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Congo red (CR) type self-assembled ribbon-like structures (SRLS) were previously shown to interact with some proteins, including albumin. SRLS also complex with some drugs with a flat, ring-shaped structure with aromatic characteristics, intercalating them into their ribbon structure. The combination of interaction with proteins and drug binding by SRLS enables the use of such systems for immunotargeting. It is especially interesting in the case of chemotherapeutic agents. The present experiments aimed to show that the model carrier system composed of supramolecular albumin and Congo red efficiently binds doxorubicin (Dox) and that the drug can be released at reduced pH. The presented results come from the studies on such complexes differing in the molar ratio of CR to Dox. The following methods were used for the analysis: electrophoresis, dialysis, gel filtration, spectral analysis, and analysis of the size of the hydrodynamic radius using the dynamic light scattering method (DLS). The applied methods confirmed the formation of the CR-Dox complex, with large dimensions and changed properties compared with free CR. The presented results show that albumin binds both CR and its complex with Dox. Various CR-Dox molar ratios, 5:1, 2:1, and 1:1, were analyzed. The confirmation of the possibility of releasing the drug from the carriers thus formed was also obtained. The presented research is important due to the search for optimal solutions for the use of SRLS in drug immunotargeting, with particular emphasis on chemotherapeutic agents.
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Antineoplásicos , Vermelho Congo , Albuminas , Antineoplásicos/química , Corantes , Vermelho Congo/química , Vermelho Congo/metabolismo , Doxorrubicina/química , Sistemas de Liberação de Medicamentos/métodos , Ligantes , Proteínas , Diálise RenalRESUMO
BACKGROUND: One of the greatest success of pediatric hematology is a prominent improvement of survival in acute lymphoblastic leukemia (ALL). Therefore, special attention needs to be paid to long-term side effects of the treatment such as neurotoxicity. One of the few diagnostic methods that allow an objective assessment of sensory systems are evoked potentials (EP). METHODS: The analyzed group consisted of 167 ALL long-term survivors, aged 4.9-28.4 years, without auditory, visual and sensory deviations. Patients were treated with New York (NY, n = 35), previous modified Berlin-Frankfurt-Münster (pBFM, n = 47) and BFM95 (n = 85) protocols. In order to assess the impact of radiotherapy on recorded EP, a joint analysis of NY and pBFM groups was performed. The control group consisted of 35 patients, aged 6-17 years. The analyzed patients underwent a complex assessment with visual EP (VEP), somatosensory EP (SEP) and brainstem auditory EP (BAEP) in accordance with current standards. RESULTS: ALL treatment contributed to the shortening of wave I latency (1.59 vs 1.90, P = 0.003) and prolongation of I-III (2.23 vs 2.04, P = 0.004) and I-V (4.57 vs 4.24, P = 0.002) interwave latencies of BAEP. A significant effect was also noticed in P100 (106.32 vs 101.57, P < 0.001) and N135 (151.42 vs 138.22, P < 0.001) latencies of VEP and N18 amplitude (3.24 vs 4.70, P = 0.007) and P25 latency (21.32 vs 23.39, P < 0.001) of SEP. The distribution of abnormalities between protocols was similar in BAEP (NY - 68.6%, pBFM - 61.7%, BFM95-69.4%, P = 0.650), VEP (NY - 68.6%, pBFM - 42.5%, BFM95-58.3%, P = 0.053) and significantly different for SEP (NY - 62.9%, pBFM - 36.2%, BFM95-53.0%, P = 0.045). The harmful effect of radiotherapy was most clearly marked in numerous disturbances of SEP parameters. CONCLUSIONS: The presented analysis indicates a high frequency of subclinical abnormalities in EP regardless of the analyzed protocol. To our knowledge current study is the largest and one of the most complex research examining the role of EP in ALL patients. The obtained results indicate the possibility of using a single, objective and non-invasive measurement of EP in ALL survivors in order to stratify the risk of developing sensory abnormalities in adulthood.
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Sobreviventes de Câncer/estatística & dados numéricos , Terapia Combinada/métodos , Potenciais Evocados Auditivos do Tronco Encefálico , Potenciais Somatossensoriais Evocados , Potenciais Evocados Visuais , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
OBJECTIVES: The Fontan procedure is the treatment of choice in congenital cardiac malformations defined as the single ventricle. Fontan patients are at high risk of thromboembolism, but the exact mechanism of this is poorly understood. The aim of this study was to evaluate an involvement of thrombin generations and microparticles (MPs) in prothrombotic state in adults with Fontan circulation. METHODS: This study included hospitalized patients after Fontan procedure and healthy volunteers. We assessed laboratory tests including thrombin generation by calibrated automated thrombography in three variants [platelet-poor plasma (impact of coagulation factors), platelet-rich plasma (PRP) (influence of platelets) and related with MPs]. The technique allows for a comprehensive evaluation of the coagulation system. RESULTS: The study groups consisted of 81 adult Fontan patients [41 females (50.6%); median age 22 interquartile range [20-27] years] and 54 control subjects. In patients with Fontan circulation, higher values of endogenous thrombin potential and peak values were observed for both platelet-poor plasma (+17% and +33%) and MPs (+29% and 41%) compared to controls (all P < 0.05). Moreover, in the Fontan group, we found a 64.9% shorter lag time and a 70.4% time to peak for MP variant (both P < 0.001). Contrarily, analysis in the PRP showed 17.1% of reduced endogenous thrombin potential in Fontan. Furthermore, there were no differences in thrombin synthesis in PRP in Fontan patients receiving aspirin or those with thrombocytopaenia (all P > 0.05). CONCLUSIONS: This study for the first time showed that thrombin generation associated with MPs may be an important contributor to the prothrombotic state in the Fontan population.
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Técnica de Fontan , Tromboembolia , Feminino , Humanos , Adulto , Adulto Jovem , Trombina , Técnica de Fontan/efeitos adversos , Coagulação Sanguínea , Plaquetas , Testes de Coagulação SanguíneaRESUMO
BACKGROUND: Primary melanoma of the esophagus (PME) represents a rare type of gastrointestinal malignancy with an exceptionally poor diagnosis. So far, only few descriptions of PME which satisfactorily summarize their clinical characteristics and prognosis have been published. OBJECTIVES: The aim of our study was to summarize our experience with PME patients. MATERIAL AND METHODS: In a group of 1387 patients who underwent esophagectomy due to neoplastic process in the years 2000-2020 in 2 high-volume university thoracic surgery centers, we identified those with confirmed PME diagnosis. Subsequently, their clinical characteristics, imaging and histopathological results were compared. The data regarding the long-term survival were obtained from the Polish National Death Registry. RESULTS: The PME was identified in 4 (0.29%) patients. Three of them (75%) were males. The mean age on admission was 64.3 ±17.5 years. The main symptom in all patients was dysphagia. In 1 patient with the most advanced PME, the clinically relevant weight loss was noted. In 3 patients, Ivor Lewis esophagectomy was performed, and 1 patient underwent McKeown resection. Histopathologic examination revealed a metastasis of lymph nodes only in 1 patient. The average maximum size of tumor was 6.9 ±4.7 cm and all tumors were located in distal part of the esophagus. Two out of those 4 patients are still alive and the longest survival time is 17 years. One patient died due to postoperative massive gastrointestinal bleeding complicated with cardiac arrest and the other one due to progression of PME systemic dissemination 6 months after surgical treatment. CONCLUSION: The PME is an extremely rare diagnosis. A long-term survival can be achieved with the complete resection. Clinical scenarios of surgically treated PME patients may significantly differ.
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Neoplasias Esofágicas , Melanoma , Cirurgia Torácica , Idoso , Idoso de 80 Anos ou mais , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Feminino , Humanos , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , UniversidadesRESUMO
BACKGROUND: Ventricular septal defect (VSD) is one of the most common congenital heart defects. Currently, surgery remains the treatment of choice. However, transcatheter techniques for closing of various types of VSDs have become an alternative. AIMS: The objective of our study was to present the outcomes of transcatheter closure of various types of VSD based on a systematic review of recent publications. METHODS: A systematic review of studies published in English between January 2014 and March 2020 was performed using the PubMed database (MEDLINE) independently by 2 reviewers. Data on success and complication rates were extracted. Studies including fewer than 5 patients and those with acquired VSD were excluded from the analysis. RESULTS: Finally, 44 studies were included for analysis, with a total number of 4050 patients. The pooled estimate of the overall success rate based on the random effects model was 97.96% (95% CI, 97.37-98.56; Q test P 0.99; I 2 = 0%) for permanent VSD. CONCLUSIONS: Transcatheter closure of selected VSDs appears to be an effective and safe method of treatment. Recent studies have shown high rates of successful interventions with a low incidence of complications.
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Cateterismo Cardíaco , Comunicação Interventricular , Cateterismo Cardíaco/efeitos adversos , Comunicação Interventricular/cirurgia , Humanos , Projetos de Pesquisa , Resultado do TratamentoRESUMO
BACKGROUND: Recently heart failure (HF) has been found to be a new dementia risk factor; nevertheless, their relations in patients following HF decompensation remain unknown. We sought to investigate whether a screening diagnosis for dementia (SDD) in this high-risk population may predict unfavorable long-term clinical outcomes. METHODS: One hundred forty-two patients following HF decompensation requiring hospitalization were enrolled. Within a median time of 55 months all patients were screened for dementia with ALFI-MMSE scale whereas their compliance was assessed with the Morisky Medication Adherence Scale. Any incidents of myocardial infarction, coronary revascularization, stroke or transient ischemic attack (TIA), revascularization, HF hospitalization and bleedings during follow-up were collected. RESULTS: SDD was established in 37 patients (26%) based on the result of an ALFI-MMSE score of <17 points. By multivariate analysis the lower results of the ALFI-MMSE score were associated with a history of stroke/TIA (ß=-0.29, P<0.001), peripheral arterial disease (PAD) (ß=-0.20, P=0.011) and lower glomerular filtration rate (ß=0.24, P=0.009). During the follow-up, patients with SDD were more often rehospitalized following HF decompensation (48.7% vs. 28.6%, P=0.042) than patients without SDD, despite a similar level of compliance (P=0.25). Irrespective of stroke/TIA history, SDD independently increased the risk of rehospitalization due to HF decompensation (HR 2.22, 95% CI: 1.23-4.01, P=0.007). CONCLUSIONS: In patients following decompensated HF, a history of stroke/TIA, PAD and impaired renal function independently influenced SDD. In this high-risk population, SDD was not related with patients' compliance but irrespective of the stroke/TIA history it was associated with the increased risk of HF rehospitalization.
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Demência , Insuficiência Cardíaca , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Idoso , Demência/diagnóstico , Insuficiência Cardíaca/diagnóstico , Humanos , Volume SistólicoRESUMO
INTRODUCTION: As severe complication of appendicitis as effusive pericarditis is a rare phenomenon. Taking into consideration open access data in a 50-year period we perceived three pediatric cases with pericarditis as a complication of appendicitis. PRESENTATION OF CASE: We report a 15-year-old boy who presented cardiac tamponade, bilateral pleural effusions, liver enlargement and ascites as a presentation of atypical appendicitis. DISCUSSION: Even nowadays appendicitis could be difficult to diagnose in children. A delayed diagnosis could be responsible for severe morbidity and mortality. CONCLUSION: This report is aimed to be a reminder of serious life-threatening complications after a common abdomen condition - appendicitis.
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Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with one of the highest survival rates. Long-term complications that occur after intensive oncological treatment often impair normal daily functioning. However, existing data on peripheral nervous system condition in ALL survivors remain conflicting. Materials and Methods: The study group consisted of 215 ALL survivors. Patients were treated with New York (NY, n = 45), previous modified Berlin-Frankfurt-Münster (pBFM, n = 64), and BFM95 (n = 106) protocols. Time elapsed between the end of the treatment and the control examination varied from 0.3 to 20.9 years. The analyzed patients underwent a neurophysiological analysis with electroneurography (ENG) of motor (median and peroneal) and sensory (median and sural) nerves as well as electromyography (EMG) of tibialis anterior, vastus lateralis, and interosseous I muscles. To estimate the influence of radiotherapy on recorded neurophysiological responses, a joint analysis of NY, and pBFM groups was performed. Results: Clinical symptoms of polyneuropathy were noted among 102 (47.4%) children during the ALL therapy and in 111 (51.6%) during follow-up. At the time of treatment, polyneuropathy was diagnosed in 57.8% participants from NY group, 35.9%-pBFM and 50.0%-BFM95 (p = 0.145). A significantly higher incidence of polyneuropathy was observed during a follow-up in the NY group (68.9%; p < 0.001 vs. pBFM, p = 0.002 vs. BFM95). The most frequent abnormality within all the protocols was demyelination (NY: 44.4%, pBFM: 59.4%, BFM95: 41.5%), in contrast to the least frequently registered isolated axonal changes. The negative influence of oncological treatment on neurophysiological parameters in ALL survivors was observed. Complex disorders of motor nerves, sensory nerves, and motor unit potentials were registered. Motor-sensory neuropathy was the most frequently found pathology in all analyzed protocols. The harmful effect of radiotherapy was also observed in EMG results. Conclusions: Detailed neurophysiological analysis in long-term childhood ALL survivors has shown generalized abnormalities in registered parameters. To our knowledge, the current study is the largest and one of the most comprehensive ones among those examining disturbances in ENG and EMG in this group of patients. Moreover, we are the first ones to demonstrate the negative influence of radiotherapy on peripheral nerve conduction parameters.
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BACKGROUND: We sought to investigate whether baseline characteristics of patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) may predict their coronary artery disease (CAD) burden. METHODS: Baseline clinical, ECG and laboratory data were compared with angiographic findings of 693 consecutive NSTEACS patients. According to the angiography result all patients were assigned to one of the three groups with: significant stenosis of left main and/or three-vessel CAD (LM-3VD, N.=114), single- or two-vessel CAD (1-2VD, N.=335) or without significant CAD (noVD, N.=244). RESULTS: Baseline characteristics of compared groups were different. By multivariable logistic regression necrotic enzyme negative ACS (odds ratio [OR] 5.57, 95% CI: 3.74-8.29), female gender (OR=2.23, 95% CI: 1.54-3.24), no previous myocardial infarction (OR=2.06, 95% CI: 1.38-3.08), no diabetes mellitus (OR=1.53, 95% CI: 1.04-2.25), no peripheral arterial disease (OR=1.77, 95% CI: 1.05-2.99) and hematocrit level (0.95 per 1%, 0.91-0.99) independently predicted noVD (χ2=145.8, P<0.0001) with c-statistics of 0.80. All independent predictors were ranked according to the results of multivariable model and the new score for prediction of noVD was introduced with the area under the ROC curve of 0.77 (95% CI: 0.73-0.80, P<0.0001) and sensitivity of 70% and specificity of 66% for <5 points. Also, independent predictors of LM-3VD (age, male gender, diabetes mellitus, peripheral arterial disease, necrotic enzyme positive ACS and baseline Killip Class 3/4) were determined, however their predictive accuracy was moderate with the area under the ROC curve of 0.69 (95% CI: 0.64-0.75). CONCLUSIONS: In patients with NSTEACS, baseline characteristics are useful in predicting a lack of significant CAD, whereas their correlations with multivessel CAD remain moderate.
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Síndrome Coronariana Aguda/fisiopatologia , Doença da Artéria Coronariana/fisiopatologia , Síndrome Coronariana Aguda/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/fisiopatologia , Efeitos Psicossociais da Doença , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
Introduction Lung cancer is the most common cause of cancerrelated death. Accurate and easytouse prognostic factors are necessary. Increased platelet count might be a potential prognostic factor. Objectives We aimed to investigate the relationship between thrombocytosis and stage of lung cancer and to assess the frequency and clinical importance of thrombocytosis in this patient group. Patients and methods We retrospectively analyzed hospital records of consecutive patients with non-small cell lung cancer (NSCLC) who underwent curativeintent pulmonary resections. Results Of 323 patients, 285 patients with NSCLC were selected (mean [SD] age, 66.55 [8.52] years; men, 63.86%). Squamous cell carcinoma was diagnosed in 130 patients (45.61%); adenocarcinoma, in 128 (44.91%); large cell carcinoma, in 16 (5.61%); and adenosquamous carcinoma, in 11 (3.86%). The prevalence of preoperative thrombocytosis in the whole sample was 10.18% (n = 29). Anemia was more common in patients with thrombocytosis compared with those without thrombocytosis (65.52% vs 30.08%; P <0.001). Thrombocytosis was found in 22.41% of patients with stage III+IV cancer and in 3.82% of those with stage I (P <0.001). Moreover, in patients with no metastases (N0, M0 according to the 7th edition of the TNM classification), thrombocytosis was more frequent in the group with stage II than in that with stage I cancer (3.85% vs 20.00%; P = 0.002). Thrombocytosis was also more frequent in patients with N2 than with N1 disease (9.76% vs 23.81%; P = 0.09). Conclusions Thrombocytosis is often observed in patients with NSCLC and is significantly associated with the higher stage of disease.