RESUMO
Patients with acute respiratory distress syndrome due to COVID-19 require intensive care unit (ICU) admission with consecutive endotracheal intubation and invasive mechanical ventilation. In patients with long-term mechanical ventilation, percutaneous dilatational tracheostomy (PDT) may be considered. This retrospective analysis includes clinical data on patients treated at the ICUs of the COVID Hospital of the Clinical Center of Vojvodina in the period from September 3, 2021 to May 1, 2022, and underwent PDT. Patients were predominantly male (n=48; 65.8%). Weaning from mechanical ventilation was achieved in 31 (42.5%) and decannulation in 25 (34.2%) patients. The mean time from polymerase chain reaction SARS CoV-2 positivity until PDT was 15.59±6.85 days. The mean time of endotracheal intubation before the PDT procedure was 7.37±4.89 days. The mean weaning time from mechanical ventilation was 10.45±7.92 days. Twenty-five (34.2%) patients were decannulated at the mean time of 19.60±11.81 days. The complications were tracheostomy related bleeding (2 patients), pneumothorax (4 patients), subcutaneous emphysema (1 patient) and cricoid cartilage injury (1 patient). PDT is a simple, safe, and effective procedure performed in COVID-19 patients in the ICU.
Assuntos
COVID-19 , Unidades de Terapia Intensiva , Traqueostomia , Humanos , COVID-19/terapia , Traqueostomia/métodos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Dilatação/métodos , Idoso , Respiração Artificial/métodos , SARS-CoV-2 , Desmame do Respirador/métodos , AdultoRESUMO
Phenotypic characterization of T cells in myelofibrosis (MF) is intriguing owing to increased inflammation, markedly elevated pro-inflammatory cytokines, and altered distribution of T-cell subsets. Constitutive activation of Janus kinase-2 (JAK2) in the majority of MF patients contributes to the expression of the programmed cell death protein-1 (PD1) and T-cell exhaustion. We wondered whether T-cell activation affects treatment outcome of patients with MF and sought to determine whether the JAK1/2 inhibitor ruxolitinib affects the activation of T-cell subsets. T cells from 47 MF patients were analyzed and the percent of either helper (CD4+) or cytotoxic (CD8+) naive, central memory, effector memory, or effector T cells; and fractions of PD1-expressing cells in each subset were assessed. An increased number of T cells coexpressing CD4/PD1 and CD8/PD1 in MF compared to healthy controls (n=28) was found, and the T cells were significantly skewed toward an effector phenotype in both CD4+ and CD8+ subsets, consistent with a shift from a quiescent to an activated state. Over the course of ruxolitinib treatment, the distribution of aberrant T-cell subsets significantly reversed towards resting cell phenotypes. CD4+ and CD8+ subsets at baseline correlated with monocyte and platelet counts, and their PD1-positive fractions correlated with leukocyte counts and spleen size. Low numbers of PD1+/CD4+ and PD1+/CD8+ cells were associated with complete resolution of palpable splenomegaly and improved survival rate, suggesting that low levels of exhausted T cells confer a favorable response to ruxolitinib treatment.
Assuntos
Mielofibrose Primária , Linfócitos T CD8-Positivos , Citocinas , Humanos , Mielofibrose Primária/tratamento farmacológico , Subpopulações de Linfócitos T , Resultado do TratamentoRESUMO
AIM: To evaluate the clinical utility of incorporating a novel heavy/light chain immunoassay (HLC) into the existing methods for the assessment of multiple myeloma (MM) patients. METHODS: Convenience sera samples from 90 previously treated IgG and IgA MM patients in different disease stages were analyzed. The study was conducted in Clinical Hospital Center Zagreb between 2011 and 2013. The collected sera were analyzed by standard laboratory techniques (serum protein electrophoresis, quantification of total immunoglobulins, serum immunofixation, serum free light chain [FLC] assay) and HLC assay. RESULTS: HLC ratios outside the normal range were found in 58 of 90 patients, including 28 out of 61 patients with total immunoglobulin measurements within the normal range and 5 out of 23 patients in complete response. Both elevated HLC isotype level and abnormal HLC ratio correlated with the parameters of tumor burden, including percentage of plasma cells in the bone marrow (P<0.001 and P=0.002, respectively) and an abnormal serum FLC ratio (for both P<0.001). In addition, abnormal HLC isotype level correlated with serum beta-2-microglobulin level (P=0.038). In terms of prognosis, abnormal HLC isotype level and abnormal HLC ratio were significantly associated with shorter overall survival (P<0.001 and P=0.002, respectively). Interestingly, suppression of the uninvolved (polyclonal) isotype pair, but not other non-myeloma immunoglobulin isotypes, was also associated with a shorter overall survival (P=0.021). In a multivariate analysis, an abnormal HLC ratio and ß2-microglobulin level >3.5mg/L were independent risk factors for survival. CONCLUSION: The new HLC assay has greater sensitivity in detecting monoclonal protein, correlates with tumor burden markers, and affects patients' outcome.
Assuntos
Imunoensaio/métodos , Cadeias Pesadas de Imunoglobulinas/imunologia , Cadeias Leves de Imunoglobulina/sangue , Cadeias Leves de Imunoglobulina/imunologia , Mieloma Múltiplo/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoglobulina A , Imunoglobulina G , Masculino , Pessoa de Meia-Idade , Proteínas do Mieloma/imunologia , Prognóstico , Fatores de RiscoRESUMO
Background: Surgical stress and pain result in activation of hypothalamus-pituitary-adrenal axis. The aim of this study was to establish the effects of postoperative pain and various modalities of analgesic administration on salivary and serum cortisol levels, as well as to establish the validity of salivary cortisol as a stress indicator in surgical patients. Methods: A randomized controlled trial involved 60 patients scheduled for elective abdominal aortic aneurysm surgery. Patients were randomly divided into two groups depending on the model of postoperative analgesia. The first group (MI - morphine intermittently) included patients given morphine doses 0.1 mg/kg/6h s.c. intermittently. The second group (MPCA - morphine patient-controlled analgesia) included patients who received morphine via the PCA system - intravenous administration of morphine adjusted to a dose of 1 mg per shot and a lockout interval of 6 minutes.
RESUMO
Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF. In this study, we show that BM from patients with PMF harbors an abundance of clonal, neoplastic collagen- and fibronectin-producing fibrocytes. Immunodeficient mice transplanted with myelofibrosis patients' BM cells developed a lethal myelofibrosis-like phenotype. Treatment of the xenograft mice with the fibrocyte inhibitor serum amyloid P (SAP; pentraxin-2) significantly prolonged survival and slowed the development of BM fibrosis. Collectively, our data suggest that neoplastic fibrocytes contribute to the induction of BM fibrosis in PMF, and inhibiting fibrocyte differentiation with SAP may interfere with this process.
Assuntos
Fibroblastos/fisiologia , Monócitos/citologia , Mielofibrose Primária/etiologia , Animais , Medula Óssea/patologia , Transplante de Medula Óssea , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibrose , Proteínas de Homeodomínio/farmacologia , Humanos , Camundongos , Camundongos SCID , Nitrilas , Mielofibrose Primária/patologia , Pirazóis/farmacologia , Pirimidinas , Proteínas Recombinantes/farmacologia , Componente Amiloide P Sérico/farmacologiaRESUMO
Acute myeloid leukemia (AML) is a malignant hematopoietic disease with poor clinical course and outcome. There is a constant need for new prognostic factors that could facilitate patient risk stratification. The aim of our research was to determine the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways in leukemic cells, their relation to P-glycoprotein (P-gp) expression/activity and their prognostic significance in adult de novo AML. A total of 118 patients with AML were enrolled in the study. In a multivariate Cox regression analysis we found that P-gp activity and Akt phosphorylation were independent poor prognostic factors of overall survival (OS). In contrast, phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) represented a favorable prognostic factor of OS and relapse-free survival (RFS). A negative correlation between P-gp activity and p38 phosphorylation level was found, implying a possible role of this MAPK pathway in P-gp regulation. In addition, we found correlation between Akt and p38 phosphorylation levels, indicative of co-activation of two signaling cascades in AML.