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1.
Eur Rev Med Pharmacol Sci ; 27(12): 5507-5514, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37401286

RESUMO

OBJECTIVE: In this study, we measured the levels of Kelch-like ECH-associated protein 1 (KEAP1), which has the potential antioxidant capacity, among non-ST elevation myocardial infarction (NSTEMI) patients compared with healthy controls. We also investigated the possible association between KEAP1 levels and the GRACE score, which is a universal risk score commonly used for patients with acute myocardial infarction. PATIENTS AND METHODS: As the patient group, 78 patients admitted to our center with a diagnosis of NSTEMI were included in the study. As the control group, 77 individuals found to have normal coronary arteries after coronary arteriography were included (155 patients in total). GRACE risk scores and left ventricular ejection fractions (LVEFs) were calculated, KEAP1 levels were measured, and the usual blood tests were performed. RESULTS: KEAP1 levels were significantly higher among the NSTEMI patients compared to the healthy control group (671.1 ± 120.7 vs. 262.7 ± 105.7, p < 0.001). We also found a moderate positive correlation between KEAP1 levels and GRACE risk scores among patients with NSTEMI (r = +0.521, p < 0.001). Additionally, a negative correlation between KEAP1 levels and LVEFs was detected (r = -0.264, p < 0.001). CONCLUSIONS: Elevated KEAP1 levels have the potential to be used as a risk factor for NSTEMI in terms of clinical adverse events and poor prognosis at admission.


Assuntos
Infarto do Miocárdio , Infarto do Miocárdio sem Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Proteína 1 Associada a ECH Semelhante a Kelch , Medição de Risco , Fator 2 Relacionado a NF-E2 , Fatores de Risco , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/complicações , Prognóstico
2.
Eur Rev Med Pharmacol Sci ; 27(13): 6437-6444, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37458667

RESUMO

OBJECTIVE: In this study, we aimed to assess the predictive value of Intermountain Risk Score (IMRS) in intensive care unit (ICU) patients with COVID-19. PATIENTS AND METHODS: Our retrospective study included the data of 194 patients who were admitted to the COVID-19 ICU of a tertiary care center. COVID-19 diagnoses were made by a positive result from a real-time reverse-transcriptase (RT) polymerase chain reaction (PCR) assay of nasal and pharyngeal swab specimens. Patients who had negative RT-PCR results or who were not admitted to ICU and patients under 18 years old were excluded from the study. Complete blood count, biochemistry panel, and blood gas analysis results were gathered and compiled. RESULTS: 194 ICU patients with COVID-19 (PCR positive) were included in the study. The patients were divided into two groups according to IMRS (if IMRS was <15 in women and <17 in men, patients were included in the non-high-risk group, while patients with IMRS ≥15 in women and ≥17 in men were defined as a high-risk group). Multivariate regression analysis was performed to predict in-hospital mortality. The IMRS [OR: 1.17 (1.08-1.27) p<0.001)] was found to predict in-hospital mortality. CONCLUSIONS: In this study, we showed that the IMRS score at admission can predict in-hospital mortality in intensive care unit patients with a diagnosis of COVID-19.


Assuntos
COVID-19 , Masculino , Humanos , Feminino , Adolescente , Prognóstico , COVID-19/diagnóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Unidades de Terapia Intensiva , Teste para COVID-19
3.
Nutr Cancer ; 74(9): 3284-3291, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35543082

RESUMO

PURPOSE: The aim of this study was to investigate the effect of the body fat mass ratio on survival and prognosis in advanced non-small-cell lung cancer patients. METHODS: The study includes 200 patients who were diagnosed with advanced non-small-cell lung cancer between 2014 and 2018 and whose body fat mass percentage and body mass index (BMI) were determined using the Tanita Body Composition Analyzer during admission. RESULTS: All patients had advanced incurable non-small-cell lung cancer (30% had locally advanced disease, 70% were stage IV). In the univariate and multivariate analyses, age, gender, histopathological type, smoking history, comorbidities, weight loss in the last six months and body mass index had no statistically significant effect on survival (p > 0.05). However, the performance status (p = 0.008), metastatic status (p = 0.003) and body fat mass ratio (p = 0.01) were found to have a significant effect on overall survival (OS): the median OS was 16.4 mo, in patients with the BFM ratio ≤ 22% and 29.2 mo, in those with > 22% (p = 0.01). CONCLUSION: In this study, it was found that the body fat mass ratio was an important prognostic factor in patients with advanced non-small-cell lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Tecido Adiposo , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Lactente , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
4.
Ann Oncol ; 33(5): 488-499, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35124183

RESUMO

BACKGROUND: In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up. PATIENTS AND METHODS: Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or six cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including four-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs). RESULTS: With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months [hazard ratio (95% confidence interval), 0.73 (0.61-0.87)], and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the four-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for 1 year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation. CONCLUSIONS: With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.


Assuntos
Mesotelioma Maligno , Nivolumabe , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Ipilimumab/efeitos adversos , Nivolumabe/uso terapêutico , Intervalo Livre de Progressão
5.
Niger J Clin Pract ; 25(2): 197-199, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35170447

RESUMO

In patients with type 1 neurofibromatosis (NF1), there is an increased susceptibility to tumor development in the central nervous system due to the loss of neurofibromin, an inactivator of the protooncogene Ras. NF1 has a broad clinical spectrum,which includes spinal tumors. Although the most common intramedullary tumor of the spinal cord in adults is ependymoma, few patients with NF1 accompanied by spinal ependymoma have been reported to date, and the localization of the tumors is cervical and thoracic in these cases. In this study, we report the case of a patient with NF1 presenting to our clinic with low back pain and gait disturbance. The patient had an intradural extramedullary ependymoma at the L2-3 vertebra level. This report is the first case of NF1 with spinal ependymoma localized in the lumbar region.


Assuntos
Ependimoma , Neurofibromatoses , Neurofibromatose 1 , Adulto , Ependimoma/cirurgia , Humanos , Vértebras Lombares/diagnóstico por imagem , Região Lombossacral , Imageamento por Ressonância Magnética , Neurofibromatose 1/complicações
6.
Sci Immunol ; 6(65): eabk1741, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34591653

RESUMO

Severe coronavirus disease 2019 (COVID-19) pneumonia survivors often exhibit long-term pulmonary sequelae, but the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high-dimensional characterization of the pathophysiological and immune traits of aged COVID-19 convalescents, and correlated the local and systemic immune profiles with pulmonary function and lung imaging. We found that chronic lung impairment was accompanied by persistent respiratory immune alterations. We showed that functional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)­specific memory T and B cells were enriched at the site of infection compared with those of blood. Detailed evaluation of the lung immune compartment revealed that dysregulated respiratory CD8+ T cell responses were associated with the impaired lung function after acute COVID-19. Single-cell transcriptomic analysis identified the potential pathogenic subsets of respiratory CD8+ T cells contributing to persistent tissue conditions after COVID-19. Our results have revealed pathophysiological and immune traits that may support the development of lung sequelae after SARS-CoV-2 pneumonia in older individuals, with implications for the treatment of chronic COVID-19 symptoms.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/microbiologia , Memória Imunológica , Pulmão/imunologia , SARS-CoV-2/imunologia , Linfócitos B/patologia , Linfócitos T CD8-Positivos/patologia , COVID-19/patologia , Feminino , Humanos , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade
7.
Bull Exp Biol Med ; 171(4): 468-471, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34542759

RESUMO

The efficacy of a new photosensitizer of chlorin E6 conjugated with a prostate-specific membrane antigen (PSMA) in photodynamic therapy of murine melanoma B16 was studied in in vivo experiments. The dynamics of photosensitizer accumulation in the tumor and surrounding tissues was evaluated and antitumor efficacy of photodynamic therapy was assessed by parameters of regression and morphological characteristics of experimental transplanted melanoma B16. The inhibitory effect of photodynamic therapy on melanoma was evaluated by complete regression of the tumor, absolute tumor growth coefficient in animals with continuation of tumor growth, and the increase in life span in comparison with the control; the criterion of cure was the absence of signs of tumor recurrence in mice within 90 days after therapy. The therapeutic potential of photodynamic therapy was determined by devitalization of tumor cells (histological examination of the zones of laser exposure on day 21 after treatment). The photosensitizer with PSMA-ligand exhibited high antitumor activity in photodynamic therapy for melanoma B16. Photodynamic therapy carried out at the optimum time after photosensitizer injection with experimentally determined parameters of laser exposure allows achieving the maximum inhibitory effect on melanoma. Pathomorphological study in the zones of exposure detected no survived tumor cells.


Assuntos
Clorofilídeos/uso terapêutico , Melanoma Experimental/tratamento farmacológico , Fotoquimioterapia/métodos , Neoplasias Cutâneas/tratamento farmacológico , Ureia/análogos & derivados , Animais , Linhagem Celular Tumoral , Clorofilídeos/química , Clorofilídeos/farmacocinética , Feminino , Ligantes , Melanoma Experimental/diagnóstico por imagem , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Ureia/química , Ureia/farmacocinética , Ureia/uso terapêutico
8.
Bratisl Lek Listy ; 122(9): 636-642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34463109

RESUMO

PURPOSE: The geriatric nutritional risk index (GNRI) is a simple and objective nutritional assessment tool for elderly patients. Lower GNRI values are associated with a worse prognosis in heart failure with reduced ejection fraction (HFrEF). Our aim is to investigate the relationship between malnutrition and follow-up cardiovascular (CV) events in HFrEF. METHODS: A retrospective study was performed on 362 patients with HFrEF. The baseline GNRI was calculated at the first visit. The patients were divided into three groups according to the GNRI: >98, no-risk group; 92 to ≤98, low risk group; 82 to <92, moderate­to­high­risk group. The study endpoint was a composite of follow-upCV events, including all-cause mortality, non-valvular atrial fibrillation (NVAF) , need for cardioverter defibrillator (ICD) therapy, HfrEF­related hospitalizations and need for percutaneous coronary interventions (PCIs). RESULTS: Follow-up data showed that the group with moderate-to-high risk had a significantly higher incidence of NVAF, PCIs and all-cause mortality compared to other groups (p<0.001, p: 0.026 and p0.05). Mean GNRI value was 83.3 in NVAF patients and 101.1 in patients without NVAF (p<0.001). Kaplan Meier survival analysis showed that patients from the group with moderate-to-high risk had a significantly worse survival rate (p < 0.001). In the multivariate Cox regression analysis, the group with moderate-to­high risk (HR=3.872) and ICD implantations (HR=4.045) were associated with increased mortality. CONCLUSION: The GNRI value may have a potential role for predicting future events, especially NVAF in patients with HfrEF (Tab. 4, Fig. 2, Ref. 27).


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Avaliação Geriátrica , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Humanos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico
9.
Acta Gastroenterol Belg ; 84(2): 283-288, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34217176

RESUMO

BACKGROUND AND STUDY AIMS: Percutaneous endoscopic gastrostomy (PEG) is a procedure that provides long term enteral nutrition. To investigate the predictors of PEG-related complications and 30-day mortality rates and evaluate the indicators for deciding whether to recommend elective PEG insertions, we sought to determine the complications and early mortality rates of patients who underwent PEG. PATIENTS AND METHODS: We performed a retrospective analysis of consecutive adult patients who had undergone PEG for the first time between October 2016 and January 2019. The predictors of complications and 30-day mortality were analyzed with receiver operating characteristic (ROC) and logistic regression analysis. RESULTS: This study included 309 patients. Patients were excluded from the study if they were < 18 years of age or there were missing data about them. Out of 253 patients, 33 (13%) had complications and 32 (12.6%) died within one month after PEG insertion. A higher C-reactive protein (CRP) to albumin ratio was the only independent factor predicting the complications (odds ratio (OR) : 3.17 ; 95% CI : 1.26-8.00 ; p = 0.014). The independent predictive factors for 30-day mortality after PEG placement included higher urea levels and higher CRP to albumin ratios (OR : 3.78 ; 95% CI : 1.41-10.17 ; p = 0.008) (OR : 6.67 ; 95% CI : 1.87- 23.75 ; p = 0.003). The only predictor for both complications and 30-day mortality was the CRP to albumin ratio. CONCLUSIONS: When appropriate, the PEG procedure can provide a safe and effective method for enteral feeding. The CRP to albumin ratio can be used to predict complications and early mortality after PEG insertion. Because PEG is elective, higher CRP to albumin ratios can be helpful in deciding to select patients for the procedure.


Assuntos
Proteína C-Reativa , Gastrostomia , Adulto , Proteína C-Reativa/análise , Nutrição Enteral , Humanos , Estudos Retrospectivos , Fatores de Risco
10.
Bull Exp Biol Med ; 170(4): 479-484, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33713230

RESUMO

We studied the effectiveness of photodynamic therapy with the photosensitizer Photoran E6 on the model of rat sarcoma M-1 positive for mutant p53 gene. Experiments showed that Photoran E6 exhibits high antitumor activity in photodynamic therapy of solid tumor of the connective tissue. Photodynamic therapy carried out during the optimal period after injections of Photoran E6 with the determined parameters of laser exposure allows achieving the maximum inhibitory effect on sarcoma M-1: 100% cured animals. Immunohistochemical study revealed no live tumor cells with expression of the mutant p53 protein in areas of photodynamic exposure.


Assuntos
Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Sarcoma/terapia , Animais , Imuno-Histoquímica , Ratos , Proteína Supressora de Tumor p53/metabolismo
11.
Future Oncol ; 17(13): 1611-1624, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33631986

RESUMO

Aim: To assess the efficacy and tolerability of the first-line treatment options for hormone-refractory prostate cancer patients with visceral metastases. Materials & methods: The records of 191 patients diagnosed with hormone-refractory prostate cancer with visceral metastases were analyzed retrospectively. Results: Docetaxel was administered to 61.2% (n = 117), abiraterone to 14.2% (n = 27) and enzalutamide to 9.4% (n = 18) as the first-line treatment. The median survival of the patients receiving docetaxel, abiraterone and enzalutamide as the first-line treatment during the hormone-refractory period was 15 (95% Cl: 12.9-17) months, 6 (95% Cl: 1.8-10.1) months and 11 (95% Cl: 0.9-23.1) months (p = 0.038), respectively. Conclusion: The present study established a statistically significant difference in favor of docetaxel in terms of overall survival and progression-free survival.


Lay abstract The optimal therapeutic option for castration-resistant prostate cancer (CRPC) patients with visceral metastases is unknown. We assessed the efficacy and tolerability of the first-line treatment options for CRPC patients with visceral metastasis. One hundred ninety-one patients diagnosed with CRPC with visceral metastases were included in the study. The present study established a statistically significant difference in favor of docetaxel in terms of overall survival and progression-free survival between first-line docetaxel, abiraterone and enzalutamide treatments in CRPC patients with visceral metastases. For patients who cannot undergo chemotherapy, enzalutamide, among novel androgen pathway inhibitors, may be the most appropriate option, given its numerical, although statistically insignificant, difference in overall survival and its fewer side effects compared with abiraterone.


Assuntos
Androstenos/administração & dosagem , Benzamidas/administração & dosagem , Docetaxel/administração & dosagem , Nitrilas/administração & dosagem , Feniltioidantoína/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstenos/efeitos adversos , Benzamidas/efeitos adversos , Docetaxel/efeitos adversos , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Feniltioidantoína/efeitos adversos , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos
12.
Allergol. immunopatol ; 48(6): 701-710, nov.-dic. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-199261

RESUMO

INTRODUCTION AND OBJECTIVES: As well as increased susceptibility to infections, autoimmune and inflammatory manifestations also eventuate due to dysregulation of immune system in a substantial proportion of patients with primary immunodeficiency (PID). Autoimmune and inflammatory manifestations can occur prior or after diagnosis of PID. This study aimed to evaluate autoimmune and inflammatory complications among all types of PID patients in childhood and to emphasize the importance of these findings as a warning sign to diagnose PIDs. METHODS: Medical records of 1036 patients with PID, followed up between 2003 and 2019, were retrospectively screened for occurrence of autoimmunity and inflammation. During this time, demographic features, autoimmune/inflammatory findings and initial time, genetic mutations, laboratory and clinical follow up findings, treatment regimens and outcomes were recorded. RESULTS: Autoimmune and inflammatory manifestations were observed in 83 patients (10.1%). The median age of autoimmunity initial time was 61.3 ± 53 months. Sixty-seven (80.7%) patients presented with autoimmune and inflammatory manifestations, and these findings had occurred during 16 patients' (19.3%) follow-up. The most common autoimmune manifestations were autoimmune hematologic (51.8%) and endocrine diseases (26.5%). Fifty patients (60.2%) had a single autoimmune/inflammatory manifestation, however 23 patients (27.7%) had two, eight patients (9.6%) had three and two patients (2.4%) had four different types of autoimmune/inflammatory manifestations. The frequency of autoimmune and inflammatory manifestations in phagocyte defects (56%), combined immune deficiencies (53%) and immune dysregulation diseases (52%) were observed higher than other forms of PIDs. During follow-up 13 (15.7%) patients died. CONCLUSION: Autoimmune/inflammatory manifestations are associated with high morbidity in patients with PIDs and may precede the diagnosis of PID in childhood. Therefore, physicians must be aware of underlying possible immune deficiency and patients with known PIDs should be evaluated for autoimmune and inflammatory complications


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Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Síndromes de Imunodeficiência/epidemiologia , Doenças Autoimunes/epidemiologia , Inflamação/epidemiologia , Estudos Retrospectivos , Síndromes de Imunodeficiência/patologia , Doenças Autoimunes/patologia , Inflamação/patologia , Prevalência , Fatores Etários , Estatísticas não Paramétricas , Mutação , Seguimentos , Turquia/epidemiologia
13.
Prague Med Rep ; 121(3): 181-193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33030147

RESUMO

Rare tumours of the testis includes a wide variety of tumours. We aim to present clinical and histological characteristics of our patients with rare tumours of the testis. The medical records of 33 patients who were treated and followed-up for testicular rare tumours in our center between 2007 and 2020 were retrospectively reviewed. Of all the 243 testicular tumours, 222 cases (91.4%) were germ cell tumours and 21 cases (8.6%) were non-germ cell tumours. Thirty-three rare tumours of the testis including rare germ cell tumours and non-germ cell tumours were detected. The mean age of the patients at diagnosis was 34 years (range 18-68 years). The histological types of rare testicular tumours were as follows: teratoma 4.5% (n=11), sex-cord stromal tumours 4.5% (n=11), paratesticular tumours 3.2% (n=8), and the others [lymphoma 0.4% (n=1), mesothelioma 0.4% (n=1) and choriocarcinoma 0.4% (n=1)]. The median duration of follow-up was 32 months (range 1 to 256 months). None of the patients with non-metastatic disease stage developed recurrence after having received appropriate therapy. Metastatic disease was documented in 9 cases at the time of diagnosis (five patients with teratomas, two patients with Leydig cell tumour, one patient with choriocarcinoma and rhabdomyosarcoma). The most common subtypes of testicular rare tumours in our center was teratoma and sex-cord stromal tumours. Because of testicular rare tumours have different biological features and different clinical outcomes, the management of each tumour requires a different approach.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Adolescente , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Estudos Retrospectivos , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Adulto Jovem
14.
Lung Cancer ; 148: 48-54, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32799090

RESUMO

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1(+) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. METHODS: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. RESULTS: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK(+) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 ±â€¯1.6 months and median overall survival (mOS) was 89.1 ±â€¯19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 ±â€¯2.5 months and mOS of 90.3 ±â€¯24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. CONCLUSION: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 ±â€¯19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 ±â€¯24 months is unprecedented for ROS1(+) NSCLC.


Assuntos
Neoplasias Pulmonares , Proteínas Tirosina Quinases , Aminopiridinas , Feminino , Humanos , Lactamas , Lactamas Macrocíclicas , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Proteínas Proto-Oncogênicas , Pirazóis , Receptores Proteína Tirosina Quinases/genética , Estudos Retrospectivos
15.
Acta Gastroenterol Belg ; 83(2): 279-284, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603047

RESUMO

OBJECTIVE: In this study, we aimed to investigate the diagnostic availability of oxidant and antioxidant parameters in ascites for spontaneous bacterial peritonitis (SBP). MATERIAL AND METHODS: This study was carried out between July and October 2018 with 25 patients with SBP and 24 patients without SBP. Patients with acute infection, those taking vitamin supplements and antioxidant medication, smoking and drinking alcohol, and patients without ascites culture were excluded from the study. RESULTS: In patients with SBP compared those without SBP median paraoxonase (3.1 vs 15.6 ; p <0.001), median stimulated paraoxonase (12.6 vs 53.1 ; p <0.001), median arylesterase (769,9 vs 857,5 ; p = 0,003) and median catalase (10 vs 22,2 ; p = 0,003) were found to be lower and median myeloperoxidase (8.1 vs 1.1 ; p <0.001) were found to be higher. There was a positive correlation between paraoxonase levels and stimulated paraoxonase levels, arylesterase levels and catalase levels, there was a negative correlation between paraoxonase levels and myeloperoxidase levels. Paraoxonase levels 3.7 and lower, stimulated paraoxonase levels 25.8 and lower, arylesterase levels 853.4 and lower, catalase levels 11.8 and lower and myeloperoxidase levels 2.7 and more predicted the the presence of SBP with high specificity and high sensitivity. Paraoxonase and stimulated paraoxo-nase levels were found to have superior performance in predicting the presence of SBP compared to arylesterase levels (p <0.05). CONCLUSION: In this study it was shown that paraoxonase, stimulated paraoxonase, arylesterase, catalase and myeloperoxidase activities can be used for the diagnosis and severity of SBP.


Assuntos
Ascite , Peritonite , Arildialquilfosfatase , Ascite/diagnóstico , Biomarcadores , Humanos , Estresse Oxidativo , Peritonite/diagnóstico
16.
Allergol Immunopathol (Madr) ; 48(6): 701-710, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32446782

RESUMO

INTRODUCTION AND OBJECTIVES: As well as increased susceptibility to infections, autoimmune and inflammatory manifestations also eventuate due to dysregulation of immune system in a substantial proportion of patients with primary immunodeficiency (PID). Autoimmune and inflammatory manifestations can occur prior or after diagnosis of PID. This study aimed to evaluate autoimmune and inflammatory complications among all types of PID patients in childhood and to emphasize the importance of these findings as a warning sign to diagnose PIDs. METHODS: Medical records of 1036 patients with PID, followed up between 2003 and 2019, were retrospectively screened for occurrence of autoimmunity and inflammation. During this time, demographic features, autoimmune/inflammatory findings and initial time, genetic mutations, laboratory and clinical follow up findings, treatment regimens and outcomes were recorded. RESULTS: Autoimmune and inflammatory manifestations were observed in 83 patients (10.1%). The median age of autoimmunity initial time was 61.3±53 months. Sixty-seven (80.7%) patients presented with autoimmune and inflammatory manifestations, and these findings had occurred during 16 patients' (19.3%) follow-up. The most common autoimmune manifestations were autoimmune hematologic (51.8%) and endocrine diseases (26.5%). Fifty patients (60.2%) had a single autoimmune/inflammatory manifestation, however 23 patients (27.7%) had two, eight patients (9.6%) had three and two patients (2.4%) had four different types of autoimmune/inflammatory manifestations. The frequency of autoimmune and inflammatory manifestations in phagocyte defects (56%), combined immune deficiencies (53%) and immune dysregulation diseases (52%) were observed higher than other forms of PIDs. During follow-up 13 (15.7%) patients died. CONCLUSION: Autoimmune/inflammatory manifestations are associated with high morbidity in patients with PIDs and may precede the diagnosis of PID in childhood. Therefore, physicians must be aware of underlying possible immune deficiency and patients with known PIDs should be evaluated for autoimmune and inflammatory complications.


Assuntos
Doenças Autoimunes/epidemiologia , Doenças da Imunodeficiência Primária/complicações , Idade de Início , Doenças Autoimunes/imunologia , Criança , Pré-Escolar , Suscetibilidade a Doenças/imunologia , Feminino , Seguimentos , Humanos , Lactente , Inflamação/epidemiologia , Inflamação/imunologia , Doenças da Imunodeficiência Primária/imunologia , Estudos Retrospectivos
17.
Niger J Clin Pract ; 23(5): 596-602, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32367864

RESUMO

AIM: The aim of this retrospective study is to evaluate and compare the 3-dimensional (3D) crown sizes of the left and right sides of upper and lower dental arches in patients with unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: Dental casts of 94 patients all in permanent dentition were included in this study. Dental casts were divided into three groups as 36 casts with unilateral left cleft lip and palate (ULCLP), 18 casts with unilateral right cleft lip and palate (URCLP), and 40 casts without cleft (control). Mesiodistal (MD), buccolingual (BL), and gingiva incisal (GI) values of each tooth were measured by scanning the dental models with a high-precision optical 3D scanner. Paired t-test and independent t-test were used for statistical analysis. RESULTS: U1 MD, U6 MD (P = 0.001) and BL (P = 0.01), L3 GI (P = 0.05) were greater in UCLP patients on the non-cleft side while U1 GI, L1 BL, L5 MD (P = 0.001), L4 MD, and BL (P = 0.01) values were found to be greater on the cleft side. Comparison of the cleft-sides and the control group showed that MD, BL, and GI dimensions of teeth on the cleft sides were generally found to be smaller, excluding the UR7 GI values for URCLP group (P = 0.05). CONCLUSION: In the measurements of teeth size, reliable and repeatable results were acquired through 3D software. Tooth size asymmetries can occur non-syndromic UCLP patients in both jaws. MD, BL, and GI dimensions of teeth are mostly found to be smaller in patients with CLP.


Assuntos
Fenda Labial , Imageamento Tridimensional/métodos , Odontometria/métodos , Coroa do Dente/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Fissura Palatina/patologia , Oclusão Dentária , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Maxila , Estudos Retrospectivos , Coroa do Dente/patologia
18.
Bratisl Lek Listy ; 121(2): 133-136, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115966

RESUMO

OBJECTIVE: We aimed to investigate whether a simple and easily calculated parameter such as monocyte/ HDL ratio (MHR) may be used in predicting non-dipper (NDHT)-dipper HT (DHT) end organ damage. METHODS: 70 NDHT and 73 DHT patient groups were included in the study according to ambulatory blood pressure screening results. Basic laboratory parameters and spot urine samples were evaluated. Transthoracic echocardiography and ophthalmological examination were performed for end-organ damages. RESULTS: The MHR among the groups was higher in the NDHT group; which was statistically significant (p≤0.001). In the NDHT group, albumin, creatinine, protein values, protein/creatinine ratio in the spot urine were significantly higher than in the DHT group (p≤0.05). Left ventricular hypertrophy (LVH) and retinopathy were also more frequently observed in the NDHT group (p≤0.001 and p=0.001, respectively). MHR in patients with LVH and retinopathy was significantly higher than in those without these complications (p=0.001). CONCLUSION: Easy to use, non-invasive and simple calculation, MHR can be used to predict end organ damage in hypertensive cases, and can be also used to distinguish between DHT/NDHT groups. This data supports the role of inflammation (Tab. 7, Ref. 14).


Assuntos
Monitorização Ambulatorial da Pressão Arterial , HDL-Colesterol , Hipertensão , Hipertrofia Ventricular Esquerda , Monócitos , Pressão Sanguínea , HDL-Colesterol/sangue , Ecocardiografia , Humanos , Hipertensão/diagnóstico
19.
Sci Immunol ; 5(43)2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005680

RESUMO

Reassessment of citrullinome cargo in neutrophil extracellular traps confirms the presence of citrullinated peptides.

20.
Sci Rep ; 9(1): 12207, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434914

RESUMO

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is currently 0.053-4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is  retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.


Assuntos
Bancos de Espécimes Biológicos , Hidradenite Supurativa , Proteômica , Manejo de Espécimes , Pesquisa Translacional Biomédica , Negro ou Afro-Americano , Feminino , Humanos , Masculino , Estudos Retrospectivos
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