nodule (TN) is not universally accepted. The present study raised the question whether a TN patient with an initial normal CT can have suspicious CT levels (i.e., at least >20 pg/ml) later during his follow-up. METHODS: The historical database of our institution was searched to select TN patients undergone multiple CT tests, having an initial normal CT, and clinically followed up for years. The event of a CT above 20 pg/ml (mild-to-moderate suspicion) and 100 pg/ml (high suspicion) was searched in the follow-up of the included patients. RESULTS: According to the study design, the study sample encompassed 170 patients (131 female, 39 male) with initial CT value ≤10 pg/ml. On the first CT test, patients were 54.8 years and median CT was 2.1 pg/ml in both females and males. Over a period of 14.5 years and a median clinical follow-up of patients of 53.0 (23.9-102.5) months, MTC could be excluded by histology or cytology in 109 (64%) and clinically in the remaining ones. On the follow-up over time, no patients had CT >20 pg/ml and only two cases had CT just above 10 pg/ml. CONCLUSION: According to the present results, one single CT testing with normal value could be reasonably used as a rule-out strategy in patients with TN to avoid further CT measurements.

Parathyroid hormone and calcitonin response during the calcium infusion test in patients with primary hyperparathyroidism.

OBJECTIVE: While activation of the calcium (Ca) sensing receptor (CaSR) suppresses parathyroid hormone (PTH) secretion, calcitonin (CT) secretion is stimulated via CaSR. The aim of this study was to evaluate PTH and CT responses during a calcium infusion test (CIT) in patients with primary hyperparathyroidism (PHPT). METHODS: This pivotal prospective study included 64 patients (44 PHPT patients vs. 20 healthy controls [HCs], median age 57 [25-79] vs. 56 [39-74] years). All PHPT patients underwent parathyroidectomy (PTX). A week before and 1 month after PTX, the CIT was performed (bolus infusion of Ca gluconate 0.2 ml/kg body weight), followed by plasma sampling for Ca2+, PTH, and CT at 0, 1, 2, 3, 5, 8, and 10 min. RESULTS: PTH suppression was lower in PHPT patients compared to HCs (49.82 vs. 64.06%, p = 0.006), but after PTX suppression, it was higher (76.3%, p < 0.001). PHPT patients had attenuated CT response vs. HCs during the CIT (3.1- vs. 8.0-fold increase, p < 0.001), but after PTX, it improved (5.8-fold increase). The PTHmin > 19.3 ng/l and CTmax ≤ 27.5 ng/l cut-off values predict diagnosis of PHPT (sensitivity 90.9%, 97.7%, and specificity 100%, 75%, respectively). Patients with adenoma had lower basal CT levels vs. hyperplasia both before and after PTX (4.5 vs. 6.8 and 5.4 vs. 7.9 ng/l, respectively, p = 0.008, p = 0.018). CONCLUSION: PTH and CT responses during the CIT in PHPT patients may be an additional diagnostic tool. The CIT could play a role in both the diagnosis of PHPT and in the differential diagnosis between adenoma and hyperplasia.

Calcitriol supplementation attenuates cisplatin-induced behavioral and cognitive impairments through up-regulation of BDNF in male rats.

Chemotherapy-induced cognitive impairment such as memory impairment and concentration problems are now extensively recognized as side effects of chemotherapy. These problems reduce the quality of life in patients. Therefore, the present study aims to examine the effects of calcitriol supplementation (100 ng/kg /day for five weeks) on cognitive impairment, behavioral deficits, and hippocampal brain-derived neurotrophic factor (BDNF) changes following cisplatin treatment (5 mg/kg/ once a week for five weeks). We also determined the impact of cisplatin and calcitriol administration on reaction time against the thermal stimulus and muscle strength. Our findings showed that cisplatin administration resulted in a significant increase in anxiety-like behaviors. Treatment of rats with cisplatin also impaired performance in the passive avoidance and novel object recognition tasks which are indicating cognitive deficits. Co-administration of calcitriol prevented the cisplatin-induced behavioral and cognitive impairments. Cisplatin exposure also resulted in enhanced reaction time to the thermal stimulus and decreased muscle ability. Besides, hippocampal BDNF levels were reduced in cisplatin-treated rats; however, calcitriol alleviated these effects of cisplatin and up-regulated BDNF mRNA in the hippocampus. In addition, calcitriol alone indicated a significant change in BDNF level compared to the control group. We conclude that increased hippocampal BDNF mediates the beneficial effects of calcitriol against neurotoxicity in cisplatin-exposed rats. However, further studies are required to explore the other mechanisms that mediate the beneficial effect of calcitriol.

Dispelling myths and misconceptions about the treatment of acute hyperkalemia.

Hyperkalemia represents a widespread and potentially lethal condition that affects millions of people across their lives. Despite the prevalence and severity of the condition, there are no consensus guidelines on the treatment of hyperkalemia or even a standard definition. Herein, we provide a succinct review of what we believe to be the most significant misconceptions encountered in the emergency care of hyperkalemia, examine current available literature, and discuss practical points on several modalities of hyperkalemia treatment. Additionally, we review the pathophysiology of the electrocardiographic effects of hyperkalemia and how intravenous calcium preparations can antagonize these effects. We conclude each section with recommendations to aid emergency physicians in making safe and efficacious choices for the treatment of acute hyperkalemia.

Evaluation of a Pharmacy-Driven Calcitonin Protocol for Treating Hypercalcemia in Hospitalized Patients: A Multisite Study.

BACKGROUND: The dramatic increase in the acquisition cost of injectable calcitonin led to creating a pharmacy-driven calcitonin protocol to improve the appropriate use of calcitonin and other treatment modalities for hypercalcemia. OBJECTIVE: This study aimed to characterize the use of calcitonin before and after implementation of a pharmacy-driven calcitonin protocol. METHODS: This was a multi-center, retrospective study of the use of injectable calcitonin in adult hospitalized patients with hypercalcemia. The study included patients treated with calcitonin from October 2014 to September 2016 and from October 2017 to September 2019. The primary outcomes were percentage of patients with a complete response, partial response, and non-responders. The secondary outcomes were time to relapse, duration of partial response, number of doses, and associated costs of calcitonin. RESULTS: Of the 131 patients included in this study, 93 were included in a pre-protocol group and 38 were included in a post-protocol group. The primary outcome of complete response by 3 days was met in 28% of patients in the pre-protocol group and 53% of patients in the post-protocol group (P = 0.007). Calcitonin spending in dollars in the pre-protocol group was $818,956 compared to $224,320 in the post-protocol group; a difference of $594,636. CONCLUSION: Implementation of a pharmacy-driven calcitonin protocol effectively improved calcium levels, reduced inappropriate calcitonin use, and reduced calcitonin spending during a period of 2 fiscal years.

Renal complications and quality of life in postsurgical hypoparathyroidism: a case-control study.

PURPOSE: Conventional therapy (calcium and activated vitamin D) does not restore calcium homeostasis in patients with chronic hypoparathyroidism (HypoPT) and is associated with renal complications and reduced quality of life (QoL). The aim of this study was to evaluate in a case-control, cross-sectional study, the rate of renal complications and QoL in two sex- and age-matched cohort of patients with differentiated thyroid cancer with (n = 89) and without (n = 89) chronic post-operative HypoPT (PoHypoPT) and their relationship with the biochemical control of the disease. METHODS: Serum and urinary parameters, renal ultrasound and QoL were assessed by SF-36 and WHO-5 questionnaires. RESULTS: Forty-three (48.3%) PoHypoPT patients reported symptoms of hypocalcemia. Twenty-six (29.2%) patients were at target for all 6 parameters, 46 (51.6%) for 5. The most frequently unmet targets were gender-specific 24-h urinary calcium (44.9%) and serum calcium (37.1%). Serum phosphate, magnesium and 25(OH)D were in the normal range in > 90% of patients. Renal calcifications were found in 26 (29.2%) patients, with no correlation with 24-h urinary calcium. eGFR did not differ between patients and controls. Conversely, patients had a significant higher rate of renal calcifications and a lower SF-36, but not WHO-5, scores. SF-36 scores did not differ between PoHypoPT patients who were, or not, hypocalcemic. CONCLUSIONS: Our study shows that the rate of renal calcifications was higher in patients with PoHypoPT than in those without. This finding, together with the reduced QoL and the presence of hypocalcemic symptoms in about half patients, underscores that the treatment of chronic HypoPT with conventional therapy is suboptimal.

Effect of vitamin D supplementation on OPG/RANKL signalling activities in endothelial tissue damage in diet-induced diabetic rat model.

BACKGROUND: Type 2 Diabetes Mellitus is a chronic metabolic disease that causes endothelial damage and is an important risk factor for atherosclerosis. In the present study vitamin D3 supplementation in rats was used to determine the role of Osteoprotegerin (OPG)/Receptor activator kB ligand (RANKL) signalling in endothelial damage and changes in the expression levels of genes involved in this pathway. We hypothesized that vitamin D3 supplementation affects OPG and RANKL activity in the aorta. METHODS: Diabetes was induced in rats via injections of 40 mg/kg of streptozotocin followed by a high fructose (10%) diet. Group 2 (healthy) and 4 (diabetic) received 170 IU/kg of vitamin D3 weekly for 5 weeks, while Group 1 (healthy) and 2 (diabetic) received sterile saline. The aortas of each group were collected to analyse mRNA expression using the real-time PCR method and also to evaluate magnesium and calcium levels using inductively coupled plasma mass spectrometry. RESULTS: Opg and Il-1b expression levels were significantly associated with both diabetes and vitamin D3 supplementation in the aortas of the study groups (p ≤ 0.05). Opg mRNA expression was also found to correlate with both Icam-1 and Nos3 mRNA expression levels (r = 0.699, p = 0.001 and r = 0.622, p = 0.003, respectively). In addition, when mineral levels in the aortic tissues were compared among all groups, it was found that the interaction of diabetes and vitamin D3 supplementation significantly affected Mg levels and Mg/Ca ratios. CONCLUSIONS: It is concluded that vitamin D3 supplementation has a modulatory effect on OPG/RANKL activity in the vessel wall by ameliorating endothelial damage in diabetes. This effect may contribute to the regulation of cytokine-mediated vascular homeostasis and mineral deposition in the aorta; therefore, further comprehensive studies are proposed to demonstrate this relationship.

Characterization of Medication Trends for Chronic Kidney Disease: Mineral and Bone Disorder Treatment Using Electronic Health Record-Based Common Data Model.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage (p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.