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This position paper of the International Osteoporosis Foundation reports the findings of an IOF Commission to consider to recommend rules of partnership with scientists belonging to a country which is currently responsible for an armed conflict, anywhere in the world. The findings and recommendations have been adopted unanimously by the Board of IOF., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Radiofrequency Echographic Multi Spectrometry (REMS) is a radiation-free, portable technology, which can be used for the assessment and monitoring of osteoporosis at the lumbar spine and femoral neck and may facilitate wider access to axial BMD measurement compared with standard dual-energy x-ray absorptiometry (DXA).There is a growing literature demonstrating a strong correlation between DXA and REMS measures of BMD and further work supporting 5-year prediction of fracture using the REMS Fragility Score, which provides a measure of bone quality (in addition to the quantitative measure of BMD).The non-ionising radiation emitted by REMS allows it to be used in previously underserved populations including pregnant women and children and may facilitate more frequent measurement of BMD.The portability of the device means that it can be deployed to measure BMD for frail patients at the bedside (avoiding the complications in transfer and positioning which can occur with DXA), in primary care, the emergency department, low-resource settings and even at home.The current evidence base supports the technology as a useful tool in the management of osteoporosis as an alternative to DXA., (© 2024. The Author(s).)

Introduction: These guidelines aim to provide evidence-based recommendations for the supplementation of Vitamin D in maintaining bone health. An unmet need persists in Latin American regarding the availability of clinical and real-world data for rationalizing the use of vitamin D supplementation. The objective of these guidelines is to establish clear and practical recommendations for healthcare practitioners from Latin American countries to address Vitamin D insufficiency in clinical practice., Methods: The guidelines were developed according to the GRADE-ADOLOPMENT methodology for the adaptation or adoption of CPGs or evidence-based recommendations. A search for high quality CPGs was complemented through a comprehensive review of recent literature, including randomized controlled trials, observational studies, and systematic reviews evaluating the effects of Vitamin D supplementation on bone health. The evidence to decision framework proposed by the GRADE Working Group was implemented by a panel of experts in endocrinology, bone health, and clinical research., Results: The guidelines recommend Vitamin D supplementation for individuals aged 18 and above, considering various populations, including healthy adults, individuals with osteopenia, osteoporosis patients, and institutionalized older adults. These recommendations offer dosing regimens depending on an individualized treatment plan, and monitoring intervals of serum 25-hydroxyvitamin D levels and adjustments based on individual results., Discussion: The guidelines highlight the role of Vitamin D in bone health and propose a standardized approach for healthcare practitioners to address Vitamin D insufficiency across Latin America. The panel underscored the necessity for generating local data and stressed the importance of considering regional geography, social dynamics, and cultural specificities when implementing these guidelines., (© 2024. The Author(s).)

Background: In the modern world, mobile apps are essential for human advancement, and pandemic control is no exception. The use of mobile apps and technology for the detection and diagnosis of COVID-19 has been the subject of numerous investigations, although no thorough analysis of COVID-19 pandemic prevention has been conducted using mobile apps, creating a gap., Objective: With the intention of helping software companies and clinical researchers, this study provides comprehensive information regarding the different fields in which mobile apps were used to diagnose COVID-19 during the pandemic., Methods: In this systematic review, 535 studies were found after searching 5 major research databases (ScienceDirect, Scopus, PubMed, Web of Science, and IEEE). Of these, only 42 (7.9%) studies concerned with diagnosing and detecting COVID-19 were chosen after applying inclusion and exclusion criteria using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol., Results: Mobile apps were categorized into 6 areas based on the content of these 42 studies: contact tracing, data gathering, data visualization, artificial intelligence (AI)-based diagnosis, rule- and guideline-based diagnosis, and data transformation. Patients with COVID-19 were identified via mobile apps using a variety of clinical, geographic, demographic, radiological, serological, and laboratory data. Most studies concentrated on using AI methods to identify people who might have COVID-19. Additionally, symptoms, cough sounds, and radiological images were used more frequently compared to other data types. Deep learning techniques, such as convolutional neural networks, performed comparatively better in the processing of health care data than other types of AI techniques, which improved the diagnosis of COVID-19., Conclusions: Mobile apps could soon play a significant role as a powerful tool for data collection, epidemic health data analysis, and the early identification of suspected cases. These technologies can work with the internet of things, cloud storage, 5th-generation technology, and cloud computing. Processing pipelines can be moved to mobile device processing cores using new deep learning methods, such as lightweight neural networks. In the event of future pandemics, mobile apps will play a critical role in rapid diagnosis using various image data and clinical symptoms. Consequently, the rapid diagnosis of these diseases can improve the management of their effects and obtain excellent results in treating patients., (©Mehdi Gheisari, Mustafa Ghaderzadeh, Huxiong Li, Tania Taami, Christian Fernández-Campusano, Hamidreza Sadeghsalehi, Aaqif Afzaal Abbasi. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 22.02.2024.)

Background: Due to shared modes of transmission, coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is common, and HBV vaccination is recommended for all persons with HCV who remain susceptible to HBV. To identify potential gaps in HBV vaccination among this high-risk population, we aimed to determine the patterns of HBV susceptibility in persons undergoing community-based HCV treatment., Methods: We performed a cross-sectional study within two community-based HCV treatment programs in an urban US setting. Participants were identified for HCV screening and confirmatory testing via street-outreach recruitment directed at persons experiencing homelessness and currently using drugs. Participants were excluded if HBsAg was reactive. Cohort characteristics were obtained via intake surveys and descriptive analysis was performed by exposure status., Results: Among 150 participants without chronic HBV receiving community-based HCV treatment, 43% had evidence of prior HBV infection, 26% were immune from vaccination, and 31% were non-immune. Among the subset of the cohort reporting current injection drug use (IDU) (N = 100), 31% (n = 10) of those aged 24-40 and 47% (n = 23) of those aged 41-57 remained susceptible to HBV infection. By contrast only two participants aged 58-74 were HBV non-immune (11%), with 84% immune due to prior exposure., Conclusions: Our data reflect a high prevalence of HBV susceptibility among persons undergoing community-based HCV treatment. Although younger patients were more likely to be immune due to vaccination, a high proportion remained non-immune to HBV, particularly among those reporting current IDU. Our data reflect a gap in HBV vaccination among younger persons with HCV and suggest a potential role for co-localizing HBV vaccination with community-based HCV screening and treatment., (© 2024. The Author(s).)

Background: In addition to the role of vitamin D in bone mineralization, calcium and phosphate homeostasis, and skeletal health, evidence suggests an association between vitamin D deficiency and a wide range of chronic conditions. This is of clinical concern given the substantial global prevalence of vitamin D deficiency. Vitamin D deficiency has traditionally been treated with vitamin D 3 (cholecalciferol) or vitamin D 2 (ergocalciferol). Calcifediol (25-hydroxyvitamin D 3 ) has recently become available more widely., Methods: By means of targeted literature searches of PubMed, this narrative review overviews the physiological functions and metabolic pathways of vitamin D, examines the differences between calcifediol and vitamin D 3 , and highlights clinical trials conducted with calcifediol in patients with bone disease or other conditions., Results: For supplemental use in the healthy population, calcifediol can be used at doses of up to 10 µg per day for children ≥ 11 years and adults and up to 5 µg/day in children 3-10 years. For therapeutic use of calcifediol under medical supervision, the dose, frequency and duration of treatment is determined according to serum 25(OH)D concentrations, condition, type of patient and comorbidities. Calcifediol differs pharmacokinetically from vitamin D 3 in several ways. It is independent of hepatic 25-hydroxylation and thus is one step closer in the metabolic pathway to active vitamin D. At comparable doses to vitamin D 3 , calcifediol achieves target serum 25(OH)D concentrations more rapidly and in contrast to vitamin D 3 , it has a predictable and linear dose-response curve irrespective of baseline serum 25(OH)D concentrations. The intestinal absorption of calcifediol is relatively preserved in patients with fat malabsorption and it is more hydrophilic than vitamin D 3 and thus is less prone to sequestration in adipose tissue., Conclusion: Calcifediol is suitable for use in all patients with vitamin D deficiency and may be preferable to vitamin D 3 for patients with obesity, liver disease, malabsorption and those who require a rapid increase in 25(OH)D concentrations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Guidelines and recommendations developed and endorsed by the International Osteoporosis Foundation (IOF) are intended to provide guidance for particular pattern of practice for physicians who usually prescribe glucocorticoid (GC) therapy, and not to dictate the care of a particular patient. Adherence to the recommendations within this guideline is voluntary and the ultimate determination regarding their application should be made by the physician in light of each patient's circumstances. Guidelines and recommendations are intended to promote a desirable outcome but cannot guarantee any specific outcome. This guideline and its recommendations are not intended to dictate payment, reimbursement or insurance decisions. Guidelines and recommendations are subjected to periodic revisions as a consequence of the evolution of medicine, technology and clinical practice. A panel of Latin American (LATAM) experts specialized in osteoporosis with recognized clinical experience in managing patients with glucocorticoid-induced osteoporosis (GIO) met to produce evidence-based LATAM recommendations for the diagnosis and management of GIO. These guidelines are particularly intended to general practitioners and primary care physicians who prescribe GC treatments in LATAM to guide their daily clinical practice in terms of evaluation, prevention and treatment of GIO. These recommendations were based on systematic literature review using MEDLINE, EMBASE, SCOPUS and COCHRANE Library database during the period from 2012 to 2021. Randomized clinical trials (RCT), systematic reviews of RCT, controlled observational studies, guidelines and consensus were considered. Based on the review and expert opinion the panel members voted recommendations during two successive rounds of voting by panel members. Agreements for each statement were considered if a concordance of at least 70% was achieved following Delphi methodology. Grading of recommendations was made according to the Oxford Centre for the Evidence-based Medicine (EBM) criteria. Among five GIO guidelines and consensus initially identified, two of them (American College of Rheumatology 2017 and the Brazilian Guidelines 2021) were selected for comparison considering the latter as the most current guides in the LATAM region. Based on this methodology fifty statements were issued. All of them but four (1.20, 1.21, 1.23 and 4.2) attained agreement., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Streptococcus pneumoniae is a Gram-positive bacterium and the leading cause of bacterial pneumonia in children and the elderly worldwide. Currently, two types of licensed vaccines are available to prevent the disease caused by this pathogen: the 23-valent pneumococcal polysaccharide-based vaccine and the 7-, 10, 13, 15 and 20-valent pneumococcal conjugate vaccine. However, these vaccines, composed of the principal capsular polysaccharide of leading serotypes of this bacterium, have some problems, such as high production costs and serotype-dependent effectiveness. These drawbacks have stimulated research initiatives into non-capsular-based vaccines in search of a universal vaccine against S. pneumoniae. In the last decades, several research groups have been developing various new vaccines against this bacterium based on recombinant proteins, live attenuated bacterium, inactivated whole-cell vaccines, and other newer platforms. Here, we review and discuss the status of non-capsular vaccines against S. pneumoniae and the future of these alternatives in a post-pandemic scenario., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Silva, Vázquez, Campusano, Retamal-Díaz, Lay, Muñoz, González, Kalergis and Bueno.)

Competing Interests: None disclosed.

The Public Health Service in Chile consists of different levels of complexity and coverage depending on the severity and degree of specialization of the pathology to be treated. From primary to tertiary care, tertiary care is highly complex and has low coverage. This work focuses on an analysis of the public health system with emphasis on the healthcare network and tertiary care, whose objectives are designed to respond to the needs of each patient. A review of the literature and a field study of the problem of studying the perception of internal and external users is presented. This study intends to be a contribution in the detection of opportunities for the relevant actors and the processes involved through the performance of Triage. The main causes and limitations of the excessive use of emergency services in Chile are analyzed and concrete proposals are generated aiming to benefit clinical care in emergency services. Finally, improvements related to management are proposed and the main aspects are determined to improve decision-making in hospitals, which could be a contribution to public health policies.

Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.

Objective: Thyroid dysfunction and obesity during pregnancy have been associated with negative neonatal and obstetric outcomes. Thyroid hormone reference ranges have not been established for the pregnant Hispanic population. This study defines thyroid hormone reference ranges during early pregnancy in Chilean women and evaluates associations of body mass index (BMI) with thyroid function., Design, Patients, Measurements: This is a prospective observational study of 720 healthy Chilean women attending their first prenatal consultation at an outpatient clinic. Thyroid function [TSH, Free T4, Total T4 and antithyroid peroxidase antibodies (TPOAb)] and BMI were assessed at 8·8 ± 2·4 weeks of gestational age., Results: Median, 2·5th percentile (p2·5), and 97·5th percentile (p97·5) TSH values were higher, while median, p2·5, and p97·5 free T4 values were lower in obese patients compared with normal weight patients. Obesity was associated with a median TSH 16% higher (P = 0·035) and a median free T4 6·5% lower (P < 0·01) than values from patients with normal weight. BMI had a small, but statistically significant effect on TSH (P = 0·04) and free T4 (P < 0·01) when adjusted by maternal age, TPO antibodies, parity, sex of the newborn, gestational age and smoking. In all TPOAb (-) patients, median (p2·5-p.97·5) TSH was 1·96 mIU/l (0·11-5·96 mIU/l) and median (p2·5-p.97·5) free T4 was 14·54 pmol/l (11·1 - 19·02 pmol/l). Applying these reference limits, we found a prevalence of overt and subclinical hypothyroidism of 0·9% and 3·05% respectively., Conclusions: TSH distributes at higher values and free T4 at lower values in obese pregnant women compared to normal weight pregnant women. Thyroid hormone reference ranges derived from Chilean patients with negative TPOAb are different from the fixed internationally proposed reference ranges and may be used in the Hispanic population., (© 2016 John Wiley & Sons Ltd.)

Background: Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk of developing osteoporosis., Aim: To determine the frequency and severity of Vitamin D deficiency, secondary hyperparathyroidism and low bone mass in patients undergoing HCT., Patients and Methods: Analysis of the database of patients undergoing HCT in our institution in the 2010-2015 period. We searched for patients with measurements of 25-OH vitamin D (25OHD), parathyroid hormone (PTH) and bone densitometry by double beam X ray absorptiometry (DXA) prior and up to one year after HCT., Results: Ninety patients were included, 53 were evaluated prior to HCT and 37 after HCT. They represent 73% of all patients undergoing HCT in the period. Median 25OHD was 12 ng/ml (range 4-41.4). Ninety seven percent of patients had levels considered insufficient and 85% compatible with deficiency. Median PTH was 60.5 pg/ml (range 21-186). Forty five percent of patients had secondary hyperparathyroidism. DXA was performed in 65 patients (prior to HCT in 54 and after HCT in 11). Of these, 11% had had a low bone mineral density., Conclusions: Patients undergoing HCT have a high risk of vitamin D deficiency, secondary hyperparathyroidism and low bone mineral density.

Cellular migration and contractility are fundamental processes that are regulated by a variety of concerted mechanisms such as cytoskeleton rearrangements, focal adhesion turnover, and Ca2+ oscillations. TRPM4 is a Ca2+-activated non-selective cationic channel (Ca2+-NSCC) that conducts monovalent but not divalent cations. Here, we used a mass spectrometry-based proteomics approach to identify putative TRPM4-associated proteins. Interestingly, the largest group of these proteins has actin cytoskeleton-related functions, and among these nine are specifically annotated as focal adhesion-related proteins. Consistent with these results, we found that TRPM4 localizes to focal adhesions in cells from different cellular lineages. We show that suppression of TRPM4 in MEFs impacts turnover of focal adhesions, serum-induced Ca2+ influx, focal adhesion kinase (FAK) and Rac activities, and results in reduced cellular spreading, migration and contractile behavior. Finally, we demonstrate that the inhibition of TRPM4 activity alters cellular contractility in vivo, affecting cutaneous wound healing. Together, these findings provide the first evidence, to our knowledge, for a TRP channel specifically localized to focal adhesions, where it performs a central role in modulating cellular migration and contractility.

Background: The prevalence of thyroid cancer has increased, particularly in nodules smaller than 10 mm, probably due to the growing use of routine thyroid ultrasound. There is controversy about the biological behavior of micro carcinomas and the relevance of their early detection., Aim: To characterize the clinical presentation of thyroid cancer over 20 years in an University medical center and to evaluate the differences between macro and micro carcinomas., Patients and Methods: We reviewed 1547 surgical biopsy records of thyroid cancer in our institution obtained between 1991 and 2010., Results: We observed a sustained increase in the rate of thyroidectomies for thyroid cancer (per 1000 surgical procedures) in the study period. Papillary, follicular, mixed, medullary and anaplastic carcinomas were observed in 95, 3, 2, 0.5 and 0.1% of biopsies, respectively. The incidence of tumors of less than 10 mm (micro carcinoma) also increased. Those findings were associated with a significant decrease in tumor aggressiveness, determined by a low frequency of surgical margin involvement of thyroid capsule, perithyroid tissue invasion, vascular permeation and lymph node metastases., Conclusions: The increased prevalence of thyroid cancer, especially of micro carcinomas, may reflect the greater use of diagnostic ultrasound or represent a real change in the biological behavior of this disease and our data suggest that further studies are needed to know the impact of early treatment in the outcome of those patients because of the real less histologic agressiveness of micro carcinomas.

Rationale and Objectives: Thyroid nodules are common on ultrasonographic examination and are mostly benign. Ultrasound characteristics may help discriminate thyroid carcinoma (TC) from benign nodules. The aims of this study were to identify ultrasonographic characteristics associated with TC and to validate a previously proposed model based on the presence of three ultrasonographic characteristics., Materials and Methods: From a protocolized prospective registry of 1108 fine needle aspiration biopsies performed during a 16-month period at an ambulatory center, the ultrasonographic characteristics of TC and non-TC biopsies were compared. Adjusted odds ratios (ORs) and likelihood ratios for TC were estimated for eight combinations of three previously identified characteristics (microcalcifications, hypoechogenicity, and irregular borders)., Results: Microcalcifications (OR, 6.6; 95% confidence interval [CI], 4.4-9.9), hypoechogenicity (OR, 4.7; 95% CI, 2.8-8.0), and irregular borders (OR, 4.3; 95% CI, 2.8-6.5) were independently associated with TC. When added to a logistic regression model, the three ultrasonographic characteristics remained statistically significant. In the absence of these three features, the likelihood ratio for TC was 0.1 (95% CI, 0.0-0.2), while in their simultaneous presence, the likelihood ratio was 11 (95% CI, 6.6-19.0)., Conclusions: The absence or simultaneous presence of three simple ultrasonographic characteristics generates a large change of pretest probability of TC and could avoid unnecessary fine needle aspiration biopsy., (Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.)

Background: The aim of the surgical treatment of primary hyperparathyroidism (PHPT) is to achieve its complete cure, evidenced by normal serum calcium in the postoperative period. Measurement of intraoperative serum parathormone (PTH) can be useful to predict complete cure of the disease., Aim: To assess the usefulness of intraoperative PTH measurement to predict complete cure of PHPT., Material and Methods: Serum PTH was measured to all patients operated for PHPT between 2003 and 2008, before and five and ten minutes after the excision of the parathyroid gland causing the disease. The criteria for complete cure were normal serum calcium at 24 hours and 6 months after surgery and the pathological confirmation of parathyroid gland excision., Results: Eighty-eight operated patients, aged 58+/-15 years (72 females) were studied. Sixty four percent were asymptomatic and their preoperative serum calcium was 11.6+/- 1.2 mg/dl. A normal serum calcium was achieved in 86 patients (98%) at 24 hours and 50 of 52 patients followed for six months (96%). The pathological study disclosed an adenoma in 69 (78%), and multiglandular disease in 16 (18%), a parathyroid cancer in one and a normal gland in one patient. Intraoperative PTH predicted early and definitive cure in 97% and 100% of patients with a single adenoma, respectively. Among patients with multiglandular disease, the predictive figures were 94% and 100%, respectively., Conclusions: Intraoperative PTH measurement efficiently predicts early and definitive surgical cure of PHPT.

Background: Thyroid nodules are common and associated to a low risk of malignancy. Their clinical assessment usually includes a fine needle aspiration biopsy (FNAB)., Aim: To identify ultrasonographic characteristics associated to papillary thyroid carcinoma (PTC) and generate a score that predicts the risk of PTC., Material and Methods: Retrospective review of all fine needle aspiration biopsies of the thyroid performed in a lapse of two years. Biopsies that were conclusive for PTC were selected and compared with an equal amount of randomly selected biopsies that disclosed a benign diagnosis., Results: One hundred twenty two biopsies of a total of 1,498 were conclusive for PTC. Univariate analysis showed associations with PTC for the presence of micro-calcifications (Odds ratio (OR) 49.2: 95% confidence intervals (CI) 18.7-140.9), solid predominance (OR 25.1; 95% CI 6-220), hypoechogenicity (OR 23.5, 95% CI 6.5-122.6), irregular borders (OR 17, 95% CI 7.2-42.9), lymph node involvement (OR 12.3, 95% CI2.7-112), central vascularization (OR 12.2, 95% CI 4.8-33.3), local invasion and hyperechogenicity (OR 0.2; CI 95% CI 0.03-0.6). Multivariate analysis disclosed microcalcifications (OR 28.1; CI 95% 8.9-89), hypoechogenicity (OR 9.4; 95% CI 1.5-59.5) and irregular borders (OR 4.7; CI 95% 1.5-15) as the variables independently associated with the presence of PTC. The prevalence of PTC in the presence of the three variables was 97.6% (Likelihood ratio (LR) 45) and 5.4% in their absence (LR 0.06)., Conclusions: This scale predicts the presence or absence of PTC using simple ultrasound characteristics.

Background: Thyroid microcarcinoma is a tumor of 10 mm or less, that should have a low risk of mortality. However, a subgroup of these carcinomas is as aggressive as bigger tumors., Aim: To describe the pathological presentation of these tumors, and compare them with larger tumors., Material and Methods: All pathological samples of thyroid carcinoma that were obtained between 1992 and 2003, were studied. In all biopsies, the pathological type, tumor size, the focal or multifocal character, the presence of lymph node involvement and the presence of lymphocytic thyroiditis or thyroid hyperplasia, were recorded., Results: One hundred eighteen microcarcinomas and 284 larger tumors were studied. The mean age of patients with microcarcinoma and larger tumors was 42.7+/-14 and 49.3+/-16 years respectively (p <0,001) and 83% were female, without gender differences between tumor types. Mean size of microcarcinomas was 8.6 mm and 116 (98%) were papillary carcinomas. Of these, 109 (94%) were well differentiated and seven (6%) were moderately differentiated. Thirty six (31%) were multifocal and in 10 (8,6%), there was lymph node involvement. The mean size of larger tumors was 23.8 mm and 241 (85%) were papillary carcinomas. Of these, 200 (83%) were well differentiated, and 41 (17%) were moderately differentiated. Eighty five (35%) were multifocal and in 44 (18%) there was lymph node involvement. The prevalence of thyroiditis and hyperplasia was significantly higher among microcarcinomas than in larger tumors (15 and 2.5%, respectively, p <0.001, for the former; 32.4 and 1.7%, respectively, p <0.001, for the latter)., Conclusions: In this series, one third of microcarcinomas were multifocal and 10% had lymph node involvement. Therefore, the aggressiveness of these tumors is higher than what is reported in the literature and they should be treated with total thyroidectomy.

Primary hyperparathyroidism may occur as part of hereditary syndromes, including multiple endocrine neoplasia types 1 and 2A (MEN1 and MEN2A), hyperparathyroidism-jaw tumor syndrome, and the familial isolated hyperparathyroidism (FIHP). It is unclear whether FIHP corresponds to a different genetic entity or a variant of MEN1 (or hyperparathyroidism-jaw tumor syndrome). We report a patient and 11 family members with FIHP in whom we identified a heterozygous G-to-A mutation at nucleotide 7361 of tumor suppressor MEN1 gene. This mutation is located in the first base of intron 9 (IVS9 + 1 G>A). All the family members with hyperparathyroidism were heterozygous for the intronic mutation. In vitro studies were performed in COS cells transfected with minigenes carrying the coding regions spanning exon-intron 9 and 10 with the mutant and the wild-type sequences. RT-PCR analyses showed an abnormal mRNA of greater size (829 bp) in the mutated MEN1 gene than the normal transcript (629 bp). The longer PCR product includes the exon 9, the unspliced intron 9, and part of exon 10. RT-PCR of MEN1 mRNA from patient's blood confirmed the existence of unspliced intron 9 in mature mRNA. In summary, we report a case of FIHP associated with a new intronic heterozygous germline mutation (IVS9 + 1 G>A) of MEN1 gene. This mutation produces an aberrant splicing of mRNA that could lead to a truncated protein, without activity, explaining the clinical picture of this patient and his family.

We report a 29 years old woman with a highly symptomatic primary hyperparathyroidism. After parathyroid adenoma excision, she presented a prolonged and life threatening hypocalcemia, due to a severe hungry bone syndrome. Conventional treatment with oral and intravenous calcium and calcitriol supplementation failed to raise serum and urinary calcium or to relief symptoms. After one month, we indicated a continuous intravenous calcium infusion allowing, during 6 months, an adequate outpatient management. Initial T scores for bone density were markedly low (L2-L4: -3.14; femoral neck: -3.07) and they increased 17% after 18 days of calcium infusion. After 147 days of treatment bone density was normal, increasing by 61%. The present case shows that the hungry bone syndrome can be a real risk for patients and a complex therapeutic challenge. With an appropriate calcium supply an early, fast and complete recovery of bone mass can be achieved.

Experimental and clinical studies have shown that the administration of recombinant human growth hormone can improve deteriorated left ventricular function and hemodynamics in patients with heart failure. Herein, we compared the effects of growth hormone versus placebo upon resting left ventricular ejection fraction, exercise capacity and neurohormonal status in patients with advanced heart failure. Nineteen patients with advanced cardiac heart failure (ejection fraction <30%) were studied at baseline and after 8 weeks of treatment with growth hormone (0.03 U/kg per day) or placebo. Primary end points were resting left ventricular ejection fraction, peak oxygen consumption and neurohormonal status, including plasma norepinephrine levels and insulin like growth factor-1 and its binding protein-3. Results are presented as median and interquartile ranges. Patients receiving growth hormone had a significant increase in insulin growth factor-1 plasma levels (median difference growth hormone=83 ng/ml [57-170] versus placebo=-6 ng/ml [-23-6], P<0.05) and its binding protein-3. However, no significant increase in left ventricular ejection fraction after growth hormone treatment (ejection fraction pre=16% [13-18] and post=17% [14-27]) was noticed when compared to placebo (ejection fraction pre=20% [15-24] and post=20% [15-26]). Also, no significant effect of growth hormone treatment was seen on peak oxygen consumption or norepinephrine plasma levels. Although the administration of growth hormone to patients with advanced cardiac heart failure was associated with a significant increase in insulin growth factor-1, there were no significant changes in ejection fraction, exercise capacity and/or neurohormonal status.