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Toll-like-receptor (TLR) family members were detected in the central nervous system (CNS). TLR occurrence was noticed and widely described in glioblastomamultiforme (GBM) cells. After ligand attachment, TLR-4 reorients domains and dimerizes, activates an intracellular cascade, and promotes further cytoplasmatic signaling. There is evidence pointing at a strong relation between TLR-4 signaling and micro ribonucleic acid (miRNA) expression. The TLR-4/miRNA interplay changes typical signaling and encourages them to be a target for modern immunotherapy. TLR-4 agonists initiate signaling and promote programmed death ligand-1 (PD-1L) expression. Most of those molecules are intensively expressed in the GBM microenvironment, resulting in the autocrine induction of regional immunosuppression. Another potential target for immunotreatment is connected with limited TLR-4 signaling that promotes Wnt/DKK-3/claudine-5 signaling, resulting in a limitation of GBM invasiveness. Interestingly, TLR-4 expression results in bordering proliferative trends in cancer stem cells (CSC) and GBM. All of these potential targets could bring new hope for patients suffering from this incurable disease. Clinical trials concerning TLR-4 signaling inhibition/promotion in many cancers are recruiting patients. There is still a lot to do in the field of GBM immunotherapy.
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Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Proteínas de Checkpoint Imunológico/metabolismo , MicroRNAs/genética , Receptor 4 Toll-Like/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Ensaios Clínicos como Assunto , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Imunoterapia , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Wnt/metabolismoRESUMO
INTRODUCTION: Lymphangioleiomyomatosis (LAM) occurs either associated with tuberous sclerosis complex (TSC) or as sporadic disease (S-LAM). Risk factors for development of S-LAM are unknown. We hypothesised that DNA sequence variants outside of TSC2/TSC1 might be associated with susceptibility for S-LAM and performed a genome-wide association study (GWAS). METHODS: Genotyped and imputed data on 5â426â936 single nucleotide polymorphisms (SNPs) in 426 S-LAM subjects were compared, using conditional logistic regression, with similar data from 852 females from COPDGene in a matched case-control design. For replication studies, genotypes for 196 non-Hispanic White female S-LAM subjects were compared with three different sets of controls. RNA sequencing and immunohistochemistry analyses were also performed. RESULTS: Two noncoding genotyped SNPs met genome-wide significance: rs4544201 and rs2006950 (p=4.2×10-8 and 6.1×10-9, respectively), which are in the same 35â kb linkage disequilibrium block on chromosome 15q26.2. This association was replicated in an independent cohort. NR2F2 (nuclear receptor subfamily 2 group F member 2), a nuclear receptor and transcription factor, was the only nearby protein-coding gene. NR2F2 expression was higher by RNA sequencing in one abdominal LAM tumour and four kidney angiomyolipomas, a LAM-related tumour, compared with all cancers from The Cancer Genome Atlas. Immunohistochemistry showed strong nuclear expression in both LAM and angiomyolipoma tumours. CONCLUSIONS: SNPs on chromosome 15q26.2 are associated with S-LAM, and chromatin and expression data suggest that this association may occur through effects on NR2F2 expression, which potentially plays an important role in S-LAM development.
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Fator II de Transcrição COUP/genética , Neoplasias Renais/genética , Neoplasias Pulmonares/genética , Linfangioleiomiomatose/genética , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Internacionalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Birt-Hogg-Dubé syndrome (BHDS) is a rare, genetic, autosomal dominant disease caused by mutation in a folliculin gene. This syndrome is characterised by three main symptoms: benign lesions originating from hair follicles, variously shaped cysts in the lungs, and various types of benign and malignant kidney neoplasms. In our article we are going to present cases of two sisters with BHDS. In the case of the first sister skin lesions were accompanied by lung abnormalities. The second sister, however, presented with recurrent pneumothoraces associated with variously shaped lung cysts located mainly below the tracheal carina. In both instance diagnosis was confirmed by genetic test.
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OBJECTIVES: Nasal carriage of Staphylococcus aureus and its superantigens (SAg) seem to be a risk factor disease exacerbation in granulomatosis with polyangiitis (GPA). We investigated the association between the presence of SAg in nasal swabs and activity of disease in GPA patients also taking into account correlation with an antimicrobial treatment. METHODS: In a prospective study of a total of 150 GPA patients hospitalised in the period 2009-2016, nasal swabs were examined for the presence of Staphylococcus aureus and SAg. Subsequently, the association with disease activity was assessed. RESULTS: Of 362 Staphylococcus aureus-positive nasal swab cultures from 115 of the 150 patients, the presence of at least one SAg in 126 samples (34.8%) from 56 patients (48.7%) was found. Among the 17 patients with limited to subglottic stenosis (SGS) disease, SAg were detected in 6 cases (35.3%). We did not find a significant correlation between the presence of SAg and disease activity (p=0.986), although when individual SAg were analysed separatively, SED and TSST-1 were more frequently present in active disease. Additionally, the results of the analysis demonstrated a protective effect of trimethoprim/sulfamethoxazole (T/S) treatment (0R 0.52, p<0.0092) in GPA patients. Interestingly, GPA limited to SGS appeared as an unfavourable factor associated with disease activity (0R 1.84, p=0.05). CONCLUSIONS: The association between staphylococcal SAg in nasal swabs and GPA activity is not evident. Multiple mechanisms that may lead to disease activation still need to be investigated.
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Antígenos de Bactérias/imunologia , Portador Sadio/imunologia , Granulomatose com Poliangiite/imunologia , Mucosa Nasal/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Superantígenos/imunologia , Adulto , Portador Sadio/microbiologia , Feminino , Granulomatose com Poliangiite/microbiologia , Granulomatose com Poliangiite/fisiopatologia , Humanos , Laringoestenose/imunologia , Laringoestenose/microbiologia , Laringoestenose/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Estafilocócicas/microbiologia , Staphylococcus/imunologia , Staphylococcus aureus/isolamento & purificaçãoRESUMO
Pulmonary Langerhans cell histiocytosis (LCH) is a rare disease, affecting usually young people. The course of the disease is variable. In some pulmonary LCH patients a severe lung destruction and progression in spite of chemotherapy is observed, but in others just a cessation of smoking induces a regression of the disease. In the present study we seek to determine the influence of pregnancy on pulmonary function in LCH patients, an unchartered area of research. We addressed the issue by investigating eight pregnant women out of the 45 women hospitalized with the diagnosis of pulmonary LCH in the period from 2000 to 2015. For five of the eight pregnant women it was the second gestation. The median follow-up period was 120 months (range 72-175 months). Ten healthy children were born by a C-section. Two spontaneous miscarriages in the seventh week of gestation, and one tubal ectopic pregnancy were recorded. We found that pregnancy did not significantly influence pulmonary function assessed by the following indices: forced expiratory volume in 1 s (FEV1), lung vital capacity (VC), total lung capacity (TLC), residual volume (RV), diffusing capacity of the lungs for carbon monoxide (DLCO), and the distance and arterial oxygen saturation in 6-min walk test. Only one patient in the third trimester of pregnancy experienced bilateral pneumothorax, with persistent air leak. In all patients, delivery and postpartum period were uneventful. We conclude that pregnancy in pulmonary LCH patients is safe and not associated with deterioration of pulmonary function or blood oxygenation.
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Histiocitose de Células de Langerhans/fisiopatologia , Pulmão/fisiopatologia , Adulto , Idoso , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Pessoa de Meia-Idade , Oxigênio/metabolismo , Gravidez , Capacidade Vital/fisiologia , Caminhada , Adulto JovemRESUMO
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are recommended as first-line treatment of renal angiomyolipoma associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sporadic LAM), but follow-up is limited. Longer term efficacy and tolerability data from a Phase 3, double-blind, placebo-controlled trial are presented. METHODS: Following favorable results from the primary analysis (data cutoff 30 June 2011) of the EXIST-2 trial, patients still receiving study treatment were allowed to enter an open-label extension. Everolimus was initiated at 10 mg once daily and titrated based on tolerability. The primary outcome was angiomyolipoma response rate (≥ 50% reduction from baseline in target lesion volumes). Safety was a secondary endpoint. RESULTS: As of the cutoff date (1 May 2013), 112 patients had received everolimus, and the response rate in 107 patients with angiomyolipoma (median duration of medication exposure of 28.9 months) was 54%. The proportion of patients achieving angiomyolipoma reductions of ≥ 30% and ≥ 50% increased over time, reaching 81.6% (62/76) and 64.5% (49/76), respectively, by Week 96. No everolimus-treated patients experienced renal bleeding. The long-term safety profile was consistent with previous reports; adverse events (AEs) were mostly Grade 1/2, and there were no new safety issues. The frequency of emerging AEs and severe AEs lessened over time. CONCLUSIONS: Longer term everolimus treatment appeared safe and effective in patients with TSC- or sporadic LAM-associated renal angiomyolipoma not requiring surgical intervention. Continued reduction in angiomyolipoma volume was demonstrated, and there was no angiomyolipoma-related bleeding; AEs were predictable and generally manageable. TRIAL REGISTRATION: clinicaltrialsgov identifier: NCT00790400 (http://clinicaltrials.gov/ct2/show/NCT00790400).
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Angiomiolipoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Everolimo/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Linfangioleiomiomatose/tratamento farmacológico , Esclerose Tuberosa/tratamento farmacológico , Adolescente , Adulto , Angiomiolipoma/patologia , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Rim/patologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Adulto JovemRESUMO
Lymphangioleiomyomatosis (LAM) is a rare multisystem disease, occurs in women, usually premenopausal, caused by the proliferation of neoplastic smooth muscle-derived cells. Mutations in the tuberous sclerosis complex genes, lead to the activation of mammalian target of rapamycin kinase (mTOR), results in proliferation of LAM cells, its increasing motility, and survival. Polycystic lung destruction, extensive involvement of lymphatic channels, chylothorax, chyloperitoneum, and renal angiomyolipomas can develop in LAM patients. The new, promising treatment strategies have been recently introduced due to discovery of the genetic and molecular mechanisms of LAM. Comprehension of the disease pathogenesis has resulted in the implementation of other therapeutic agents such as mTOR inhibitors, VEGF-D inhibitors, statins, interferon, chloroquine analogs, cyclin-dependent kinase inhibitors, matrix metalloproteinase inhibitors, aromatase inhibitors, and their combinations. The mTOR inhibitors appear to be the most important, and the efficacy of sirolimus in LAM treatment has been proved. The article discussed the new control studies with mTOR inhibitors, doxycycline, simvastatin, and combination of them in LAM patients.
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Linfangioleiomiomatose/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Autofagia/efeitos dos fármacos , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Antagonistas de Estrogênios/uso terapêutico , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imunoterapia , Metaloproteases/antagonistas & inibidores , Fatores Sexuais , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fator D de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
BACKGROUND: Angiomyolipomas are slow-growing tumours associated with constitutive activation of mammalian target of rapamycin (mTOR), and are common in patients with tuberous sclerosis complex and sporadic lymphangioleiomyomatosis. The insidious growth of these tumours predisposes patients to serious complications including retroperitoneal haemorrhage and impaired renal function. Everolimus, a rapamycin derivative, inhibits the mTOR pathway by acting on the mTOR complex 1. We compared the angiomyolipoma response rate on everolimus with placebo in patients with tuberous sclerosis or sporadic lymphanioleiomyomatosis-associated angiomyolipomata. METHODS: In this double-blind, placebo-controlled, phase 3 trial, patients aged 18 years or older with at least one angiomyolipoma 3 cm or larger in its longest diameter (defined by radiological assessment) and a definite diagnosis of tuberous sclerosis or sporadic lymphangioleiomyomatosis were randomly assigned, in a 2:1 fashion with the use of an interactive web response system, to receive oral everolimus 10 mg per day or placebo. The primary efficacy endpoint was the proportion of patients with confirmed angiomyolipoma response of at least a 50% reduction in total volume of target angiomyolipomas relative to baseline. This study is registered with ClinicalTrials.gov number NCT00790400. RESULTS: 118 patients (median age 31·0 years; IQR 18·061·0) from 24 centres in 11 countries were randomly assigned to receive everolimus (n=79) or placebo (n=39). At the data cutoff, double-blind treatment was ongoing for 98 patients; two main reasons for discontination were disease progression (nine placebo patients) followed by adverse events (two everolimus patients; four placebo patients). The angiomyolipoma response rate was 42% (33 of 79 [95% CI 3153%]) for everolimus and 0% (0 of 39 [09%]) for placebo (response rate difference 42% [2458%]; one-sided Cochran-Mantel-Haenszel test p<0·0001). The most common adverse events in the everolimus and placebo groups were stomatitis (48% [38 of 79], 8% [3 of 39], respectively), nasopharyngitis (24% [19 of 79] and 31% [12 of 39]), and acne-like skin lesions (22% [17 of 79] and 5% [2 of 39]). INTERPRETATION: Everolimus reduced angiomyolipoma volume with an acceptable safety profile, suggesting it could be a potential treatment for angiomyolipomas associated with tuberous sclerosis. FUNDING: Novartis Pharmaceuticals.
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Angiomiolipoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Sirolimo/análogos & derivados , Adulto , Angiomiolipoma/complicações , Método Duplo-Cego , Everolimo , Feminino , Humanos , Linfangioleiomiomatose/complicações , Masculino , Estudos Prospectivos , Sirolimo/uso terapêutico , Esclerose Tuberosa/complicaçõesRESUMO
INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a rare disease characterised by the abnormal accumulation of surfactant-like material in macrophages within the alveolar spaces and distal bronchioles. The course of the disease is variable and the prognosis is often good. However, progressive disease in some patients can cause respiratory dysfunction and can be life threatening. In this situation, the only effective treatment is whole lung lavage. The objective of the study was to present the characteristics and the course of pulmonary alveolar proteinosis in our own material, the diagnostic methods used, the indications for treatment and the treatment efficacy. MATERIAL AND METHODS: Retrospective analysis included 17 patients: 6 women and 11 men, aged from 32 to 56 years, who were observed in the Third Lung Department of Pneumonology at the National Institute of Tuberculosis and Lung Diseases between 1984 and 2013. In all patients chest X-ray, pulmonary function test and blood gases were performed. In 15 patients, high-resolution computed tomography (HRCT) was obtained. Bronchoscopy was performed in all of the patients, and in 7/17, bronchoalveolar lavage (BAL) was carried out. Fourteen patients underwent open lung biopsy. The indications for whole lung lavage (WLL) were progression of dyspnoea with restriction of daily activity and/or hypoxaemia. RESULTS: In most of the patients (13/17) the diagnosis was established outside our institute. Patients were referred to our department to establish further procedures. The criteria of diagnosis of PAP in most patients (16/17) was the histological examination of lung tissue, obtained by open lung biopsy (14 cases) and transbronchial lung biopsy (TBLB) (2 cases). Only in one patient the diagnosis was established on the basis of BAL. HRCT imaging was characteristic of proteinosis in 11/15 patients, and BAL examination in 6/7 patients, in whom BAL was performed. In four patients, who had been exposed to injurious factors for many years, secondary proteinosis was recognised; in other patients, no exposure or no other disease was found, and primary alveolar proteinosis was diagnosed. In one patient granulocyte macrophage colony stimulating factor autoantibody was detected. The majority of patients (10/17) had clinical symptoms at the diagnosis. The most commonly reported was dyspnoea, followed by respiratory tract infections. The most common abnormality (12/17) in pulmonary lung test was a decrease of diffusing capacity of the lung for carbon monoxide (DLCO). Respiratory distress at rest was found in two patients. Patients were observed for the period of 6 months to 19 years. Spontaneous partial remission was observed in 10 out of 13 untreated patients, including one complete remission; in 3 cases stabilisation was found in radiological examinations; and in other 4 patients, whole lung lavagewas used, resulting in clinical improvement with partial resolution of lesions in radiological examinations in 3 patients. In one patient, despite WLL being repeated three times, improvement was not achieved. CONCLUSIONS: Pulmonary alveolar proteinosis is a rare interstitial disease with a mild course in most cases. In 13/17 patients diagnosis was based on histological examination of samples from open lung biopsy. The presented patients were observed in the years 1984-2004, and at that time histologic examination was the main diagnostic method. The most common abnormality in pulmonary function tests was decrease of DLCO. In most cases, spontaneous remission of the disease was observed. In four patients with severe course of PAP, WLL was performed with subjective, functional and radiological improvement in 3 of them.
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Pulmão/patologia , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/terapia , Adulto , Lavagem Broncoalveolar/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos RetrospectivosRESUMO
Until recently, the basic test to identify latent tuberculosis infection (LTBI) was the tuberculin skin test, despite its limitations in the form of low sensitivity and specificity. Currently, Interferon Gamma Release Assays from peripheral blood are used for a rapid diagnosis of LTBI and measurement of the interferon gamma (IFN-g) levels secreted by specific T cells stimulated with Mycobacterium tuberculosis antigens. Detection of LTBI is important in the control of people potentially at risk of TB disease, such as people remaining in close contact with BK (+) tb patient and for patients evaluated for biological treatment. The paper presents the value of IGRA in three selected clinical situations: in two cases of latent tuberculosis infection and in one case of active tuberculosis.
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Testes de Liberação de Interferon-gama , Tuberculose Latente/sangue , Tuberculose Latente/patologia , Adolescente , Adulto , Antígenos de Bactérias/análise , Feminino , Humanos , Tuberculose Latente/diagnóstico , Masculino , Mycobacterium tuberculosis/imunologia , Sensibilidade e Especificidade , Linfócitos T/imunologia , Teste TuberculínicoRESUMO
Birt-Hogg-Dubé syndrome (BHD syndrome) is an autosomal dominant multisystem disorder with variable expression due to pathogenic constitutional variants in the FLCN gene. Patients with BHD syndrome are predisposed to benign cutaneous fibrofolliculomas/trichodischomas, pulmonary cysts with an associated risk of spontaneous pneumothorax, and renal cell carcinoma. A requirement for updated International consensus recommendations for the diagnosis and management of BHD syndrome was identified. Based on a comprehensive literature review and expert consensus within the fields of respiratory medicine, urology, radiology, dermatology, clinical oncology and clinical genetics, updated recommendations for diagnosis, surveillance and management in BHD syndrome were developed. With the widespread availability of FLCN genetic testing, clinical scenarios in which a diagnosis should be considered and criteria for genetic testing were defined. Following a clinical and/or molecular diagnosis of BHD syndrome, a multidisciplinary approach to disease management is required. Regular renal cancer surveillance is recommended in adulthood and life-long, but the evidence base for additional tumour surveillance is limited and further research warranted. Recommendations for the treatment of cutaneous, pulmonary and renal manifestations are provided. Awareness of BHD syndrome needs to be raised and better knowledge of the clinical settings in which the diagnosis should be considered should enable earlier diagnosis. Further details, including areas for future research topics are available at: https://www.genturis.eu/l=eng/Guidelines-and-pathways/Clinical-practice-guidelines.html .
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Neoplasias Laríngeas/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Linfangioma/diagnóstico por imagem , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Papiloma/complicações , Infecções por Papillomavirus/diagnóstico por imagem , Adulto , Dor no Peito/etiologia , Dispneia/etiologia , Feminino , Hemoptise/etiologia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Linfangioma/complicações , Linfangioma/patologia , Imageamento por Ressonância Magnética , Neoplasias Primárias Múltiplas/complicações , Neoplasias Primárias Múltiplas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/patologia , Derrame Pleural/etiologiaRESUMO
UNLABELLED: One of the methods for correction of "whistle" deformity following a primary bilateral cleft lip repair is a Skoog procedure. It consists of orbicularis oris muscle mobilization and suture following vermilion closure in a V-Y manner. The aim of the study was to evaluate late results of Skoog procedure in "whistle" deformity correction. MATERIAL AND METHODS: Between 2000 and 2009 12 patients with whistle deformity underwent Skoog procedure. All of them were operated by the same surgeon. Aesthetic outcome in terms of lip fullness, symmetry and overall appearance was evaluated by patient and three independent examiners in four-point scale (1 - dissatisfied, 4 - very good). Pre- and postoperative vertical vermilion height was calculated bydigital analysis of photographs. in addition, complications and patient problems such as lip pain, microstomia, smiling or speech disturbances and scabbing of malpositioned wet vermilion were recorded. RESULTS: Six patients (4 men, 2 women, aged 23-44 years, mean 29 years) were included into the study. The average follow-up was 69.5 months. Patients higher evaluated overall appearance (mean 3.83) than symmetry (mean 3.16) and lip fullness (mean 3.16). Lip symmetry evaluated by independent examiners was assessed higher (mean 3.5) than overall appearance (mean 3.33) and lip fullness (mean 3). Digital analysis of photographs shows that mean vertical vermilion height increased after Skoog procedure from 34 to 142% (mean 71.5%). Besides acceptable scabbing of malpositioned wet vermilion no complications and patient problems occurred. CONCLUSIONS: Skoog procedure provided a simple and reliable option for the correction of "whistle" deformity.
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Fenda Labial/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adulto , Feminino , Seguimentos , Humanos , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
A 47-year-old, non-smoking woman was admitted to the National Tuberculosis and Lung Diseases Research Institute for diagnosis of progressive exertional dyspnoea and numerous small thin-walled, air-filled cysts equally distributed throughout both lungs revealed in HRCT (high resolution computed tomography) examination. Histological assessment of specimens obtained by open lung biopsy revealed proliferation of immature smooth muscle, showing the expression of the antigen HMB45. On this basis, diagnosis of lymphangioleiomyomatosis was established. The disease caused essential ventilation damage of the lungs (FEV1 1.34 L; 39.71% pred, VC 4.02 L; 94.96% pred, FEV1/ /VC 0.33-4 1.81% pred, DLCO 3.65 mmol/min/Kpa 38.35% pred).During the observation, despite the lack of immunological disorders, the patient developed Pneumocystis jiroveci pneumonia (PCP) that was treated with trimethoprimsulfamethoxazole. Lymphangioleiomyomatosis is a rare disease which results from a defect of TSC genes. The disease is not related to immunological defects or disorders. However, the considerable cystic destruction of the lungs can predispose the patient to opportunistic infections such as the one in the presented case.
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Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Linfangioleiomiomatose/complicações , Linfangioleiomiomatose/diagnóstico , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/diagnóstico , Anti-Infecciosos/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Linfangioleiomiomatose/tratamento farmacológico , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/tratamento farmacológico , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/administração & dosagemRESUMO
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by eosinophil-rich granulomatous inflammation and necrotizing vasculitis, pre-dominantly affecting small-to-medium-sized vessels. It is categorized as a primary antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) but also shares features of hypereosinophilic syndrome (HES); therefore, both vessel inflammation and eosinophilic infiltration are suggested to cause organ damage. This dual nature of the disease causes variable clinical presentation. As a result, careful differentiation from mimicking conditions is needed, especially from HES, given the overlapping clinical, radiologic, and histologic features, and biomarker profile. EGPA also remains a diagnostic challenge, in part because of asthma, which may pre-dominate for years, and often requires chronic corticosteroids (CS), which can mask other disease features. The pathogenesis is still not fully understood, however, the interaction between eosinophils and lymphocytes B and T seems to play an important role. Furthermore, the role of ANCA is not clear, and only up to 40% of patients are ANCA-positive. Moreover, two ANCA-dependent clinically and genetically distinct subgroups have been identified. However, a gold standard test for establishing a diagnosis is not available. In practice, the disease is mainly diagnosed based on the clinical symptoms and results of non-invasive tests. The unmet needs include uniform diagnostic criteria and biomarkers to help distinguish EGPA from HESs. Despite its rarity, notable progress has been made in understanding the disease and in its management. A better understanding of the pathophysiology has provided new insights into the pathogenesis and therapeutic targets, which are reflected in novel biological agents. However, there remains an ongoing reliance on corticosteroid therapy. Therefore, there is a significant need for more effective and better-tolerated steroid-sparing treatment schemes.
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Cryptogenic organizing pneumonia (COP) is a form of idiopathic interstitial pneumonia that results from the pulmonary reaction to various unidentified injuries. Secondary organizing pneumonia is diagnosed when the triggering factor has been identified; it is mainly caused by infections, toxic substance exposure, drugs, connective tissue diseases, malignancies, autoimmune diseases, bone marrow, or organ transplantation, and radiotherapy. There has been an increase in the number of reports of drug-induced organizing pneumonia (OP). New biological therapies, interferon, monoclonal antibodies, anti-interleukin antibodies, and PD1/PDL-1 inhibitors may induce this specific pulmonary reaction. The classical form of COP is usually subacute and does not manifest as severe disease. Patients maintain sufficient respiratory function, and treatment with steroids is usually effective. Several specific forms of OP (e.g., the cicatricial variant or acute fibrinous type) have distinct clinical and histological features, require higher doses of immunosuppressive drugs, and have a worse prognosis. In the era of administering steroid-sparing therapies for the treatment of interstitial lung diseases, connective tissue dases, and other conditions, it is important to emphasize this type of therapy for patients with COP.
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Adult PAP patients experience similar #COVID19 rates to the general population, and high rates of hospitalisation and deaths, underscoring their vulnerability and the need for measures to prevent infection. The impact of iGM-CSF must be considered. https://bit.ly/3M0wKnZ.
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INTRODUCTION: It is uncertain whether timeliness improves clinical outcomes in lung cancer patients. The goal of the study was to analyse the influence of patient's and doctor's delays on survival of unselected population of NSCLC patients. MATERIAL AND METHODS: From 1995 to 1998, 8705 squamous cell lung cancer patient's and 1881 adenocarcinoma patient's were registered in Pulmonary Outpatients Clinics in all parts of Poland and subsequently in National Tuberculosis and Lung Diseases Research Institute Register (NTLDRIR). RESULTS: The median time from first symptom(s) to the beginning of a treatment was 92 days (mean -138.5 days).The median waiting time between first symptom(s) and first visit to a doctor's was 30 days (mean 57 days) and from first visit to a doctor's to referral to a chest physician - was 17 days (mean 41days). Diagnosis of the NSCLC was established in a mean time of 71 days (median 40 days), but chest physician diagnosed patients in a mean time of 51days (median 28 days). The multivariate analysis revealed that ECOG performance status (PS) 2 (HR = 1.4) and 3+4 (HR = 2.23), clinical stage of the disease II (HR = 1.32), III (HR = 1.41), and IV (HR = 1.82) were independent negative predictors of survival. Non-surgically treated patients had worse prognosis than patients treated surgically (HR = 3.03). Lack of patient's delay had a significant positive impact on survival (HR = 0.88), particularly for patients in PS 0+1 (HR = 0.9) and 3+4 (HR = 0.9). Lack of doctor's delay was a negative predictive factor of survival (HR = 1.14). It was observed particularly in patients in performance status 2 (HR = 1.28). CONCLUSIONS: The patient's delay and lack of doctor's delay had a negative impact on survival of NSCLC patients.
Assuntos
Adenocarcinoma/terapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Adenocarcinoma/epidemiologia , Adenocarcinoma de Pulmão , Adulto , Diagnóstico Tardio , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Polônia/epidemiologia , Prognóstico , Análise de SobrevidaRESUMO
Benign metastasizing leiomyoma (BML) is a rare condition in middle-aged women with a history of uterine leiomyomata. It is characterized by the proliferation of, usually multiple, smooth muscle nodules. Approximately 100 cases have been reported in the literature, and the lungs were the most common site of metastases. We report a case of 52-year-old obese woman (BMI 31), hospital worker, smoker, admitted to the hospital with exertional dyspnoea, night sweats, loss of weight, and productive cough. Hysterectomy for a uterine leiomyoma was performed 9 years earlier. In addition, a history of two episodes of superficial vein thrombosis 3 and 2 years before admission was noted. Chest X-ray and subsequently CT chest examinations revealed multiple, non-calcified nodules within the middle and lower parts of both lungs. Specimens obtained by transbronchial biopsy (TBLB) and from open lung biopsy displayed benign muscle cell proliferation compatible with BML. The levels of sex hormones were characteristic for the menopause; therefore, observation was advised. Additionally, Streptococcus pneumoniae was cultured from bronchial washing, and bronchitis was diagnosed. Antibiotics, bronchodilators, and mucolytics were administered, and dyspnoea and cough with expectoration were diminished. Two years later pulmonary lesions have been stable; however, she has put on weight. Subsequently the patient has developed deep vein thrombosis with pulmonary embolism. Anticoagulant treatment was introduced, with some improvement.
Assuntos
Leiomiomatose/patologia , Neoplasias Pulmonares/secundário , Nódulos Pulmonares Múltiplos/secundário , Neoplasias Uterinas/patologia , Feminino , Humanos , Histerectomia , Leiomiomatose/cirurgia , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/cirurgia , Resultado do Tratamento , Neoplasias Uterinas/cirurgiaRESUMO
Autoimmunological pulmonary alveolar proteinosis (APAP) is a rare interstitial lung disease with abnormal surfactant homeostasis. Autoimmunological pulmonary alveolar proteinosis is diagnosed most often in the third or fourth decade of life. Predominant symptoms are dyspnea and cough. In most cases, disease is mild but in more severe cases when dyspnea limits patient physical activity a treatment is required. The most common treatment procedure is a whole-lung lavage. We present a case study of 37 years old woman with the patchy consolidations in the chest radiograph. High resolution computed tomography (HRCT) image suggested hipersensivity pneumonitis. At the beginning due to limited disease symptoms no specific proceedings was implemented. After two year follow-up of non-resolving pulmonary changes the decision about open lung biopsy was made. On the basis of histological examination of samples and presence of anty GM-CSF antibodies the diagnosis of autoimmunological pulmonary alveolar proteinosis was established.