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BackgroundThe Procalcitonin Antibiotic Consensus Trial (ProACT) found provision of a procalcitonin antibiotic prescribing guideline to hospital-based clinicians did not reduce antibiotic use. Possible reasons include clinician reluctance to follow the guideline, with an observed 64.8% adherence rate. In this study we sought to determine the threshold adherence rate for reduction in antibiotic use, and to explore opportunities to increase adherence.MethodsThis study is a retrospective analysis of ProACT data. ProACT randomized 1656 patients presenting to 14 U.S. hospitals with suspected lower respiratory tract infection to usual care or provision of procalcitonin assay results and an antibiotic prescribing guideline to the treating clinicians. We simulated varying adherence to guideline recommendations for low procalcitonin levels and determined which threshold adherence rate could have resulted in rejection of the null hypothesis of no difference between groups at alpha = 0.05. We also performed sensitivity analyses within specific clinical settings and grouped patients initially prescribed antibiotics despite low procalcitonin into low, medium, and high risk of illness severity or bacterial infection.ResultsOur primary outcome was number of antibiotic-days by day 30 using an intention-to-treat approach and a null hypothesis of no difference in antibiotic use. We determined that an 84% adherence rate in the hospital setting (emergency department and inpatient) for low procalcitonin could have allowed rejection of the null hypothesis (3.7 vs 4.3 antibiotic-days, p = 0.048). The threshold adherence rate was 76% for continued guideline adherence after discharge. Even 100% adherence in the emergency department alone failed to reduce antibiotic-days. Of the 218 patients prescribed antibiotics in the emergency department despite low procalcitonin, 153 (70.2%) were categorized as low or medium risk.ConclusionsHigh adherence in the hospital setting to a procalcitonin antibi

The article gives information about type 2 diabetes and bone mineral density in postmenopausal women.

The article gives information about type 2 diabetes and bone mineral density in postmenopausal women.

Medullary Thyroid Carcinoma (MTC) constitutes around 5% of all thyroid cancers. Trace elements assessment has emerged as a useful strategy in the diagnostics of MTC combined with Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Matrix Metalloproteinases (TIMPs) analysis. The aim of this study was to compare the presence and content of trace elements (i.e., Copper (Cu), Zinc (Zn), Iron (Fe), and Manganese (Mn)) in MTC with respect to control samples and their potential relationship with markers of MTC in tissues. The study included 26 patients who had undergone thyroidectomy, due to the diagnosis of MTC and 17 patients as control. We combined tumour pathology and staging, immunohistochemical analysis of calcitonin, MMPs, and TIMPs, with analytical biochemistry using Inductively Coupled Plasma – Mass Spectrometry (ICP-MS) to determine the levels of trace elements. No differences by MTC type for MMPs and their TIPMs, although strong TIMP-1 and TIMP-2 immunohistochemical expression of MTC were unveiled. Additionally, Zn, Fe, and Mn tended to be decreased, and Cu to be increased in samples presenting MTC with respect to controls. Moreover, Zn was the unique trace element which seemed to be correlated with MMPs and TIMPs. Trace elements such as Zn, Fe, and Mn are decreased in tissues affected by MTC. In addition, Zn may be the trace element which saves more relationship with the proportion and intensity of MMPs, being considered altogether useful biomarkers of MTC. We therefore suggest the analysis of novel and traditional markers of MTC as a novel approach in this pathology.

Thyroid nodules (TN) are localized morphological changes in the thyroid gland and can be benign or malignant.Objective: The present study investigates the relationships between biochemical markers in serum (s) and their homologs in washout (w) after fine-needle aspiration biopsy (FNAB) of the TN of interest and their correlation with cytology specimen findings.We investigated the relationships between serum biochemical markers nitric oxide (NO), thyroglobulin (TG), and calcitonin (CT), their homologs in washout after FNAB of the TN of interest, and cytology findings of biopsy samples classified according to the Bethesda system for thyroid cytopathology in this study, which included 86 subjects.Results: Washout TG (TGw) level positively correlates with the cytology finding of the biopsy. A higher level of TGw correlates with higher categories of the Bethesda classification and indicates a higher malignant potential. The levels of serum NO (NOs), serum TG (TGs), serum CT (CTs), and washout CT (CTw) do not correlate with the cytology finding of the biopsy, and the higher levels of washout NO (NOw) correspond to the more suspicious ultrasound findings.The findings of our study suggest that TGw and NOw could be used as potential predictors of malignancy in TN.

There are several endogenous molecules that can trigger migraine attacks when administered to humans. Notably, calcitonin gene-related peptide (CGRP) has been identified as a key player in a signalling cascade involved in migraine attacks, acting through the second messenger cyclic adenosine monophosphate (cAMP) in various cells, including intracranial vascular smooth muscle cells. However, it remains unclear whether intracellular cAMP signalling requires CGRP receptor activation during a migraine attack in humans. To address this question, we conducted a randomized, double-blind, placebo-controlled, parallel trial using a human provocation model involving the administration of CGRP and cilostazol in individuals with migraine pretreated with erenumab or placebo. Our study revealed that migraine attacks can be provoked in patients by cAMP-mediated mechanisms using cilostazol, even when the CGRP receptor is blocked by erenumab. Furthermore, the dilation of cranial arteries induced by cilostazol was not influenced by the CGRP receptor blockade. These findings provide clinical evidence that cAMP-evoked migraine attacks do not require CGRP receptor activation. This discovery opens up new possibilities for the development of mechanism-based drugs for the treatment of migraine., There are several endogenous molecules that can trigger migraine attacks when administered to humans. Notably, calcitonin gene-related peptide (CGRP) has been identified as a key player in a signalling cascade involved in migraine attacks, acting through the second messenger cyclic adenosine monophosphate (cAMP) in various cells, including intracranial vascular smooth muscle cells. However, it remains unclear whether intracellular cAMP signalling requires CGRP receptor activation during a migraine attack in humans. To address this question, we conducted a randomized, double-blind, placebo-controlled, parallel trial using a human provocation model involving the administration of CGRP and cilostazol in individuals with migraine pretreated with erenumab or placebo. Our study revealed that migraine attacks can be provoked in patients by cAMP-mediated mechanisms using cilostazol, even when the CGRP receptor is blocked by erenumab. Furthermore, the dilation of cranial arteries induced by cilostazol was not influenced by the CGRP receptor blockade. These findings provide clinical evidence that cAMP-evoked migraine attacks do not require CGRP receptor activation. This discovery opens up new possibilities for the development of mechanism-based drugs for the treatment of migraine.

There are several endogenous molecules that can trigger migraine attacks when administered to humans. Notably, calcitonin gene-related peptide (CGRP) has been identified as a key player in a signalling cascade involved in migraine attacks, acting through the second messenger cyclic adenosine monophosphate (cAMP) in various cells, including intracranial vascular smooth muscle cells. However, it remains unclear whether intracellular cAMP signalling requires CGRP receptor activation during a migraine attack in humans. To address this question, we conducted a randomized, double-blind, placebo-controlled, parallel trial using a human provocation model involving the administration of CGRP and cilostazol in individuals with migraine pretreated with erenumab or placebo. Our study revealed that migraine attacks can be provoked in patients by cAMP-mediated mechanisms using cilostazol, even when the CGRP receptor is blocked by erenumab. Furthermore, the dilation of cranial arteries induced by cilostazol was not influenced by the CGRP receptor blockade. These findings provide clinical evidence that cAMP-evoked migraine attacks do not require CGRP receptor activation. This discovery opens up new possibilities for the development of mechanism-based drugs for the treatment of migraine., There are several endogenous molecules that can trigger migraine attacks when administered to humans. Notably, calcitonin gene-related peptide (CGRP) has been identified as a key player in a signalling cascade involved in migraine attacks, acting through the second messenger cyclic adenosine monophosphate (cAMP) in various cells, including intracranial vascular smooth muscle cells. However, it remains unclear whether intracellular cAMP signalling requires CGRP receptor activation during a migraine attack in humans. To address this question, we conducted a randomized, double-blind, placebo-controlled, parallel trial using a human provocation model involving the administration of CGRP and cilostazol in individuals with migraine pretreated with erenumab or placebo. Our study revealed that migraine attacks can be provoked in patients by cAMP-mediated mechanisms using cilostazol, even when the CGRP receptor is blocked by erenumab. Furthermore, the dilation of cranial arteries induced by cilostazol was not influenced by the CGRP receptor blockade. These findings provide clinical evidence that cAMP-evoked migraine attacks do not require CGRP receptor activation. This discovery opens up new possibilities for the development of mechanism-based drugs for the treatment of migraine.

Osteoclast (OC) abnormalities represent osteoporosis's critical mechanism (OP). OCs undergo multiple processes that range from monocytic to functional. Different drugs target OCs at different developmental stages; however, almost no Suitable drug-targeted delivery systems exist. Therefore, we designed two dual-targeting nanoparticles to target OCs at different functional stages. Using the calcitonin gene-related peptide receptor (CGRPR), which OC precursors highly express, and specific TRAPpeptides screened in the bone resorption lacuna, where mature OCs function, respectively, two types of dual-targeted nanoparticles were constructed. Afterwards, nanoparticles were grafted with hyaluronic acid (HA), which specifically binds to CD44 on the surface of the OCs. In vivo and in vitro experiments show that both nanoparticles have noticeable targeting effects on OCs. This suggests that dual-targeting nanoparticles designed for different functional periods of OC can be well targeted to the corresponding OC, and further promote the more precise delivery of drugs used to treat OP., QC 20221214

Introduction: Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignant tumor derived from the parafollicular cells or thyroid C cells. At the time of diagnosis, over 50% of patients have lymph node metastases, and 10% have distant metastases. Prognosis is largely dependent on tumor stage and, therefore, early diagnosis is essential. Objective: The aim of this work is to present an updated review of the diagnostic approach for MTC. Summary: Thyroid ultrasound is the main tool used for thyroid nodule stratification; however, most studies have focused on papillary thyroid carcinoma. In MTC, ultrasonographic findings suggestive of malignancy are usually less frequent and this could delay diagnosis and treatment. Therefore ultrasound examination should be combined with additional diagnostic techniques. The sensitivity of the fine-needle aspiration cytology is generally low for these types of tumors and when MTC is suspected, it is recommended to perform immunohistochemical for calcitonin and measurement of calcitonin in washout fluid of thyroid nodule aspirate. Serum calcitonin is the most sensitive marker for diagnosing this condition; however, its routine measurement in the evaluation of thyroid nodule is controversial. Serum calcitonin levels are related to C-cell mass and the presence of lymph node metastases. When these levels are above 500 pg/mL suggest distant metastatic disease and additional imaging procedures are indicated. Genetic testing should be offered to all patients because 25% of these carcinomas are hereditary and are part of multiple endocrine neoplasia type 2 syndrome associated with a germline RET mutation., Introducción: El carcinoma medular de tiroides (CMT) es un tumor maligno neuroendocrino poco frecuente derivado de las células parafoliculares o células C del tiroides. En el momento del diagnóstico presentan metástasis ganglionares más del 50% y a distancia el 10%. Su pronóstico depende en gran parte del estadio del tumor, por lo que su diagnóstico temprano es fundamental. Objetivo: El objetivo de este trabajo es realizar una revisión actualizada sobre el abordaje diagnóstico del CMT. Síntesis: La ecografía es la principal herramienta en la estratificación del nódulo tiroideo, pero la mayor parte de los estudios se han centrado en el carcinoma papilar de tiroides. En el caso del CMT las características ecográficas sospechosas de malignidad suelen ser menos frecuentes y esto podría conducir a un retraso diagnóstico y terapéutico, por lo que se debe combinar con técnicas diagnósticas adicionales. En estos tumores la sensibilidad del estudio citológico del nódulo mediante punción aspiración con aguja fina generalmente es baja, y en aquellos casos de sospecha de CMT se recomienda realizar inmunohistoquímica para calcitonina y determinar la calcitonina en el aspirado de la punción. La calcitonina plasmática es el marcador más sensible para el diagnóstico de estos pacientes, pero su determinación rutinaria en el estudio del nódulo tiroideo es controvertida. Sus niveles se relacionan con la masa de células C y la presencia de metástasis ganglionares. Si son superiores a 500 pg/ml se recomienda realizar estudio de extensión con pruebas de imagen complementarias por sospecha de enfermedad metastásica. Es importante solicitar estudio genético a todos los pacientes, ya que el 25% son hereditarios formando parte de la neoplasia endocrina múltiple tipo 2 asociada a mutación en el gen RET.

The hormones amylin and calcitonin interact with receptors within the same family to exert their effects on the human organism. Calcitonin, derived from thyroid C cells, is known for its inhibitory effect on osteoclasts. Calcitonin of mammalian origin promotes insulin sensitivity, while the more potent calcitonin extracted from salmon additionally inhibits gastric emptying, promotes gallbladder relaxation, increases energy expenditure and induces satiety as well as weight loss. Amylin, derived from pancreatic beta cells, regulates plasma glucose by delaying gastric emptying after meal ingestion, and modulates glucagon secretion and central satiety signals in the brain. Thus, both hormones seem to have metabolic effects of relevance in the context of non-alcoholic fatty liver disease (NAFLD) and other metabolic diseases. In rats, studies with dual amylin and calcitonin receptor agonists have demonstrated robust body weight loss, improved glucose tolerance and a decreased deposition of fat in liver tissue beyond what is observed after a body weight loss. The translational aspects of these preclinical data currently remain unknown. Here, we describe the physiology, pathophysiology, and pharmacological effects of amylin and calcitonin and review preclinical and clinical findings alluding to the future potential of amylin and calcitonin-based drugs for the treatment of obesity and NAFLD.

The hormones amylin and calcitonin interact with receptors within the same family to exert their effects on the human organism. Calcitonin, derived from thyroid C cells, is known for its inhibitory effect on osteoclasts. Calcitonin of mammalian origin promotes insulin sensitivity, while the more potent calcitonin extracted from salmon additionally inhibits gastric emptying, promotes gallbladder relaxation, increases energy expenditure and induces satiety as well as weight loss. Amylin, derived from pancreatic beta cells, regulates plasma glucose by delaying gastric emptying after meal ingestion, and modulates glucagon secretion and central satiety signals in the brain. Thus, both hormones seem to have metabolic effects of relevance in the context of non-alcoholic fatty liver disease (NAFLD) and other metabolic diseases. In rats, studies with dual amylin and calcitonin receptor agonists have demonstrated robust body weight loss, improved glucose tolerance and a decreased deposition of fat in liver tissue beyond what is observed after a body weight loss. The translational aspects of these preclinical data currently remain unknown. Here, we describe the physiology, pathophysiology, and pharmacological effects of amylin and calcitonin and review preclinical and clinical findings alluding to the future potential of amylin and calcitonin-based drugs for the treatment of obesity and NAFLD.

Calcitonin, a potent hypocalcemic hormone, plays a vital role in inhibiting osteoclastic activities and suppressing bone removal. The physiological characteristics of calcitonin have long been discussed, along a few recommending calcitonin as a vestigial hormone. The basis for this article is to discuss the role of low and high levels of calcitonin in normal and osteoprotic bone turnover. The effect of calcitonin on the receptor activator of nuclear factor kappa-ligand and osteoclasts has been demonstrated using numerical simulations. This behavior recommends that treatment of osteoporosis via calcitonin does not provide the required upshots. For effectiveness calcitonin must be advised along with a combined therapy like aspirin which agrees with the experimental results available in the literature.

Medullary thyroid cancer is the third most common thyroid malignancy. It originates from the parafollicular or calcitonin-producing C cells and it presents a high prevalence of advanced cases at diagnosis. Can be presented as sporadic or familial, in 75% and 25% of cases, respectively: genetic screening of RET oncogene can distinguish the two forms. Calcitonin is the specific serum marker and it is one of the most important prognostic factors both for survival and progression of the disease. Approximately 30% of MTC patients arrive at first observation when already metastatic. The early identification of gene carriers allows their early thyroidectomy and their definitive cure. An accurate evaluation of the case must be performed by a multidisciplinary team to choose the drug and to follow-up the patient., El carcinoma medular de tiroides es la tercera patología maligna tiroidea más frecuente. Tiene su origen en las células parafoliculares productoras de calcitonina y presenta una elevada prevalencia de enfermedad avanzada al diagnóstico. Puede presentarse de forma esporádica o familiar, con un 75% y 25% respectivamente: el screening genético del oncogen RET permite distinguir las dos formas. La calcitonina es el marcador sérico específico y es el factor pronóstico más importante en la supervivencia y progresión de la enfermedad. Aproximadamente el 30% de los pacientes con carcinoma medular presentan metástasis al diagnóstico. La identificación temprana de los portadores del oncogen RET y la tiroidectomía precoz es el tratamiento definitivo. La evaluación de los casos debe llevarse a cabo por un equipo multidiciplinar, siendo necesario la individualización de los fármacos y seguimiento de cada paciente.

Objective: New Daily Persistent Headache (NDPH) is a distinct clinical syndrome which can represent a primary headache disorder or be secondary in aetiology, such as an antecedent viral trigger. NDPH can be bland or be accompanied by migrainous symptoms like photophobia; it's as yet unclear how the endophenotype influences therapeutic response. There are two published cases of a flavivirus, Dengue, causing NDPH, but not yet Zika virus (ZV). This single case report of NDPH secondary to ZV aims to track the clinical progress of multiple medical and interventional management strategies. Method(s): The clinical notes were reviewed regarding the headache semiology, other symptoms of note and comorbidities. The patient was investigated to ensure there were no persistent foci of infection utilising magnetic resonance imaging and repeated lumbar puncture. Response to treatments were measured with a headache diary and Headache Impact Test Score (HIT-6). Result(s): This 63 year-old man acquired ZV infection in the Cook Islands in March 2014, confirmed with a positive ZV neutralisation test. Prior to infection there was no personal or family history of migraine. During follow-up investigations there was no demonstrable evidence of ongoing infection. His headaches with migrainous features were not responsive to the triptan class of medications. Since the acute presentation, headache persisted every hour of every day, irrespective of any of the 17 prophylactic treatments trialled. Erenumab 140 mg every 28 days was the only treatment to give a 50% reduction in the migraine days-defined as moderate to severe headache associated with sensitivity to light and noise and movement sensitivity-at both 3 and 6 month follow-up. His ability to exercise and function improved significantly. The HIT-6 score improved from a baseline of 64 to 56 at three months and 36 at six months subsequent to the initiation of erenumab treatment. Conclusion(s): This is the first reported case of ZV triggerin

У статті висвітлена роль сироваткових пухлинних маркерів у діагностиці та лікуванні захворювань щитоподібної залози, передусім різних форм раку. Систематизовано клінічні показання до призначення та сучасні рекомендації щодо оцінки результатів визначення тиреоглобуліну, кальцитоніну, раково-ембріонального антигена. Наведено перспективи використання тестів на прокальцитонін, хромогранін А, а також окремих молекулярно-генетичних досліджень., The article highlights the role of serum tumor markers in the diagnosis and treatment of thyroid diseases, primarily various forms of cancer. Clinical indications for the prescription and current recommendations for evaluating the results of thyroglobulin, calcitonin, and carcinoembryonic antigen determination are systematized. Prospects for the use of procalcitonin, chromogranin A tests, as well as individual molecular genetic studies are presented., В статье освещена роль сывороточных опухолевых маркеров в диагностике и лечении заболеваний щитовидной железы, прежде всего различных форм рака. Систематизированы клинические показания к назначению и современные рекомендации по оценке результатов определения тиреоглобулина, кальцитонина, раково-эмбрионального антигена. Указаны перспективы использования тестов на прокальцитонин, хромо­гранин А, а также отдельных молекулярно-генетических исследований.

Objective: New Daily Persistent Headache (NDPH) is a distinct clinical syndrome which can represent a primary headache disorder or be secondary in aetiology, such as an antecedent viral trigger. NDPH can be bland or be accompanied by migrainous symptoms like photophobia; it's as yet unclear how the endophenotype influences therapeutic response. There are two published cases of a flavivirus, Dengue, causing NDPH, but not yet Zika virus (ZV). This single case report of NDPH secondary to ZV aims to track the clinical progress of multiple medical and interventional management strategies. Method(s): The clinical notes were reviewed regarding the headache semiology, other symptoms of note and comorbidities. The patient was investigated to ensure there were no persistent foci of infection utilising magnetic resonance imaging and repeated lumbar puncture. Response to treatments were measured with a headache diary and Headache Impact Test Score (HIT-6). Result(s): This 63 year-old man acquired ZV infection in the Cook Islands in March 2014, confirmed with a positive ZV neutralisation test. Prior to infection there was no personal or family history of migraine. During follow-up investigations there was no demonstrable evidence of ongoing infection. His headaches with migrainous features were not responsive to the triptan class of medications. Since the acute presentation, headache persisted every hour of every day, irrespective of any of the 17 prophylactic treatments trialled. Erenumab 140 mg every 28 days was the only treatment to give a 50% reduction in the migraine days-defined as moderate to severe headache associated with sensitivity to light and noise and movement sensitivity-at both 3 and 6 month follow-up. His ability to exercise and function improved significantly. The HIT-6 score improved from a baseline of 64 to 56 at three months and 36 at six months subsequent to the initiation of erenumab treatment. Conclusion(s): This is the first reported case of ZV triggerin

Migraine is a common neurological disorder that afflicts up to 15% of the adult population in most countries, with predominance in females. It is characterized by episodic, often disabling headache, photophobia and phonophobia, autonomic symptoms (nausea and vomiting), and in a subgroup an aura in the beginning of the attack. Although still debated, many researchers consider migraine to be a disorder in which CNS dysfunction plays a pivotal role while various parts of the trigeminal system are necessary for the expression of associated symptoms.Treatment of migraine has in recent years seen the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are now approved for use in frequent episodic and in chronic migraine. CGRP-related therapies offer considerable improvements over existing drugs, as they are the first to be designed specifically to act on the trigeminal pain system: they are more specific and have little or no adverse effects. Small molecule CGRP receptor antagonists, gepants, are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (Eptinezumab, Fremanezumab, and Galcanezumab) or the CGRP receptor (Erenumab) effectively prevent migraine attacks. The neurobiology of CGRP signaling is briefly summarized together with key clinical evidence for the role of CGRP in migraine headache, including the efficacy of CGRP-targeted treatments.

Until the 1950s, the first results in the studies of calcitonin-thy-rocalcitonin were ignored in the accepted research scheme. However, it was José Fernández Nonídez from the Spanish School of Histology, died in Augusta (Georgia, USA) in 1947, whose expertise in the parafollicular cells of the mammalian thyroid had led him to an advanced understanding of this separate endocrine organ, which secretes calcitonin. The antecedent of the secretion was present in the cytoplasm of these cells, which Nonídez explained in a paper published in 1932. In 1973, a Spanish group from the Instituto Gregorio Marañón (Madrid) leading the research into the ectopic production of calcitonin identified the precursor responsible for its biosynthesis. Nonetheless, given the informal power in connection with the communication between the scientists, this significative contribution was absolutely discarded in terms of acknowledgment within their social circle. The services responsible for dissemination of scientific knowledge considered that priority should be given to another group of young scientists dedicated to pro-calcitonin evidence. The nature and extent of informal communication are highlighted in countries with different measures to guarantee the autonomy and independence of their state powers. Irrespectively of political circumstances, the paper is focused on the competition between two different approaches in science particularly important for progress in medicine: the perspective presented by experimental studies in basic sciences (in animals) and the models developed in clinical sciences.

BackgroundThe effect of procalcitonin-guided use of antibiotics on treatment for suspected lower respiratory tract infection is unclear.MethodsIn 14 U.S. hospitals with high adherence to quality measures for the treatment of pneumonia, we provided guidance for clinicians about national clinical practice recommendations for the treatment of lower respiratory tract infections and the interpretation of procalcitonin assays. We then randomly assigned patients who presented to the emergency department with a suspected lower respiratory tract infection and for whom the treating physician was uncertain whether antibiotic therapy was indicated to one of two groups: the procalcitonin group, in which the treating clinicians were provided with real-time initial (and serial, if the patient was hospitalized) procalcitonin assay results and an antibiotic use guideline with graded recommendations based on four tiers of procalcitonin levels, or the usual-care group. We hypothesized that within 30 days after enrollment the total antibiotic-days would be lower - and the percentage of patients with adverse outcomes would not be more than 4.5 percentage points higher - in the procalcitonin group than in the usual-care group.ResultsA total of 1656 patients were included in the final analysis cohort (826 randomly assigned to the procalcitonin group and 830 to the usual-care group), of whom 782 (47.2%) were hospitalized and 984 (59.4%) received antibiotics within 30 days. The treating clinician received procalcitonin assay results for 792 of 826 patients (95.9%) in the procalcitonin group (median time from sample collection to assay result, 77 minutes) and for 18 of 830 patients (2.2%) in the usual-care group. In both groups, the procalcitonin-level tier was associated with the decision to prescribe antibiotics in the emergency department. There was no significant difference between the procalcitonin group and the usual-care group in antibiotic-days (mean, 4.2 and 4.3 days, respectively

BackgroundThe effect of procalcitonin-guided use of antibiotics on treatment for suspected lower respiratory tract infection is unclear.MethodsIn 14 U.S. hospitals with high adherence to quality measures for the treatment of pneumonia, we provided guidance for clinicians about national clinical practice recommendations for the treatment of lower respiratory tract infections and the interpretation of procalcitonin assays. We then randomly assigned patients who presented to the emergency department with a suspected lower respiratory tract infection and for whom the treating physician was uncertain whether antibiotic therapy was indicated to one of two groups: the procalcitonin group, in which the treating clinicians were provided with real-time initial (and serial, if the patient was hospitalized) procalcitonin assay results and an antibiotic use guideline with graded recommendations based on four tiers of procalcitonin levels, or the usual-care group. We hypothesized that within 30 days after enrollment the total antibiotic-days would be lower - and the percentage of patients with adverse outcomes would not be more than 4.5 percentage points higher - in the procalcitonin group than in the usual-care group.ResultsA total of 1656 patients were included in the final analysis cohort (826 randomly assigned to the procalcitonin group and 830 to the usual-care group), of whom 782 (47.2%) were hospitalized and 984 (59.4%) received antibiotics within 30 days. The treating clinician received procalcitonin assay results for 792 of 826 patients (95.9%) in the procalcitonin group (median time from sample collection to assay result, 77 minutes) and for 18 of 830 patients (2.2%) in the usual-care group. In both groups, the procalcitonin-level tier was associated with the decision to prescribe antibiotics in the emergency department. There was no significant difference between the procalcitonin group and the usual-care group in antibiotic-days (mean, 4.2 and 4.3 days, respectively

BackgroundOveruse of antibiotics is a major public health problem, contributing to growing antibiotic resistance. Procalcitonin has been reported to be commonly elevated in bacterial, but not viral infection. Multiple European trials found procalcitonin-guided care reduced antibiotic use in lower respiratory tract infection, with no apparent harm. However, applicability to US practice is limited due to trial design features impractical in the US, between-country differences, and residual safety concerns.MethodsThe Procalcitonin Antibiotic Consensus Trial (ProACT) is a multicenter randomized trial to determine the impact of a procalcitonin antibiotic prescribing guideline, implemented with basic reproducible strategies, in US patients with lower respiratory tract infection.DiscussionWe describe the trial methods using the Consolidated Standards of Reporting Trials (CONSORT) framework, and the rationale for key design decisions, including choice of eligibility criteria, choice of control arm, and approach to guideline implementation.Trial registrationClinicalTrials.gov NCT02130986 . Registered May 1, 2014.

IntroductionPatients with cardiogenic shock (CS) are at a high risk of developing infectious complications; however, their early detection is difficult, mainly due to a frequently occurring noninfectious inflammatory response, which accompanies an extensive myocardial infarction (MI) or a postcardiac arrest syndrome. The goal of our prospective study was to describe infectious complications in CS and the immune/inflammatory response based on a serial measurement of several blood-based inflammatory biomarkers.MethodsEighty patients with CS were evaluated and their infections were monitored. Inflammatory markers (C-reactive protein, procalcitonin, pentraxin 3, presepsin) were measured seven times per week. The control groups consisted of 11 patients with ST segment elevation myocardial infarction without CS and without infection, and 22 patients in septic shock.ResultsInfection was diagnosed in 46.3% of patients with CS; 16 patients developed an infection within 48 h. Respiratory infection was most common, occurring in 33 out of 37 patients. Infection was a significant or even the main reason of death only in 3.8% of all patients with CS, and we did not find statistically significant difference in 3-month mortality between group of patients with CS with and without infection. There was no statistically significant prolongation of the duration of mechanical ventilation associated with infection. Strong inflammatory response is often in patients with CS due to MI, but we found no significant difference in the course of the inflammatory response expressed by evaluated biomarkers in patients with CS with and without infection. We found a strong relationship between the elevated inflammatory markers (sampled at 12 h) and the 3-month mortality: the area under the curve of receiver operating characteristic ranged between 0.683 and 0.875.ConclusionThe prevalence of infection in patients with CS was 46.3%, and respiratory tract infections were the most common type. Infections

BackgroundOveruse of antibiotics is a major public health problem, contributing to growing antibiotic resistance. Procalcitonin has been reported to be commonly elevated in bacterial, but not viral infection. Multiple European trials found procalcitonin-guided care reduced antibiotic use in lower respiratory tract infection, with no apparent harm. However, applicability to US practice is limited due to trial design features impractical in the US, between-country differences, and residual safety concerns.MethodsThe Procalcitonin Antibiotic Consensus Trial (ProACT) is a multicenter randomized trial to determine the impact of a procalcitonin antibiotic prescribing guideline, implemented with basic reproducible strategies, in US patients with lower respiratory tract infection.DiscussionWe describe the trial methods using the Consolidated Standards of Reporting Trials (CONSORT) framework, and the rationale for key design decisions, including choice of eligibility criteria, choice of control arm, and approach to guideline implementation.Trial registrationClinicalTrials.gov NCT02130986 . Registered May 1, 2014.

IntroductionPatients with cardiogenic shock (CS) are at a high risk of developing infectious complications; however, their early detection is difficult, mainly due to a frequently occurring noninfectious inflammatory response, which accompanies an extensive myocardial infarction (MI) or a postcardiac arrest syndrome. The goal of our prospective study was to describe infectious complications in CS and the immune/inflammatory response based on a serial measurement of several blood-based inflammatory biomarkers.MethodsEighty patients with CS were evaluated and their infections were monitored. Inflammatory markers (C-reactive protein, procalcitonin, pentraxin 3, presepsin) were measured seven times per week. The control groups consisted of 11 patients with ST segment elevation myocardial infarction without CS and without infection, and 22 patients in septic shock.ResultsInfection was diagnosed in 46.3% of patients with CS; 16 patients developed an infection within 48 h. Respiratory infection was most common, occurring in 33 out of 37 patients. Infection was a significant or even the main reason of death only in 3.8% of all patients with CS, and we did not find statistically significant difference in 3-month mortality between group of patients with CS with and without infection. There was no statistically significant prolongation of the duration of mechanical ventilation associated with infection. Strong inflammatory response is often in patients with CS due to MI, but we found no significant difference in the course of the inflammatory response expressed by evaluated biomarkers in patients with CS with and without infection. We found a strong relationship between the elevated inflammatory markers (sampled at 12 h) and the 3-month mortality: the area under the curve of receiver operating characteristic ranged between 0.683 and 0.875.ConclusionThe prevalence of infection in patients with CS was 46.3%, and respiratory tract infections were the most common type. Infections

Background: Single soft tissue metastasis of medullary thyroid carcinoma is extremely rare. In addition, several occult medullary thyroid carcinomas with distant metastasis were reported, but undetectable primary lesion at diagnosis was also extremely rare. Case presentation: A 74-year-old man was admitted to our hospital because of a painful nodule in his left buttock for over 1 year. Needle biopsy was performed, and the histological findings revealed adenocarcinoma positive for thyroid transcription factor-1. No evidence of a primary tumor, including the lung and thyroid gland, could be found elsewhere despite detailed examinations, including thyroid echography, chest computed tomography, and fluorodeoxyglucose-positron emission tomography. The soft tissue tumor was resected with a wide margin. Immunohistochemical analysis showed the tumor cells to be positive for cytokeratin-AE1/3, cytokeratin 7, synaptophysin, chromogranin A, calcitonin, and carcinoembryonic antigen, but negative for cytokeratin 20, Napsin A, Pax8, and p40, resulting in a diagnosis of metastasis of medullary thyroid carcinoma. Conclusion: Initial presentation with a single metastasis to soft tissue and undetectable primary tumor in the thyroid gland is an extremely rare clinical manifestation in patients with medullary thyroid carcinoma., Article, World journal of surgical oncology 15(1) : 221(2017)

Background and purposeChronic infections and cardiac dysfunction are risk factors for stroke. We hypothesized that blood biomarkers of infection (procalcitonin) and cardiac dysfunction (midregional proatrial natriuretic peptide [MR-proANP]), previously associated with small vessel stroke and cardioembolic stroke are also associated with subclinical cerebrovascular damage, including silent brain infarcts and white matter hyperintensity volume.MethodsThe NOMAS (Northern Manhattan Study) was designed to assess risk factors for incident vascular disease in a multiethnic cohort. A subsample underwent brain magnetic resonance imaging and had blood samples available for biomarker measurement (n=1178). We used logistic regression models to estimate the odds ratios and 95% confidence intervals (95% CIs) for the association of these biomarkers with silent brain infarcts after adjusting for demographic, behavioral, and medical risk factors. We used linear regression to assess associations with log-white matter hyperintensity volume.ResultsMean age was 70±9 years; 60% were women, 66% Hispanic, 17% black, and 15% were white. After adjusting for risk factors, subjects with procalcitonin or MR-proANP in the top quartile, compared with the lowest quartile were more likely to have silent brain infarcts (adjusted odds ratio for procalcitonin, 2.2; 95% CI, 1.3-3.7 and for MR-proANP, 3.3; 95% CI, 1.7-6.3) and increased white matter hyperintensity volume (adjusted mean change in log-white matter hyperintensity volume for procalcitonin, 0.29; 95% CI, 0.13-0.44 and for MR-proANP, 0.18; 95% CI, 0.004-0.36).ConclusionsHigher concentrations of procalcitonin, a marker of infection, and MR-proANP, a marker of cardiac dysfunction, are independently associated with subclinical cerebrovascular damage. If further studies demonstrate an incremental value for risk stratification, biomarker-guided primary prevention studies may lead to new approaches to prevent cerebrovascular disease.

Calcitonin (CT) is a hormone that decreases serum calcium level by suppressing osteoclastic activity in the vertebrate bone. In vertebrates, the structure-function relationship of CTs has been studied extensively. We recently identified three CT superfamily peptides, Bf-CTFP1 to 3, and clarified the molecular and functional characteristics of their receptor and receptor activity-modifying protein in amphioxus, Branchiostoma floridae. However, the CT activity of Bf-CTFPs has yet to be investigated. In the present study, a functional analysis of Bf-CTFPs was performed using goldfish scales having both osteoclasts and osteoblasts. All Bf-CTFPs suppressed osteoclastic activity via a goldfish CT receptor. Although the primary amino acid sequences of the Bf-CTFPs showed low sequence similarity to vertebrate CTs, Bf-CTFP1 to 3 share three amino acids, Thr25, Thr27, and Pro32-NH2, that are required for receptor binding, with salmon CT. Moreover, homology model analysis revealed that the Bf-CTFPs form alpha-helical structures. The alpha-helical position and length of Bf-CTFP1 and 2 were conserved with those of a highly potent ligand, teleost CT. Interestingly, the composition of the alpha-helix of Bf-CTFP3 differed from those of teleost CT, despite that the action of Bf-CTFP3 on goldfish scales was the same as that of Bf-CTFP1 and 2. Collectively, the present study provides new insights into the structure-function relationship of CT and its functional evolution in chordates. © 2017 Elsevier Inc., Embargo Period 12 months

Among the four different types of thyroid cancer, treatment of medullary thyroid carcinoma poses a major challenge because of its propensity of early metastasis. To further investigate the molecular mechanisms of medullary thyroid carcinoma and discover candidates for targeted therapies, we developed a new mouse model of medullary thyroid carcinoma based on our CGRPCreER mouse line. This system enables gene manipulation in parafollicular C cells in the thyroid, the purported cells of origin of medullary thyroid carcinoma. Selective inactivation of tumor suppressors, such as p53, Rb, and Pten, in mature parafollicular C cells via an inducible Cre recombinase from CGRPCreER led to development of murine medullary thyroid carcinoma. Loss of Pten accelerated p53/Rb-induced medullary thyroid carcinoma, indicating interactions between pathways controlled by tumor suppressors. Moreover, labeling differentiated parafollicular C cells by CGRPCreER allows us to follow their fate during malignant transformation to medullary thyroid tumor. Our findings support a model in which mutational events in differentiated parafollicular C cells result in medullary thyroid carcinoma. Through expression analysis including RNA-Seq, we uncovered major signaling pathways and networks that are perturbed following the removal of tumor suppressors. Taken together, these studies not only increase our molecular understanding of medullary thyroid carcinoma but also offer new candidates for designing targeted therapies or other treatment modalities.

Background: Single soft tissue metastasis of medullary thyroid carcinoma is extremely rare. In addition, several occult medullary thyroid carcinomas with distant metastasis were reported, but undetectable primary lesion at diagnosis was also extremely rare. Case presentation: A 74-year-old man was admitted to our hospital because of a painful nodule in his left buttock for over 1 year. Needle biopsy was performed, and the histological findings revealed adenocarcinoma positive for thyroid transcription factor-1. No evidence of a primary tumor, including the lung and thyroid gland, could be found elsewhere despite detailed examinations, including thyroid echography, chest computed tomography, and fluorodeoxyglucose-positron emission tomography. The soft tissue tumor was resected with a wide margin. Immunohistochemical analysis showed the tumor cells to be positive for cytokeratin-AE1/3, cytokeratin 7, synaptophysin, chromogranin A, calcitonin, and carcinoembryonic antigen, but negative for cytokeratin 20, Napsin A, Pax8, and p40, resulting in a diagnosis of metastasis of medullary thyroid carcinoma. Conclusion: Initial presentation with a single metastasis to soft tissue and undetectable primary tumor in the thyroid gland is an extremely rare clinical manifestation in patients with medullary thyroid carcinoma., Article, World journal of surgical oncology 15(1) : 221(2017)

UVOD: Kolorektalna anastomoza koja se formira u dubini karlice radi uspostavljanja kontinuiteta gastrointestinalnog trakta nakon resekcije dijela crijeva ima svoje specifičnosti u toku formiranja, zarastanja, kao i kada se jave komplikacije. Na sam proces zarastanja kolorektalnih anastomoza utiču sistemski, lokalni i tehnički faktori. Bilo kakav kompromis po pitanju ovih principa nosi povećan rizik od komplikacija! Najteža komplikacija na anastomozi je dehiscencija. „Samo neučinjena anastomoza neće dehiscirati“. Ova stara hirurška poslovica je važeća i danas, a što je anastomoza distalnija, mogućnost dehiscencije je veća, posebno kod niskih subperitonealnih anastomoza sa rektumom ili anusom. Učestalost dehiscencija ovih anastomoza u literaturi varira od 0,5 - 69 %, što može ukazivati na kvalitet hirurškog rada, korišćenje definicije dehiscencije, način dijagnostike, itd. Međunarodna grupa za karcinom rektuma definisala je dehiscenciju anastomoze kao defekt crijevnog zida, uključujući šavnu ili staplersku liniju neorektalnog rezervoara, što dovodi do komunikacije između intra i ekstra luminalnog prostora. CILJEVI: Osnovni cilj ove studije je bio da se utvrde preoperativni i perioperativni faktori rizika značajni za nastanak dehiscencija kolorektalnih anastomoza, kao i značaj prokalcitonina i C-reaktivnog proteina u detekciji dehiscencija kolorektalnih anastomoza u subkliničkoj fazi bolesti. MATERIJAL I METODOLOGIJA: Istraživanjem je obuhvaćeno 100 pacijenata operisanih u elektivnom programu, kod kojih je urađena radikalna operacija karcinoma rektuma uz kreiranje dvostruke staplerske kolorektalne anastomoze. Svi pacijenti uključeni u istraživanje, odabrani metodom slučajnog izbora, bili su podijeljeni u dvije grupe. Grupa A: pacijenti kod kojih je urađena radikalna operacija karcinoma rektuma i kreirana primarna staplerska kolorektalna anastomoza. Grupa B: pacijenti kod kojih je urađena radikalna operacija karcinoma rektuma Hartmanovom procedurom u prvom aktu, a rekon, INTRODUCTION: Colorectal anastomosis, which is formed deep in the pelvis because of establishment of continuity of gastrointestinal tract after resection of the part of intestines, has got its specifities during forming and healing process and when complications occur. Systemic, local and technical factors influence the healing process of anastomosis itself. Any kind of compromise in terms of these principles causes higher risk of complications! The most serious complication of anastomosis is dehiscence. “Only anastomosis which is not carried out will not dehisce.” This old surgical saying is still true, and the more distal anastomosis is, the possibility of development of dehiscence is higher, especially in lower subperitoneal anastomosis with rectum and anus. Incidence of dehiscence of these anastomosis in literature varies from 0,5 to 69 %, which may indicate the quality of surgical work, use of definition of dehiscence, kind of diagnostics etc. International group for rectal cancer defined dehiscence of anastomosis as a defect of intestinal wall, including suturing or stapler line of neorectal reservoir, which leads to communication between intra and extra luminal space. AIMS: Basic aim of this study was to determine preoperative and postoperative risk factors significant for the development of dehiscence of colorectal anastomosis, as well as significance of procalcitonin and C-reactive protein in detection of dehiscence of colorectal anastomosis at the subclinical stage of the disease. MATERIAL AND METHODOLOGY: The study included 100 patients operated on in the elective programme, on which radical operation of the rectal cancer was carried out with creation of double stapler colorectal anastomosis. All patients included in the study were randomly chosen and divided into two groups. Group A: the patients on which radical operation of the rectal cancer was carried out and primary stapler colorectal anastomosis created. Group B: the patients on which radical opera

BackgroundMultiple endocrine neoplasia type 2 is an autosomal dominant inherited syndrome caused by activating mutations in the RET proto-oncogene. The RETK666N DNA variant was previously reported in two isolated medullary thyroid carcinoma (MTC) cases, but no family studies are available, and its oncogenic significance remains unknown.MethodsThe clinical features, genetic data, and family information of eight index MTC patients with a germline RETK666N variant were assessed.ResultsFour probands presented with MTC and extensive nodal metastasis, one with biopsy-confirmed distant metastasis. Two additional probands presented with localized disease. However, nodal status was not available. Of the final two probands, one had an incidental 1.5 mm MTC and C-cell hyperplasia uncovered after surgery for papillary thyroid carcinoma, and one had two foci of MTC (largest dimension 2.3 cm) detected after surgery for dysphagia. Genetic screening identified 16 additional family members carrying the K666N variant (aged 5-90 years), 11 of whom have documented evaluation for MTC. Of these, only two were found to have elevated basal serum calcitonin upon screening, and the remaining patients had calcitonin levels within the reference range. One patient who elected to have a thyroidectomy at 70 years of age was confirmed to have MTC. The other subject, 57 years old, elected surveillance. Four prophylactic thyroidectomies were performed, with one case of C-cell hyperplasia at 20 years and three cases that revealed normal pathology at ages 21, 30, and 30 years. None of the K666N DNA variant carriers had evidence of primary hyperparathyroidism or pheochromocytoma.ConclusionsFrom this case series, the largest such experience to date, it is concluded that the RETK666N variant is likely pathogenic and associated with low penetrance of MTC. However, the findings are insufficient to define its pathogenicity clearly and make firm recommendations for screening and treatment. Given the potentia

type:Original Article, identifier:http://igakkai.kms-igakkai.com/wp/wp-content/uploads/1987en/13(3)103-109.1987.pdf

Background: Intervertebral disc (IVD) degeneration and pathological changes in the spinal cord are major causes of back pain. In addition to its well-established anti-resorptive effect on bone, calcitonin (CT) potentially exerts protective effects on IVD degeneration in ovariectomized rats. However, possible therapeutic effects of CT on lumbar fusion-induced adjacent-segment disc degeneration (ASDD) have not been investigated yet. In this study, we examined the effects of CT on IVD degeneration adjacent to a lumbar fusion in ovariectomized rats. Methods: Posterolateral lumbar fusion (PLF) at L4-5 was performed 4 weeks after ovariectomy (OVX) or sham surgery in female Sprague-Dawley rats. Following PLF + OVX, rats received either salmon CT (OVX + PLF + sCT, 16 IU/Kg/2d) or vehicle (OVX + PLF + V) treatment for 12 weeks; the remaining rats were divided into Sham + V, OVX + V, and PLF + V groups. Fusion status was analyzed by manual palpation and radiography. Adjacent segment disc was assessed by histological, histomorphometric, immunohistochemical analysis. L6 vertebrae microstructures were evaluated by micro-computed tomography. Results: Histological analysis showed more severe ASDD occurred in OVX + PLF + V rats compared with the OVX + V or PLF + V groups. CT treatment suppressed the score for ASDD, increased disc height, and decreased the area of endplate calcification. Immunohistochemical staining demonstrated that CT decreased the expression of collagen type-I, matrix metalloproteinase-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4, whereas it increased the expression of collagen type-II and aggrecan in the disc. Micro-computed tomography indicated that CT increased bone mass and improved the microstructure of the L6 vertebrae. Conclusions: These results suggest that CT can prevent ASDD, induce beneficial changes in IVD metabolism, and inhibit deterioration of the trabecular microarchitecture of vertebrae in osteoporotic rats with lumbar

Background: Intervertebral disc (IVD) degeneration and pathological changes in the spinal cord are major causes of back pain. In addition to its well-established anti-resorptive effect on bone, calcitonin (CT) potentially exerts protective effects on IVD degeneration in ovariectomized rats. However, possible therapeutic effects of CT on lumbar fusion-induced adjacent-segment disc degeneration (ASDD) have not been investigated yet. In this study, we examined the effects of CT on IVD degeneration adjacent to a lumbar fusion in ovariectomized rats. Methods: Posterolateral lumbar fusion (PLF) at L4-5 was performed 4 weeks after ovariectomy (OVX) or sham surgery in female Sprague-Dawley rats. Following PLF + OVX, rats received either salmon CT (OVX + PLF + sCT, 16 IU/Kg/2d) or vehicle (OVX + PLF + V) treatment for 12 weeks; the remaining rats were divided into Sham + V, OVX + V, and PLF + V groups. Fusion status was analyzed by manual palpation and radiography. Adjacent segment disc was assessed by histological, histomorphometric, immunohistochemical analysis. L6 vertebrae microstructures were evaluated by micro-computed tomography. Results: Histological analysis showed more severe ASDD occurred in OVX + PLF + V rats compared with the OVX + V or PLF + V groups. CT treatment suppressed the score for ASDD, increased disc height, and decreased the area of endplate calcification. Immunohistochemical staining demonstrated that CT decreased the expression of collagen type-I, matrix metalloproteinase-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4, whereas it increased the expression of collagen type-II and aggrecan in the disc. Micro-computed tomography indicated that CT increased bone mass and improved the microstructure of the L6 vertebrae. Conclusions: These results suggest that CT can prevent ASDD, induce beneficial changes in IVD metabolism, and inhibit deterioration of the trabecular microarchitecture of vertebrae in osteoporotic rats with lumbar

Thyroid C-cells produce calcitonin (CT), a hypocalcemic hormone, that acts as an inhibitor of bone resorption. In this study, we investigated the effects of tamoxifen (TAM) as a selective estrogen receptor modulator on thyroid C-cells, trabecular bone and biochemical markers of bone metabolism in an animal model of androgen deficiency, represented by middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were divided into: Orx and sham-operated (SO) groups. Rats from one Orx group were injected subcutaneously with TAM citrate (Orx + TAM; 0.3 mgkg(-1) b.w.), while the rats from SO and a second Orx group received vehicle alone, once a day for 3 weeks. The peroxidase-antiperoxidase method was applied for localization of CT in C-cells. Thyroid C-cells were morphometrically and ultrastructurally analyzed. An ImageJ image-processing program was used to measure bone histomorphometric parameters. Blood serum samples were analyzed for CT, osteocalcin (OC), calcium (Ca2+) and phosphorus (P). Urinary Ca2+ concentrations were measured. TAM treatment significantly increased thyroid C-cell volume (V-c) and serum CT when compared with vehicle-treated Orx rats. Analysis of trabecular microarchitecture of the tibia showed that administration of TAM significantly increased cancellous bone area, trabecular thickness and trabecular number, whereas trabecular separation was significantly decreased compared with vehicle-treated Orx rats. Serum OC and urinary Ca2+ concentrations were significantly lower in comparison with the control Orx group. These results indicate that in our rat model of androgen deficiency, TAM stimulated calcitonin-producing thyroid C-cells and increased trabecular bone mass.

The plasma concentrations of calcium, phosphate, and magnesium are dependent on the net balance of bone mineral deposition and resorption, intestinal absorption, and renal excretion. These ions are important for many biologic and cellular functions such as intracellular signaling, neural transmission, and muscle contraction. The principal hormones regulating the homeostasis of these processes are parathyroid hormone (PTH), calcitonin, 1.25-dihydroxy vitamin D and fibroblast growth factor-23 (FGF-23). Through their actions on bone, kidney and the gastrointestinal tract, the calciotropic hormones (parathyroid hormone, calcitonin, and vitamin D metabolites, especially the 1.25-dihydroxy vitamin D) act to maintain serum calcium within a normal range, that allows the optimally function of many calcium-requiring physiological functions. The improved procedures for the assays of different components of mineral and bone metabolism are useful in understanding their role in health and disease. This paper provides a review of the physiology, clinical and analytic aspects of these protagonists in bone and mineral metabolism., Las concentraciones plasmáticas de calcio, fósforo y magnesio dependen del balance neto del depósito mineral óseo y su resorción, la absorción intestinal y la excreción renal. Estos iones son importantes para muchas funciones biológicas y celulares como la señalización intracelular, la transmisión neural y la contracción muscular. Las principales hormonas que regulan la homeostasis de estos procesos son la hormona paratiroidea (PTH), la calcitonina, la 1,25-dihidroxi vitamina D y el factor de crecimiento fibroblástico-23 (FGF- 23). A través de sus acciones e interacciones sobre el hueso, el riñón y el tracto gastrointestinal las hormonas calciotrópicas (la hormona paratiroidea, la calcitonina y los metabolitos de la vitamina D, especialmente la 1,25-dihidroxi vitamina D) actúan para mantener la calcemia dentro de un rango normal, lo que permite el funcionamiento óptimo de muchos procesos fisiológicos dependientes de calcio. Los avances en las técnicas de análisis de los diferentes componentes del metabolismo mineral y óseo son útiles en la comprensión de su papel en la salud y la enfermedad. En este artículo se ofrece una revisión de los aspectos fisiológicos, clínicos y analíticos de estos protagonistas en el metabolismo óseo y mineral.

Introduction: Sepsis is the leading cause of morbidity and mortality in neonates; however, due to the low specificity of signs and symptoms in this population the early clinical diagnosis is considered difficult. Objectives: to evaluate the usefulness of procalcitonin for the diagnosis of sepsis in neonates with presumptive diagnosis of sepsis. Materials and methods: A descriptive prospective study was made in patients from zero to 30 days of born that were admitted to the Neonatal Care Unit from Clínica El Rosario (Medellin, Colombia), headquarters Centro and headquarters El Tesoro, between September 2010 and September 2011, with suspicious of neonatal sepsis or that presented a compatible clinical with sepsis during their permanence. Results: From 65 captured neonates, it was confirmed a clinical diagnosis of sepsis in 39 (60%). No significant differences were observed between neonates with and without sepsis related to clinical and haematological parameters or morphological abnormalities in erythrocytes. The median values of the infection markers evaluated, C-reactive protein and procalcitonin, were significantly higher in neonates with sepsis, as well as the proportion of procalcitonin and C-reactive protein results interpreted as abnormal according to the reference values, that in the case of procalcitonin were adjusted according with the hours since birth. Conclusions: The results of this study demonstrate that acute phase reactants such as C-reactive protein and procalcitonin are the best indicators of neonatal sepsis., Introducción: La sepsis es la principal causa de morbi-mortalidad en neonatos; sin embargo, debido a la poca especificidad de los signos clínicos en esta población el diagnóstico clínico precoz se considera difícil. Objetivos: evaluar la utilidad de la procalcitonina para el diagnóstico de sepsis en neonatos con diagnóstico presuntivo de esta. Materiales y métodos: se realizó un estudio descriptivo prospectivo en pacientes entre cero y 30 días de nacidos que ingresaron a las Unidades de Cuidados Neonatales de la Clínica El Rosario, sede Centro y sede El Tesoro (Medellín, Colombia), durante septiembre de 2010 y septiembre de 2011, con sospecha de sepsis neonatal o que presentaron un cuadro compatible durante su permanencia. Resultados: de los 65 neonatos captados se confirmó el diagnóstico clínico de sepsis en 39 (60%). No se encontraron diferencias significativas entre los grupos de neonatos con y sin sepsis respecto a los signos clínicos, parámetros hematológicos o la presencia de alteraciones morfológicas en los eritrocitos. La mediana de los marcadores de infección evaluados, procalcitonina y proteína C reactiva, fueron significativamente superiores en los neonatos con sepsis, así como la proporción de los resultados de procalcitonina y proteína C reactiva interpretados como anormales de acuerdo a los valores de referencia que, en el caso de la procalcitonina, fueron ajustados de acuerdo a las horas transcurridas desde el nacimiento. Conclusiones: los resultados de este estudio demuestran que los reactantes de fase aguda como la procalcitonina y proteína C reactiva son los mejores indicadores de sepsis en neonatos.

The duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD. METHODS AND FINDINGS: We investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe ECOPD. For this multicenter, randomized, non-inferiority trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in Italy. Patients were assigned to receive antibiotics for 10 days (standard group) or for either 3 or 10 days (PCT group). The primary outcome was the rate of ECOPD at 6 months. Having planned to recruit 400 patients, we randomized only 183: 93 in the PCT group and 90 in the standard group. Thus, the completed study was underpowered. The ECOPD rate at 6 months between PCT-guided and standard antibiotic treatment was not significant (% difference, 4.04; 90% confidence interval [CI], -7.23 to 15.31), but the CI included the non-inferiority margin of 15. In the PCT-guided group, about 50% of patients were treated for 3 days, and there was no difference in primary or secondary outcomes compared to patients treated for 10 days. CONCLUSIONS: Although the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group, the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT cannot be substantiated statistically. Thus, the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the standard antibiotic treatment. The study was funded by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH). Clinical trial registered with www.clinicaltrials.gov (NCT01125098). TRIAL REGISTRATION: ClinicalTrials.gov NCT01125098., journal.pone.0118241 Background The duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD. Methods and Findings We investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe ECOPD. For this multicenter, randomized, non-inferiority trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in Italy. Patients were assigned to receive antibiotics for 10 days (standard group) or for either 3 or 10 days (PCT group). The primary outcome was the rate of ECOPD at 6 months. Having planned to recruit 400 patients, we randomized only 183: 93 in the PCT group and 90 in the standard group. Thus, the completed study was underpowered. The ECOPD rate at 6 months between PCT-guided and standard antibiotic treatment was not significant (% difference, 4.04; 90% confidence interval [CI], -7.23 to 15.31), but the CI included the non-inferiority margin of 15. In the PCT-guided group, about 50% of patients were treated for 3 days, and there was no difference in primary or secondary outcomes compared to patients treated for 10 days. Conclusions Although the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group, the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT cannot be substantiated statistically. Thus, the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the standard antibiotic treatment. The study was funded by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH). Clinical trial registered with www.clinicaltrials.gov (NCT01125098).

Thyroid C-cells produce calcitonin (CT), a hypocalcemic hormone, that acts as an inhibitor of bone resorption. In this study, we investigated the effects of tamoxifen (TAM) as a selective estrogen receptor modulator on thyroid C-cells, trabecular bone and biochemical markers of bone metabolism in an animal model of androgen deficiency, represented by middle-aged orchidectomized (Orx) rats. Fifteen-month-old male Wistar rats were divided into: Orx and sham-operated (SO) groups. Rats from one Orx group were injected subcutaneously with TAM citrate (Orx + TAM; 0.3 mgkg(-1) b.w.), while the rats from SO and a second Orx group received vehicle alone, once a day for 3 weeks. The peroxidase-antiperoxidase method was applied for localization of CT in C-cells. Thyroid C-cells were morphometrically and ultrastructurally analyzed. An ImageJ image-processing program was used to measure bone histomorphometric parameters. Blood serum samples were analyzed for CT, osteocalcin (OC), calcium (Ca2+) and phosphorus (P). Urinary Ca2+ concentrations were measured. TAM treatment significantly increased thyroid C-cell volume (V-c) and serum CT when compared with vehicle-treated Orx rats. Analysis of trabecular microarchitecture of the tibia showed that administration of TAM significantly increased cancellous bone area, trabecular thickness and trabecular number, whereas trabecular separation was significantly decreased compared with vehicle-treated Orx rats. Serum OC and urinary Ca2+ concentrations were significantly lower in comparison with the control Orx group. These results indicate that in our rat model of androgen deficiency, TAM stimulated calcitonin-producing thyroid C-cells and increased trabecular bone mass.

Background: Intervertebral disc (IVD) degeneration and pathological changes in the spinal cord are major causes of back pain. In addition to its well-established anti-resorptive effect on bone, calcitonin (CT) potentially exerts protective effects on IVD degeneration in ovariectomized rats. However, possible therapeutic effects of CT on lumbar fusion-induced adjacent-segment disc degeneration (ASDD) have not been investigated yet. In this study, we examined the effects of CT on IVD degeneration adjacent to a lumbar fusion in ovariectomized rats. Methods: Posterolateral lumbar fusion (PLF) at L4-5 was performed 4 weeks after ovariectomy (OVX) or sham surgery in female Sprague-Dawley rats. Following PLF + OVX, rats received either salmon CT (OVX + PLF + sCT, 16 IU/Kg/2d) or vehicle (OVX + PLF + V) treatment for 12 weeks; the remaining rats were divided into Sham + V, OVX + V, and PLF + V groups. Fusion status was analyzed by manual palpation and radiography. Adjacent segment disc was assessed by histological, histomorphometric, immunohistochemical analysis. L6 vertebrae microstructures were evaluated by micro-computed tomography. Results: Histological analysis showed more severe ASDD occurred in OVX + PLF + V rats compared with the OVX + V or PLF + V groups. CT treatment suppressed the score for ASDD, increased disc height, and decreased the area of endplate calcification. Immunohistochemical staining demonstrated that CT decreased the expression of collagen type-I, matrix metalloproteinase-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4, whereas it increased the expression of collagen type-II and aggrecan in the disc. Micro-computed tomography indicated that CT increased bone mass and improved the microstructure of the L6 vertebrae. Conclusions: These results suggest that CT can prevent ASDD, induce beneficial changes in IVD metabolism, and inhibit deterioration of the trabecular microarchitecture of vertebrae in osteoporotic rats with lumbar

BACKGROUND AND OBJECTIVE: In low and middle-income countries where HIV infection is prevalent, identifying patients at high risk of dying from lower respiratory tract infections is challenging and validated prognostic models are lacking. Serum procalcitonin may be a useful prognostic tool in these settings. We sought to determine if elevated serum procalcitonin is associated with increased in-hospital mortality and to combine serum procalcitonin with available clinical characteristics to create a clinically useful prognostic model. METHODS: We conducted a prospective, nested case-control study of 241 HIV-infected adults admitted to Mulago Hospital in Kampala, Uganda with cough ≥2 weeks in duration. We collected demographic and clinical information, baseline serum for procalcitonin analysis, and followed patients to determine in-hospital mortality. RESULTS: Serum procalcitonin was a strong and independent predictor of inpatient mortality (aOR = 7.69, p = 0.01, sensitivity = 93%, negative predictive value = 97%). Best subset multivariate analysis identified 3 variables that were combined into a prognostic model to risk stratify patients; these variables included respiratory rate ≥30 breaths/minute (aOR = 2.07, p = 0.11), oxygen saturation <90% (aOR = 3.07, p = 0.02), and serum procalcitonin >0.5 ng/ml (aOR = 7.69, p = 0.01). The predicted probability of inpatient mortality ranged from 1% when no variables were present, to 42% when all variables were present. CONCLUSIONS: Elevated serum procalcitonin >0.5 ng/ml is an independent predictor of in-hospital mortality. Elevated serum procalcitonin, tachypnea, and hypoxemia may be combined into a prognostic model to identify patients at high risk of dying in the hospital. This model may be used to estimate the probability of death and to guide triage and treatment decisions.