[Procalcitonin as sepsis predictor in cardiovascular surgery with cardiopulmonary bypass]. / Procalcitonina como predictor de sepsis en cirugía cardiovascular con circulación extracorpórea.

Background: Cardiopulmonary bypass generates an exacerbated response that may lead to sepsis. Objective: To describe the association between procalcitonin levels and sepsis diagnosis in cardiovascular surgery subjects with cardiopulmonary bypass. Methods: A case-series study was conducted in 142 patients. Serum procalcitonin levels were measured at 24 hours and at 72 hours after surgery using a point of care testing based on quantitative immunochromatographic method. To assess association between procalcitonin levels and sepsis status, we calculated area under the curve (AUC) and sensitivity, specificity, and predictive values for the best cut-off point. Results: From 142 patients studied, 7 developed sepsis after surgery (4.9%). For 24-hours procalcitonin levels AUC was 0.921 and best cut-off point was 3.8 ng/mL (sensitivity 0.857 and specificity 0.904). In the case of 72-hours procalcitonin levels, we observed a value of 0.868 for AUC and best cut-off point was 8.4 ng/mL (sensitivity 0.86 and specificity 0.97). Conclusions: Procalcitonin levels at 24 and 72 hours after cardiovascular surgery with cardiopulmonary bypass are associated with sepsis presence at cut-off points of 3.8 and 8.4 ng/mL respectively.

Introducción: la circulación extracorpórea durante la cirugía cardiovascular genera una respuesta exacerbada que puede asociarse con sepsis. Objetivo: describir la asociación entre los niveles de procalcitonina y el diagnóstico de sepsis en sujetos de cirugía cardiovascular con circulación extracorpórea. Material y métodos: se realizó un estudio de serie de casos en 142 pacientes. Los niveles de procalcitonina fueron medidos a las 24 horas y a las 72 horas después de la cirugía. Para evaluar la asociación entre los niveles de procalcitonina y la identificación de sepsis, se calculó el área bajo la curva (AUC) y la sensibilidad y especificidad identificando el mejor punto de corte. Resultados: de un total de 142 pacientes estudiados, 7 desarrollaron sepsis (4.9%). En los niveles de procalcitonina en las 24 horas, el AUC fue de 0.921 y el mejor punto de corte fue 3.8 ng/mL (sensibilidad de 0.857 y especificidad de 0.904). En el caso de los niveles de procalcitonina a las 72 horas, observamos un AUC de 0.868 y el mejor punto de corte fue 8.4 ng/mL (sensibilidad de 0.86 y especificidad de 0.97). Conclusiones: los niveles de procalcitonina a las 24 y 72 horas de la cirugía cardiovascular con circulación extracorpórea se asociaron con la presencia de sepsis con los puntos de corte de 3.8 ng/mL y 8.4 ng/mL respectivamente.

Respuesta de procalcitonina ante co-infección e infección secundaria por bacterias multirresistentes en pacientes COVID -19 / Procalcitonin response in co-infection and secondary infection by multidrug resistant bacteria in COVID -19 patients

INTRODUCCIÓN. La procalcitonina, es un biomarcador que puede usarse como apoyo diagnóstico en infecciones bacterianas y la monitorización del tratamiento antibiótico, sobre todo en pacientes con sepsis. De ahí que, fue utilizado durante la pandemia COVID-19 OBJETIVO. Determinar los valores de procalcitonina en pacientes con COVID-19 y definir una p osible correlación entre su incremento y vinculación en coinfección o infección secundaria por Klebsiella pneumoniae y Pseudomonas aeruginosa con multidrogo resistencia y resistencia extendida a los antibióticos. MATERIALES Y MÉTODOS. Estudio retrospectivo observacional, descriptivo transversal, realizado del 1 de mayo al 31 de octubre del 2020 en el Hospital de Especialidades Carlos Andrade Marín sobre 7028 pacientes adultos, hospitalizados, con diagnóstico de COVID-19, y resultados de procalcitonina, cuyas muestras de secreción traqueal y/o hemocultivo presentaron desarrollo de Klebsiella pneumoniae y Pseudomonas aeruginosa. Su análisis estadístico fue desarrollado mediante la prueba Chi Cuadrado de Pearson. RESULTADOS. Se recibieron 861 muestras de hemocultivo y 391 de secreción traqueal, obteniéndose: 32% aislamientos de Klebsiella pneumoniae y Pseudomonas aeruginosa multidrogo y extremadamente resistente. Entre los pacientes COVID-19 que fallecieron, 34,4% mostraron incrementos de procalcitonina. Al contrario, entre los pacientes que sobrevivieron sólo en 8,8% se observó incrementos de procalcitonina evidenciándose un vínculo entre el incremento de procalcitonina y mortalidad. CONCLUSIONES. No existe diferencia en relación al incremento en los valores de procalcitonina en pacientes COVID-19 con co-infección o infección secundaria por Klebsiella pneumoniae y Pseudomonas aeruginosa multidrogo y extremadamente resistente y los valores de procalcitonina en pacientes con coinfección e infección secundaria con otro tipo de aislamientos bacterianos.

INTRODUCTION. Procalcitonin is a biomarker that can be used as a diagnostic support in bacterial infections and the monitoring of antibiotic treatment, especially in patients with sepsis. Hence, it was used during the COVID-19 pandemic OBJECTIVE. To determine the values of procalcitonin in patients with COVID-19 and to define a possible correlation between its increase and linkage in co-infection or secondary infection by Klebsiella pneumoniae and Pseudomonas aeruginosa with multidrug resistance and extended resistance to antibiotics. MATERIALS AND METHODS. Retrospective observational, descriptive cross-sectional study, conducted from May 1 to October 31, 2020 at the Hospital de Especialidades Carlos Andrade Marín on 7028 adult patients, hospitalized, with diagnosis of COVID-19, and procalcitonin results, whose tracheal secretion and/or blood culture samples presented development of Klebsiella pneumoniae and Pseudomonas aeruginosa. Their statistical analysis was developed using Pearson's Chi-squared test. RESULTS. We received 861 blood culture and 391 tracheal secretion samples, obtaining: 32% isolates of Klebsiella pneumoniae and multidrug-resistant and extremely resistant Pseudomonas aeruginosa. Among the COVID-19 patients who died, 34.4% showed increased procalcitonin levels. On the contrary, among patients who survived, only 8.8% showed increased procalcitonin levels, showing a link between increased procalcitonin levels and mortality. CONCLUSIONS. There is no difference in relation to the increase in procalcitonin values in COVID-19 patients with co-infection or secondary infection by Klebsiella pneumoniae and multidrug-resistant and extremely resistant Pseudomonas aeruginosa and procalcitonin values in patients with co-infection and secondary infection with other types of bacterial isolates.

[Translated article] Consensus recommendations on the preventive treatment of migraine.

OBJECTIVE: The objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. METHODOLOGY: Recommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into 3 themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analysed through different metrics. RESULTS: After both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving 1 statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). CONCLUSIONS: The high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine.

Characteristics of hospitalized patients with hypercalcemia in the province of Malaga: a longitudinal, retrospective, multicenter study.

BACKGROUND AND OBJECTIVE: There are limited studies analyzing hypercalcemia in hospitalized patients. Our objectives were to describe the clinical characteristics of hospitalized patients with hypercalcemia, estimate its prevalence in the hospital setting, analyze the rate of correction of hypercalcemia, and identify prognostic variables. MATERIALS AND METHODS: Observational, longitudinal, retrospective, and bicentric study. Adult patients admitted to two hospitals in Málaga (2014-2018) with a diagnosis of hypercalcemia were included. The minimum follow-up was 2 years or until death. RESULTS: A total of 205 patients with hypercalcemia were included (incidence: 0.13%). The mean age (SD) was 68.2 (13.1) years, with a predominance of males (55.1%). The median (IQR) serum calcium at admission was 13.1 (11.8-14.6) mg/dl. The most common etiologies were neoplasms (75.1%), primary hyperparathyroidism, and medications (both 8.8%). The median (IQR) follow-up period was 5.1 (1.7-60.3) weeks. The most commonly used treatments were fluid therapy (86.8%), loop diuretics (70.9%), bisphosphonates (60.7%), and glucocorticoids (46.2%). The rate of correction of hypercalcemia was 65.2%, with a median (IQR) of 6 (3-10) days. The mortality rate was 81.5%. The median (95% CI) survival was 5.1 (3-7.3) weeks. Factors associated with higher mortality were advanced age, neoplastic etiology, serum calcium at admission, and failure to correct hypercalcemia. CONCLUSIONS: Hypercalcemia in hospitalized patients is mainly due to neoplastic processes and is associated with high mortality. We observed a low rate of adherence to recommendations for the management of hypercalcemia.

Beyond the Recommendations of the Clinical Guidelines for Medullary Thyroid Cancer - A Case Report / Más allá de las recomendaciones de las guías clínicas de cáncer medular de tiroides - a propósito de un caso

Medullary thyroid cancer (MTC) is a rare disease from parafollicular C cells. Calcitonin has been suggested as a screening; its levels are proportional to the tumor size and predictive of metastatic disease. We present a case where an early action was taken with lower cut-off points. Male patient, 49 years old. Thyroid ultrasound (US) with a suspicious nodule. Fine Needle Aspiration Biopsy (FNAB) suggests MTC, with pre-operative serum calcitonin (CTN) of 591 pg/mL. Total thyroidectomy with central and bilateral dissection was performed. Biopsy: MTC in left nodule of 26 mm without lymph nodes (LN) metastases. Follow-up with undetectable CTN for six years. After that, CT was 4.7 pg/mL, and carcinoembryonic antigen (CEA) was 1.2 ng/mL. Neck US showed bilateral LN. FNAB of LN does not show recurrence. A progressive rise of markers with doubling time of CTN and CEA was 16 and 51.3 months, respectively. CTN raised until 112 pg/mL. Given the lack of cervical compromise, a neck and lung CT, liver MRI, and bone scintigraphy were ordered despite CTN levels < 150 pg/mL. MRI showed hypervascular hepatic lesions, contrasted with gadoxetic acid. PET Ga68-DOTATATE showed lesions with overexpression of somatostatin receptors in the liver. Surgery was done, and a biopsy confirmed metastases. Conclusions: The clinical guidelines may allow the management of cases; however, they should be used considering each case context. In our patient, if the guidelines had been strictly followed, it would not have been possible to detect liver metastases to achieve a surgical resection with curative intent.

Paciente masculino, 49 años. Ecografía tiroidea con nódulo sospechoso. Biopsia por aspiración con aguja fina (PAAF) sugiere cáncer medular de tiroides (CMT), calcitonina sérica preoperatoria (CTN) de 591 pg/mL. Se realizó tiroidectomía total con disección central y bilateral. Biopsia: CMT en nódulo tiroideo izquierdo de 2,6 cm sin metástasis en 29 ganglios linfáticos (GL). En el seguimiento, CTN sérica indetectable durante 6 años. Posteriormente CTN sérica de 4,7 pg/mL y antígeno carcinoembrionario (CEA) de 1,2 ng/mL. Ecografía cervical de control mostró GL subcentimétricos bilaterales en grupo IV. PAAF de GL sin evidencia de malignidad, con niveles de CTN indetectables en la muestra. El doblaje de CTN y CEA fue 16 y 51,3 meses respectivamente. Dado ausencia de compromiso cervical, se solicitó TC de cuello y tórax, RM hepática y gammagrafía ósea, a pesar de no presentar niveles de CTN > 150 pg/mL. La RM mostró 3 lesiones hepáticas hipervasculares; se complementa con un PET Ga-DOTATATE que mostró 2 lesiones focales con sobreexposición de receptores de somatostatina en el parénquima hepático, con SUVmáx de 6,8 y 7,3. Se realiza cirugía extirpando 5 lesiones; la biopsia confirmó metástasis de CMT. Conclusiones: Las guías clínicas pueden dar orientaciones generales y permitir el manejo de casos basados en la evidencia; sin embargo, siempre deben usarse considerando el contexto de cada caso en particular. Si se hubieran seguido estrictamente las pautas, no habría sido posible detectar las metástasis hepáticas dentro de la ventana de oportunidad para lograr una resección quirúrgica con intención curativa.

Consensus recommendations for the treatment of migraine prevention. / Recomendaciones de consenso para el tratamiento de la prevención de la migraña.

OBJECTIVE: The objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-CGRP monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. METHODOLOGY: Recommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into three themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analyzed through different metrics. RESULTS: After both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving one statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). CONCLUSIONS: The high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-CGRP monoclonal antibodies in the treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine.

Avaliação da procalcitonina como tecnologia de saúde a ser incorporada em um hospital universitário para redução de tempo de tratamento com antimicrobianos / Evaluation of procalcitonin as a health technology to be incorporated in a university hospital to reduce treatment time with antimicrobials

Introdução: O uso do biomarcador procalcitonina (PCT) de forma racionalizada pode contribuir para reduzir o uso excessivo de antimicrobianos, poupar recursos e qualificar o cuidado com o paciente. Objetivo: Avaliar a eficácia da PCT na redução do tempo de tratamento com antimicrobianos e o impacto financeiro e factibilidade da incorporação desta tecnologia a partir de cenários simulados em um hospital de pequeno porte e média complexidade. Material e Métodos: Revisão da literatura, a partir da base de dados Pubmed seguida de análise de custo em quatro cenários simulados, comparando o PCR com a PCT. Foram incluídos ensaios clínicos randomizados e revisões sistemáticas cuja intervenção consistia no uso de PCT para guiar o tempo de tratamento com antimicrobianos. A seleção e extração dos dados foi realizada por quatro revisores independentes. A análise de custo foi realizada por meio de cenários simulados com os antimicrobianos de maior impacto na instituição totalizando doze terapias analisadas, a partir de dados de custos efetivamente desembolsados. Resultados: Foram selecionados 8 artigos para a análise final. A PCT possibilitou redução significativa de tempo de tratamento, redução de mortalidade, tempo de internação, eventos adversos e custos. A simulação de custo demonstrou que o cenário com PCT foi mais econômico para 67% das terapias analisadas, chegando à uma economia de até R$567,86 por tratamento, no caso da terapia combinada com meropenem, vancomicina e polimixina. Conclusão: A terapia guiada pela PCT reduz tempo de tratamento, internação e mortalidade apresentando impacto considerável na redução dos custos diretos, sendo factível a sua incorporação no cenário analisado

Introduction: The use of the procalcitonin (PCT) biomarker in a rationalized manner can contribute to reducing the excessive usage of antimicrobial, saving resources and improving patient care. Objective: To evaluate the effectiveness of PCT in reducing antimicrobial treatment time and the financial impact and feasibility of incorporating this technology based on simulated scenarios in a small and medium-complexity hospital. Material and Methods: Literature review, based on the Pubmed database followed by cost analysis in four simulated scenarios, comparing PCR with PCT test. Randomized clinical trials and systematic reviews whose intervention consisted of the use of PCT to guide the duration of antimicrobial treatment were included. Data selection and extraction was carried out by four independent reviewers. The cost analysis was carried out through simulated scenarios with the twelve therapies with the greatest impact on the institution, based on data of costs actually disbursed. Results: The final analysis included 8 articles. PCT resulted in significant reduction of duration of antibiotic treatment, reduction in mortality, length of stay, adverse events and costs. The cost simulation demonstrated that the PCT scenario was more economical for 67% of therapies analyzed, reaching savings up to R$567.86 per treatment, in the case of combined therapy with meropenem, vancomycin and polymyxin.Conclusion: PCT-guided therapy reduces treatment duration, hospitalization and mortality, presenting a considerable impact on reducing direct costs, making it feasible to incorporate it into the analyzed scenario.

Distribution of calcitonin gene-related peptide and vascular endothelial growth factor in the mouse lung at the embryonic and postnatal stages / Distribución del péptido relacionado con el gen de la calcitonina y el factor de crecimiento endotelial vascular en el pulmón de ratón en las etapas embrionaria y posnatal

SUMMARY: Neuropeptide calcitonin gene-related peptide (CGRP) is a neurotransmitter related to vasculogenesis during organ development. The vascular endothelial growth factor A (VEGF-A) is also required for vascular patterning during lung morphogenesis. CGRP is primarily found in organs and initially appears in pulmonary neuroendocrine cells during the early embryonic stage of lung development. However, the relationship between CGRP and VEGF-A during lung formation remains unclear. This study investigates CGRP and VEGF-A mRNA expressions in the embryonic, pseudoglandular, canalicular, saccular, and alveolar stages of lung development from embryonic day 12.5 (E12.5) to postnatal day 5 (P5) through quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization. Further, we analyzed the expression of CGRP via immunohistochemistry. The VEGF-A mRNA was mainly scattered across the whole lung body from E12.5. CGRP was found to be expressed in a few epithelial cells of the canalicular and the respiratory bronchiole of the lung from E12.5 to P5. An antisense probe for CGRP mRNA was strongly detected in the lung from E14.5 to E17.5. Endogenous CGRP may regulate the development of the embryonic alveoli from E14.5 to E17.5 in a temporal manner.

El péptido relacionado con el gen de la calcitonina (CGRP) es un neurotransmisor vinculado con la vasculogénesis durante el desarrollo de órganos. El factor de crecimiento endotelial vascular A (VEGF-A) también se requiere para el patrón vascular durante la morfogénesis pulmonar. El CGRP se encuentra principalmente en los órganos y aparece inicialmente en las células neuroendocrinas pulmonares durante la etapa embrionaria temprana del desarrollo pulmonar. Sin embargo, la relación entre CGRP y VEGF-A durante la formación de los pulmones sigue sin estar clara. Este estudio investiga las expresiones de ARNm de CGRP y VEGF-A en las etapas embrionaria, pseudoglandular, canalicular, sacular y alveolar del desarrollo pulmonar desde el día embrionario 12,5 (E12,5) hasta el día postnatal 5 (P5) a través de la reacción en cadena de la polimerasa cuantitativa en tiempo real. (qRT-PCR) e hibridación in situ. Además, analizamos la expresión de CGRP mediante inmunohistoquímica. El ARNm de VEGF-A se dispersó principalmente por todo parénquima pulmonar desde E12,5. Se encontró que CGRP se expresaba en unas pocas células epiteliales de los bronquiolos canaliculares y respiratorios del pulmón desde E12,5 a P5. Se detectó fuertemente una sonda antisentido para ARNm de CGRP en el pulmón de E14,5 a E17,5. El CGRP endógeno puede regular el desarrollo de los alvéolos embrionarios de E14,5 a E17,5 de manera temporal.

[Effectiveness of anti-CGRP monoclonal antibodies in the preventive treatment of migraine: A prospective study of 63 patients]. / Efectividad de anticuerpos monoclonales anti-PRGC en el tratamiento preventivo de la migraña: estudio prospectivo de 63 pacientes.

INTRODUCTION: Calcitonine Gen-Related Peptide (CGRP) established a revolution in migraine pathophysiology knowledge and has led to the development of new drugs specifically targeting this disease. METHODS: We present a prospective study in which 63 episodic and chronic migraine patients have been treated with anti-CGRP monoclonal antibodies describing their efficacy, security and relapses after their interruption. Response predictors have been analyzed such they can help us to create a better treatment plan. RESULTS: Average age was 48.3 ± 11.81 years old, 84.1% of them being women. The average was of 15.59 migraine days per month (MDM). 63.5% of all patients suffered chronic migraine. The initial dose of Erenumab in all patient was 70 mg subcutaneous. This was increased to 140 mg in 47.6% of the patients. An MDM reduction between 49.85% and 59.53% was obtained within three to twelve months from the start of treatment. Constipation was present in 17.5% of the patients and 4.8% suffered injection site reaction. The treatment was changed to Galcanezumab in 17.9% of the patients. After interrupting the treatment, 23 patients relapsed with a good response on reintroduction of the treatment. It was not possible to establish a clear response predictor, however a statistically significant increase in the number of days of improvement was observed with more MDM at baseline level (p = 0.002). CONCLUSIONS: Anti-CGRP monoclonal antibodies are effective, safe, and well tolerated drugs. We have observed that their discontinuation, in some cases can lead to frequent and early relapses so we strongly recommend to extend the treatment in those patients with a higher MDM.

Intercritical photophobia in the migrainous patient. Proposal for diagnostic criteria.

INTRODUCTION: Photophobia is a symptom of abnormal light intolerance without pain sensation that requires an anamnesis and an examination to diagnose an underlying etiology. BASIC PROCEDURE: This article focuses on 30 clinical cases with isolated intense photophobia and on the review of the literature. OBJECTIVE: The purpose of this article is to establish diagnostic criteria for photophobia. RESULTS: The etiology of photophobia appears to be at the level of the intrinsically photosensitive retinal ganglion cells known as melanopsin cells and at a neurochemical level mediated by calcitonin-related peptide and the pituitary activating peptide cyclase. CONCLUSION: The treatment of photophobia could consist of monoclonal antibodies against calcitonin-related peptide and/or pituitary activating peptide cyclase.

Cherubism in Saudi population: a rare case report / Querubismo na população Saudi: relato de um caso raro

Cherubism is a rare hereditary benign fibro-osseous disorder characterised by bilateral swelling of the mandible and/or maxilla with varying severity of involvement. It occurs because of dominant mutations in SH3BP2 gene on the chromosome 4p16.3. On radiography cherubic lesions appear as multilocular cystic radiolucencies in the jaw bones giving a soap bubble appearance. These lesions usually heal by themselves by the time the patient attains puberty. Treatment is necessary only in aggressive cases where there is severe facial deformity or vital functions are hampered. Surgical corrections are preferred when the lesion is in its dormant phase. The aim of the present case report is to illustrate a case of cherubism in a 9-year-old Saudi boy which is a very rare occurrence as only 1 case of cherubism has been reported so far in the Saudi Arabian population (AU)

Querubismo é uma desordem fibro-óssea hereditária rara caracterizada por aumento de volume bilateral da mandíbula e/ou maxila com graus variáveis de severidade. Ocorre devido a mutação dominante no gene SH3BP2 no cromossomo 4p16.3. Radiograficamente as lesões de querubismo aparecem como radiolucência multilocular semelhantes a bolhas de sabão nos ossos maxilares. Geralmente as lesões involuem espontaneamente quando o paciente atinge a puberdade. O tratamento se faz necessário apenas nos casos mais agressivos que demonstram deformidade facial severa ou comprometimento de funções vitais. Correções cirúrgicas são preferíveis quando a lesão está na fase dormente. O objetivo do presente relato é ilustrar um caso de querubismo em um paciente de 9 anos da Arábia Saudita, sendo este um evento raríssimo com apenas um outro caso relatado na população da Arábia Saudita (AU)

Evaluation of the use of CGRP monoclonal antibodies (mAbs) in migraine prophylaxis in a private clinic / Avaliação do uso de anticorpos monoclonais (mAbs) CGRP na profilaxia de enxaqueca em clínica privada

Introduction: Migraine is considered the second most prevalent neurological disorder in the population and highly disabling. Objective: The aim of this study is to evaluate the use of calcitonin gene-related peptide (CGRP) monoclonal antibodies in migraine prophylaxis, with emphasis on therapeutic response, adverse effects, and impacts on quality of life. Method; A quantitative, retrospective, and descriptive study was carried out, through the analysis of medical records and telephone interviews with patients seen at the Serviço de Neurologia e Neurocirurgia, in the city of Passo Fundo, RGS, Brazil, currently or previously having used at least one dose of the medication. Conclusion: Thus, it is understood that CGRP monoclonal antibodies are able to reduce monthly headache days, reduce pain intensity and promote improvement in work capacity. Therefore, they can be considered effective, safe and well-adhered medications for migraine prophylaxis.

Introdução: A enxaqueca é considerada o segundo distúrbio neurológico mais prevalente na população e altamente incapacitante. Objetivo: O objetivo deste estudo é avaliar o uso de anticorpos monoclonais do peptídeo relacionado ao gene da calcitonina (CGRP) na profilaxia da enxaqueca, com ênfase na resposta terapêutica, efeitos adversos e impactos na qualidade de vida. Método; Foi realizado um estudo quantitativo, retrospectivo e descritivo, por meio de análise de prontuários e entrevistas telefônicas com pacientes atendidos no Serviço de Neurologia e Neurocirurgia, na cidade de Passo Fundo, RGS, Brasil, que já usaram ou usaram pelo menos uma dose do medicamento. Conclusão: Assim, entende-se que os anticorpos monoclonais CGRP são capazes de reduzir os dias mensais de cefaleia, reduzir a intensidade da dor e promover melhora na capacidade de trabalho. Portanto, podem ser considerados medicamentos eficazes, seguros e de boa adesão para a profilaxia da enxaqueca.

Calcitonin gene-related peptide (CGRP) concentrations outside migraine attacks in peripheral blood as a potential biomarker for chronic migraine / Concentrações de peptídeo relacionado ao gene da calcitonina (CGRP) fora dos ataques de enxaqueca no sangue periférico como um potencial biomarcador para enxaqueca crônica

Introduction: Chronic migraine is a debilitating condition that affects a significant portion of the population. Accurate diagnosis and treatment of chronic migraine remain a challenge due to the lack of objective biomarkers. Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in the pathophysiology of migraine and has been proposed as a potential biomarker for migraine. Methods: We measured CGRP levels in peripheral blood samples collected from 142 participants with chronic or episodic migraine and 24 healthy controls during ictal periods, i.e., outside migraine attacks. We compared CGRP levels between the three groups and assessed the correlation between CGRP levels and clinical features of chronic migraine. Conclusion: Our study provides evidence that CGRP levels in peripheral blood during ictal periods may serve as a potential biomarker for chronic migraine. Further studies are needed to validate these findings and to explore the clinical utility of CGRP as a biomarker for chronic migraine.

Introdução: A enxaqueca crônica é uma condição debilitante que afeta uma parcela significativa da população. O diagnóstico preciso e o tratamento da enxaqueca crónica continuam a ser um desafio devido à falta de biomarcadores objetivos. O peptídeo relacionado ao gene da calcitonina (CGRP) é um neuropeptídeo envolvido na fisiopatologia da enxaqueca e foi proposto como um potencial biomarcador para enxaqueca. Métodos: Medimos os níveis de CGRP em amostras de sangue periférico coletadas de 142 participantes com enxaqueca crônica ou episódica e 24 controles saudáveis ​​durante períodos ictais, ou seja, fora das crises de enxaqueca. Comparamos os níveis de CGRP entre os três grupos e avaliamos a correlação entre os níveis de CGRP e as características clínicas da enxaqueca crônica. Conclusão: Nosso estudo fornece evidências de que os níveis de CGRP no sangue periférico durante os períodos ictais podem servir como um potencial biomarcador para enxaqueca crônica. Mais estudos são necessários para validar estes resultados e explorar a utilidade clínica do CGRP como biomarcador para enxaqueca crónica.

It is time anti-CGRP monoclonal antibodies be considered first-line prophylaxis for migraine / Já é tempo de os anticorpos monoclonais anti-CGRP serem reconhecidos como profilaxia de primeira linha para a migrânea

ABSTRACT The result of more than thirty years of research, anti-CGRP monoclonal antibodies are currently the state of the art for migraine preventive therapy. Their efficacy and safety, supported by an already large and growing body of evidence, are added by many other advantages: an early onset of action, favorable posology, negligible pharmacological interaction, and a broad-reaching efficacy in many challenging clinical contexts. When compared to standard prophylactics, these novel medications seem at least as efficacious, clearly more tolerable and, consequently, with a superior adherence profile. Furthermore, recently published analyses indicate that they are cost-effective, especially among those with chronic migraine. Yet, current guidelines endorse their use only after multiple other preventives have failed or have been deemed not tolerable. Although this recommendation may have been sensible at first, the now available data strongly point that time has come for anti-CGRP monoclonal antibodies to be acknowledged as first-line treatments for migraine patients with severe disability. For these individuals, delaying treatment until several other alternatives have failed incurs in significant losses, both economically and to many relevant aspects of their lives.

RESUMO Frutos de mais de 30 anos de pesquisa, os anticorpos monoclonais anti-CGRP são atualmente o que há de mais moderno no tratamento preventivo da migrânea. À sua eficácia e segurança, já bem estabelecidos por um grande corpo de evidências, acrescentam-se outras vantagens: um início precoce de ação, posologia favorável, mínima interação farmacológica, e eficácia comprovada em uma variedade de contextos clínicos frequentemente desafiadores. Quando comparados a outros profiláticos, estas medicações aparentam ser ao menos tão eficazes, evidentemente mais toleráveis e, portanto, com melhor perfil de adesão. Ademais, estudos recentemente publicados indicam que elas são custo-efetivas, especialmente entre pacientes com migrânea crônica. Ainda assim, as diretrizes atuais orientam o seu uso apenas caso haja refratariedade ou intolerância a múltiplos outros preventivos. Apesar de esta recomendação poder ter sido sensata a priori, os dados disponíveis atualmente corroboram que já é tempo de estes anticorpos monoclonais serem reconhecidos como tratamentos de primeira linha para a migrânea associada à incapacidade grave. Para estes pacientes, demorar a oferecer este tratamento até que outras múltiplas alternativas tenham falhado, leva a perdas significativas, tanto economicamente quanto em múltiplos outros aspectos relevantes das suas vidas.

Evaluation of Hormonal Influence in Patients with Fractures Attributed to Osteoporosis / Avaliação da influência hormonal em pacientes com fraturas atribuídas a osteoporose

Abstract Objective The present study aims to evaluate the influence of hormonal levels of vitamin D, calcitonin, testosterone, estradiol, and parathyroid in patients with fractures attributed to osteoporosis when compared with young patients with fractures resulting from high-impact accidents. Methods Blood samples were collected from 30 elderly patients with osteoporosisattributed fractures (T-score ≤-2.5) (osteoporotic group), and from 30 young patients with fractures resulting from high-impact accidents (control group). Measurement of 1,25-hydroxyvitamin D (Kit Diasorin, Saluggia, Italy), calcitonin (Kit Siemens, Tarrytown, NY, USA), testosterone, estradiol, and parathyroid hormone (Kit Beckman Couter, Indianapolis, IN, United States) was performed using a chemiluminescence technique. Data were inserted into a Microsoft Excel (Microsoft Corp., Armonk, WA, USA) spreadsheet and analyzed using Statview statistical software. Results showing non-normal distribution were analyzed with nonparametric methods. The Mann-Whitney test was applied for group comparison, and a Spearman test correlated hormonal levels. Statistical significance was set at p < 0.05. All analyzes compared gender and subjects with and without osteoporosis. Results Women with osteoporosis had significantly lower levels of estradiol and vitamin D (p = 0.047 and p = 0.0275, respectively). Men with osteoporosis presented significantly higher levels of parathyroid hormone (p = 0.0065). There was no significant difference in testosterone and calcitonin levels. Conclusion Osteoporosis patients presented gender-related hormonal differences. Women had significantly lower levels of estradiol and vitamin D, whereas men had significantly higher parathyroid hormone levels, apparently impacting the disease.

Resumo Objetivo Avaliar a influência dos níveis hormonais de vitamina D, calcitonina, testosterona, estradiol e paratormônio em pacientes com fratura atribuída a osteoporose, quando comparados com pacientes jovens que tiveram fraturas decorrentes de acidente de alto impacto. Métodos Foram coletadas amostras de sangue de 30 pacientes idosos com fratura atribuída a osteoporose (T-score ≤-2,5) (grupo com osteoporose) e 30 amostras de sangue de pacientes jovens que sofreram fraturas decorrentes de acidentes de alto impacto (grupo controle). Foram realizadas dosagem de 1,25-hidroxivitamina D (Kit Diasorin, Saluggia, Italy), calcitonina (Kit Siemens, Tarrytown, NY, USA), testosterona, estradiol e paratormônio (Kit Beckman Couter, Indianapolis, IN, United States) pela técnica de quimiluminescência. Os dados foram inseridos em uma planilha de dados no programa Microsoft Excel (Microsoft Corp., Redmond, WA, EUA) e analisados pelo programa de estatística Statview. Os resultados que apresentaram distribuição não normal foram analisados com métodos não paramétricos. Para análise de variáveis comparando-se os dois grupos, aplicou-se o teste Mann-Whitney. Foi utilizado o teste de correlação de Spearman para a correlacionar os níveis hormonais. Um valor-p >0.05 foi considerado significante. Todas as análises foram feitas comparando gênero e grupos de pacientes come sem osteoporose. Resultados Mulheres com osteoporose apresentam níveis significativamente menores de estradiol e vitamina D (p = 0.047 e p = 0.0275), respectivamente. Homens com osteoporose demonstraram níveis significativamente maiores de paratormônio (p = 0.0065). Não houve diferença significativa nos níveis de testosterona e calcitonina. Conclusão Existem diferenças hormonais entre os gêneros na osteoporose. Em mulheres, níveis significativamente menores de estradiol e vitamina D e, nos homens, níveis significativamente maiores de paratormônio, parecem influenciar na doença.

Tratamiento preventivo en migraña: anticuerpos monoclonales contra la vía del péptido relacionado con el gen de la calcitonina / Migraine preventive treatment: monoclonal antibodies against calcitonine gene related peptide

Resumen La migraña es un trastorno muy prevalente que afecta a alrededor del 15% de los sujetos adultos. Es clasificada por la Organización Mundial de la Saludentre los primeros puestos como causa de discapacidad. Los tratamientos preventivos habituales hasta ahora derivan de otras indicaciones y por serendipia se utilizan en prevención de migraña: betabloqueantes, drogas antiepilépticas, antidepresivos tricíclicos, bloquean tes de canales de calcio, toxina botulínica. Todas ellas han mostrado eficacia similar al 50% en reducir el número de episodios migrañosos pese a efectos secundarios indeseados. Durante los últimos años, se ha evaluado la eficacia y seguridad de los anticuerpos monoclonales (AM) que actúan sobre la vía del péptido relacionado con el gen de la calcitonina (CGRP) en migraña. Dicho péptido es relevante en la activación del dolor en territorio meníngeoy es mediado por terminales nerviosas trigeminales una vez activado el proceso migrañoso. Su dosaje en crisis migrañosas ha sido elevado en diversos estudios y su neutralización/bloqueo, redunda en alivio del dolor. Los anticuerpos monoclonales erenumab, galcanezumab, fremanezumab, eptinezumab aprobados en el mercado EE.UU./Europa desde 2018 y tras varios trabajos de Fase III y abiertos de extensión, mostraron clara seguridad yeficacia y están presentes en nuestro medio desde mediados de 2019. Desarrollamos la racionalidad e indicaciones de uso de los mismos.

Abstract Migraine is a very prevalent disorder that is estimated to affect about 10-15% of adult subjects. Ac cording to the World Health Organization migraine is one of the first causes of disability. Traditional preventive treatments discovered by serendipity include Beta blockers, antinconvulsants drugs, calcium channel blockers, tricyclic antidepressants and onabotulinum A and offer about 50% efficacy after controlled placebo trials and real life use. Because of lack of adherence and adverse events, there is a loss of beneficial sustain on these treat ments. Recently, the efficacy and safety of monoclonal antibodies (MA) that act on the peptide pathway related to the calcitonin gene (CGRP) has been evaluated in migraine, being the first specific tailored treatment on one of the multiple targets on migraine. This family of drugs: erenumab, galcanezumab, fremanezumab, eptinezumab, finished Fase III, extensions trials and many of them are in the market approved since 2018.Since 2019 are available in Argentina. We will describe the rationale for the prescription of this family of new drugs for migraine.

Calcitonin negative neuroendocrine thyroid carcinoma: Case report and literature review

SUMMARY Medullary thyroid carcinoma (MTC) is a relatively rare neuroendocrine tumor that originates in the parafollicular C cells of the thyroid gland. It is characterized by the synthesis and secretion of calcitonin. Usually, serum calcitonin is used as part of the diagnosis and follow-up of these patients. Few cases of MTC with negative calcitonin have been reported worldwide, whose diagnosis is a clinical challenge.

El carcinoma medular de tiroides (MTC) es un tumor neuroendocrino relativamente raro que se origina en las células C para foliculares de la glándula tiroides. Se caracteriza por la síntesis y secreción de calcitonina. Por lo general, la calcitonina sérica se utiliza como parte del diagnóstico y seguimiento de estos pacientes. Se han notificado pocos casos de MTC con calcitonina negativa en todo el mundo, cuyo diagnóstico es un desafío clínico.

Intercritical photophobia in the migraineous patient. Proposal for diagnostic criteria. / Fotofobia intercrítica en el paciente migrañoso. Propuesta de criterios diagnósticos.

INTRODUCTION: Photophobia is a symptom of abnormal light intolerance without pain sensation that requires an anamnesis and an examination to diagnose an underlying etiology. BASIC PROCEDURE: This article focuses on 30 clinical cases with isolated intense photophobia and on the review of the literature. OBJECTIVE: The purpose of this article is to establish diagnostic criteria for photophobia. RESULTS: The etiology of photophobia appears to be at the level of the intrinsically photosensitive retinal ganglion cells known as melanopsin cells and at a neurochemical level mediated by calcitonin-related peptide and the pituitary activating peptide cyclase. CONCLUSION: The treatment of photophobia could consist of monoclonal antibodies against calcitonin-related peptide and/or pituitary activating peptide cyclase.

The correlation between tumor markers and Ga-68 DOTA-TATE PET/CT findings in patients with advanced medullary thyroid cancer. / La correlación entre los marcadores tumorales y los hallazgos de Ga-68DOTA-TATE PET/TC en pacientes con cáncer medular de tiroides avanzado.

BACKGROUND: Medullary thyroid cancer is a rare type of neuroendocrine tumor. Calcitonin (Ctn) and carcinoembryonic antigen (CEA) are used as markers for medullary thyroid cancer. The aim of the study was to evaluate the importance of serum Ctn and CEA levels in predicting total tumor volume. MATERIAL AND METHODS: Ga-68 DOTA-TATE PET/CT findings such as whole-body somatostatin receptor-expressing metabolic tumor volume (SSR-E MTV) and total lesion volume (SSR-E TLV) were calculated and correlation analysis was done for tumor markers and whole-body SSR-E MTV and TLV. RESULTS: A total of 28 patients with advanced medullary thyroid cancer were included in this retrospective study. In the correlation analysis, there was a statistically significant positive correlation between Ctn and whole-body SSR-E MTV (rho=0.503 and P=.008). Similarly, significant positive correlation was observed between Ctn and whole-body SSR-E TLV (rho=0.436 and P=.023). There was a significant positive correlation between CEA and whole-body SSR-E MTV (rho=0.584 and P=.007). Also, a positive correlation was observed between CEA and whole-body SSR-E TLV (rho=0.436 and P=.023). These correlations were most marked in patients with Ctn≥152pg/mL and/or both nodal and bone involvement. CONCLUSION: These results could stimulate clinicians to perform Ga-68 PET for treatment decisions, especially in patients with high CEA and Ctn levels at the time of diagnosis.

Medicina de precisión en sepsis: utilidad de los en sepsis: utilidad de los biomarcadores en pacientes críticamente enfermos / Precision medicine in sepsis: usefulness of biomarkers In critically ill patientsbiomarkers In critically ill patients

Durante años la evolución del cuidado intensivo ha intentado ofrecer una atención basada en protocolos y paquetes de manejo agrupados por patologías y cuadro sindromáticos. Aunque se logró disminuir la mortalidad en diferentes patologías (sepsis y síndromes coronario agudo y de distrés respiratorio agudo), no se han resuelto por completo los problemas clínicos, en especial el diagnóstico y el manejo. Una nueva opción ha surgido en el horizonte denominada "medicina de precisión", entendida como estrategia de prevención y tratamiento que tiene en cuenta la variabilidad individual. La sepsis es un síndrome con múltiples aristas en cuanto al fenotipo y genotipo, cuyo diagnóstico temprano es relevante para los desenlaces clínicos. Hasta el momento el enfoque principal ha sido la identificación de un germen etiológico para diferenciarla del síndrome de respuesta inflamatoria sistémica (SIRS). En los últimos años el paradigma en enfermedades infecciosas ha cambiado debido a estudios que demuestran como la respuesta inmunitaria del paciente séptico tiene un papel clave en el desarrollo de la enfermedad, con implicaciones en el diagnóstico, pronóstico y tratamiento, que podrían ayudar a cambiar el abordaje en los próximos años gracias a una estrategia basada en medicina de precisión. Hoy los aislamientos microbiológicos y los cultivos siguen siendo el estándar de referencia con varias desventajas como el tiempo para obtener resultados, sobre todo en infecciones por gérmenes resistentes u hongos, que pueden retrasar el inicio de la terapia antimicrobiana. Como alternativa se ha planteado el uso de biomarcadores en sepsis que, siendo productos de la respuesta inflamatoria del individuo ante la infección, son útiles para el diagnóstico y pronóstico primordialmente en los críticamente enfermos. Decidimos realizar esta revisión narrativa acerca de la utilidad de los biomarcadores en pacientes con sepsis críticamente enfermos, para enfocarlos en un modelo de medicina personalizada.

For many years, critical care practice has been based on protocols and management guidelines categorized by pathologies or syndromes. Although mortality caused by various diseases such as sepsis, acute coronary syndrome and acute respiratory distress has decreased, clinical problems, particularly diagnosis and management, have not been completely resolved. A new option known as "precision medicine" is on the horizon, a prevention and treatment strategy based on individual variability. Sepsis is a syndrome encompassing multiple clinical phenotypes and genotypes coding and a prompt diagnosis is relevant to obtain better outcomes. To this moment the main approach has been the identification of microorganisms causing sepsis to distinguish sepsis from systemic inflammatory response (SIRS). Infectious diseases paradigm has changed during recent years due to studies demonstrating how septic patient immune response plays a key role in the development of the disease, with implications on diagnosis, prognosis and treatment, which may help change the approach in the next years thanks to a strategy based on precision medicine. Today microbiological identification and cultures continue to be the reference standard with several disadvantages such as turnaround time for test results predominantly in infections caused by resistant bacteria or fungi that may delay commencement of antibiotic therapy. The use of sepsis biomarkers determined by the individual ́s inflammatory response to infection have been proposed as a useful alternative for establishing diagnosis and prognosis mainly in critically ill patients. We decided to conduct this narrative review on the usefulness of biomarkers in critically ill septic patients using a personalized medicine model.