RESUMO
Neuroendocrine tumors (NETs, originally termed “carcinoids”) create a relatively rare group of neoplasms with an approximate incidence rate of 5 to 8 cases per 10 000 persons. NETs predominantly demonstrate indolent disease biology for many years. They become symptomatic when they are large enough or when they metastasize to the liver or the lungs, bones, or other sites. Roughly 30% to 40% of subjects with NETs develop carcinoid syndrome. Signs and symptoms of carcinoid syndrome are bronchospasm, flushing, diarrhea and cramping, cyanosis and pellagra. White plaque-like deposits on the endocardial surface of heart structures are characteristic for carcinoid heart disease. The treatment of patients with carcinoid syndrome is multi-faceted due to the necessity to manage simultaneously the systemic cancer disease as well as the signs of carcinoid syndrome and includes resection or debulking of tumor mass, biological treatment with somatostatin analogues and peptide receptor radionuclide treatment.
Assuntos
Doença Cardíaca Carcinoide , Tumor Carcinoide , Tumores Neuroendócrinos , Doença Cardíaca Carcinoide/complicações , Doença Cardíaca Carcinoide/diagnóstico , Doença Cardíaca Carcinoide/terapia , Tumor Carcinoide/complicações , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/terapia , Humanos , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , SomatostatinaRESUMO
AIM: Mortality is the hardest outcome characterising the severity of diseases and the result of the health care. It is connected mainly with elderly patients (pts.). Information on 24-hours hospital mortality (M24) in seniors admitted to nonsurgical departments is scarce. PATIENTS AND METHODS: In a retrospective observational study, we investigated M24 in pts. of 65 years of age and older, who were discharged from an university geriatric department in years 2016-2018. The identification of diseases which primarily led to M24 and their classification was independently performed by authors from geriatric and internal medicine departments. RESULTS: We proved that M24 is rather frequent (2.3 % out of all hospitalised pts.). There was a 2.4-fold M24 incidence increase from the age 65-69 years up to 90 years (from 1.4 to 3.3 %). The average age of deceased M24 pts. (n = 101) was 80.8 years and was not different from the age of those who deceased later. The majority of M24 (58.4 %) occurred during the first 12 hours after the admission to the hospital. There were many diseases (n = 25) that primarily led to M24 with dominating cardiovascular pathologies (39.6 %), followed closely by infective diseases (33.7 %). Therapeutically irreversible advanced chronic diseases led to M24 in 15.8 %. There was a higher frequency of acute diseases therapeutically irreversibly decompensating pre-existing diseases (43.6 %) than that of acute diseases incompatible with survival (33.7 %).
Assuntos
Hospitalização , Medicina Interna , Doença Aguda , Idoso , Mortalidade Hospitalar , Humanos , Estudos RetrospectivosRESUMO
Thymic carcinoid account for cca 0.4 % of all carcinoid tumors in the body [1]. As compared to other neuroendocrinne tumors, high rates of reccurences after surgery, more aggressive behaviour and relatively high rates of paraneoplastic syndromes are characteristic for thymic carcinoid. The mainstay of treatment is radical surgery [2-4]. Therapy of locally advanced and metastatic stages is influenced by other neuroendocrinne tumors´guidelines. We present a case report of patient with locally advanced, atypical thymic carcinoid, treated with different modalities, including newer procedures like peptide radionuclide receptor therapy (PRRT).
Assuntos
Tumor Carcinoide , Neoplasias do Timo , Tumor Carcinoide/terapia , Terapia Combinada , Humanos , Neoplasias do Timo/terapiaRESUMO
In the treatment of dyslipidemias about 5-6 years back a new class of drugs emerged, CETP (cholesteryl ester transfer protein)-inhibitors. Their benefit was due to an increase of HDL-cholesterol (HDL-C) serum levels. This treatment mode was supported by epidemiological and clinical studies, as people with high serum HDL-C levels suffered less from cardiovascular (CV) events. Three studies with CETP inhibitors (ILLUMINATE with torcetrapib, dal-OUTCOMES with dalcetrapib and ACCELERATE with evacetrapib) were unfortunately negative, and torcetrapib was even harmful to patients due to an increase of aldosterone serum levels. Treatment with dalcetrapib was safe, but without benefit. Similar it was with evacetrapib. There is still running also a study with anacetrapib (REVEAL), but a benefit is here not expected. Evacetrapib and anacetrapib in comparison to dalcetrapib can reduce serum LDL-cholesterol (LDL-C) much more, and similar results were found also in another CETP-inhibitor TA-8995 (TULIP study). Authors try to explain why there is no benefit with CETP-inhibitors (dysfunctional HDL particle, another effective mechanism than reverse cholesterol transport). A genetic analysis in dalcetrapib studies (dal-OUTCOMES and dal-PLAQUE-2) showed, that a cardiovascular benefit from this treatment is concentrated only to a subgroup of patients with a genotype AA in the gene ADCY9 on 16th chromosome. In the population there are about 20% of people with this AA genotype. A clinical study DAL-301 will test this data in a near future. Framingham Offspring study showed that the association of" HDL-C serum level - CV risk in the future" is greatly influenced by serum levels of LDL-C and triglycerides (if these are increased, than the CV future prediction with HDL-C levels is lost). HDL particles are complex and we do not know which subtype of HDL particles is for cardiovascular prognosis important. The research here continues.Key words: acute coronary syndrome - CETP-inhibitors - dalcetrapib - dysfunctional HDL particles - dyslipidemia - HDL-cholesterol - pharmacogenomics of ADCY9 gene.
Assuntos
Anticolesterolemiantes/uso terapêutico , Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Dislipidemias/tratamento farmacológico , Amidas , Benzodiazepinas/uso terapêutico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/sangue , Ésteres , Humanos , Oxazolidinonas/uso terapêutico , Quinolinas/uso terapêutico , Compostos de Sulfidrila/uso terapêutico , Triglicerídeos/sangueRESUMO
Neuroendocrine neoplasmas are a form of cancer arising from cells of diffuse neuroendocrine system. They produce peptides or amines that act as hormones or neurotransmitters. Incidence of NENs is relatively low. Diagnostic work-up and treatment requires a multidisciplinary team approach. The aim of this study was an analysis of data from patients with well-differentiated neuroendocrine neoplasmas of gastrointestinal tract. The study included patients followed up from 1998 to 2013 with histologically confirmed well-differentiated digestive neuroendocrine neoplasm with low or intermediate malignant potential. 97 patients were included; 34 men (35.1%) and 63 women (64.9%). In patients being diagnosed after 2005 interferon treatment is significantly less used than endoscopic and peptide receptor radionuclide therapy. We have identified more appropriate discriminant values of 5-HIAA and chromogranin A (6.8 mg/24 hours; 70 ng/ml) for predicting the presence of metastases at the time of diagnosis. We have identified following risk factors for overall mortality: liver metastases, presence of diarrhea, flush, small bowel primary tumor, high values of CgA and 5-HIAA at the time of diagnosis (5-HIAA > 520.52 mg/24 hours, CgA > 174.5 ng/ml). Surgical treatment was found to be a positive prognostic factor.
Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Endoscopia do Sistema Digestório , Neoplasias Gastrointestinais/terapia , Interferons/uso terapêutico , Intestino Delgado/cirurgia , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/terapia , Radioterapia/métodos , Adulto , Cromogranina A/sangue , Feminino , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/patologia , Humanos , Ácido Hidroxi-Indolacético/sangue , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/patologia , PrognósticoRESUMO
UNLABELLED: Neuroendocrine neoplasmas are a form of cancer arising from cells of diffuse neuroendocrine system. They produce peptides or amines that act as hormones or neurotransmitters. Incidence of NENs is relatively low. Diagnostic work-up and treatment requires a multidisciplinary team approach. The aim of this study was an analysis of data from patients with well-differentiated neuroendocrine neoplasmas of gastrointestinal tract. The study included patients followed up from 1998 to 2013 with histologically confirmed well-differentiated digestive neuroendocrine neoplasm with low or intermediate malignant potential. 97 patients were included; 34 men (35.1 %) and 63 women (64.9 %). In patients being diagnosed after 2005 interferon treatment is significantly less used than endoscopic and peptide receptor radionuclide therapy. We have identified more appropriate discriminant values of 5-HIAA and chromogranin A (6.8 mg/24 hours; 70 ng/ml) for predicting the presence of metastases at the time of diagnosis. We have identified following risk factors for overall mortality: liver metastases, presence of diarrhea, flush, small bowel primary tumor, high values of CgA and 5-HIAA at the time of diagnosis (5-HIAA > 520.52 mg/24 hours, CgA > 174.5 ng/ml). Surgical treatment was found to be a positive prognostic factor. KEY WORDS: chromogranin A - 5-hydroxyindoleacetic acid - neuroendocrine neoplasm.
RESUMO
UNLABELLED: The case study describes a case of 49-year-old man with morbid obesity since childhood (BMI 40 kg/m2), arterial hypertension (approx. since aged 15, treated since 2004), dyslipidemia (since 2006), type 2 diabetes mellitus (since 2006, on insulin therapy since 2008) and smoking (until 2011, 20 cigarettes a day). TREATMENT: 16 types of medication, 8 for hypertension, statin, therapy for diabetes, aspirin, allopurinol. In 2010 (when aged 45) hospitalized in our clinic with dyspnoea and chest pain with a high pressure reading of 180/110 mm Hg (identified symptoms of heart failure with LV ejection fraction of 33 %, in NYHA II functional class, echocardiographically: left atrium: 46 mm, left ventricular chamber size in diastole: 70 mm, interventricular septum: 12 mm, septal hypokinesis, Doppler ultrasonography of lower limb arteries (calcification, diffuse atherosclerotic changes, absent stenosis), CT coronary angiography (significant stenosis of the left coronary artery). Treatment started with 40 mg oral dose of furosemide daily. In May 2011 he was hospitalized with an acute coronary syndrome: acute NSTEMI of the inferior wall (coronarography: 2-vascular problems, implemented PKI, implanted DES - ramus circumflexus, paroxysmal atrial fibrillation, NYHA III functional class, left ventricular ejection fraction: 30 %, pulmonary hypertension). In 2012 renal denervation for resistant hypertension was carried out, carotid stent implanted for stenosis of the carotid artery, presence of diabetic nephropathy (KDOQI stage 3, GF 40 ml/min). In August 2014 admitted to our clinic with pulmonary oedema, cardiogenic shock, acute ischemia of the right calf with peripheral embolisation, presence of atrial flutter, impairment of renal parameters, echocardiographically: left atrium: 55 mm, left ventricle size: 75 mm, akinesis of the septum and posterior wall, occlusion of the right leg arteries (given the patients serious state angio-surgical intervention was contraindicated, vitally indicated leg amputation considered), the patient died after 4 days of hospitalization in an intensive care unit after unsuccessful treatment. A combination of diabetes, hypertension and ischemic heart disease is frequent and prognostically serious. Diabetes increases cardiovascular morbidity and mortality and therefore we should check for diabetes in all cardiovascular patients.
Assuntos
Diabetes Mellitus Tipo 2/etiologia , Hipertensão/complicações , Isquemia Miocárdica/complicações , Função Ventricular Esquerda , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologiaRESUMO
Chronic heart failure is a disease of epidemic extent and has a high mortality and morbidity. Etiology is multifactorial, but the issue is that heart does not have "enough fuel" to produce energy for its work or available fuel can´t be properly utilized. Components of cardiac energy metabolism are substrate utilization, oxidative phosphorylation and ATP (adenosine triphosphate) transfer and utilization. The aim of article is to present the function of heart metabolism and how "metabolic dysfunction" contributes to heart failure. Perhaps, drug effect on heart metabolism is an approach to treatment of chronic heart failure.
Assuntos
Trifosfato de Adenosina/metabolismo , Insuficiência Cardíaca/metabolismo , Miocárdio/metabolismo , Metabolismo Energético , Humanos , Mitocôndrias Cardíacas/metabolismo , Fosforilação Oxidativa , Especificidade por SubstratoRESUMO
BACKGROUND: Thiopurines seem to have positive effect on the pharmacokinetics of anti-tumor necrosis factor biologics. It has been suggested that a reduced dose of thiopurines is sufficient to achieve this synergism. AIMS: To assess the differences of infliximab (IFX) trough levels according to the dose of concomitantly used azathioprine (AZA). PATIENTS & METHODS: All IBD patients treated with IFX (Remicade®) in two IBD centres between November 2015 and April 2017 were eligible. Infliximab trough levels were assessed by ELISA (Ridascreen®, R-Biopharm). The differences in IFX trough levels according to AZA dose were analyzed statistically. RESULTS: In total, 125 patients were included, 42 pts (33.6%) on infliximab monotherapy, 83 pts (66.4%) using combined immune suppression. The respective median IFX levels according to AZA dose were as follows: group 1 (no concomitant AZA) 2.83⯵g/ml (range 0-12); group 2 (AZA dose less than 1â¯mg/kg) 4.91⯵g/ml (range 0.09-15.36); group 3 (AZA dose 1â¯<â¯2â¯mg/kg) 5.67 (range 0.16-16.97); group 4 (AZA dose above 2â¯mg/kg) 7.53⯵g/ml (range 1.15-8.73). The differences in IFX trough levels between the respective groups according to AZA dose were statistically significant (pâ¯=â¯0.0159). CONCLUSION: The positive effect of azathioprine on infliximab levels seems to be dependent on the dose of concomitantly used azathioprine.
Assuntos
Anticorpos/sangue , Azatioprina/administração & dosagem , Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Azatioprina/farmacocinética , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Fármacos Gastrointestinais/farmacocinética , Humanos , Doenças Inflamatórias Intestinais/sangue , Infliximab/farmacocinética , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Eslováquia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
With the increase of ageing population, rates of chronic diseases and complex medical conditions, the management of high-risk surgical patients is likely to become a great concern in most countries. Considering all these factors, it is certainly rational and intuitive that internists should be included into a collaborative model of medical and surgical co-management, where their multi-potentiality and synthesis capacity require them to coordinate the multidisciplinary team and to be the leading agent of change. In this regard, our aim was to present the official position and approach of the Working Group on Professional Issues and Quality of Care of the European Federation of Internal Medicine (EFIM), for implementation of this strategy of care, encouraging internists to assume an important role and to provide continuity of multidisciplinary care, from the decision to operate through to rehabilitation and recovery. Moving from the traditional model of medical care of the surgical patients to the co-management model, from a reactive simple consultation to a new pro-active continued service, may optimize the quality and perioperative care, improving the survival, shortening hospital stays, replacing the old strategy of late and complication treatment to an early and preventive one.
Assuntos
Médicos Hospitalares/organização & administração , Hospitalização , Medicina Interna/organização & administração , Assistência Perioperatória/normas , Europa (Continente) , HumanosRESUMO
AIMS: Lipid parameters, lipid risk indexes and lipid-related oxidative stress markers (paraoxonase 1 [PON1] and lipid peroxides [LPO]) reflect the actual status of lipid metabolism in type 2 diabetes (T2DM). We hypothesized that relationships of high-density lipoprotein cholesterol (HDL-c) with PON1 and apolipoprotein A1 (ApoA1) and/or PON1 with ApoA1 under conditions of hyperglycaemia and oxidative stress might reveal HDL functionality. We investigated relationships between PON1, LPO, and lipid risk markers in T2DM subjects and compared them with those in healthy subjects. METHODS: A total of 107 Caucasian subjects, 67 T2DM outpatients (mean age 52.2⯱â¯6.9â¯years) and 40 healthy subjects (mean age 48.1⯱â¯7.5â¯years) were included in the study. Serum levels of total cholesterol (CHOL-T), HDL-c, low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), apolipoprotein B (ApoB), ApoA1, LPO, and PON1 activity were measured. Non-HDL-c, ApoB/ApoA1 and non-HDL/HDL (lipid risk indexes) were calculated. RESULTS: Higher levels of TG, LPO (Pâ¯<â¯0.0001), nonHDL/HDL and ApoB/ApoA1 (Pâ¯<â¯0.001, 0.05, respectively), and lower levels of HDL-c, ApoA1, and PON1 (Pâ¯<â¯0.0001) were observed in T2DM subjects than in controls. There is a lack of relationship among PON1, HDL-c, and ApoA1 in T2DM patients. PON1 activity positively correlated with these parameters (Pâ¯<â¯0.0001) in controls. Strong correlations between non-HDL-c and ApoB (râ¯=â¯0.956 vs. 0.756; Pâ¯<â¯0.0001), LPO and TG (râ¯=â¯0.831 vs. 0.739; Pâ¯<â¯0.0001) were recorded in both study groups (Pâ¯<â¯0.0001). CONCLUSIONS: Impaired anti-oxidant and anti-atherogenic HDL properties associated with weakened PON1 function and lipid peroxidation may contribute to the development of atherosclerosis-related diseases in T2DM.
Assuntos
Apolipoproteína A-I/sangue , Arildialquilfosfatase/sangue , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Aterosclerose/sangue , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologiaRESUMO
Addressing the current collision course between growing healthcare demands, rising costs and limited resources is an extremely complex challenge for most healthcare systems worldwide. Given the consensus that this critical reality is unsustainable from staff, consumer, and financial perspectives, our aim was to describe the official position and approach of the Working Group on Professional Issues and Quality of Care of the European Federation of Internal Medicine (EFIM), for encouraging internists to lead a thorough reengineering of hospital operational procedures by the implementation of innovative hospital ambulatory care strategies. Among these, we include outpatient and ambulatory care strategies, quick diagnostic units, hospital-at-home, observation units and daycare hospitals. Moving from traditional 'bed-based' inpatient care to hospital ambulatory medicine may optimize patient flow, relieve pressure on hospital bed availability by avoiding hospital admissions and shortening unnecessary hospital stays, reduce hospital-acquired complications, increase the capacity of hospitals with minor structural investments, increase efficiency, and offer patients a broader, more appropriate and more satisfactory spectrum of delivery options.
Assuntos
Assistência Ambulatorial/economia , Atenção à Saúde/normas , Hospitalização/economia , Europa (Continente) , Humanos , Medicina Interna/organização & administraçãoRESUMO
BACKGROUND/AIMS: There is no established standard care of carcinoids as all experts agree. Endogenous somatostatin diurnal rhythm is influenced by administration of lanreotid. The purpose of this study is to evaluate efficacy of lanreotid on the clinical course in a group of patients with metastatic carcinoid. METHODOLOGY: In 43 patients with carcinoid tumors somatostatin serum level, 5-HIAA (5-hydroxyindolacetic acid), NSE (neuron-specific enolase), and chromogranin A were examined. Fifteen patients received 30mg of somatulin (Lanreotid) in two-week intervals. RESULTS: Therapy with somatostatin analogue improved symptoms in 70-80% of patients with metastases and carcinoid syndrome. 5-HIAA significantly decreased after lanreotid therapy. NSE values are undulating. With progression of the disease they rise. Chromogranin is higher in patients with advanced metastatic disease. Mesor of the diurnal excretion of somatostatin is higher (32 pg/mL) in patients with metastatic disease than in patients without (20 pg/mL). After lanreotid administration mesor decreased (16 pg/mL) in the group of patients with metastases. CONCLUSIONS: Intermittent lanreotid therapy is efficient. A rise--(ascend) of endogenous SMS level could be one of the markers of increased activity of carcinoid cells and an indication for the next application of lanreotid therapy. Mean survival of patients with metastatic carcinoid in our study was 46.3 months.
Assuntos
Antineoplásicos/uso terapêutico , Tumor Carcinoide/tratamento farmacológico , Peptídeos Cíclicos/uso terapêutico , Somatostatina/análogos & derivados , Adulto , Idoso , Cromogranina A/sangue , Feminino , Humanos , Ácido Hidroxi-Indolacético/sangue , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Fosfopiruvato Hidratase/sangue , Somatostatina/sangue , Somatostatina/metabolismo , Somatostatina/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: We report the presentation and novel therapy of a calcitonin-secreting pancreatic neuroendocrine tumor (PNET) and review the literature on this unusual neoplasm. METHODS: We cite the history of a 38-year-old male who presented with fatigue, weight loss, and diarrhea and was found to have a pancreatic head mass on cross-sectional imaging, as well as liver metastases. RESULTS: The patient's laboratory evaluation was notable for a >100-fold elevation of the peptide hormone calcitonin in serum. As calcitonin is typically secreted by thyroid C-cells, hypercalcitoninemia is considered a marker for medullary thyroid cancer (MTC) or C-cell hyperplasia, but it may be present in several physiologic or pathologic conditions or may be ectopically secreted in rare PNETs. An octreotide scan confirmed the presence of somatostatin (SST) receptors on the pancreatic mass and liver metastases, leading to the diagnosis of a calcitonin-secreting PNET. We initiated treatment with long-acting SST analogs and peptide receptor radionuclide therapy (90Yttrium-DOTATOC) and achieved disease regression while maintaining a high quality of life. CONCLUSION: Functional PNETs that secrete calcitonin are exceedingly rare, but they are important to consider in the differential diagnosis of nonthyroid-mediated hypercalcitonemia or pancreatic tumors that present with diarrhea, as the management differs markedly from both MTC and other pancreatic malignancies.
RESUMO
Cardiac myxomas make up approximately 50% of all benign cardiac tumors and represented 86% of all surgically treated cardiac tumors. Most of them originated from the left atrium, in some cases from both of atria. We report a case of male patient with biatrial myxomas and other extra-cardiac involvement: hypophyseal adenoma, enlargement of thyroid gland, tubular adenoma polyp of colon and bilateral large cell calcifying Sertoli cell tumor (LCCSCT) of testis. These findings led to the diagnosis of Carney's complex, which is a syndrome with multiple neoplasias, cardiac myxomas, lentigines, and endocrine abnormalities. A genetic test confirm this diagnosis.