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1.
Int J Mol Sci ; 25(7)2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38612799

RESUMEN

EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naïve patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.


Asunto(s)
Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas , Indoles , Neoplasias Pulmonares , Pirimidinas , Masculino , Humanos , Femenino , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Exones
2.
Croat Med J ; 64(2): 84-92, 2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37131310

RESUMEN

AIM: To assess the frequency of human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and high-risk types of human papillomavirus (HPV16 and HPV18) infections in lung adenocarcinoma samples. METHODS: Lung adenocarcinoma cytological smears and their DNA isolates were obtained from patients hospitalized at the Department for Lung Diseases Jordanovac, Zagreb, in 2016 and 2017. Overall, 67 lung adenocarcinoma samples were examined: 34 with epidermal growth factor receptor gene (EGFR) mutations and 33 without EGFR mutations. The EGFR mutation status and virus presence were assessed with a polymerase chain reaction, and random samples were additionally tested for EBV with Sanger sequencing. HCMV, EBV, HPV16, and HPV18 infections were evaluated in relation to EGFR mutation, smoking status, and sex. A meta-analysis of available data about HPV infection in non-small cell lung cancer was performed. RESULTS: More frequent HCMV, EBV, HPV16, and HPV18 infections were observed in lung adenocarcinoma samples with EGFR mutations than in samples without these mutations. Coinfection of the investigated viruses was observed only in lung adenocarcinoma samples with mutated EGFR. In the group with EGFR mutations, smoking was significantly associated with HPV16 infection. The meta-analysis showed that non-small cell lung cancer patients with EGFR mutations had a higher odds of HPV infection. CONCLUSION: HCMV, EBV, and high-risk HPV infections are more frequent in EGFR-mutated lung adenocarcinomas, which indicates a possible viral impact on the etiology of this lung cancer subtype.


Asunto(s)
Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Infecciones por Virus de Epstein-Barr , Neoplasias Pulmonares , Infecciones por Papillomavirus , Humanos , Herpesvirus Humano 4/genética , Citomegalovirus/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/genética , Virus del Papiloma Humano , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Genes erbB-1 , Neoplasias Pulmonares/genética , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/complicaciones , Receptores ErbB/genética
3.
Int J Mol Sci ; 24(16)2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37629023

RESUMEN

BRAF and cMET exon 14 skipping are rare mutations of NSCLC. The treatment sequence in these cases for the first and second line is not clear. An international registry was created for patients with advanced NSCLC harboring BRAF or cMET exon 14 skipping mutations, diagnosed from January 2017 to June 2022. Clinicopathological and molecular data and treatment patterns were recorded. Data on 58 patients, from eight centers across five countries, were included in the final analysis. We found that 40 patients had the cMET exon 14 skipping mutation and 18 had the BRAF V600E mutation. In total, 53 and 28 patients received first- and second-line treatments, respectively, among which 52.8% received targeted therapy (TT) in the first line and 53.5% in the second line. The overall response rate (ORR) and disease control rate (DCR) for first-line treatment with TT vs. other treatment such as immune checkpoint inhibitors ± chemotherapy (IO ± CT) were 55.6% vs. 21.7% (p = 0.0084) and 66.7% vs. 39.1% (p = 0.04), respectively. The type of treatment in first-line TT vs. other affected time to treatment discontinuation (TTD) was 11.6 m vs. 4.6 m (p= 0.006). The overall survival for the whole group was 15.4 m and was not statistically affected by the type of treatment (19.2 m vs. 13.5 m; p = 0.83).


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Exones/genética , Mutación
4.
Artículo en Inglés | MEDLINE | ID: mdl-37753773

RESUMEN

C-reactive protein (CRP) and leukocyte count are standard tools for recognising inflammation in COPD patients. This study aimed to find if there is a pattern in monocyte related haematological indices - monocyte to neutrophil ratio (MNR) and monocyte to lymphocyte ratio (MLR) - which could be helpful in differentiating COPD patients in need for hospitalization due to acute exacerbation of COPD or differentiating frequent COPD exacerbators from non-frequent COPD exacerbators. The study included 119 patients with COPD and 35 control subjects, recruited at the Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Croatia. Complete blood count was performed on Sysmex XN-1000, CRP on Cobas c501, and Fbg on BCS XP analyser. Data were analysed with MedCalc statistical software. The COPD patients were divided into three groups - frequent exacerbators (FE), non-frequent exacerbators (NFE), patients hospitalized for acute COPD exacerbations (HAE) and the control group were healthy smokers (HS). A statistically significant difference was found in the values of MNR while comparing these groups of patients: FE vs HAE (p<0.000), NFE vs HAE (p<0.000) and HS vs HAE (p<0.001); and for the values of MLR: FE vs HAE (p<0.022), NFE vs HAE (p<0.000) and HS vs HAE (p<0.000). As MLR and MNR have shown the statistical difference comparing the group of HAE to NFE, FE and HS, MLR and MNR could be valuable and available markers of acute COPD exacerbations and need for hospitalization.

5.
Nat Chem Biol ; 16(5): 577-586, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32094923

RESUMEN

Receptor tyrosine kinases (RTKs) are transmembrane receptors of great clinical interest due to their role in disease. Historically, therapeutics targeting RTKs have been identified using in vitro kinase assays. Due to frequent development of drug resistance, however, there is a need to identify more diverse compounds that inhibit mutated but not wild-type RTKs. Here, we describe MaMTH-DS (mammalian membrane two-hybrid drug screening), a live-cell platform for high-throughput identification of small molecules targeting functional protein-protein interactions of RTKs. We applied MaMTH-DS to an oncogenic epidermal growth factor receptor (EGFR) mutant resistant to the latest generation of clinically approved tyrosine kinase inhibitors (TKIs). We identified four mutant-specific compounds, including two that would not have been detected by conventional in vitro kinase assays. One of these targets mutant EGFR via a new mechanism of action, distinct from classical TKI inhibition. Our results demonstrate how MaMTH-DS is a powerful complement to traditional drug screening approaches.


Asunto(s)
Ensayos Analíticos de Alto Rendimiento/métodos , Inhibidores de Proteínas Quinasas/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular , Línea Celular Tumoral , ADN Nucleotidiltransferasas/genética , Descubrimiento de Drogas , Resistencia a Antineoplásicos/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Genes Reporteros , Humanos , Luciferasas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Fosforilación/efectos de los fármacos , Reproducibilidad de los Resultados , Bibliotecas de Moléculas Pequeñas/farmacología , Estaurosporina/análogos & derivados , Estaurosporina/farmacología
6.
Int J Mol Sci ; 23(23)2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36499394

RESUMEN

Patients with cancer are more susceptible to a higher risk of coronavirus infection and its severe complications than the general population. In addition, these patients were not included in the pivotal clinical trials for COVID-19 vaccines. Therefore, considerable uncertainty remains regarding the management of cancer patients during the COVID-19 pandemic and the safety of COVID-19 vaccinations in cancer patients. In this review, we summarize the current knowledge generated from the beginning of the COVID-19 pandemic on the vulnerability of cancer patients to the coronavirus disease, as well as the effectiveness of COVID-19 vaccines in this population. We also discuss the available data on the effects of anticancer treatment with immune checkpoint inhibitors on the immune responses to SARS-CoV-2 in cancer patients. Special attention in this review will be given to patients with lung cancer, as such patients are at an increased risk for severe effects from COVID-19.


Asunto(s)
COVID-19 , Neoplasias Pulmonares , Vacunas Virales , Humanos , Vacunas contra la COVID-19/efectos adversos , SARS-CoV-2 , Pandemias/prevención & control , Neoplasias Pulmonares/tratamiento farmacológico
7.
Psychiatr Danub ; 33(Suppl 10): 137-139, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34672287

RESUMEN

BACKGROUND: To determine the effect of lockdown measures on lung transplant patients during the COVID-19 pandemic. SUBJECTS AND METHODS: We collected data from Croatian lung transplant patients before and after the lockdown and analyzed changes in weight, BMI, lung function and blood lipid status. RESULTS: An average increase of 3.74 kg (+4.92%) body weight during the 4 month lockdown period was observed. Lung function values and blood lipid status remained stable. CONCLUSION: Such weight gain could have detrimental effects on the morbidity and mortality of lung transplant patients. Further follow up is needed to determine the long term impacts of this observation.


Asunto(s)
COVID-19 , Trasplante de Pulmón , Índice de Masa Corporal , Control de Enfermedades Transmisibles , Croacia/epidemiología , Humanos , Pandemias , SARS-CoV-2 , Aumento de Peso
8.
Oncologist ; 25(3): e598-e601, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32162818

RESUMEN

BACKGROUND: Treatment of non-small cell lung cancer (NSCLC) improved substantially in the last decades. Novel targeted and immune-oncologic drugs were introduced into routine treatment. Despite accelerated development and subsequent drug registrations by the European Medicinal Agency (EMA), novel drugs for NSCLC are poorly accessible in Central and Eastern European (CEE) countries. MATERIAL AND METHODS: The Central European Cooperative Oncology Group conducted a survey among experts from 10 CEE countries to provide an overview on the availability of novel drugs for NSCLC and time from registration to reimbursement decision in their countries. RESULTS: Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors were reimbursed and available in all countries, for other registered therapies-even for ALK inhibitors and checkpoint inhibitors in first-line-there were apparent gaps in availability and/or reimbursement. There was a trend for better availability of drugs with longer time from EMA marketing authorization. Substantial differences in access to novel drugs among CEE countries were observed. In general, the availability of drugs is not in accordance with the Magnitude of Clinical Benefit Scale (MCBS), as defined by the European Society for Medical Oncology (ESMO). Time spans between drug registrations and national decisions on reimbursement vary greatly, from less than 3 months in one country to more than 1 year in the majority of countries. CONCLUSION: The access to novel drugs for NSCLC in CEE countries is suboptimal. To enable access to the most effective compounds within the shortest possible time, reimbursement decisions should be faster and ESMO MCBS should be incorporated into decision making.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Preparaciones Farmacéuticas , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Europa (Continente) , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Oncología Médica
9.
Histopathology ; 77(1): 55-66, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32170970

RESUMEN

AIMS: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal prognosis. While the epithelioid type is associated with a more favourable outcome, additional factors are needed to further stratify prognosis and to identify patients who can benefit from multimodal treatment. As epithelioid MPM shows remarkable morphological variability, the prognostic role of the five defined morphologies, the impact of the nuclear grading system and the mitosis-necrosis score were investigated in this study. METHODS AND RESULTS: Tumour specimens of 192 patients with epithelioid MPM from five European centres were histologically subtyped. Nuclear grading and mitosis-necrosis score were determined and correlated with clinicopathological parameters and overall survival (OS). Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histological subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer OS than the solid/trabecular group (732 days versus 397 days, P = 0.0013). Pleomorphic tumours had the shortest OS (173 days). The solid/trabecular variants showed a significant association with high nuclear grade and mitosis-necrosis score. The mitosis-necrosis score was a robust and independent prognostic factor in our patient cohort. The prognostic significance of all three parameters was externally validated in the TCGA cohort. Patients with tubulopapillary or microcystic tumours showed a greater improvement in OS after receiving multimodal therapy than those with solid or trabecular tumours. CONCLUSIONS: Histological subtypes of epithelioid MPM have a prognostic impact, and might help to select patients for intensive multimodal treatment approaches.


Asunto(s)
Mesotelioma Maligno/patología , Neoplasias Pleurales/patología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
10.
Anticancer Drugs ; 30(10): 1061-1063, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31609765

RESUMEN

We present unusual treatment outcome in a 59-year-old male diagnosed with metastatic lung adenocarcinoma with a very good response to ruxolitinib as monotherapy. In June 2017, this patient was diagnosed with myeloproliferative neoplasm - Janus-associated kinases 2 positive - and in December 2017 ruxolitinib therapy was started. At the same time, patient was diagnosed with lung adenocarcinoma in the left lower lobe with positive anaplastic lymphoma kinase mutation and with right lower lobe metastasis. Because of partial regression of tumor size noted on the computed tomography (CT) scans during tumor investigation, we did not apply any therapy for lung adenocarcinoma. A follow-up CT scan done in March 2018 showed further size reduction of tumor lesion in lower left lobe (91%), while follow-up CT scan done in June 2018 showed further size reduction of tumor lesion in lower right lobe (82%).


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Quinasa de Linfoma Anaplásico/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Pirazoles/uso terapéutico , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/metabolismo , Quinasa de Linfoma Anaplásico/genética , Antineoplásicos/uso terapéutico , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Nitrilos , Pirimidinas , Tomografía Computarizada por Rayos X
11.
World J Surg Oncol ; 17(1): 147, 2019 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-31426804

RESUMEN

BACKGROUND: Primary sarcoma of the lung is a very rare malignant tumor accounting for less than 0.5% of all lung tumors and presenting diagnostic and treatment challenge. We describe a case of a patient diagnosed with primary lung undifferentiated pleomorphic sarcoma developing subsequent peritoneal and small bowel metastases, which stand for highly unusual disease presentation. CASE PRESENTATION: A 57-year-old male presented with extensive partially necrotic tumor in the left upper lobe (LUL) of the lung that involved LUL bronchus and extended to the visceral pleura. There was no evidence of nodal or visceral dissemination. After initial presentation, the patient was admitted to the hospital's pulmonology department for further workup. The most likely diagnosis based on biopsy specimen was poorly differentiated sarcoma. Left pneumonectomy with mediastinal lymph node dissection was performed. The final pathohistological diagnosis (PHD) was undifferentiated pleomorphic sarcoma (UPS). Three months after lung surgery, a follow-up CT scan was done which showed a 60-mm obstructive metastatic intraabdominal lesion with small bowel infiltration and further separate peritoneal deposits. Unfortunately, an urgent surgery had to be performed as the patient developed signs of acute abdomen due to bowel perforation. Only 2 months later, the patient passed away at home. CONCLUSIONS: Treatment options of UPS are based on algorithms used in treatment of extremity lesions with well-established role of surgery. However, the role of perioperative chemotherapy remains equivocal with no strong evidence-based data due to the rarity of the disease. Small bowel is an unexpected metastatic site, but of significant clinical relevance.


Asunto(s)
Neoplasias Intestinales/secundario , Intestino Delgado/patología , Neoplasias Pulmonares/patología , Neoplasias Peritoneales/secundario , Sarcoma/patología , Humanos , Neoplasias Intestinales/cirugía , Intestino Delgado/cirugía , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/cirugía , Pronóstico , Sarcoma/cirugía
12.
Monaldi Arch Chest Dis ; 89(2)2019 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-31162486

RESUMEN

Interstitial lung diseases (ILD) are a heterogeneous group of diseases and one of the differential diagnosis which have to be excluded during diagnostic procedures are malignancies. We will present four patients who were referred to our Department because of suspicion of interstitial lung diseases according to radiology finding. In one case only, one of the radiologist's differential diagnosis was pulmonary lymphangitic carcinomatosis. All four patients had exertional dyspnea and dry cough which are nonspecific and can be first manifestation of ILD or obstructive lung diseases. After diagnostic evaluation in three cases, diagnosis was pulmonary lymphangitic carcinomatosis due to metastatic lung adenocarcinoma and in one due to metastatic adenocarcinoma of unknown primary origin. Patients with lymphangitic carcinomatosis have poor prognosis without treatment and usually die because of respiratory failure. With these four cases we want to highlight importance of thinking about malignancies when we have patients with suspicion of interstitial lung disease especially when reticular pattern is present on chest X ray. We also wanted to show how important is radiology finding and multidisciplinary approach, and how radiologist's differential diagnosis can be very helpful in making decisions in further investigations and way of clinicians thinking.


Asunto(s)
Adenocarcinoma del Pulmón/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , Neoplasias Pulmonares/diagnóstico , Anciano , Tos/etiología , Diagnóstico Diferencial , Disnea/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo
13.
Monaldi Arch Chest Dis ; 89(2)2019 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-31315351

RESUMEN

Lung cancer incidence in heart transplant patients is higher than in general population and correlates with smoking history. EGFR-mutations are more frequent in adenocarcinoma and among non-smoking women but incidence in solid organ transplanted patients is still not known. We present case of a 65-year-old ex-smoker male with history of heart transplantation and EGFR positive metastatic lung adenocarcinoma. At admission he was in a severe clinical condition and treatment with erlotinib was started. Initially he had good clinical and radiologic response to treatment with only grade 1 side effects.  Data about drug interactions between cyclosporine and erlotinib are insufficient but we have to take this interaction into consideration during treatment because both drugs are substrates and inhibitors of CYP34A. In our case erlotinib was safe and well tolerated drug, there were no relevant toxicity, but close monitoring and dose reduction of cyclosporine was needed.


Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Trasplante de Corazón/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Ciclosporina/administración & dosificación , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Receptores ErbB/genética , Clorhidrato de Erlotinib/administración & dosificación , Clorhidrato de Erlotinib/efectos adversos , Humanos , Inmunosupresores/administración & dosificación , Neoplasias Pulmonares/genética , Masculino , Mutación
14.
Acta Clin Croat ; 58(1): 3-12, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31363319

RESUMEN

Pulmonary hypertension (PH) is a chronic disease which severely impairs quality of life (QoL). The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific tool to assess patient-reported symptoms, functioning and QoL in PH patients. The aim of this study was to adapt and validate the CAMPHOR for use in Croatia. The adaptation process involved three stages: translation (bilingual and lay panel), cognitive debriefing interviews with patients and psychometric validation. For the latter stage, a postal survey was conducted with 50 patients to examine the reliability and validity of the adapted scale. All three scales of the Croatian CAMPHOR demonstrated excellent internal consistency (Symptoms = 0.93; Activity limitations = 0.94; QoL = 0.92) and test-retest reliability correlations (Symptoms = 0.90; Activity limitations = 0.95; QoL = 0.90). Predicted correlations with the SF-36 scales provided evidence for construct validity of the CAMPHOR scales. Evidence for known group validity was shown by the ability of the scales to distinguish between participants based on patient-perceived general health and disease severity. The Croatian version of the CAMPHOR is a valid and reliable tool for use in clinical routine and clinical research.


Asunto(s)
Hipertensión Pulmonar/psicología , Calidad de Vida/psicología , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios/normas , Actividades Cotidianas/psicología , Adaptación Fisiológica , Adulto , Anciano , Croacia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Reproducibilidad de los Resultados , Traducción
15.
Psychiatr Danub ; 30(1): 11-20, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29546853

RESUMEN

Dyspnea or breathlessness is a term primarily used in respiratory medicine. Nevertheless, in the last fifteen years, studies from other fields focus on the affective component of this complex phenomenon due to the frequent observation that psychological states can cause or be caused by dyspnea. Research so far shows that besides the biological component, dyspnea has a strong emotional and psychosocial determinant. This means that apart from its biological factors, dyspnea and its intensity are affected by emotions, personality, anxiety and depression, etc. Individuals with psychiatric disorders, in the same conditions, will evaluate their dyspnea as more intense and disturbing compared to individuals without psychiatric comorbidity. Emotional states in healthy individuals can amplify the sense of dyspnea which is of extreme importance for clinical practice in order to consider the whole person and not just the symptom which is being presented. Also, dyspnea seems to be frequent complaint in some groups of patients with psychiatric disorders (e.g.panic disorder), where the fear of suffocation is presented as clinical symptom. Futher research of dyspnea as a complex, multicomponent phenomenon, can contribute to better treatment options and better differential diagnosis concerning possible psychiatric background of physical symptoms.


Asunto(s)
Trastornos de Ansiedad , Disnea , Trastorno de Pánico , Ansiedad , Trastornos de Ansiedad/complicaciones , Disnea/psicología , Miedo , Humanos , Trastorno de Pánico/complicaciones
16.
Croat Med J ; 58(6): 395-405, 2017 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-29308831

RESUMEN

AIM: To determine in-hospital and post-discharge mortality, readmission rates, and predictors of invasive mechanical ventilation (IMV) in patients treated at intensive care unit (ICU) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD). METHODS: A retrospective observational cohort study included all patients treated at a respiratory ICU for AECOPD during one year. A total of 62 patients (41 men) with mean age 68.4±10.4 years were analyzed for outcomes including in-hospital and post-discharge mortality, readmission rates, and IMV. Patients' demographic, hematologic, biochemical data and arterial blood gas (ABG) values were recorded on admission to hospital. Mean duration of follow-up time was 2.4 years. RESULTS: Of 62 patients, 7 (11.3%) died during incident hospitalization and 21 (33.9%) died during the follow-up. The overall 2.4-year mortality was 45.2%. Twenty nine (46.8%) patients were readmitted due to AECOPD. The average number of readmissions was 1.2. Multivariate analysis showed that blood pH, bicarbonate levels, low albumin, low serum chloride, and low hemoglobin were significant predictors of IMV during incident hospitalization (P<0.001 for the overall model fit). CONCLUSION: High in-hospital and post-discharge mortality and high readmission rates in our patients treated due to AECOPD at ICU indicate that these patients represent a high risk group in need of close monitoring. Our results suggested that anemia, hypoalbuminemia, and elevated troponin levels were risk factors for the need of IMV in severe AECOPD. Identification of such high-risk patients could provide the opportunity for administration of an appropriate and timely treatment.


Asunto(s)
Anemia/epidemiología , Hipoalbuminemia/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Respiración Artificial , Insuficiencia Respiratoria/etiología , Troponina/sangre , Anciano , Femenino , Mortalidad Hospitalaria , Hospitalización , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Readmisión del Paciente/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Insuficiencia Respiratoria/terapia , Estudios Retrospectivos , Factores de Riesgo
17.
J Pathol ; 237(2): 203-14, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26011651

RESUMEN

Malignant pleural mesothelioma (MPM) is a devastating malignancy characterized by invasive growth and rapid recurrence. The identification and inhibition of molecular components leading to this migratory and invasive phenotype are thus essential. Accordingly, a genome-wide expression array analysis was performed on MPM cell lines and a set of 139 genes was identified as differentially expressed in cells with high versus low migratory activity. Reduced expression of the novel tumour suppressor integrin α7 (ITGA7) was found in highly motile cells. A significant negative correlation was observed between ITGA7 transcript levels and average displacement of cells. Forced overexpression of ITGA7 in MPM cells with low endogenous ITGA7 expression inhibited cell motility, providing direct evidence for the regulatory role of ITGA7 in MPM cell migration. MPM cells showed decreased ITGA7 expressions at both transcription and protein levels when compared to non-malignant mesothelial cells. The majority of MPM cell cultures displayed hypermethylation of the ITGA7 promoter when compared to mesothelial cultures. A statistically significant negative correlation between ITGA7 methylation and ITGA7 expression was also observed in MPM cells. While normal human pleura samples unambiguously expressed ITGA7, a varying level of expression was found in a panel of 200 human MPM samples. In multivariate analysis, ITGA7 expression was found to be an independent prognostic factor. Although there was no correlation between histological subtypes and ITGA7 expression, importantly, patients with high tumour cell ITGA7 expression had an increased median overall survival compared to the low- or no-expression groups (463 versus 278 days). In conclusion, our data suggest that ITGA7 is an epigenetically regulated tumour suppressor gene and a prognostic factor in human MPM.


Asunto(s)
Antígenos CD/metabolismo , Movimiento Celular , Epigénesis Genética , Cadenas alfa de Integrinas/metabolismo , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Neoplasias Pleurales/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Antígenos CD/genética , Línea Celular Tumoral , Metilación de ADN , Regulación hacia Abajo , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica , Estudio de Asociación del Genoma Completo , Humanos , Cadenas alfa de Integrinas/genética , Estimación de Kaplan-Meier , Laminina/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Mesotelioma/genética , Mesotelioma/mortalidad , Mesotelioma/patología , Mesotelioma Maligno , Análisis Multivariante , Invasividad Neoplásica , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias Pleurales/genética , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/patología , Pronóstico , Regiones Promotoras Genéticas , Modelos de Riesgos Proporcionales , ARN Mensajero/metabolismo , Factores de Riesgo , Transducción de Señal , Factores de Tiempo , Transfección , Proteínas Supresoras de Tumor/genética
18.
Chemotherapy ; 61(4): 167-70, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26821270

RESUMEN

BACKGROUND/AIMS: Species-level identification of nontuberculous mycobacteria (NTM) is important in making decisions about the necessity and choice of antimicrobial treatment. The reason is predictable clinical significance and the susceptibility profile of specific NTM species. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is recognized as a diagnostic tool for routine identification of bacteria and yeasts in the clinical laboratory based on protein fingerprint analysis. The aim of the study was to evaluate MALDI-TOF MS in the identification of NTM. METHODS: A total of 25 NTM isolates from liquid cultures were identified with both polymerase chain reaction (PCR)-based hybridization assay and MALDI-TOF MS at the University Hospital Center Zagreb. RESULTS: PCR-based hybridization assay identified 96% (24/25) and MALDI-TOF MS 80% (20/25) of tested NTM isolates. Five isolates with no reliable MALDI-TOF MS identification belonged to the Mycobacterium avium-intracellulare complex. Seventy percent (14/20) of NTM isolates successfully identified with MALDI-TOF MS had a score higher than 2.0, indicating reliable species identification. CONCLUSION: MALDI-TOF MS is a promising tool for the identification of NTM. With a further improvement of the protein extraction protocol, especially regarding the M. avium-intracellulare complex, MALDI-TOF MS could be an additional standard method for identification of NTM.


Asunto(s)
ADN Bacteriano/análisis , Micobacterias no Tuberculosas/genética , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , ADN Bacteriano/genética , ADN Bacteriano/metabolismo , Complejo Mycobacterium avium/genética , Complejo Mycobacterium avium/aislamiento & purificación , Micobacterias no Tuberculosas/aislamiento & purificación , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa
19.
Lijec Vjesn ; 139(1-2): 17-23, 2016.
Artículo en Croata | MEDLINE | ID: mdl-30148587

RESUMEN

Treatment of oncological patients must be based upon multidisciplinary approach, and takes place in specialized oncological centers. By the end of a specific oncological treatment further follow-up is being managed mostly by the oncologists, but the role of the general practitioners becomes more important every day and therefore should be precisely defined. Nowadays, most of the existing follow-up guidelines are not being based on prospective studies, yet on the expert's opinion of a precise oncological center or specialists. The aim of the Croatian Society of Medical Oncology (CSMO) with these recommendations is to standardize and rationalize the diagnostic procedures' algorithm in follow­up of oncological patients after primary treatment, in patients with melanoma, sarcomas, central nerve system tumors and lung cancer.


Asunto(s)
Cuidados Posteriores , Neoplasias del Sistema Nervioso Central/terapia , Neoplasias Pulmonares/terapia , Melanoma/terapia , Sarcoma/terapia , Cuidados Posteriores/métodos , Cuidados Posteriores/normas , Croacia , Humanos , Oncología Médica/métodos
20.
J Water Health ; 13(1): 125-30, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25719472

RESUMEN

Nontuberculous mycobacteria (NTM) are opportunistic pathogens found in natural and human-engineered waters. In 2009, a relative increase in the isolation of Mycobacterium gordonae from pulmonary samples originating from General Hospital Zabok was noted by the National Mycobacteria Reference Laboratory. An epidemiological survey revealed a contamination of the cold tap water with M. gordonae and guidelines regarding sputum sample taking were issued. In addition, all incident cases of respiratory infection due to NTM reported from 2007 to 2012 at General Hospital Zabok were included in a retrospective review. Out of 150 individual NTM isolates, M. gordonae was the most frequently isolated species (n = 135; 90%) and none of the cases met the criteria of the American Thoracic Society for pulmonary NTM disease. While concomitant Mycobacterium tuberculosis infection was confirmed in only 6 (4%) patients, anti-tuberculosis treatment was initiated for a significant portion of patients (n = 64; 42.6%) and unnecessary contact tracing was performed. This study points out the need to enhance the knowledge about NTM in our country and indicates the importance of faster NTM identification, as well as the importance of good communication between laboratory personnel and physicians when evaluating the significance of the isolated NTM.


Asunto(s)
Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Micobacterias no Tuberculosas , Abastecimiento de Agua/análisis , Anciano , Croacia/epidemiología , Infección Hospitalaria/microbiología , Femenino , Hospitales Generales/estadística & datos numéricos , Humanos , Pulmón/microbiología , Masculino , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/aislamiento & purificación , Microbiología del Agua
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