Higher Incidence Of Hypocalcemia Research Articles

Risk Factors for Calcium-Phosphate Disorders after Thyroid Surgery.

Iatrogenic hypoparathyroidism following thyroidectomy is one of the most common complications significantly reducing patients' quality of life. This study aimed to analyze the risk factors for calcium-phosphate disorders following thyroidectomy. The study group consisted of 211 patients who underwent thyroidectomy for different conditions in 2018-2020. Demographic, clinical and surgical risk factors were analyzed against hypoparathyroidism and hypocalcemia. Hypoparathyroidism occurred in 15.63% of patients, and hypocalcemia occurred in 45% of those operated on. There was statistical significance between hypoparathyroidism and the extent of thyroid surgery: thyroidectomy vs. lobectomy (p = 0.02, OR = 4.5) and surgeon experience (p = 0.016, OR = 6.9). Low preoperative PTH levels were associated with a higher incidence of hypoparathyroidism (p = 0.055, OR = 0.9). There was a statistically significant correlation between the occurrence of hypocalcemia and preoperative vitamin D deficiency (p = 0.04, OR = 3.5). Low calcium levels before surgery were associated with a higher incidence of hypocalcemia (p = 0.051, OR = 0.5). Meta-analyses of selected risk factors confirmed that the most significant factor in the incidence of hypocalcemia was a decrease in PTH levels (p < 0.001). The extent of thyroid surgery and the experience of the surgeon are the most significant risk factors for hypoparathyroidism. Hypocalcemia is much more common than hypoparathyroidism. Among the risk factors for hypocalcemia, in addition to the decrease in parathormone levels due to iatrogenic parathyroid damage, we should mention vitamin D deficiency in the preoperative period.

Adverse Effects of Denosumab in Kidney Transplant Recipients: A 20-Year Retrospective Single-Center Observation Study in Central Taiwan

Bone loss can be noted in kidney transplantation recipients (KTRs) and can be related to fracture events. Denosumab, a potent monoclonal antibody to RANK ligand, increases lumbar bone mineral density. However, safety data for denosumab remain limited regarding transplant recipients. Hypocalcemia and increased genital tract infections have been mentioned as adverse effects in KTRs after being prescribed denosumab. We retrospectively analyzed the electronic medical records of KTRs during the recent 20 years who had been prescribed antiresorptive therapy and were >18 years old. Medical records and their clinical data were reviewed and analyzed. We compared the frequency of adverse effects between denosumab with other antiresorptive therapies. A total of 70 KTRs were enrolled, with 46 patients being given denosumab and the first injection being noted on October 31, 2014. No significant differences were seen in mortality rate, opportunistic infection, pneumonia, or genitourinary tract infection. One diagnosis of osteonecrosis of the jaw was noted in the denosumab group (2.2%). A higher incidence of hypocalcemia (<8.4 mg/dL) was noted in the denosumab group (34.8%), and a higher but nonsignificant difference in the incidence of severe hypocalcemia was also noted in the group. Denosumab may be considered as safe as other antiresorptive therapies for KTRs. However, more hypocalcemia events have been noted, so medical personnel may need to be cautious when prescribing its use.

The structure of mineral and bone disorders in patients with сhronic kidney disease of the 5th dialysis stage, taking into account the presence or absence of a diagnosis of type 1 diabetes mellitus

BACKGROUND: In patients with end-stage CKD, receiving renal replacement therapy (RRT) with programmed hemodialysis (HD), the severity of complications is associated with metabolic disturbances: accumulation of uremic toxins, nephrogenic anemia, secondary hyperparathyroidism (SHPT), extraskeletal calcification, impaired clearance and rhythm of hormone secretion.AIM: To evaluate the main biochemical and hormonal parameters, and manifestations of mineral bone disease (MBD) in patients receiving RRT with HD, before and after hemodialysis, taking into account the presence or absence of diabetes mellitus.MATERIALS AND METHODS: We divided all patients receiving RRT with HD in two groups: #1 (n=24) — patients with DM, #2 (n=16) — patients without DM. All of them had their blood analyzed before and immediately after the HD. Data analysis was performed with the Statistica 13 (StatSoft, USA). A prognostically significant model was considered at p&lt;0.05.RESULTS: The level of iPTH, both at baseline and after HD, was lower in group #1 (p&lt;0.001). The level of alkaline phosphatase (AP) was significantly higher in group #2 (p=0.012). In both groups before HD, a high incidence of hypocalcemia was detected (according to albumin-corrected calcium in group #1 in 58.3%, in group #2 in 43.7% of cases, p = 0.366) and hyperphosphatemia (in 66.7% and in 43 .7% of cases, respectively, p=0.151). Hypocalcemia after HD in group #1 persisted in 14%, in group #2 — in 20% of cases (p&gt;0.05); hyperphosphatemia in group #1 was completely leveled, in group #2 it persisted in 7% of cases (p=0.417). Prior to the HD session, group #1 had significantly higher levels of RAGE, glucagon, immunoreactive insulin (IRI), cortisol, and glucose than after the HD session (p&lt;0.05). In group #2, after HD, the levels of glucagon, IRI and cortisol significantly decreased (p&lt;0.05), and the level of 3-nitrotyrosine (3-HT) increased significantly (p=0.026). In group #1, fibrocalcinosis of the heart valves according to ECHO and calcification of the arteries of the lower extremities according to ultrasonic doplerography were more common than in group #2 (42% vs 25%, p&lt;0.001 and 75% vs 37.5%, p=0.018, respectively). (χ2)). Compression fractures occurred with the same frequency in both groups (60%). A decrease in bone mineral density (BMD) to the level of osteopenia was noted more often in group #1 (50% vs 18.8%), and osteoporosis was more common in group #2 (68.8% vs 33.3%) (p&lt;0.001, χ2).CONCLUSION: The low level of PTH in group #1 may reflect the effect of diabetes on calcium-phosphorus metabolism. Patients with DM have an increased risk of renal osteodystrophy with a low bone turnover because of a number of metabolic factors inherent in diabetes. At the same time, the dynamics of phosphorus and calcium indicators during the HD procedure were similar.

Comparison of outcomes and costs of extracorporeal blood purification therapies in critically ill COVID-19 patients.

Plasmapheresis and hemoperfusion are used against cytokine release syndrome in COVID-19. This study aims to compare their outcomes, costs, and side-effects. Survival, costs and side-effects were compared in intensive care unit (ICU) patients receiving plasmapheresis (n= 49), hemoperfusion (n= 20), or none (n= 107), followed until death or discharge. Plasmapheresis survival time was higher than hemoperfusion or controls (HR=0.764, p= 0.397 and HR=0.483, p= 0.002, respectively), although the latter diminished after controlling for age and disease severity (p= 0.979). There was no significant difference in ICU costs for plasmapheresis and hemoperfusion (p= 0.738) while both costed more than controls (both p< 0.001). Hypocalcemia and thrombocytopenia incidence did not differ between two groups (p= 0.124 and p=0.389, respectively) while being higher than controls in plasmapheresis (both p< 0.001) and hemoperfusion (p< 0.001 and p= 0.056, respectively). Plasmapheresis and hemoperfusion do not differ significantly in patient survival, ICU costs and side-effects with a higher incidence of hypocalcemia and thrombocytopenia compared witcontrols.

The long-term need for calcium supplementation after incidental parathyroidectomy

ObjectivesHypocalcaemia and hypoparathyroidism are the most frequent complications of total thyroidectomy that may result in the need for lifelong calcium supplementation. This study aims to investigate the impact of incidental parathyroidectomy on short- and long-term hypocalcaemia. MethodsThis retrospective study was conducted on patients who underwent total thyroidectomy with or without central neck dissection between March 2016 to May 2018. All procedures were performed by three surgeons with similar experience levels. Histopathology reports were reviewed, the number of resected parathyroid glands and the underlying pathology reports were recorded, and the patients were divided into two groups; groups A and B comprised those with and without parathyroid glands respectively. The incidence rates of short- and long-term hypocalcaemia were recorded. The former was obtained through blood tests during hospitalisation and the latter via phone calls to patients 3, 6, and 12 months postoperatively. ResultsA total of 116 patients participated, 18 (15.5%) in group A and 98 (84.5%) in group B. No statistical significance was detected between the two groups regarding early postoperative (p = 0.109) or long-term hypocalcaemia (p = 0.48). These results were similar in patients with cancer (n = 40) (p = 0.855, p = 0.08). ConclusionIncidental parathyroidectomy of one parathyroid gland was not correlated with a higher incidence of hypocalcaemia, even in cases with thyroid cancer.

Prolonged Hypocalcemia After a Single Dose of Denosumab in Chronic Kidney Disease

Introduction: Denosumab, a monoclonal antibody that inhibits RANK L (receptor activator nuclear factor-kappa beta ligand), is one of the few medications that can be used to treat osteoporosis in patients with chronic kidney disease (CKD). However, its use is associated with a much higher incidence of hypocalcemia in this patient population. What remains unclear is the duration of hypocalcemia after denosumab use. We describe a case of prolonged hypocalcemia of 9 months in a patient with CKD after a single dose of denosumab. Case: A 64-year-old Caucasian man with a history of bilateral lung transplant for interstitial pulmonary fibrosis and CKD Stage IV was referred to the Endocrinology clinic for evaluation of steroid-induced osteoporosis. Bone density scan was consistent with osteoporosis with the lowest T-score of -2.8 at the left femoral neck, which showed a 25.3% decline from a previous one two years prior. His labs upon initial visit: 25 hydroxy Vitamin D: 36.5 ng/mL (30–100), 1, 25 hydroxy vitamin D 32 pg/ml (19.9–79.3), corrected Serum Calcium 8.9 mg/dL (8.5–10.5), Serum Cr 4.38 mg/dL (0.6–1.4), PTH 157 pg/mL (10–65), Serum Alkaline Phosphatase 61 Units/L (25–125), Urine NTX 39 nM BCE/mM creatinine (21–83). After discussing risks and benefits, he was given a dose of subcutaneous denosumab 60 mg. He had been started on Calcium/Vitamin D (600 mg/400 IU BID) prior to receiving his dose. Keeping in mind the increased risk of hypocalcemia given his history of CKD, his corrected serum calcium was checked one week later, and it was 6.5 mg/dL. The patient was asymptomatic. However, given the severity of his hypocalcemia, he was started on calcitriol 0.25 mcg oral BID and calcium carbonate 1200 mg daily. He did show mild improvement in three days to a corrected calcium of 7.0 mg/dL. His calcitriol was briefly increased to 0.5 mcg BID and calcium carbonate was increased to 1800 mg daily. The regimen was weaned to calcitriol 0.25 mcg daily and previous calcium/Vitamin D dosing later that month. Thereafter, his labs were monitored regularly and there were several unsuccessful attempts made to decrease the calcitriol/calcium carbonate. Given persistent hypocalcemia, other bloodwork including a bone specific alkaline phosphatase and celiac screen were checked which were unremarkable. Finally, nine months after his denosumab dose, calcitriol was discontinued safely. Serum calcium levels have remained stable thereafter. Given prolonged hypocalcemia, it was decided not to administer another dose of denosumab. Conclusion: Patients with CKD who receive denosumab are not only at risk for developing severe, but also prolonged hypocalcemia. Therefore, it is imperative to monitor serum calcium levels, not only immediately after receiving a dose, but serially.

Оценка уровня кальциемии у пациентов с сахарным диабетом по данным обследования в мобильном медицинском центре (Диамодуль)

Background. Diabetes mellitus (DM) is characterized by multiple risk factors for the combined development of disorders of phosphorus-calcium metabolism, due to more frequent overweight, decreased renal filtration function and vitamin D deficiency in this category of patients. Aim. To assess the level of calcium in blood serum and its correlations with parameters of carbohydrate metabolism, body mass index (BMI) and renal function in patients with type 1 and type 2 diabetes. Materials and methods. The object of the study: adult patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) ≥18 years old who underwent examination in Diamodule (n=294) in 2019 in the Voronezh region, who were additionally tested for serum calcium. The examination at the mobile medical center includes: assessment of anthropometric data (height, weight, BMI), biochemical data of blood lipids and creatinine levels with calculation of glomerular filtration rate (GFR-EPI), albuminuria and the albumin/creatinine in a single portion of urine, measurement of glycated hemoglobin (HbA1c), blood pressure, electrocardiogram, consultation with a cardiologist, ophthalmologist, specialist of the Diabetic Foot office, diabetologist. All biochemical parameters was carried out using commercial kits on a biochemical express analyzer Spotchem EZ ArkraySP-4430. Determination of HbA1c, albuminuria, albumin/creatinine was performed by immunochemical method on a DCA Vantage analyzer. Data analysis was carried out using the Statistica v.13.3 software package (TIBCO Software Inc., USA). The results are presented as medians and quartiles [25; 75], the level of reliability is taken as p&lt;0.05. Results. Hypocalcemia (serum calcium level less 2.15 mmol/L) was detected in 88.3% of patients with T1DM and 73.6% of patients with T2DM. The level of serum calcium in T1DM was 1.96 [1.83; 2.07], in T2DM – 2.04 [1.97; 2.16] (p&lt;0.001) with significant differences in GFR: in T1DM 69.6 [57.8; 82.5], with T2DM 50.5 [44.1; 59.9] (p&lt;0.001). We observed correlation between GFR and calcium level r=-0.3 (p&lt;0.05,). GFR&lt;60 ml/min/1.73 m² was observed in 30.5% of T1DM patients, in 75.0% of T2DM. The HbA1c in T1DM was 8.7% [7.7; 9.8], in T2DM – 8.3% [6.8; 9.4] (p=0.01). Obesity was revealed in T1DM in 12.3%, in T2DM in 71.4%; the median BMI in T1DM was 25.5 kg/m2 [21.9; 28.4], in T2DM – 33.2 kg/m2 [29.7; 37.9]. There was correlation between BMI and calcium level r=0.26 (p&lt;0.05). Conclusion. The results of the study revealed a high prevalence of hypocalcemia among patients with diabetes, the most pronounced in type 1 diabetes. In the presence of a correlation between calcium and GFR, there was a high incidence of hypocalcemia in patients with T1DM, even in the absence of a significant decrease in GFR, which may indicate to additional risk factors. Since the assessment of the level of calcium is not included in the list of standard clinical examination, it is recommended to include this parameter and conduct regular screening in risk groups, which include patients with diabetes. More extensive research is needed to analyze the factors.

Meta-analysis of clinical trials to assess denosumab over zoledronic acid in bone metastasis.

Background Bone metastases-induced skeletal complications result in reduced patient survival, lower quality of life, and an increase in healthcare costs. Previously, zoledronic acid (ZA) was the standard choice of treatment for bone metastases, but another drug, denosumab, has also shown promise. However, the clinical utility of these two drugs requires further exploration. Aim of the review Due to the lack of direct comparisons regarding the efficacy of these drugs in both solid tumors and multiple myeloma (MM), we herein tried to conduct a meta-analysis to compare their efficacy in parallel for bone metastases treatment in both solid tumor and MM patients. Methods Multiple databases including Cochrane Library, MEDLINE, EMBASE, and Web of Science were searched to identify randomized controlled trials (RCTs) reported up to March 2019 directly comparing denosumab with ZA in solid tumors and MM. Information about the following events was primarily searched: time to first on-study skeletal-related event (SRE), time to first and subsequent SREs, and overall survival. Information about secondary outcomes including disease progression, pain, health-related quality of life, and adverse events was also recorded. Results Overall, we analyzed data from four distinct RCTs including 7441 patients, and our analysis revealed that patients in the denosumab group had a significantly delayed incidence to the first and subsequent SREs. In addition, denosumab resulted in a higher incidence of hypocalcemia and osteonecrosis of the jaw (ONJ), and a lower incidence of renal toxicity and acute phase reactions, in comparison to ZA. Conclusion Overall, denosumab showed superiority in delaying the first and subsequent SREs, and hence seems to be a promising choice for managing bone metastases in both solid tumors and MM. However, it can induce a higher incidence of ONJ and hypocalcaemia, but these are preventable and manageable effects.

Age, Gender and Season Are Good Predictors of Vitamin D Status Independent of Body Mass Index in Office Workers in a Subtropical Region.

This study aimed at determining the prevalence and predictors of hypovitaminosis D (serum 25-hydroxyvitamin D < 30 ng/mL) among office workers in a subtropical region from an electronic hospital database. Totally, 2880 office workers aged 26–65 years who received health examinations with vitamin D status and total calcium concentrations at a tertiary referral center were retrospectively reviewed. Subjects were divided into groups according to genders, age (i.e., 26–35, 36–45, 46–55, 56–65), body-mass index (BMI) (i.e., obese BMI ≥ 30, overweight 25 ≤ BMI < 30, normal 20 ≤ BMI < 25, and underweight BMI < 20) and seasons (spring/winter vs. summer/autumn) for identifying the predictors of hypovitaminosis D. Corrected total calcium level <8.4 mg/dL is considered as hypocalcemia. Multivariate logistic regression demonstrated that females (AOR 2.33, (95% CI: 1.75, 3.09)), younger age (4.32 (2.98, 6.24), 2.82 (1.93, 4.12), 1.50 (1.03, 2.17)), and season (winter/spring) (1.55 (1.08, 2.22)) were predictors of hypovitaminosis D, whereas BMI was not in this study. Despite higher incidence of hypocalcemia in office workers with hypovitaminosis D (p < 0.001), there was no association between vitamin D status and corrected total calcium levels. A high prevalence (61.9%) of hypovitaminosis D among office workers in a subtropical region was found, highlighting the importance of this occupational health issue.

Complications following thyroidectomy for benign thyroid diseases and their correlation with clinical, anatomical, and biochemical parameters

Background: Hypocalcemia and recurrent laryngeal nerve (RLN) palsy are common complications following thyroidectomy. The study was designed to assess the effect of preoperative clinical and biochemical features and the intraoperative anatomical features on the rate of complications following total thyroidectomy (TT) for benign thyroid disease. Materials and Methods: The prospective observational study was conducted on patients undergoing TT for benign thyroid diseases. All patients underwent complete assessment followed by the estimation of thyroid function (free T4 and thyroid-stimulating hormone). Ultrasound imaging of the neck and guided aspiration from the suspicious area for cytology were performed routinely. All patients were followed for minimum 6 months. Parameters used for the analysis included demographic features, feel of the gland, presence of adhesions to surrounding soft tissue, presence of retrosternal extension, and anatomical features of laryngeal nerves and parathyroid glands. Results: One hundred and twenty-five eligible candidates were included in the study and temporary hypocalcemia and temporary RLN palsy occurred in 48 (38%) and 9 (6.5%) patients, respectively. None of the patients had permanent complications. Failure to identify all four parathyroids was associated with a higher incidence of hypocalcemia (P Conclusion: Meticulous surgical dissection and thorough knowledge of anatomy prevent the development of both hypocalcemia and RLN palsy in TT for benign thyroid disorders.

The prevalence of endocrinopathies among patients with thalassemia major in the district of Batticaloa, Sri Lanka

Introduction: Thalassaemia major is an inherited haemoglobinopathy characterised by chronic anaemia. Excessive iron overload and suboptimal chelation result in deposition of iron in various tissues including endocrine glands. Objective: To estimate the prevalence of endocrinopthies in patients with thalassemia major among patients attending clinics at Teaching Hospital Batticaloa. Materials and Methods: Cross sectional descriptive study of patients with thalassemia major on active follow up from June 2015 to 2016 at Teaching Hospital Batticaloa. Height, weight, and tanner staging, serum ferritin, oral glucose tolerance test, bone profile, liver and renal function, thyroid function, cortisol for all patients and FSH, LH, testosterone or oestradiol for girls over 13 years of age and boys over 14 years of age were assessed. Results: A total of 95 patients including 50 females with the mean age of 11.83±4.53 years were evaluated. Shortstature was found in 55(57.8%). Hypocalcaemia was present in 36(37.8%) and 24(25%) had hypothyroidism. Diabetes mellitus and impaired glucose tolerance (IGT) were found in 7(7.4%) and 13(13.2%) respectively. Only 2 (2.1%) had cortisol deficiency. Among girls over 13 and boys over 14 years of age, 33(78.6%) had hypogonadism. Sixty six patients with mean serum ferritin level above 2500ng/mL had higher incidence of hypocalcaemia, hypothyroidism, hypogonadism, and short stature (28 vs 5;p=0.004, 18 vs 6;p=0.048, 28 vs 5;p=0.03, and 39 vs 16;p=0.054 respectively) than those who had less than 2500ng/mL. Patients who were above 9 years of age had higher incidence of hypocalcaemia (32 vs 2;p=0.00), short stature (33 vs 22;p=0.026), and IGT (11 vs 2;p=0.017) when compared to younger patients. Conclusions: A significant proportion of thalassemia major patients have endocrinopathies. Hypothyroidism and short stature develop very early and other endocrinopathies also develop earlier indicating the need for early screening compared to the recommended guidelines. As the duration of thalassemia increases the risk for developing endocrinopathies is high.

Hormona Paratiróideia Como Factor Predictivo de Hipocalcemia Após Tiroidectomia: Estudo Prospectivo em 100 Doentes

Hypocalcemia is a frequent complication after total thyroidectomy and the main reason for prolonged hospitalization of these patients. We studied prospectively 112 patients who underwent total or completation thyroidectomy between June 2012 and November 2013. Twelve patients with preoperative changes in parathyroid function were excluded. Parathyroid hormone and calcium levels were determined pre-operatively, immediately after surgery, on 1st day and on 14th day after surgery. Of the 100 patients enrolled, 60 have developed hypocalcaemia (60%) but only 14 patients had symptomatic hypocalcaemia. It mostly occurs 24 hours after surgery (76.7%). It was permanent in 3 patients and temporary in the others. In the 60 patients with hypocalcaemia, it has been found hypoparathyroidism in 19 patients immediately after surgery, in 14 patients on 1st day but only 3 had hypoparathyroidism (patients with permanent hypocalcaemia). Comparing the group of patients with and without hypocalcaemia we found a decrease of parathyroid hormone in both (immediately after surgery and on 1st day) but was more important in the hypocalcaemia group (p = 0.004 and p < 0.001). The decrease of PTH levels was more pronounced in the hypocalcaemia group, with significance on the first day (22.29% vs 50.29%, p < 0.001). The best predictor of hypocalcaemia identified was the decrease of parathyroid hormone levels > 19.4% determined on the 1st day (sensitivity = 82%; specificity = 63%). In our study there was a high incidence of hypocalcemia (60%), expressed predominantly 24 hours after surgery and conditioned, in these patients, a longer hospital stay. However, only 3 patients (3%) had permanent hypocalcemia. We still found a match in the oscillation of serum calcium levels and parathyroid hormone which identified the decrease in parathyroid hormone on the first day after surgery as a reliable predictor of hypocalcemia. Decrease of parathyroid hormone levels > 19.4% determined on 1st day is a good predictor of hypocalcemia after total / completation thyroidectomy, allowing to identify patients at higher risk of hypocalcemia, medicate them prophylactically and get early and safe discharges.

Mineral homeostasis in late preterm infants

80% of mineral accretion take place in the third trimester of gestation with a fetal accretion rates of 100-150 mg/kg/day for calcium, 50-70 mg/kg/day for phosphate and 3 mg/kg/day for magnesium. During the third trimester of gestation fetal weight triples but Ca content quadruples with a faster increase in fetal body Ca accretion from 32 to 40 weeks of gestation [1]. As a result, late preterm infants will be deprived of the intrauterine supply of calcium and phosphorus during a period of rapid skeletal growth affecting bone mineral mass. Late preterm infants have a higher incidence of hypocalcemia [2] and represent an intermediate risk category as compared with term and very preterm infants. AGA late-preterm infants have a higher bone turn-over than term infants, but smaller than very pre-term newborns [3]. During the third trimester of gestation, bone mineral density (BMD) increases at a faster rate in utero (term infants) than ex utero (preterm infant) according to gestational age. At term newborns have a physiological reduction in BMD in the first 2-3 months of life with a recovery during the first year of life. Preterm newborns present a similar event with a higher reduction of mineral retention from birth to term in the presence of high skeletal growth. Inadequate supply of calcium and phosphate to newborns requiring parental nutrition and several drugs (steroids, methylxanthines, diuretics) may increase the risk of osteopenia. Drugs affect bone metabolism decreasing calcium absorption and osteoblasts proliferation and increasing calcium renal excretion and osteoclasts activation. How do we best support the rapid skeletal growth of late preterm infants? Have early nutrition during the first weeks of life been adequate? Enriched formulas for preterm newborns have a positive and probably long-term effect on bone mineralization [4,5]. In late preterm infants the goal should be to provide nutrients based on gestational age instead of relying on birthweight. However there are no specific recommendation and further studies are warranted to determine the best care for late preterm infants.

Studio EVOLVE: un'altra delusione per i Nefrologi?

Il calciomimetico Cinacalcet è ormai in uso da alcuni anni per il trattamento dell'iperparatiroidismo secondario (IPTS) nei pazienti dializzati, permettendo una buona riduzione dei livelli di paratormone. Nell'ottica di valutare un suo possibile effetto benefico nel migliorare la prognosi cardio-vascolare dei pazienti dializzati, è stato condotto lo studio randomizzato “Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events” (EVOLVE). Sono stati randomizzati a ricevere Cinacalcet o placebo 3883 pazienti dializzati affetti da iperparatiroidismo secondario moderato-severo, valutando come end-point compositi primari la mortalità e gli episodi di infarto mio-cardico, l'ospedalizzazione per angina instabile, lo scompenso cardiaco ed eventi vascolari periferici. Nell'analisi “intention-to-treat”, a causa di una bassa potenza statistica, non sono state rilevate differenze significative tra i due bracci dello studio, a fronte di una più elevata incidenza di ipocalcemia, nausea e vomito nei soggetti in terapia con il calciomimetico. I dati dello studio EVOLVE hanno sicuramente deluso la comunità nefrologica, che si sarebbe aspettata dei risultati positivi. La mancanza di risultati conclusivi e i costi elevati suggeriscono un uso giudizioso del Cinacalcet. Non di meno, anche se mancano dati conclusivi su “hard end-point”, ci sembra poco saggio negare strategie terapeutiche che includano il Cinacalcet ai pazienti con severo IPTS con elevati livelli di PTH (PTH &gt;800 pg/mL) refrattari alla terapia standard e/o ipercalcemia e/o calcifilassi e/o elevato rischio chirurgico alla paratiroidectomia.

Expert opinion 2011 on the use of new anti-resorptive agents in the prevention of skeletal-related events in metastatic bone disease

Bisphosphonates have been a mainstay in the treatment of cancer-related bone disease and have greatly reduced the risk of skeletal complications. More recently, clinical studies suggested additional benefits of denosumab over zoledronic acid in the prevention of skeletal related events. Similar adverse event profiles have been reported for bisphosphonates and denosumab, with infrequent occurrences of osteonecrosis of the jaw with both agents, higher incidence of renal deterioration with zoledronic acid, and higher incidence of hypocalcaemia with denosumab. Based on current evidence, the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines do not recommend one drug class over the other in patients with metastatic bone disease. Denosumab, however, may present advantages over bisphosphonates in patients suffering from chronic renal insufficiency. Further research and growing clinical experience will refine the evidence based on which decisions in daily clinical practice can be taken.

The EVOLVE Study: Another Disappointment for Nephrologists?

The calcimimetic cinacalcet is now being used for years to treat secondary hyperparathyroidism (SHPT) in dialysis patients, allowing a good reduction in PTH levels. In order to evaluate a possible beneficial effect on cardiovascular prognosis, a randomized trial, the EVOLVE (Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events), was conducted in 3,883 dialysis patients affected by moderate to severe SHPT.Patients were randomly assigned to receive cinacalcet or placebo. The primary composite endpoint evaluated was time until death, myocardial infarction, hospitalization for unstable angina, heart failure or peripheral vascular events. Due to a low statistical power, there was no significant difference between the two arms of the study in the intention-to-treat analysis, despite a higher incidence of hypocalcaemia, nausea, and vomiting in patients treated with cinacalcet.The results of the EVOLVE study have certainly disappointed the nephrological community that would have expected ...

Amifostine does not prevent platinum‐induced hearing loss associated with the treatment of children with hepatoblastoma

The current study was conducted to determine whether amifostine is effective in reducing the toxicities associated with the administration of platinum-containing regimens in children with hepatoblastoma (HB). Patients were enrolled on P9645 beginning in March of 1999. Patients who had stage I/II disease received treatment with 4 cycles of combined cisplatin, 5-fluorouracil, and vincristine (C5V) with or without amifostine. Patients who had stage III/IV disease were randomized to receive treatment with 6 cycles of either C5V with or without amifostine or carboplatin alternating with cisplatin (CC) with or without amifostine. Patients who were randomized to receive amifostine were given a dose of 740 mg/m2 intravenously over 15 minutes before each administration of a platinum agent. Eighty-two patients were considered in a special interim analysis of the incidence of toxicity. The disease outcome for patients who received amifostine was similar to the outcome for patients who did not receive amifostine (P=.22). The incidence of significant hearing loss (>40 dB) was similar for patients who did or did not receive amifostine (38% [14 of 37 patients] vs 38% [17 of 45 patients], respectively; P=.68). There were no differences in the incidence of renal or bone marrow toxicities evaluated. Patients who received amifostine had a higher incidence of hypocalcemia (5% vs 0.5%; P=.00006). Amifostine in the doses and schedule used in this study failed to significantly reduce the incidence of platinum-induced toxicities in patients with HB.

A randomized study of platinum based chemotherapy with or without amifostine for the treatment of children with hepatoblastoma (HB): A report of the Intergroup Hepatoblastoma Study P9645

8518 Background: Platinum-based therapy has improved the outcome for children with HB, however this therapy is associated with an increased risk of ototoxicity. Amifostine is a chemoprotectant developed to protect normal tissues from chemotherapy-induced side effects without adversely affecting anti-tumor activity. One of the goals of the P9645 study was to estimate the efficacy of Amifostine in reducing the toxicity associated with platinum agents in children with HB by randomizing patients to receive chemotherapy with or without Amifostine. Methods: A total of 203 patients were entered onto this study. Stage I/II patients received treatment with 4 cycles of Cisplatin-5-Fluorouracil-Vincristine (C5V) +/- Amifostine and patients with Stage III/IV were randomized to receive 4–6 cycles of C5V +/- Amifostine or Carboplatin alternating with Cisplatin (CC) +/- Amifostine. Amifostine (740 mg/m2/dose) was given intravenously prior to the platin agent in every cycle. Audiometric data was assessed in a cohort of surviving patients who had not progressed, and therefore had not received additional therapy off protocol. Results: The disease outcome for patients receiving Amifostine was not different from those treated without Amifostine. Audiometric data was available for 116 eligible patients, and fully evaluable in 82. Amifostine did not prevent ototoxicity as significant hearing loss (> 40 dB extending to 2 kHz) was seen in 14% (5/37) of the patients receiving Amifostine versus 9% (4/45) of the patients who did not receive Amifostine (p=0.72 ). Other organ toxicities (renal/bone marrow) were not different for patients who did or did not receive Amifostine, however, the use of Amifostine was associated with a higher incidence of hypocalcemia (5% vs. 0.5%, p=0.00006). Conclusion: Amifostine in the dose and schedule used in this study does not protect against the ototoxicity associated with platinum agents used for the treatment of children with HB. No significant financial relationships to disclose.

Effects of Intravenous Pamidronate Therapy on Paget’s Disease of Bone

Pamidronate is a second generation bisphosphonate that has been used in Europe for the treatment of Paget's disease of bone for several years. It relieves pain and reduces bone turnover in Paget's disease. To assess the effects of pamidronate on Paget's disease of bone, the authors treated 28 patients, aged 45 to 87, with longstanding Paget's disease for a period of 4-18 months. Parameters measured included pain and serum alkaline phosphatase, urinary hydroxyproline, and ionized calcium concentrations. Patients were organized into two groups. Patients in the first group had initial alkaline phosphatase concentrations below 215 U/L, which decreased to normal after one dose of pamidronate. Patients in this group also experienced symptomatic improvement. Patients in the second group had initial alkaline phosphatase values greater than 240 U/L, which did not normalize after 2-11 pamidronate infusions. More patients in this latter group did not report symptomatic improvement. Patients in the second group also had a higher incidence of hypocalcemia. It is concluded that there is a clear relation between initial alkaline phosphatase level in Paget's disease and response to treatment with pamidronate. The authors' current protocol for treating patients with pamidronate is based on this relation. Because pamidronate proved most effective when used in mild Paget's disease, therapy probably should be instituted early in the course of disease.

Hypocalcemia after thyroidectomy: mechanisms and management.

Hypocalcemia persists as a problem after thyroidectomy. We reviewed our experience with 245 thyroidectomies to define the spectrum of hypocalcemia, elucidate the mechanisms of hypocalcemia, and formulate a rational basis for its management. Postoperative hypocalcemia occurred in 8.6% of all patients undergoing thyroid surgery with incidence the highest in patients with total thyroidectomy for cancer (28%) and those with subtotal thyroidectomy for thyrotoxicosis (23%). Incidence was low in patients having subtotal thyroidectomy for other diseases (1.5%) and lobectomy (0%). The high incidence of hypocalcemia following subtotal thyroidectomy for thyrotoxicosis but not for other diseases suggests that a mechanism other than removal or damage of the parathyroids is responsible for the hypocalcemia. This may well be thyrotoxic osteodystrophy. This hypocalcemia usually occurs early, is of moderate degree, and is transient. Management includes calcium gluconate for acute symptoms and calcium lactate with vitamin D2 for chronic symptoms.