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OBJECTIVES: Stability of concentrations of urinary stone-related metabolites was analyzed from samples of recurrent urinary stone formers to assess necessity and effectiveness of urine acidification during collection and storage. METHODS: First-morning urine was collected from 20 adult calcium-stone forming patients at Tomas Bata Hospital in the Czech Republic. Urine samples were analyzed for calcium, magnesium, inorganic phosphate, uric acid, sodium, potassium, chloride, citrate, oxalate, and urine particles. The single-voided specimens were collected without acidification, after which they were divided into three groups for storage: samples without acidification ("NON"), acidification before storage ("PRE"), or acidification after storage ("POST"). The analyses were conducted on the day of arrival (day 0, "baseline"), or after storage for 2 or 7 days at room temperature. The maximum permissible difference (MPD) was defined as ±20â¯% from the baseline. RESULTS: The urine concentrations of all stone-related metabolites remained within the 20â¯% MPD limits in NON and POST samples after 2 days, except for calcium in NON sample of one patient, and oxalate of three patients and citrate of one patient in POST samples. In PRE samples, stability failed in urine samples for oxalate of three patients, and for uric acid of four patients after 2 days. Failures in stability often correlated with high baseline concentrations of those metabolites in urine. CONCLUSIONS: Detailed procedures are needed to collect urine specimens for analysis of urinary stone-related metabolites, considering both patient safety and stability of those metabolites. We recommend specific preservation steps.
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Introduction: This survey aims to assess the implementation of recommendations from the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) by clinical biochemistry laboratories in Czechia and Slovakia in their policies for reporting low-density lipoprotein cholesterol (LDL-C) concentrations. Materials and methods: The web-based survey was distributed to all 383 Czech and Slovak clinical biochemistry laboratories that measure lipids by external quality assessment provider SEKK. A total of 17 single-answer questions were included. The questionnaire was focused on the detection and decision points in familial hypercholesterolemia (FH). All survey answers were taken into account. The laboratories followed the EFLM and EAS guidelines when they reported an interpretative comment considering FH diagnosis in adults. Results: A total of 203 (53%) laboratories answered. Only 5% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 5.0 mmol/L in adults, and 3% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 4.0 mmol/L in children. Only 7% of laboratories reported goals for all cardiovascular risk categories (low, moderate, high, very high). Non-HDL cholesterol concentrations were calculated by 74% of responders. A significant number (51%) of participants did not measure apolipoprotein B, and 59% of laboratories did not measure lipoprotein(a). Conclusions: Only a small portion of laboratories from Czechia and Slovakia reported high LDL-C results with interpretative comments considering FH diagnosis in adults, the laboratories did not follow the guidelines.
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Aterosclerose , Hiperlipoproteinemia Tipo II , Adulto , Criança , Humanos , LDL-Colesterol , República Tcheca , Eslováquia , Laboratórios , Hiperlipoproteinemia Tipo II/diagnóstico , ColesterolRESUMO
Studies JVDB and JVCZ examined alternative ramucirumab dosing regimens as monotherapy or combined with paclitaxel, respectively, in patients with advanced/metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma. For JVDB, randomized patients (N = 164) received ramucirumab monotherapy at four doses: 8 mg/kg every 2 weeks (Q2W) (registered dose), 12 mg/kg Q2W, 6 mg/kg weekly (QW), or 8 mg/kg on days 1 and 8 (D1D8) every 3 weeks (Q3W). The primary objectives were the safety and pharmacokinetics of ramucirumab monotherapy. For JVCZ, randomized patients (N = 245) received paclitaxel (80 mg/m2-D1D8D15) plus ramucirumab (8 mg/kg- or 12 mg/kg-Q2W). The primary objective was progression-free survival (PFS) of 12 mg/kg-Q2W arm versus placebo from RAINBOW using meta-analysis. Relative to the registered dose, exploratory dosing regimens (EDRs) led to higher ramucirumab serum concentrations in both studies. EDR safety profiles were consistent with previous studies. In JVDB, serious adverse events occurred more frequently in the 8 mg/kg-D1D8-Q3W arm versus the registered dose; 6 mg/kg-QW EDR had a higher incidence of bleeding/hemorrhage. In JVCZ, PFS was improved with the 12 mg/kg plus paclitaxel combination versus placebo in RAINBOW; however, no significant PFS improvement was observed between the 12 mg/kg and 8 mg/kg arms. The lack of a dose/exposure-response relationship in these studies supports the standard dose of ramucirumab 8 mg/kg-Q2W as monotherapy or in combination with paclitaxel as second-line treatment for advanced/metastatic gastric/GEJ adenocarcinoma.
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BACKGROUND: Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus named SARS-CoV-2, initially emerged in China in late 2019. The rapid global spread of this novel virus led the World Health Organization declare a pandemic with > 30,000,000 confirmed cases, 946,000 deaths and > 21,000,000 recoveries reported as of 18 September 2020, according to the Johns Hopkins Coronavirus Resource Center. Initial reports from Asia suggested that elderly patients with multiple comorbidities, specifically diabetes, hypertension, and obesity were at an increased risk of developing severe COVID-19 following a SARS-CoV-2 infection. As data on these risks have evolved, evidence has increasingly shown that patients with cancer are indeed a particularly vulnerable group. However, the effects of various confounding factors, including an older than average patient population who often have underlying comorbidities including a suppressed immune system and/ or a hypercoagulable state, have been difficult to separate from the effects of having cancer. Common presenting symptoms of SARS-CoV-2 including dyspnoea, cough, fever, fatigue, dysgeusia and, less commonly, diarrhoea and/ or a hyperinflammatory syndrome are equally confusing to clinicians as they all are common symptoms of both cancer and toxicity from anti-cancer therapy. Furthermore, the radiographic dilemma of distinguishing between immune-checkpoint inhibitor-induced pneumonitis from that caused by SARS-CoV-2 infection and conflicting data on the effects of certain therapies on patient outcomes has left clinicians with considerable angst on how to help patients with acute or worsening symptoms in an optimal way. Predicted increase in mortality follows not only from the delay in discovery and progress resulting from temporary closing of research laboratories at cancer centers but also from diversion of resources to patient care and temporary suspension of clinical trial enrolment both by companies and local institutions. The possibilities of travelling to specialized medical centers whose activities are essential for the delivery and improvement of patient care were reduced, too. Viral mutations might also occur during transmission and spread; this leads to a statement that SARS-CoV-2 will forever remain a looming threat to the oncological community. What is crucial to remember is that cancer itself is a pandemic with > 18,000,000 people dia-gnosed worldwide every year. Many societies, including the European Society for Medical Oncology and the American Society of Clinical Oncology, are providing clinical recommendations for the management of patients with cancer during this challenging time, recognizing that continuation in the precise treatment of our patients is critical for our role of physicians. PURPOSE: The aim of the presentation is to point out the contact or overlapping areas of both mentioned disease entities for the purpose of possible simplification of dia-gnostic and therapeutic management of a cancer patient with suspected or already proven COVID-19 disease.
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COVID-19/complicações , Oncologia/normas , Neoplasias/terapia , Guias de Prática Clínica como Assunto/normas , SARS-CoV-2/isolamento & purificação , COVID-19/virologia , Humanos , Neoplasias/epidemiologia , Neoplasias/virologiaRESUMO
BACKGROUND: In December 2019 a new strain of coronavirus SARS-CoV-2 has emerged and affected health care worldwide. Patients with cancer and other comorbidities are at increased risk for adverse outcomes in this infection. CASE: In this case report we present a 75-year-old patient with a localized gastric adenocarcinoma, currently treated by perioperative chemotherapy regimen, who had an rT-PCR proven novel coronavirus SARS-CoV-2 infection. Laboratory and radiologic assessments were performed in order to assess disease severity; however, the findings were not altered in accordance with the findings associated with COVID-19 disease. RESULTS: On the first hospital day the patient had a low grade fever with chills. Subsequently a pharmacological therapy with hydroxychloroquine and azithromycin was started. After pharmacologic and symptomatic treatment, the patient was reassessed for SARS-CoV-2, with negative results. At discharge, the patient was ordered a 14-day mandatory quarantine. After 57 days of follow-up, the patient underwent a new rapid antibody test by Acro Biotech inc., which gave negative results for IgM and IgG. CONCLUSION: An infection with SARS-CoV-2 is associated with a more severe disease in patients with comorbidities and cancer; however, this case patient had a mild course of COVID-19 disease. The aim of this case report is to share the information on the clinical course and outcomes of a patient with malignancy. Rapid spreading of information is crucial in the management of COVID-19.
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Adenocarcinoma/complicações , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Neoplasias Gástricas/complicações , Idoso , Azitromicina/administração & dosagem , Betacoronavirus , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Humanos , Hidroxicloroquina/administração & dosagem , Masculino , Pandemias , Alta do Paciente , Pneumonia Viral/tratamento farmacológico , SARS-CoV-2 , Eslováquia , Resultado do Tratamento , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Patients taking digoxin are older with high probability of having low muscle mass, and current clinical practice in digoxin dosing relies only on estimated glomerular filtration rate from serum creatinine (eGFRcrea). The aim of the study is to compare eGFRcrea and estimated glomerular filtration rate from serum cystatin C (eGFRcys) in older adult patients with atrial fibrillation (AF) overdosed with digoxin. METHODS: A total of 80 consecutive patients overdosed with digoxin and 33 controls with AF from Department of Internal Medicine were included in the prospective observational study. The median of age of participants was 81 years in both the overdosed and the control group. The eGFRs were calculated using The Chronic Kidney Disease Epidemiology (CKD- EPI) equations using standardized methods for serum creatinine and cystatin C measurement. RESULTS: The median (IQR) of eGFRcrea was higher than that of eGFRcys (45 mL/min/1.73 m2 (35-59) vs 30 (21-38), respectively; P < .0001) in overdosed patients. The median (IQR) of eGFRcrea was higher than that of eGFRcys (61 mL/min/1.73 m2 (49-72) vs 40 (30-56), respectively; P < .0001) in control group of patients. Serum predose digoxin concentration in overdosed patients was inversely associated with eGFRcys (ρ = -0.26, P < .05). CONCLUSION: Physicians should consider GFR when changing digoxin dosing. eGFRcys was lower in both the overdosed and the control group. eGFRcys would lead to lower digoxin doses and thus prevent overdose.
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Fibrilação Atrial/sangue , Fibrilação Atrial/tratamento farmacológico , Creatinina/sangue , Cistatina C/sangue , Digoxina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/fisiopatologia , Digoxina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: The aim of the study was to investigate current practice and policies of therapeutic drug monitoring (TDM) service requesting and result reporting in Czechia and Slovakia. MATERIALS AND METHODS: All 149 laboratories that measure plasma drug concentrations were given an online questionnaire during a regular external quality assessment TDM cycle. The questionnaire consisted of 17 questions. The optimal TDM practice was defined as the application of all elements (age, body weight, time of sampling, date of the first administration, time of the last dose administration, the dose, the dosing interval, the route of administration, information on reason of testing, and information on other co-administered drugs) needed for reporting a recommendation for further drug dosing (positive response to question number 16). RESULTS: The response rate was 69%, 103 out of 149 laboratories measuring drug concentrations. Only 12% (12 out of 103 laboratories) of the laboratories implemented all elements needed for optimal TDM practice and reported a recommendation. Both paper and electronic request forms were used by 77 out of 103 (75%) laboratories. A total of 69 out of 103 laboratories (67%) specified the type of sampling tube on their request form. Cystatin C was used for prediction of renal drug elimination by 24% (25 out of 103) of participants. CONCLUSIONS: Small number of laboratories implemented all elements needed for optimal TDM practice and report a recommendation on further dosing. Further efforts in education on optimal TDM practice as well as harmonization of service are desirable.
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Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/tendências , Laboratórios/normas , República Tcheca , Monitoramento de Medicamentos/estatística & dados numéricos , Política de Saúde , Humanos , Internet , Laboratórios/estatística & dados numéricos , Garantia da Qualidade dos Cuidados de Saúde , Controle de Qualidade , Reprodutibilidade dos Testes , Eslováquia , Inquéritos e QuestionáriosRESUMO
Case (description): A 74 years old Caucasian suffering from chronic kidney disease presented with progressive asthenia and diffuse myalgia. It was revealed that the patient used three different rosuvastatin-containing preparations in a total daily dose of 120 mg for 76 days. Laboratory investigations revealed a marked elevation of serum urea, creatinine, myoglobin, creatine kinase (CK) and transaminases. Two serious medication errors have been identified as possible major factors that synergistically contributed to the development of rosuvastatin-induced rhabdomyolysis. First, 40 mg of rosuvastatin dose was prescribed to the patient, although the estimation of glomerular filtration rate (eGFR) declined below 40 ml/min/1.73 m2. Moreover, the patient used 3 different rosuvastatin formulations simultaneously in a total dose of 120 mg/day. The heterozygous CYP2C9*1/*3 genotype and warfarin co-administration could further contribute to the development of rhabdomyolysis. A number of preventive measures, notably in drug policy, are suggested to overcome unintended intoxications. Conclusion: Rosuvastatin-induced myopathy is a rare, but serious adverse effect. This case report highlights the need for a proper treatment and dose adjustment during chronic medical therapy, the need for adequate patient education and application of adequate drug policy measures in the era of fragmented health care delivery and polypragmasia.
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Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Erros de Medicação , Rabdomiólise/induzido quimicamente , Rosuvastatina Cálcica/efeitos adversos , Idoso , HumanosRESUMO
BACKGROUND: The aim of the study was to analyze the degree of obesity and its associations with age, gender, inflammation, an estimated glomerular filtration rate (eGFR), and liver function in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 874 consecutive adult Caucasian T2DM patients from outpatient diabetic clinic were included in the study. The relative fat mass (RFM) and body mass index (BMI) were used as obesity markers. Serum creatinine and cystatin C were used for the GFR estimation. Serum high-sensitive C-reactive protein (hsCRP) was used as the indicator of inflammation. RESULTS: The median, interquartile range (IQR) of RFM in females was higher than that in males (44.8 (42.3-47.2) % vs 31.3 (28.8-34.1) %, respectively; P < .0001). The median (IQR) of BMI in females was no higher than that in males (30 (27-34) kg/m2 vs 30 (27-34), respectively; P = .5152). The obesity prevalence was 99% in males and 98% in females according to RFM. BMI recognized obesity in 51% males and 53% females. RFM was positively associated with hsCRP in both males (rs = .296, P < .0001) and females (rs = .445, P < .0001). ALT was positively correlated with eGFRcys in both males (rs = .379, P < .0001) and females (rs = .308, P < .0001). CONCLUSION: The RFM equation leads to higher obesity prevalence compared to BMI. Women have higher RFM compared to men. The kidney function was positively correlated with ALT serum concentrations.
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Tecido Adiposo , Diabetes Mellitus Tipo 2/complicações , Taxa de Filtração Glomerular , Inflamação/etiologia , Tecido Adiposo/fisiopatologia , Idoso , Índice de Massa Corporal , Proteína C-Reativa/análise , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Estudos RetrospectivosRESUMO
The aim of this study was to provide evidence for the hypothesis that estimated glomerular filtration rate from serum Cystatin C (eGFRcys) is better to be determined for all elderly type 2 diabetes mellitus (T2DM) patients based on eGFRcys upward and downward reclassification rate for hypothetical metformin dose reduction by eGFRcys at the GFR decision point of 45 mL/min/1.73 m2 . A total of 265 consecutive T2DM elderly patients (age range 65-91 years) from outpatient diabetic clinic were included in the study. The Kidney Disease Improving Global Outcomes (KDIGO) guidelines for metformin dosing were strictly followed. Estimated glomerular filtration rate from serum creatinine (eGFRcrea) led to results of metformin eligibility. Each of the results of eGFRcrea-based eligibility was further compared to eGFRcys-based eligibility. Creatinine was measured by enzymatic method standardized against international reference material SRM 967. Cystatin C was determined by method traceable to DA ERM 471 international standard. eGFRcrea and eGFRcys were calculated according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. A downward reclassification rate was higher than upward reclassification rate (31 vs 3, respectively; P < 0.0001). The median (IQR) eGFRcrea was higher than eGFRcys (73 (58-85) vs 63 (50-75) mL/min/1.73 m2 , respectively; P < 0.0001). eGFRcys reclassified significant proportion of patients with T2DM from metformin eligible CKD stages to less or non-eligible stages. The downward reclassification was more frequent in patients older than 80 years (P < 0.01). Cystatin C-based eGFR selects more complicated patients, where lower doses of metformin are possibly advisable. We recommend calculating both eGFRcrea and eGFRcys for metformin dosing in elderly patients with T2DM.
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Cistatina C/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/administração & dosagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Creatinina/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Relação Dose-Resposta a Droga , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipoglicemiantes/administração & dosagem , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Estudos RetrospectivosRESUMO
Hyperkalemia is a potentially lethal condition. Pseudohyperkalemia should be always excluded before implementing treatment to prevent inappropriate cause of hypokalemia - equally a potentially lethal condition. Here we present a case report of a 62 year female with chronic myeloproliferative disorder, i.e. essential thrombocythemia. The laboratory test results for potassium concentration were 6.3 mmol/L, for platelet count 1305 x109/L and for leukocyte count 39.8 x109/L. This was due to a temporary drug withdrawal after a surgical intervention for gastric bleeding. Potassium concentration in lithium heparin plasma collected in a vacuum tube without gel separator and in whole blood syringe were 4.6 mmol/L and 3.4 mmol/L, respectively. It means that mechanical stress such as centrifugation can contribute to spurious hyperkalemia.Prior to reporting unexpected hyperkalemia result, pseudohyperkalemia should always be considered by the laboratory. Such potassium results require investigation in case it is pseudohyperkalemia, which may be due to thrombocytosis and leukocytosis. In cases where thrombocytosis or leukocytosis exists, an interpretative comment indicating these conditions inserted with the results of the potassium concentration can increase awareness for more accurate patient care decisions.
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Hiperpotassemia/diagnóstico , Potássio/sangue , Análise Química do Sangue/métodos , Coagulação Sanguínea , Plaquetas/citologia , Plaquetas/metabolismo , Centrifugação , Diagnóstico Diferencial , Feminino , Humanos , Janus Quinase 2/genética , Leucócitos/citologia , Leucócitos/metabolismo , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologiaRESUMO
Background Although measurement of drug serum levels is an objective direct method for testing compliance, it can be distorted by "white-coat compliance" or by variations in drug elimination. Objective The aim of this prospective study was to evaluate the prevalence of noncompliance with perindopril therapy in adult out-patients using pharmacokinetic simulations. The additional aim was to compare the predictive performance of two glomerular filtration rate markers-creatinine and cystatin C. Setting Department of Cardiology, Tomas Bata Regional Hospital in Zlín, Czech Republic. Method Perindoprilat pharmacokinetic models individualized according to patient characteristics were compared with measured perindoprilat serum concentrations to document compliance. Linear regression was used to evaluate the relations between perindoprilat clearance and glomerular filtration rate estimated using creatinine and cystatin C. Main outcome measure Assessment of non-compliance with medication using drug concentration measurements reinforced with therapeutic drug monitoring. Results Non-detectable perindoprilat levels were observed in 26.1% of patients. Another 21.7% were classified as non-compliant based on therapeutic drug monitoring pharmacokinetic simulations. Volume of distribution, clearance and half-life median value (interquarti°range) for perindoprilat were 408.3 (360.4-456.8) L, 10.1 (4.9-17.0) L h-1 and 24.7 (19.4-62.7) h, respectively. Linear regression models showed tight relationship between cystatin C and perindoprilat clearance. Conclusions Assessment of adherence with medication reinforced with therapeutic drug monitoring and pharmacokinetic simulations is proposed as an optimal method reducing disadvantages of simple drug concentration measurements. Cystatin C proves to be better surrogate marker for perindoprilat elimination than creatinine.
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Inibidores da Enzima Conversora de Angiotensina/metabolismo , Monitoramento de Medicamentos/métodos , Taxa de Filtração Glomerular/fisiologia , Adesão à Medicação , Taxa de Depuração Metabólica/fisiologia , Perindopril/metabolismo , Idoso , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Creatinina/metabolismo , Cistatina C/metabolismo , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Masculino , Taxa de Depuração Metabólica/efeitos dos fármacos , Perindopril/farmacologia , Projetos Piloto , Estudos ProspectivosRESUMO
OBJECTIVE: The article aimed to assess the benefit of incorporating maternal serum thyroid disease marker levels (thyroid-stimulating hormone and free thyroxine) into first trimester Down syndrome screening protocols. METHODS: Statistical modelling was used to predict performance with and without the thyroid markers. Two protocols were considered: the combined test and the contingent cell-free DNA (cfDNA) test, where 15-40% women are selected for cfDNA because of increased risk based on combined test results. Published parameters were used for the combined test, cfDNA and the Down syndrome means for thyroid-stimulating hormone and free thyroxine; other parameters were derived from a series of 5230 women screened for both thyroid disease and Down syndrome. RESULTS: Combined test: For a fixed 85% detection rate, the predicted false positive rate was reduced from 5.3% to 3.6% with the addition of the thyroid markers. Contingent cfDNA test: For a fixed 95% detection rate, the proportion of women selected for cfDNA was reduced from 25.6% to 20.2%. CONCLUSIONS: When screening simultaneously for maternal thyroid disease and Down syndrome, thyroid marker levels should be used in the calculation of Down syndrome risk. The benefit is modest but can be achieved with no additional cost. © 2017 John Wiley & Sons, Ltd.
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Biomarcadores/sangue , Síndrome de Down/diagnóstico , Diagnóstico Pré-Natal/métodos , Doenças da Glândula Tireoide/diagnóstico , Testes de Função Tireóidea/métodos , Adulto , Ácidos Nucleicos Livres/análise , Ácidos Nucleicos Livres/sangue , Síndrome de Down/sangue , Síndrome de Down/complicações , Síndrome de Down/fisiopatologia , Feminino , Humanos , Programas de Rastreamento/métodos , Valor Preditivo dos Testes , Gravidez , Primeiro Trimestre da Gravidez/sangue , Sensibilidade e Especificidade , Doenças da Glândula Tireoide/sangue , Glândula Tireoide/fisiopatologia , Tireotropina/análise , Tireotropina/sangue , Tiroxina/análise , Tiroxina/sangueRESUMO
BACKGROUND: Pegfilgrastim's role in reducing the risk of febrile neutropenia (FN) in patients with colorectal cancer (CRC) receiving chemotherapy plus bevacizumab was not previously evaluated in a prospective study. The present phase III, double-blind trial evaluated the efficacy of pegfilgrastim versus placebo in reducing the incidence of grade 3/4 FN in patients with advanced CRC receiving bevacizumab combined with first-line chemotherapy (FOLFOX [leucovorin, 5-fluorouracil, oxaliplatin] or FOLFIRI [leucovorin, 5-fluorouracil, irinotecan]). PATIENTS AND METHODS: Patients aged ≥ 18 years with locally advanced or metastatic CRC were randomized 1:1 to placebo or 6 mg of pegfilgrastim â¼24 hours after receiving chemotherapy plus bevacizumab every 14 days. The study treatment period included 4 cycles, but patients could continue treatment for ≤ 60 months. The primary endpoint was incidence of grade 3/4 FN in the first 4 cycles. The secondary endpoints included the objective response rate (ORR), overall survival, and progression-free survival, analyzed at the end of the long-term follow-up period. RESULTS: A total of 845 patients were randomized from November 2009 to January 2012 (422, pegfilgrastim; 423, placebo). Pegfilgrastim significantly reduced the incidence of grade 3/4 FN in the first 4 treatment cycles (pegfilgrastim, 2.4%; 95% confidence interval [CI], 1.1%-4.3%; placebo, 5.7%; 95% CI, 3.7%-8.3%; odds ratio [OR], 0.41; P = .014). No significant differences were observed between the 2 arms in ORR (OR, 1.15; P = .330), overall survival (hazard ratio, 0.94; P = .440), and progression-free survival (hazard ratio, 0.93; P = .300). CONCLUSION: Pegfilgrastim reduced the FN incidence in patients with advanced CRC receiving chemotherapy and bevacizumab. Administration of pegfilgrastim was tolerable and did not negatively affect the tumor response or survival in this patient population.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neutropenia Febril/prevenção & controle , Filgrastim/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Método Duplo-Cego , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/epidemiologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Incidência , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Taxa de Sobrevida , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto JovemRESUMO
BACKGROUND: The mini-invasive open posterior lumbar fusion procedure (mini PLIF) procedure is an alternative to standard open procedure (open PLIF) and is intended to reduce surgery-related trauma. The measuring of suitable biochemical factors enables objective comparison of the invasiveness of spinal surgery procedures. METHODS: Prospectively collected data on myoglobin, creatine kinase, interleukin-6, C-reactive protein levels and intensity of low back pain and radicular pain in one-level mini PLIF and open PLIF procedures were analysed. The mini PLIF and the open PLIF groups included 27 and 23 patients, respectively. The collection of blood samples and clinical data were performed preoperatively and on postoperative days 1, 3 and 7. The non-paired t-test was used for statistical evaluation. RESULTS: We did not found any statistically significant differences of myoglobin and creatine kinase levels between the groups. In the open PLIF group the IL-6 levels were significantly higher than in the mini PLIF group on postoperative day 3. CRP levels showed significant lower stress response in favour of the mini PLIF group on postoperative days 3 and 7. Levels of post-op low back pain on day 3 were significantly lower in mini PLIF group. Also intensity of radicular pain on day 1 and 3 were lower also mini PLIF group. CONCLUSION: The extent of myonecrosis was comparable in both techniques. The analysis of the IL-6 and CRP levels showed significantly lower systemic inflammatory response in mini PLIF technique. The mini PLIF technique provides transiently lower postoperative pain levels.
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Creatina Quinase/sangue , Interleucina-6/sangue , Dor Lombar/sangue , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Mioglobina/sangue , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/sangue , Fusão Vertebral/métodos , Proteína C-Reativa , Feminino , Humanos , Dor Lombar/fisiopatologia , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologiaRESUMO
BACKGROUND: One of the methods to compare the invasiveness of different surgical techniques objectively is to measure the levels of biochemical markers of systemic inflammatory response and muscle damage. METHODS: A total of 120 patients undergoing surgery for symptomatic disc herniation at L4-L5 and L5-S1 were enrolled in the study. Patients were operated on using open discectomy (OD), microsurgical discectomy (MD), or microsurgical discectomy with tubular retractor (MD-TUB). Myoglobin (MYO) and creatine kinase (CK) levels were used as indicators of muscle damage, and interleukin-6 (IL-6) and C-reactive protein (CRP) levels were used as indicators of systemic inflammatory response. Sampling and analysis of samples were performed preoperatively and on postoperative days 1, 3, and 7. Levels of postoperative low back pain and radicular pain were recorded on a 10-grade visual analog scale. Statistical evaluation was performed using the analysis of variance test. RESULTS: MYO concentrations in the MD-TUB group on postoperative day 1 were significantly lower than in the MD and OD groups. CK values on postoperative day 1 were significantly lower in microsurgical techniques (MD and MD-TUB) than in the OD group. The lowest IL-6 levels were found in the MD-TUB group, followed by the MD and OD groups. Differences in the IL-6 levels were significant between the groups on postoperative day 1. On all postoperative days that were monitored, values of CRP in the MD-TUB group were significantly lower compared with the MD and OD groups. Lower values in the MD group versus OD group were not statistically significant. CONCLUSION: All studied techniques showed similar efficacy in reducing radicular pain. The microsurgical diskectomy using a retractor in comparison with MD and OD is friendlier toward the paraspinal muscles, but the difference is significant only for the MYO levels. The total stress inflammatory response exhibited by patients undergoing the MD-TUB technique is significantly lower compared with the MD and OD techniques.
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Biomarcadores/sangue , Discotomia/métodos , Inflamação/sangue , Deslocamento do Disco Intervertebral/cirurgia , Microcirurgia/métodos , Músculo Esquelético/lesões , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/sangue , Adulto , Proteína C-Reativa/análise , Creatina Quinase/sangue , Discotomia/efeitos adversos , Discotomia/instrumentação , Feminino , Humanos , Interleucina-6/sangue , Vértebras Lombares , Masculino , Microcirurgia/efeitos adversos , Pessoa de Meia-Idade , Mioglobina/sangue , SacroRESUMO
BACKGROUND: Potentially myelosuppressive doublet and triplet chemotherapy combination regimens are considered the most active treatments in gastric cancer. This multicenter prospective observational study was designed to gain insight into the chemotherapy regimens being used in Europe and to evaluate neutropenia management in patients identified as at high risk for febrile neutropenia (FN). METHODS: Eligible patients had gastric cancer, were scheduled for ≥ 3 cycles of myelosuppressive chemotherapy, and had an investigator-assessed overall FN risk ≥ 20%. Data were collected for up to ten cycles. The primary endpoint was the proportion of patients who received granulocyte colony stimulating factor (G-CSF) primary prophylaxis (defined as G-CSF initiated on days 1-7 of cycle 1). Secondary endpoints included FN incidence, chemotherapy administration, and G-CSF use. RESULTS: Of 199 patients who met the eligibility criteria and started at least one cycle of chemotherapy, mean age was 63 years, 76% were men, 83% had an ECOG score of 0 or 1, 54% had metastatic disease, and 24% had received prior chemotherapy. A total of 27 different backbone regimens were given; the most common regimen was modified docetaxel, cisplatin, and 5-fluorouracil (DCF). Despite all patients having been identified as having a ≥ 20% FN risk, only 70 (35%) received G-CSF primary prophylaxis. FN occurred in 14 patients overall (7%). Most FN events occurred in patients who received DCF/modified DCF (9/14 events, 64%). CONCLUSIONS: The results of this study reveal a high use of myelotoxic treatment regimens in gastric cancer in Europe and low adherence to clinical practice guidelines for the use of primary and secondary G-CSF prophylaxis for FN.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/secundário , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Neoplasias Gástricas/patologiaRESUMO
AIM: The aim of this study is to compare markers of glomerular filtration rate (GFR), estimated GFR (eGFR), and metabolic parameters between admission and recovery in 13 patients of Tomas Bata hospital with methanol poisoning during methanol problems in the Czech Republic in 2012. The impact of methanol concentration and age on metabolic parameters were discovered at the time of admission to hospital. MATERIALS AND METHODS: The serum osmolality, methanol, ethanol, creatinine, cystatin C, Troponin I, ALT, plasma pH and lactate were measured in these 13 patients. The eGFR from serum creatinine (creatnine eGFR) and from cystatin C (cystatin C eGFR) were also determined. RESULTS: Increased serum osmolality and markers of metabolic acidosis are key indirect laboratory findings in patients with methanol poisoning. There were no significant changes in eGFR in our patients between admission and recovery. Increased serum troponin I concentration was confirmed as an indicator of myocardial necrosis in four patients. Two patients developed acute kidney injury (AKI) before admission. CONCLUSIONS: We found statistically significant differences in serum osmolality concentration, plasma pH and lactate between admission and recovery. We found no changes in eGFR between admission and recovery. One patient had vision problems due to damage to the occipital lobes. Methanol poisoning may cause increase in markers of cardiac damage.