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BACKGROUND: Bariatric surgery has been proven to be the most effective therapy for obesity and Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedure. However, weight regain and dumping syndrome occur over time. The transoral outlet reduction (TORe) procedure using an endoscopic suturing device may be an option to treat these conditions. We aimed to analyze outcome parameters and long-term results for this endoscopic technique. METHODS: A retrospective data analysis of patients who underwent TORe using an endoscopic suturing system at our institution from January 2015 to December 2020 was performed. A total of 71 subjects were included. Forty-five patients received the intervention for weight regain, 9 for dumping syndrome and 17 for both. The primary endpoint was weight stabilization or weight loss for subjects with weight regain, and resolution of symptoms for those with dumping syndrome. Secondary endpoints were intraoperative complications, procedure time, length of hospital stay and diameter of gastrojejunal anastomosis 1 year post-intervention. RESULTS: The median size of the gastrojejunal anastomosis was estimated at 30 mm before intervention, and after performing a median of 3 endoscopic sutures, the median estimated gastrojejunal anastomosis width was reduced to 9.5 mm. Eight perioperative complications occurred. Overall mean follow-up was 26.5 months. All interventions achieved weight stabilization or weight loss or resolution of dumping symptoms within the first 3 months, 98.2% at 12 months, 91.4% at 24 months and 75.0% at 48 months. In 22/26 subjects a persisting improvement of dumping syndrome was achieved. CONCLUSIONS: TORe is a safe and effective procedure in the treatment of patients with dumping syndrome after laparoscopic RYGB, the effect on weight stabilization is less significant. A prospective randomized trial should be conducted to compare the effects of TORe with other surgical methods like banding the gastrojejunal anastomosis.
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Síndrome de Vaciamiento Rápido , Derivación Gástrica , Aumento de Peso , Humanos , Femenino , Masculino , Derivación Gástrica/métodos , Derivación Gástrica/efectos adversos , Estudios Retrospectivos , Persona de Mediana Edad , Síndrome de Vaciamiento Rápido/etiología , Adulto , Resultado del Tratamiento , Obesidad Mórbida/cirugía , Técnicas de Sutura , Estómago/cirugía , Pérdida de Peso , Yeyuno/cirugíaRESUMEN
BACKGROUND: The indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and the results are often inaccurate. The current study compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin. METHODS: From 2013 to 2017, we recruited 156 patients with hypotonic polyuria at 11 medical centers to undergo both water-deprivation and hypertonic saline infusion tests. In the latter test, plasma copeptin was measured when the plasma sodium level had increased to at least 150 mmol per liter after infusion of hypertonic saline. The primary outcome was the overall diagnostic accuracy of each test as compared with the final reference diagnosis, which was determined on the basis of medical history, test results, and treatment response, with copeptin levels masked. RESULTS: A total of 144 patients underwent both tests. The final diagnosis was primary polydipsia in 82 patients (57%), central diabetes insipidus in 59 (41%), and nephrogenic diabetes insipidus in 3 (2%). Overall, among the 141 patients included in the analysis, the indirect water-deprivation test determined the correct diagnosis in 108 patients (diagnostic accuracy, 76.6%; 95% confidence interval [CI], 68.9 to 83.2), and the hypertonic saline infusion test (with a copeptin cutoff level of >4.9 pmol per liter) determined the correct diagnosis in 136 patients (96.5%; 95% CI, 92.1 to 98.6; P<0.001). The indirect water-deprivation test correctly distinguished primary polydipsia from partial central diabetes insipidus in 77 of 105 patients (73.3%; 95% CI, 63.9 to 81.2), and the hypertonic saline infusion test distinguished between the two conditions in 99 of 104 patients (95.2%; 95% CI, 89.4 to 98.1; adjusted P<0.001). One serious adverse event (desmopressin-induced hyponatremia that resulted in hospitalization) occurred during the water-deprivation test. CONCLUSIONS: The direct measurement of hypertonic saline-stimulated plasma copeptin had greater diagnostic accuracy than the water-deprivation test in patients with hypotonic polyuria. (Funded by the Swiss National Foundation and others; ClinicalTrials.gov number, NCT01940614 .).
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Diabetes Insípida/diagnóstico , Glicopéptidos/sangre , Polidipsia/diagnóstico , Poliuria/etiología , Solución Salina Hipertónica/administración & dosificación , Privación de Agua/fisiología , Adulto , Desamino Arginina Vasopresina/administración & dosificación , Desamino Arginina Vasopresina/efectos adversos , Diabetes Insípida/sangre , Diabetes Insípida/complicaciones , Diabetes Insípida/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Hiponatremia/inducido químicamente , Masculino , Persona de Mediana Edad , Concentración Osmolar , Polidipsia/sangre , Polidipsia/complicaciones , Curva ROC , Sensibilidad y Especificidad , Orina/químicaRESUMEN
BACKGROUND: Thyroid storm is a feared complication in patients with hyperthyroidism undergoing surgery. We assessed the risk of thyroid storm for different preoperative treatment options for patients with primary hyperthyroidism undergoing surgery. METHODS: Pubmed, EMBASE, and The Cochrane Library were searched systematically for all studies reporting on adult hyperthyroid patients undergoing elective surgery under general anaesthesia. Selected studies were categorised based on preoperative treatment: no treatment, antithyroid medication (thionamides), iodine, ß-blocking medication, or a combination thereof. Treatment effect, that is restoring euthyroidism, was extracted from the publications if available. Risk of bias was assessed using the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) or the Cochrane Risk of Bias tool for randomised studies. RESULTS: The search yielded 7009 articles, of which 26 studies published between 1975 and 2020 were selected for critical appraisal. All studies had moderate to critical risk of bias, mainly attributable to risk of confounding, classification of intervention status, and definition of the outcome. All studies reported on thyroidectomy patients. We found no randomised studies comparing the risk of thyroid storm between treated and untreated patients. Cases of thyroid storm were reported in all treatment groups with incidences described ranging from 0% to 14%. CONCLUSION: Evidence assessing the risk of perioperative thyroid storm is of insufficient quality. Given the seriousness of this complication and the impossibility of identifying patients at increased risk, preoperative treatment of these patients remains warranted.
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Hipertiroidismo/complicaciones , Hipertiroidismo/fisiopatología , Periodo Perioperatorio , Cuidados Preoperatorios/métodos , Crisis Tiroidea/complicaciones , Crisis Tiroidea/fisiopatología , Humanos , Medición de Riesgo , Procedimientos Quirúrgicos OperativosRESUMEN
BACKGROUND: Acute compartment syndrome is a rare complication of severe hypothyroidism. If the symptoms are not recognized promptly and treatment initiated immediately, there is a high risk of permanent damage. Only few other cases of compartment syndrome due to hypothyroidism have been published and the exact pathophysiological mechanism remains unknown. CASE PRESENTATIONS: A 59 year old male developed acute compartment syndrome of his right lower leg after thyroid hormone withdrawal prior to radioiodine remnant ablation after total thyroidectomy for follicular thyroid cancer. He underwent emergency fasciotomy of all four compartments of the lower leg. The muscle tissue in the anterior and lateral compartment was necrotic and was therefore excised. The second patient was a 62 year old female with Hashimoto's thyroiditis, who developed acute compartment syndrome of both lower legs after thyroid hormone withdrawal due to non-compliance. Emergency fasciotomy of all four compartments of both legs was performed. The muscle tissue was viable in all compartments. CONCLUSION: Although compartment syndrome due to hypothyroidism is uncommon, it is a complication physicians should be aware of. The majority of reported cases are caused by an acute withdrawal of thyroid hormones and not by undetected hypothyroidism. No previous case of compartment syndrome caused by an iatrogenic hormone withdrawal in preparation for radioactive iodine has been published. However, as shown in this report, it may be beneficial to inform patients of this rare complication prior to hormone withdrawal in preparation for remnant ablation after thyroidectomy.
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Síndromes Compartimentales/cirugía , Deprescripciones , Fasciotomía , Enfermedad de Hashimoto/tratamiento farmacológico , Hipotiroidismo/tratamiento farmacológico , Cumplimiento de la Medicación , Tiroxina/uso terapéutico , Adenocarcinoma Folicular/radioterapia , Síndrome del Compartimento Anterior/etiología , Síndrome del Compartimento Anterior/cirugía , Síndromes Compartimentales/etiología , Femenino , Enfermedad de Hashimoto/complicaciones , Terapia de Reemplazo de Hormonas , Humanos , Hipotiroidismo/complicaciones , Radioisótopos de Yodo/uso terapéutico , Pierna , Masculino , Persona de Mediana Edad , Neoplasias de la Tiroides/radioterapia , TiroidectomíaRESUMEN
Update: new forms of therapy for type-2-diabetes Abstract. In the past few years medical treatment of type-2-diabetes experienced fundamental changes. New medications were approved which have no intrinsic risk of hypoglycemia and exert weight loss. Cardiovascular outcome trials demonstrated positive effects on cardiovascular morbidity and mortality for GLP-1-receptor agonists and SGLT-2-inhibitors, the latter showing also specific nephroprotective effects. The growing bulk of data leads to modified therapy strategies: Persons with established cardiovascular disease or high cardiovascular risk should be treated primary with these medications. This review starts with an overview on newer antidiabetic substances (DPPIV-inhibitors, GLP-1-receptor agonists, SGLT-2-inhibitors). Then practical aspects of treatment regimens according to actual national and international guidelines are discussed.
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Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Humanos , Hipoglucemiantes/uso terapéuticoRESUMEN
Modern diagnosis and therapy of benign thyroid diseases Abstract. Benign thyroid diseases continue to be widespread endocrine disorders. Early recognition of their symptoms and exact diagnosis are the prerequisite of targeted therapy and minimal impairment of the patient's well-being. Drug treatment, radioiodine therapy, thermal ablation procedures and surgery have been shown to be successful treatment options. As guidelines for diagnosis and treatment of patients continue to evolve, an interdisciplinary approach ensures optimal diagnosis and management on every step in the care for these patients. We present three clinical scenarios for benign thyroid disease: the symptomatic goitre, the painful thyroid and the thyroid with hyperthyroidism.
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Técnicas de Ablación , Bocio , Enfermedades de la Tiroides , Bocio/diagnóstico , Bocio/terapia , Humanos , Radioisótopos de Yodo/uso terapéutico , Enfermedades de la Tiroides/diagnóstico , Enfermedades de la Tiroides/terapiaRESUMEN
BACKGROUND: Uncertainty about factors influencing the susceptibility and triggers for Graves' disease persists, along with a wide variation in the response to anti-thyroid drugs, currently at approximately 50% of non-responders. The aim of this narrative review is to summarize immunological concepts, with a combined endocrine and immunological perspective, to highlight potential new areas of research. MAIN TEXT: Relevant studies were identified through a systematic literature search using the PubMed and EMBASE databases in March 2016. No cut-offs regarding dates were imposed. We used the terms "Graves' Disease" or "Basedow" or "thyrotoxicosis" together with the terms "etiology", "pathophysiology", "immunodeficiency", "causality", and "autoimmunity". The terms "orbitopathy", "ophthalmopathy", and "amiodarone" were excluded. Articles in English, French, German, Croatian, Spanish, and Italian were eligible for inclusion. CONCLUSIONS: While concepts such as the impact of iodine, smoking, human leucocyte antigen, infections, and ethnicity are established, new ideas have emerged. Pertaining evidence suggests the involvement of autoimmunity and immunodeficiency in the pathophysiology of Graves' disease. Recent studies point to specific immunological mechanisms triggering the onset of disease, which may also serve as targets for more specific therapies.
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Enfermedad de Graves/inmunología , Síndromes de Inmunodeficiencia , Animales , Autoinmunidad , Enfermedad de Graves/genética , Humanos , Síndromes de Inmunodeficiencia/genéticaRESUMEN
OBJECTIVES: Graves' hyperthyroidism (GH) interferes with iron metabolism and elevates ferritin. The precise mechanisms remain unclear. The influence of thyroid hormones on the synthesis/regulation of hepcidin, an important regulator of iron metabolism, remains uncharacterized. DESIGN: Prospective observational study. PATIENTS: We included patients (n = 31) with new-onset and untreated GH. MEASUREMENTS: Laboratory parameters indicative of iron metabolism (ferritin, transferrin, hepcidin), inflammatory markers/cytokines and smoking status were assessed at the diagnosis of GH (T0) and at euthyroidism (T1) in the same patients using multivariable analyses. Hepcidin was measured by mass spectrometry (hepcidinMS ) and ELISA (hepcidinEL ). The impact of T3 on hepatic hepcidin expression was studied in a cell culture model using HepG2 cells. RESULTS: Median ferritin levels were significantly lower and transferrin significantly higher at T1 than at T0. HepcidinMS levels were lower in males and females at T1 (statistically significant in males only). No statistically significant difference in hepcidinEL was detected between T0 and T1. Plasma levels of inflammatory markers (high-sensitive CRP, procalcitonin) and cytokines (interleukin 6, interleukin 1ß, tumour necrosis factor α) were not different between T0 and T1. Smokers tended to have lower fT3 and fT4 at T0 than nonsmoking GH patients. T3 significantly induced hepcidin mRNA expression in HepG2 cells. CONCLUSIONS: Iron metabolism in patients with GH undergoes dynamic changes in patients with GH that resemble an acute-phase reaction. Inflammatory parameters and cytokines were unaffected by thyroid status. Gender and smoking status had an impact on ferritin, hepcidin and thyroid hormones.
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Ferritinas/sangre , Enfermedad de Graves/metabolismo , Hepcidinas/metabolismo , Hierro/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Citocinas/metabolismo , Femenino , Células Hep G2 , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Transferrina/metabolismo , Triyodotironina/farmacologíaRESUMEN
AIMS OF THE STUDY: The Eversense® CGM System is the first and only continuous glucose monitoring system (CGMS) that uses a fully subcutaneous implanted sensor. This study aimed to evaluate effectiveness, safety and patient-reported outcomes in patients using the Eversense® CGM System in a realistic clinical setting, assessed at a single Swiss diabetes centre (Luzerner Kantonsspital) with prolonged follow-up. METHODS: This was a prospective and retrospective observational study that included patients with type 1 diabetes mellitus in whom at least one Eversense® glucose sensor was implanted between 2017 and 2022. The primary endpoint was the change in HbA1c levels from the baseline (before implantation of the sensor) to 6 ± 2 and 12 ± 2 months and the last follow-up (newest available value) after implantation. The secondary outcome measures were the number of premature sensor breakdowns, adverse events related to the implantation procedure (infection, bleeding, difficulties with implantation or explantation) and patient-related outcomes (assessed with a questionnaire). RESULTS: A total of 33 patients participated in this study. The median follow-up time was 50 (IQR 22.3-58.5) months. In total, 178 sensor implantations were performed. Valid HbA1c results were available for 26 participants. Compared to the baseline values, HbA1c levels at 6 and 12 months and the last follow-up changed by -0.25%, -0.45 and -0.2 (p = 0.278, 0.308 and 0.296, respectively). We recorded 16 (9%) premature sensor breakdowns, all occurring between 2019 and 2020. Apart from one late-onset infection and four complicated sensor removals, no major complications were assessed. The results of the questionnaire showed a subjective improvement in hypoglycaemia rates, a better perception of hypoglycaemia and the impression of better diabetes management. Common issues with the device reported by the patients were technical errors (connection problems) and problems with the removal procedure. CONCLUSIONS: The use of the Eversense® CGM System resulted in changes in HbA1c of between -0.2% and -0.45%. The rate of premature sensor breakdown was low. Major complications following sensor implantation or removal were absent, apart from one case of infection and four cases of complicated removal. Patient-reported outcomes with the Eversense® CGM System showed a subjective positive impact on hypoglycaemia rates, greater confidence in managing hypoglycaemia and diabetes in general, and easy handling of the transmitter and mobile app. Technical issues must be considered but are nowadays, with the use of the newest sensor generation, very rare.
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Diabetes Mellitus Tipo 1 , Hipoglucemia , Humanos , Glucemia , Hemoglobina Glucada , Estudios Prospectivos , Automonitorización de la Glucosa Sanguínea/métodos , Monitoreo Continuo de Glucosa , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Medición de Resultados Informados por el PacienteRESUMEN
OBJECTIVE: 18F-fluorocholine PET/CT is considered the imaging gold standard for detection of hyperfunctioning parathyroid glands . However, increased uptake might also occur in the thyroid gland. The aim of our study was to assess the incidence and significance of 18F-fluorocholine uptake in the thyroid gland in patients with hyperparathyroidism. MATERIALS AND METHODS: This retrospective study includes 195 consecutive patients with hyperparathyroidism, who underwent 18F-fluorocholine PET/CT, for detection of hyperfunctioning parathyroid glands. PET/CT images were reviewed by two nuclear medicine physicians for the presence of focal or diffuse thyroid uptake. PET/CT results were compared with laboratory parameters, ultrasonography, EU-TIRADS classification in the presence of thyroid nodules, cytology, and final histology. RESULTS: 25 patients (13%) showed 18F-fluorocholine uptake in the thyroid gland: focal thyroid uptake (FTU) in 7 patients (4%), diffuse thyroid uptake (DTU) in 8 patients (4%), and combined uptake (FTUâ +â DTU) in 10 patients (5%), with a total of 20 active thyroid nodules. There was no correlation between EU-TIRADS classification and PET parameters. One highly 18F-fluorocholine active thyroid nodule and one isoactive thyroid nodule turned out to be papillary thyroid cancers in the final histology; 50% of the patients with DTU had Hashimoto's thyroiditis. CONCLUSION: Incidental 18F-fluorocholine uptake in the thyroid gland was observed in 13% of patients. As reported for 18F-FDG, focal 18F-fluorocholine uptake might represent thyroid cancer and should be evaluated with ultrasound and, if indicated, with fine-needle aspiration cytology. Diffuse 18F-fluorocholine uptake most likely represents multinodular goiter or Hashimoto's thyroiditis.
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ABSTRACT: We present the case of a 68-year-old woman with a painful tibial tumor and fatigue. Histology and laboratory studies were consistent with a brown tumor secondary to initially unrecognized, severe primary hyperparathyroidism. 18 F-fluorocholine PET/CT revealed a large hypermetabolic parathyroid mass and multiple bone foci considered as brown tumors. Unilateral neck exploration confirmed a large parathyroid adenoma. Serum calcium and parathyroid hormone levels normalized quickly, and symptoms subsided gradually after parathyroidectomy. Brown tumors are a rare complication of severe hyperparathyroidism. 18 F-fluorocholine PET/CT allows the localization of parathyroid adenomas and brown tumors, and can be used as a single imaging modality.
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Hiperparatiroidismo Primario , Osteítis Fibrosa Quística , Neoplasias de las Paratiroides , Femenino , Humanos , Anciano , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Hiperparatiroidismo Primario/diagnóstico por imagen , Hiperparatiroidismo Primario/complicaciones , Glándulas Paratiroides , Osteítis Fibrosa Quística/complicaciones , Neoplasias de las Paratiroides/complicaciones , Neoplasias de las Paratiroides/diagnóstico por imagen , ColinaRESUMEN
Background: Depression and treatment with antidepressants SSRI/SNRI are common in people with morbid obesity who are candidates for bariatric surgery. There is few and inconsistent data about the postoperative plasma concentrations of SSRI/SNRI. The aims of our study were to provide comprehensive data about the postoperative bioavailability of SSRI/SNRI, and the clinical effects on depressive symptoms. Methods: Prospective multicenter study including 63 patients with morbid obesity and therapy with fixed doses of SSRI/SNRI: participants filled the Beck Depression Inventory (BDI) questionnaire, and plasma levels of SSRI/SNRI were measured by HPLC, preoperatively (T0), and 4 weeks (T1) and 6 months (T2) postoperatively. Results: The plasma concentrations of SSRI/SNRI dropped significantly in the bariatric surgery group from T0 to T2 by 24.7% (95% confidence interval [CI], -36.8 to -16.6, p = 0.0027): from T0 to T1 by 10.5% (95% 17 CI, -22.7 to -2.3; p = 0.016), and from T1 to T2 by 12.8% (95% CI, -29.3 to 3.5, p = 0.123), respectively.There was no significant change in the BDI score during follow-up (-2.9, 95% CI, -7.4 to 1.0; p = 0.13).The clinical outcome with respect to SSRI/SNRI plasma concentrations, weight change, and change of BDI score were similar in the subgroups undergoing gastric bypass surgery and sleeve gastrectomy, respectively. In the conservative group the plasma concentrations of SSRI/SNRI remained unchanged throughout the 6 months follow-up (-14.7, 95% CI, -32.6 to 1.7; p = 0.076). Conclusion: In patients undergoing bariatric surgery plasma concentrations of SSRI/SNRI decrease significantly by about 25% mainly during the first 4 weeks postoperatively with wide individual variation, but without correlation to the severity of depression or weight loss.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Quimioterapia Combinada , Péptidos Similares al Glucagón/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Infusiones Intravenosas , Insulina/efectos adversos , Insulina/sangre , Insulina/uso terapéutico , Liraglutida/efectos adversos , Liraglutida/uso terapéutico , Selección de Paciente , Factores de Riesgo , Relación Estructura-Actividad , Pérdida de Peso/efectos de los fármacosRESUMEN
PURPOSE: Hyperparathyroidism (HPT) is a common disorder. A cure can only be achieved by removing all diseased glands. It is critical to localize the hyperfunctioning glands exactly to prevent extensive surgical exploration. The number of false negative/inconclusive results in standard imaging techniques is high. We aimed to evaluate the diagnostic accuracy of 18F-Fluorocholine-PET in combination with contrast-enhanced CT (FCH-PET/CT) and its sensitivity in patients with primary, secondary/tertiary, and familial HPT with negative and/or discordant findings in ultrasound and/or 99mTc-sestamibi scintigraphy/SPECT/CT. METHODS: A total of 96 patients with HPT and negative/equivocal conventional imaging were referred for FCH-PET/CT. In this retrospective, single institution study, 69 patients, who have undergone surgery and histopathologic workup, were analyzed. Of the 69 patients included, 60 patients suffered from primary HPT, four from secondary or tertiary HPT, and five from familial HPT. Sensitivities, positive predictive values, and accuracies were calculated. RESULTS: Sensitivity/positive predictive value (PPV) per lesion was 87.5/98.3% for primary HPT, 75/100% for secondary/tertiary HPT and 25/66.7% for familial HPT. Sensitivity/PPV per patient was 91.5/98.2% for primary HPT, 100/100% for secondary/tertiary HPT and 50/100% for familial HPT. All patients showed normalized serum calcium levels in the postoperative period. The follow-up rate was 97%. Of the patients included in the study, 58 of 60 patients with primary HPT, and four of four patients with secondary/tertiary HPT showed normal calcium and parathyroid hormone (PTH) levels after six months and were cured. Of the patients with familial HPT, four of five patients were cured. CONCLUSION: Diagnostic accuracy of 18F-Fluorocholine-PET/CT for patients with pHPT is excellent. 18F-Fluorocholine-PET/CT is a valuable tool for endocrine surgeons to optimize the surgical treatment of patients with hyperparathyroidism.
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Hiperparatiroidismo Primario , Glándulas Paratiroides , Colina/análogos & derivados , Humanos , Hiperparatiroidismo Primario/diagnóstico por imagen , Hiperparatiroidismo Primario/patología , Hiperparatiroidismo Primario/cirugía , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/patología , Glándulas Paratiroides/cirugía , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Tecnecio Tc 99m SestamibiRESUMEN
Neuropeptide Y (NPY1-36) is a vasoconstrictor peptide co-secreted with catecholamines by sympathetic nerves, the adrenal medulla, and neoplasms such as pheochromocytomas and paragangliomas (PPGLs). It is produced by the intracellular cleavage of proNPY and metabolized into multiple fragments with distinct biological activities. NPY immunoassays for PPGL have a diagnostic sensitivity ranging from 33 to 100%, depending on the antibody used. We have validated a multiplex micro-UHPLC-MS/MS assay for the specific and sensitive quantification of proNPY, NPY1-39, NPY1-37, NPY1-36, NPY2-36, NPY3-36, NPY1-35, NPY3-35, and the C-flanking peptide of NPY (CPON) (collectively termed NPYs), and determined the NPYs reference intervals and concentrations in 32 PPGL patients before, during, and after surgery. Depending on the peptide measured, NPYs were above the upper reference limit (URL) in 20% to 67% of patients, whereas plasma free metanephrine and normetanephrine, the gold standard for PPGL, were above the URL in 40% and 87% of patients, respectively. Age, sex, tachycardia, and tumor localization were not correlated with NPYs. Plasma free metanephrines performed better than NPYs in the detection of PPGL, but NPYs may be a substitute for an early diagnosis of PPGL for patients that suffer from severe kidney impairment or receiving treatments that interfere with catecholamine reuptake.
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Neoplasias de las Glándulas Suprarrenales , Paraganglioma , Feocromocitoma , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Voluntarios Sanos , Humanos , Metanefrina , Neuropéptido Y/metabolismo , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Precursores de Proteínas , Espectrometría de Masas en TándemRESUMEN
Background: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1ß (IL-1ß) blockade using canakinumab improves clinical outcome. Methods: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2 hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. Findings: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. Interpretation: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. Funding: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication.
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A 55-year-old patient had spent 12 years with unexplained seizures, initially diagnosed as epilepsy and then as a psychiatric disorder. When she was admitted with hypoglycaemia, a fasting test was performed showing blood sugar levels as low as 1 mmol/L with symptoms of neuroglycopenia. Insulinoma was suspected and an MRI showed a large tumour in the tail region of the pancreas. A Dodecanetetraacetic acid-Tyr3-octreotate (DOTATATE) positron emission tomography CT indicated no malignancy and showed no signs of metastasis. The patient underwent surgery, leaving her asymptomatic.
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Epilepsia , Insulinoma , Neoplasias Pancreáticas , Errores Diagnósticos , Femenino , Humanos , Insulinoma/diagnóstico por imagen , Insulinoma/cirugía , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
CONTEXT: Glucocorticoids regulate hemostatic and endothelial function, and they are critical for adaptive functions during surgery. No data regarding the impact of adrenal function on hemostasis and endothelial function in the perioperative setting are available. OBJECTIVE: We assessed the association of adrenal response to adrenocorticotropic hormone (ACTH) and markers of endothelial/hemostatic function in surgical patients. METHODS: This prospective observational study, conducted at a tertiary care hospital, included 60 patients (35 male/25 female) undergoing abdominal surgery. Adrenal function was evaluated by low-dose ACTH stimulation test on the day before, during, and the day after surgery. According to their stimulated cortisol level (cutoff ≥ 500 nmol/L), patients were classified as having normal hypothalamic-pituitary-adrenal (HPA)-axis function (nHPA) or deficient HPA-axis function (dHPA). Parameters of endothelial function (soluble vascular cell adhesion molecule-1, thrombomodulin) and hemostasis (fibrinogen, von Willebrand factor antigen, factor VIII [FVIII]) were measured during surgery. RESULTS: Twenty-one patients had dHPA and 39 had nHPA. Compared with nHPA, patients with dHPA had significantly lower peak cortisol before (median 568 vs 425 nmol/L, Pâ <â 0.001) and during (693 vs 544 nmol/L, Pâ <â 0.001) surgery and lower postoperative hemoglobin levels (116 g/L vs 105 g/L, Pâ =â 0.049). FVIII was significantly reduced in patients with dHPA in uni- and multivariable analyses; other factors displayed no significant differences. Coagulation factors/endothelial markers changed progressively in relation to stimulated cortisol levels and showed a turning point at cortisol levels between 500 and 600 nmol/L. CONCLUSIONS: Patients with dHPA undergoing abdominal surgery demonstrate impaired hemostasis which can translate into excessive blood loss.