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1.
Wien Med Wochenschr ; 172(3-4): 84-89, 2022 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-34383223

RESUMO

The new coronavirus (SARS-CoV-2) that arose in 2019 causes a wide spectrum of symptoms and different courses of disease. Pneumothorax, pneumomediastinum and soft tissue emphysema are rare complications in patients with pulmonary involvement. They are the sequelae of severe, virus-induced structural changes of the pulmonary architecture. High pressure artificial ventilation aggravates the problem. Hence pneumothorax and ectopic air in soft tissues are indicators of extensive pulmonary damage. Therefore, efforts should be made to treat even very small or multiply recurrent pneumothorax by drainage procedures.


Assuntos
COVID-19 , Enfisema Mediastínico , Pneumotórax , Enfisema Subcutâneo , COVID-19/complicações , Humanos , Enfisema Mediastínico/diagnóstico por imagem , Enfisema Mediastínico/etiologia , Enfisema Mediastínico/terapia , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Pneumotórax/terapia , SARS-CoV-2 , Enfisema Subcutâneo/diagnóstico por imagem , Enfisema Subcutâneo/etiologia , Enfisema Subcutâneo/terapia
3.
BMC Cancer ; 14: 40, 2014 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-24460801

RESUMO

BACKGROUND: Hypoxia-induced genes are potential targets in cancer therapy. Responses to hypoxia have been extensively studied in vitro, however, they may differ in vivo due to the specific tumor microenvironment. In this study gene expression profiles were obtained from fresh human lung cancer tissue fragments cultured ex vivo under different oxygen concentrations in order to study responses to hypoxia in a model that mimics human lung cancer in vivo. METHODS: Non-small cell lung cancer (NSCLC) fragments from altogether 70 patients were maintained ex vivo in normoxia or hypoxia in short-term culture. Viability, apoptosis rates and tissue hypoxia were assessed. Gene expression profiles were studied using Affymetrix GeneChip 1.0 ST microarrays. RESULTS: Apoptosis rates were comparable in normoxia and hypoxia despite different oxygenation levels, suggesting adaptation of tumor cells to hypoxia. Gene expression profiles in hypoxic compared to normoxic fragments largely overlapped with published hypoxia-signatures. While most of these genes were up-regulated by hypoxia also in NSCLC cell lines, membrane metallo-endopeptidase (MME, neprilysin, CD10) expression was not increased in hypoxia in NSCLC cell lines, but in carcinoma-associated fibroblasts isolated from non-small cell lung cancers. High MME expression was significantly associated with poor overall survival in 342 NSCLC patients in a meta-analysis of published microarray datasets. CONCLUSIONS: The novel ex vivo model allowed for the first time to analyze hypoxia-regulated gene expression in preserved human lung cancer tissue. Gene expression profiles in human hypoxic lung cancer tissue overlapped with hypoxia-signatures from cancer cell lines, however, the elastase MME was identified as a novel hypoxia-induced gene in lung cancer. Due to the lack of hypoxia effects on MME expression in NSCLC cell lines in contrast to carcinoma-associated fibroblasts, a direct up-regulation of stroma fibroblast MME expression under hypoxia might contribute to enhanced aggressiveness of hypoxic cancers.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Fibroblastos/enzimologia , Neoplasias Pulmonares/enzimologia , Neprilisina/metabolismo , Células Estromais/enzimologia , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Hipóxia Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Fibroblastos/patologia , Perfilação da Expressão Gênica/métodos , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neprilisina/genética , Análise de Sequência com Séries de Oligonucleotídeos , Células Estromais/patologia , Técnicas de Cultura de Tecidos , Regulação para Cima
4.
Photochem Photobiol Sci ; 13(9): 1281-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25005268

RESUMO

Photodynamic therapy (PDT) by selective photosensitization of cancer cells and subsequent laser application results in local tumor necrosis. However, the effects of PDT on immune function, which may depend on the type of immune response, are controversial. We investigated the immunological changes induced by PDT and the effect of PDT on level and function of regulatory T cells (Treg) in patients with invasive esophageal squamous cell carcinoma (ESCC). We analyzed patient's blood samples before and after PDT. Blood CD4+CD25+CD127-FoxP3+ Treg levels were quantified by FACS, and Treg function was evaluated by coculture proliferation assays with T effector (Teff) cells. We found that PDT abrogated the suppressive capacity of peripheral Treg (Days 7 and 14, p = 0.016) but had no effect on Treg levels. The effect of PDT on Treg function at Day 7 was accompanied by slight but statistically significant increases in peripheral neutrophil granulocytes (p = 0.035) and monocytes (p = 0.013) and a statistically significant increase (approximately 18-fold) in serum IL-6 levels (p = 0.008). In conclusion, PDT abolished Treg function, possibly due to increased IL-6 levels in treated ESCC patients. This may be crucial for an improved therapeutic outcome.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Linfócitos T Reguladores/imunologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Técnicas de Cocultura , Éter de Diematoporfirina/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/efeitos da radiação , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Fatores de Transcrição Forkhead/metabolismo , Granulócitos/citologia , Granulócitos/imunologia , Humanos , Interleucina-6/sangue , Lasers , Monócitos/citologia , Monócitos/imunologia , Fotoquimioterapia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta/sangue
5.
J Biomech ; 163: 111923, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38219554

RESUMO

Biomechanical simulation of the human thorax, e.g. for 3D-printed rib implant optimisation, requires an accurate knowledge of the associated articulation and tissue stiffness. The present study is focusing on determining the stiffness of the costo-vertebral articulations. Specimens of rib segments including the adjacent thoracic vertebrae and ligaments were obtained from two human post-mortem bodies at four different rib levels. The rib samples were loaded with a tensile force in the local longitudinal, sagittal and transverse direction and the resulting displacement was continuously measured. The moment-angle response of the rib articulations was also determined by applying a load at the rib end in the cranial - caudal direction and measuring the resulting displacement. The torsional load response of the costo-vertebral articulations at an applied moment between -0.1 Nm and 0.1 Nm corresponded to a median range of motion of 13.2° (6.4° to 20.9°). An almost uniform stiffness was measured in all tensile loading directions. The median displacement at the defined force of 28 N was 1.41 mm in the longitudinal, 1.55 mm in the sagittal, and 1.08 mm in the transverse direction. The measured moment-angle response of the costo-vertebral articulation is in line with the data from literature. On the contrary, larger displacements in longitudinal, sagittal and transverse directions were measured compared to the values found in literature.


Assuntos
Costelas , Tórax , Humanos , Costelas/fisiologia , Articulações/fisiologia , Vértebras Torácicas , Próteses e Implantes , Fenômenos Biomecânicos
6.
Scand J Trauma Resusc Emerg Med ; 32(1): 82, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238051

RESUMO

BACKGROUND: Pneumothorax may occur as a complication of cardiopulmonary resuscitation (CPR) and could pose a potentially life-threatening condition. In this study we sought to investigate the incidence of pneumothorax following CPR for out-of-hospital cardiac arrest (OHCA), identify possible risk factors, and elucidate its association with outcomes. METHODS: This study was a retrospective data analysis of patients hospitalized following CPR for OHCA. We included cases from 1st March 2014 to 31st December 2021 which were attended by teams of the physician staffed ambulance based at the University Medical Centre Graz, Austria. Chest imaging after CPR was reviewed to assess whether pneumothorax was present or not. Logistic regression analysis was performed to identify factors for the development of pneumothorax relevant and to assess its association with outcomes [survival to hospital discharge and cerebral performance category (CPC)]. RESULTS: Pneumothorax following CPR was found in 26 out of 237 included cases (11.0%). History of obstructive lung disease was significantly associated with presence of pneumothorax after CPR. This subgroup of patients (n = 61) showed a pneumothorax rate of 23.0%. Pneumothorax was not identified as a relevant factor to predict survival to hospital discharge or favourable neurological outcome (CPC1 + 2). CONCLUSIONS: Pneumothorax may be present in greater than one in ten patients hospitalized after CPR for OHCA. Pre-existent obstructive pulmonary disease seems to be a relevant risk factor for development of post-CPR pneumothorax. CLINICALTRIALS: gov ID: NCT06182007 (retrospectively registered). TRIAL REGISTRATION: NCT06182007 (retrospectively registered).


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Pneumotórax , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Áustria/epidemiologia , Reanimação Cardiopulmonar/métodos , Incidência , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/epidemiologia , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Estudos Retrospectivos , Fatores de Risco
7.
Crit Care ; 17(5): 1005, 2013 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-24107553

RESUMO

Over the past years there has been a significant decrease in mortality and morbidity in patients suffering from severe burns due to improved burn wound management and approaches in critical care. Survival is no longer the exception, but unfortunately death still occurs. One of the key elements concerning state-of-the-art burn care is blood glucose control and insulin therapy; it is well known that burn-induced hyperglycaemia is associated with adverse clinical outcomes. However, controversy for insulin therapy and tight glycaemic control in critically ill and burn patients exists. The increased incidence of hypoglycaemia is the dominant argument against this treatment, because hypoglycaemia is also associated with an increased risk for death in critically ill patients. Taking all current data together, insulin therapy appears both a friend and a foe in the treatment of ICU patients. In order to overcome the limits of tight glycaemic control resulting from hypoglycaemic episodes, current efforts have been directed towards the development of protocols allowing for implementation of clinically feasible and safe guidelines. Among the strategies addressing this problem are closed loop techniques, which are supported by studies demonstrating their capability of exerting tight glycaemic control without the risk of developing hypoglycaemic episodes. Although closed loop techniques have become readily available, we require further evidence to ensure their safety in various ICU environments, notably in ICUs dealing with burn patients. Nonetheless, it is important to emphasise that glycaemic control and adequate insulin therapy are crucial factors for the final outcome (survival) and require our attention.


Assuntos
Glicemia/metabolismo , Queimaduras/sangue , Queimaduras/diagnóstico , Unidades de Terapia Intensiva , Índice de Gravidade de Doença , Humanos
8.
Anat Sci Int ; 98(1): 151-154, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36471134

RESUMO

Post-mortem specimens used for anatomy teaching are commonly embalmed using compositions of chemicals, with the objective to maintain tissue quality and to avoid putrefaction. Monitoring for bacterial or fungal contamination is becoming increasingly important especially when measures are taken to minimize exposure by chemicals such as formaldehyde. In this case, random swabs were taken from six corpses embalmed with ethanol-glycerin and Thiel embalming. Cultures and MALDI-TOF analyses yielded four cases of Clostridium perfringens contamination. C. perfringens is of special interest as a human pathogen. A potential source was identified in the containers filled with the moistening solution. Cross contamination with Clostridium species has likely occurred between corpses sharing the moistening solution and soaking the cover linen directly within the containers. To minimize any risk for those exposed, the moistening solutions were discarded and all equipment thoroughly disinfected. The specimens had to be cremated as they formed a potential source of Clostridium spores. Deviating from previous routines it was formalized that the cover linen must not be submerged in the moistening contains rather than moistening the specimens directly with dedicated vessels. Follow-up analyses yielded no further contamination with C. perfringens.


Assuntos
Clostridium perfringens , Achados Incidentais , Humanos , Formaldeído , Etanol , Cadáver
9.
Cancers (Basel) ; 15(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36980620

RESUMO

This retrospective study aimed at analyzing the impact of metastasectomy on post-metastasis survival (PMS) in bone sarcoma patients with lung metastases. Altogether, 47 bone sarcoma patients (24 males, median age at diagnosis of lung metastases: 21.8 (IQR: 15.6-47.3) years) with primary (n = 8) or secondary (n = 39) lung metastases treated at a single university hospital were retrospectively included. Based on a propensity score, inverse probability of treatment weight (IPTW) was calculated to account for selection bias whether patients had undergone metastasectomy or not. The most common underlying histology was osteosarcoma (n = 37; 78.7%). Metastasectomy was performed in 39 patients (83.0%). Younger patients (p = 0.025) with singular (p = 0.043) and unilateral lesions (p = 0.024), as well as those with an interval ≥ 9 months from primary diagnosis to development of lung metastases (p = 0.024) were more likely to undergo metastasectomy. Weighted 1- and 3-year PMS after metastasectomy was 80.8% and 58.3%, compared to 88.5% and 9.1% for patients who did not undergo metastasectomy. Naive Cox-regression analysis demonstrated a significantly prolonged PMS for patients with metastasectomy (HR: 0.142; 95%CI: 0.045-0.450; p = 0.001), which was confirmed after IPTW-weighting (HR: 0.279; 95%CI: 0.118-0.662; p = 0.004), irrespective of age, time to metastasis, and the number of lesions. In conclusion, metastasectomy should be considered in bone sarcoma patients with lung metastases, after carefully considering the individual risks, to possibly improve PMS.

10.
Eur J Cardiothorac Surg ; 62(6)2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36370073

RESUMO

OBJECTIVES: The reconstruction of the chest wall defect after tumour resection presents a challenge. Titanium rib plates were presented as a reconstruction option due to its biocompatibility, flexibility and pliability. The aim of this study was to evaluate the outcome of single-centre cohort treated with chest wall reconstruction after tumour resections, with a focus on the titanium rib plates reconstruction. METHODS: We retrospectively reviewed the data of 26 patients who underwent wide resection for malignancies of the chest wall, where reconstruction was performed using polypropylene mesh, porcine dermal collagen mesh with or without titanium rib plates, operated on between 2012 and 2019. Events being associated with the surgery requiring revision were rated as complications. RESULTS: Most of the patients had primary tumours (n = 19; 73%). A mean of 3.7 ribs (range: 1-7) was resected. Reconstruction was performed with titanium rib plates (13 patients, 50%), of these 11 were performed with additional mesh grafts. The remaining 13 patients (50%) underwent reconstruction with mesh grafts only. Fourteen patients (54%) developed a complication requiring surgical revision, after a median of 5.5 months. The most common complication was wound healing deficit (n = 4), plate fracture (n = 2), mesh rupture (n = 2), infection (n = 2) and local recurrence (n = 2). The only factor being associated with the development of complications was the usage of a plate (P = 0.015), irrespective of defect size (P = 0.29). CONCLUSIONS: The high complication rate is found when using titanium plates for chest wall reconstruction after tumour resection. A high caution is recommended in choosing the chest wall reconstruction method.


Assuntos
Parede Torácica , Toracoplastia , Suínos , Animais , Titânio/efeitos adversos , Parede Torácica/cirurgia , Estudos Retrospectivos , Placas Ósseas/efeitos adversos
11.
J Biomech ; 142: 111242, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35964445

RESUMO

Surgical resection of chest wall tumours may lead to a loss of ribcage stability and requires reconstruction to allow for physical thorax functioning. When titanium implants are used especially for larger, lateral defects, they tend to break. Implant failures are mainly due to specific mechanical requirements for chest-wall reconstruction which must mimic the physiological properties and which are not yet met by available implants. In order to develop new implants, the mechanical characteristics of ribs, joints and cartilages are investigated. Rib loading is highly dependent on the global thorax kinematics, making implant development substantially challenging. Costal cartilage contributes vastly to the entire thorax load-deformation behaviour, and also to rib loading patterns. Computational models of the thoracic cage require mechanical properties on the global stiffness, to simulate rib kinematics and evaluate stresses in the ribs and costal cartilage. In this study the mechanical stiffness of human costal cartilage is assessed with bending, torsion and tensile tests. The elastic moduli for the bending in four major directions ranged from 2.2 to 60.8 MPa, shear moduli ranged from 5.7 to 24.7 MPa for torsion, and tensile elastic moduli ranging from 5.6 to 29.6 MPa. This article provides mechanical properties for costal cartilage. The results of these measurements are used for the development of a whole thorax finite element model to investigate ribcage biomechanics and subsequently to design improved rib implants.


Assuntos
Cartilagem Costal , Fenômenos Biomecânicos , Cartilagem , Humanos , Costelas/fisiologia , Tórax/fisiologia
12.
Clin Genitourin Cancer ; 20(4): 344-353, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35443915

RESUMO

INTRODUCTION: To quantify the magnitude of benefit of metastasectomy as compared to medical treatment alone in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: We therefore conducted a propensity score analysis of overall survival (OS) in 106 mRCC patients with metachronous metastasis, of whom 36 (34%) were treated with metastasectomy, and 70 (66%) with medical therapy alone. RESULTS: The most frequent metastasectomy procedures were lung resections (n = 13) and craniotomies (n = 6). Median time-to-progression after metastasectomy was 0.7 years (25th-75th percentile: 0.3-2.7). After a median follow-up of 6.2 years and 63 deaths, 5-year OS estimates were 41% and 22% in the metastasectomy and medical therapy group, respectively (log-rank P = .00007; Hazard ratio (HR) = 0.38, 95%CI: 0.21-0.68). Patients undergoing metastasectomy had a significantly higher prevalence of favorable prognostic factors, such as fewer bilateral lung metastases and longer disease-free intervals between nephrectomy and metastasis diagnosis. After propensity score weighting for these differences and adjusting for immortal time bias, the favorable association between metastasectomy and OS became much weaker (HR = 0.62, 95%CI: 0.39-1.00, P = .050). Propensity-score-weighted 5-year OS estimates were 24% and 20% in the metastasectomy and medical therapy group, respectively (log-rank P = .001). In exploratory analyses, the benefit of metastasectomy was confined to patients who achieved complete resection of all known metastases. CONCLUSION: Within the limitations of an observational study, these findings support the concept of metastasectomy being associated with an OS benefit in mRCC patients. Metastasectomies not achieving complete resection of all known lesions are likely without OS benefit.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Metastasectomia , Humanos , Neoplasias Renais/patologia , Metastasectomia/métodos , Nefrectomia/métodos , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida
13.
J Antimicrob Chemother ; 66(1): 160-4, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21081546

RESUMO

OBJECTIVES: the objective of the present investigation was to measure the extracellular concentrations of cefpirome in unaffected and infected lung tissue of septic patients. METHODS: a single intravenous dose of 30 mg/kg total body weight of cefpirome was administered to eight patients every 12 h prior to insertion of microdialysis probes into lung tissue. RESULTS: the median (minimum, maximum) peak concentration (C(max)), time to C(max) (T(max)), area under the concentration-time curve from 0 to 4 h (AUC(0-4)) and AUC(0-∞) of unbound cefpirome for unaffected lung were 48 (32, 107) mg/L, 0.83 (0.17, 3.17) h, 117 (60, 177) mg ·â€Šh/L and 182 (80, 382) mg ·â€Šh/L, respectively. The corresponding values for infected lung tissue were 45 (6, 122) mg/L, 1.17 (0.83, 2.83) h, 92 (17, 253) mg ·â€Šh/L and 206 (49, 379) mg ·â€Šh/L, respectively. The median apparent terminal elimination half-lives (t(½z)) of cefpirome were 2.61, 3.05 and 3.39 h for plasma, unaffected lung and infected lung, respectively. The median ratios of the AUC(0)(-∞) for lung to the AUC(0)(-∞) for plasma were 0.63 (0.19, 1.55) and 0.46 (0.32, 0.98) for unaffected and infected lung, respectively. CONCLUSIONS: we provide strong evidence that cefpirome penetrates effectively into the extracellular space fluid of lung tissue. Under steady-state conditions, the median concentrations of cefpirome in plasma, unaffected lung and infected lung exceeded the MICs of the majority of relevant bacteria over the entire dosing interval of up to 12 h after intravenous administration of a dose of 30 mg/kg total body weight.


Assuntos
Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Pulmão/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Feminino , Humanos , Injeções Intravenosas , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Cefpiroma
14.
Pharmacology ; 88(3-4): 213-24, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21986253

RESUMO

Invasive aspergillosis (IA) is a potentially lethal infection that affects mostly immunocompromised patients. The therapeutic goals are to restore leucocyte function and to reduce the fungal burden by effective antifungal agents and, contingently, by surgery. Several drugs for the treatment of IA are currently licensed. The longest known among them is amphotericin B (AmB). In well-performed clinical trials, approximately 30-50% of participants treated with AmB showed complete or partial response. However, this drug is associated with considerable acute and chronic toxicity which was somewhat mitigated by the development of lipid-based formulations. In contrast, voriconazole (VRC) is better tolerated, penetrates well into the central nervous system and may be given intravenously and orally in a sequential manner. The overall rates of favourable response to VRC were similar to that for AmB. Most notably, double-digit rates of complete remission were observed in studies including extraordinarily high proportions of patients with proven IA and specific risk factors. Disadvantages of VRC include the genetically determined interindividual variability of pharmacokinetics and the potential for drug-drug interactions that may require therapeutic drug monitoring. The recently introduced caspofungin (CPF) offers an excellent safety profile, but underperformed in terms of efficacy against mold infections. Other antifungals such as itraconazole and posaconazole are presently recommended as second-line option for the therapy or prophylaxis of (non-)IA. The value of micafungin and anidulafungin remains to be investigated in randomized clinical trials. In guidelines released by relevant medical societies, VRC is recommended as the first choice in the treatment of IA. AmB, preferably given as a liposomal preparation, or combinatory antifungal regimens combining VRC or liposomal AmB with CPF are stated as alternative options.


Assuntos
Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Anfotericina B/uso terapêutico , Animais , Quimioterapia Combinada , Equinocandinas/uso terapêutico , Humanos , Resultado do Tratamento , Triazóis/uso terapêutico
15.
Exp Mol Med ; 53(1): 81-90, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33408336

RESUMO

In cancer cells, metabolic pathways are reprogrammed to promote cell proliferation and growth. While the rewiring of central biosynthetic pathways is being extensively studied, the dynamics of phospholipids in cancer cells are still poorly understood. In our study, we sought to evaluate de novo biosynthesis of glycerophospholipids (GPLs) in ex vivo lung cancer explants and corresponding normal lung tissue from six patients by utilizing a stable isotopic labeling approach. Incorporation of fully 13C-labeled glucose into the backbone of phosphatidylethanolamine (PE), phosphatidylcholine (PC), and phosphatidylinositol (PI) was analyzed by liquid chromatography/mass spectrometry. Lung cancer tissue showed significantly elevated isotopic enrichment within the glycerol backbone of PE, normalized to its incorporation into PI, compared to that in normal lung tissue; however, the size of the PE pool normalized to the size of the PI pool was smaller in tumor tissue. These findings indicate enhanced PE turnover in lung cancer tissue. Elevated biosynthesis of PE in lung cancer tissue was supported by enhanced expression of the PE biosynthesis genes ETNK2 and EPT1 and decreased expression of the PC and PI biosynthesis genes CHPT1 and CDS2, respectively, in different subtypes of lung cancer in publicly available datasets. Our study demonstrates that incorporation of glucose-derived carbons into the glycerol backbone of GPLs can be monitored to study phospholipid dynamics in tumor explants and shows that PE turnover is elevated in lung cancer tissue compared to normal lung tissue.


Assuntos
Neoplasias Pulmonares/metabolismo , Pulmão/metabolismo , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfatidilinositóis/metabolismo , Idoso , Idoso de 80 Anos ou mais , Diacilglicerol Colinofosfotransferase/genética , Diacilglicerol Colinofosfotransferase/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo
16.
Front Pediatr ; 9: 661025, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791262

RESUMO

Introduction: Ewing sarcomas of the chest wall, historically known as "Askin tumors" represent highly aggressive pediatric malignancies with a reported 5-year survival ranging only between 40 and 60% in most studies. Multimodal oncological treatment according to specific Ewing sarcoma protocols and radical "en-bloc" resection with simultaneous chest wall repair are key factors for long-term survival. However, the surgical complexity depends on tumor location and volume and potential infiltrations into lung, pericardium, diaphragm, esophagus, spine and major vessels. Thus, the question arises, which surgical specialties should join their comprehensive skills when approaching a child with Ewing sarcoma of the chest wall. Patients and Methods: All pediatric patients with Ewing sarcomas of the chest wall treated between 1990 and 2020 were analyzed focusing on complete resection, chest wall reconstruction, surgical complications according to Clavien-Dindo (CD) and survival. Patients received neo-adjuvant chemotherapy according to the respective Ewing sarcoma protocols. Depending on tumor location and organ infiltration, a multi-disciplinary surgical team was orchestrated to perform radical en-bloc resection and simultaneous chest wall repair. Results: Thirteen consecutive patients (seven boys and six girls) were included. Median age at presentation was 10.9 years (range 2.2-21 years). Neo-adjuvant chemotherapy (n = 13) and irradiation (n = 3) achieved significant reduction of the median tumor volume (305.6 vs. 44 ml, p < 0.05). En-bloc resection and simultaneous chest wall reconstruction was achieved without major complications despite multi-organ involvement. Postoperatively, one patient with infiltration of the costovertebral joint and laminectomy required surgical re-intervention (CD IIIb). 11/13 patients were treated with clear resections margins (R1 resection in one patient with infiltration of the costovertebral joint and marginal resection <1 mm in one child with multiple pulmonary metastases). All patients underwent postoperative chemotherapy; irradiation was performed in four children. Two deaths occurred 18 months and 7.5 years after diagnosis, respectively. Median follow-up for the remaining patients was 8.8 years (range: 0.9-30.7 years). The 5-year survival rate was 89% and the overall survival 85%. Conclusion: EWING specific oncological treatment and multi-disciplinary surgery performing radical en-bloc resections and simultaneous chest wall repair contribute to an improved survival of children with Ewing sarcoma of the chest wall.

17.
J Antimicrob Chemother ; 65(5): 995-8, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20228081

RESUMO

OBJECTIVES: The present investigation explored the ability of fosfomycin to penetrate lung tissue of septic patients by utilizing the microdialysis technique. METHODS: After microdialysis probe insertion into healthy and infected lung tissue, a single intravenous dose of 4 g of fosfomycin was administered. RESULTS: The mean C(max), T(max), AUC(0-4) and AUC(0-infinity) for healthy lung were 131.6 +/- 110.6 mg/L, 1.1 +/- 0.4 h, 242.4 +/- 101.6 mgxh/L and 367.6 +/- 111.9 mgxh/L, respectively. The corresponding values for infected lung were 107.5 +/- 60.2 mg/L, 1.4 +/- 0.5 h, 203.5 +/- 118.4 mgxh/L and 315.1 +/- 151.2 mgxh/L. The half-life of fosfomycin ranged from 2.2 to 2.7 h between compartments. The magnitude of lung tissue penetration, as determined by the ratios of the AUC(0-infinity) for lung to the AUC(0-infinity) for plasma, was 0.63 +/- 0.31 and 0.53 +/- 0.31 for healthy and infected lung, respectively. CONCLUSIONS: We conclude that fosfomycin achieves antimicrobially effective concentrations in infected lung tissue.


Assuntos
Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Fosfomicina/farmacocinética , Fosfomicina/uso terapêutico , Pulmão/química , Sepse/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Feminino , Fosfomicina/administração & dosagem , Meia-Vida , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade
18.
Xenotransplantation ; 17(5): 379-90, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20955294

RESUMO

INTRODUCTION: Transplanted cells, especially islet cells, are likely to become apoptotic due to local hypoxia leading to graft dysfunction. Isolated pancreatic islet cells depend on the diffusion of oxygen from the surrounding tissue; therefore, access to sufficient oxygen supply is beneficial, particularly when microcapsules are used for immunoisolation in xenotransplantation. The aim of this study was to create a prevascularized site for cell transplantation in rats and test its effectiveness with microencapsulated HEK293 cells. METHODS: The combination of implantation of a foam dressing, vacuum-assisted wound closure (foam+VAC) and hyperbaric oxygenation (HBO) was used in 40 Sprague-Dawley rats. Blood flow and vascular endothelial growth factor (VEGF) levels were determined. Sodium cellulose sulphate (SCS)-microencapsulated HEK293 cells were xenotransplanted into the foam dressing in rats pre-treated with HBO, and angiogenesis and apoptosis were assessed. RESULTS: Vessel ingrowth and VEGF levels increased depending on the duration of HBO treatment. The area containing the foam was perfused significantly better in the experimental groups when compared to controls. Only a small amount of apoptosis occurs in SCS-microencapsulated HEK293 cells after xenotransplantation. CONCLUSION: As ischemia-damaged cells are likely to undergo cell death or loose functionality due to hypoxia, therefore leading to graft dysfunction, the combination foam+VAC and HBO might be a promising method to create a prevascularized site to achieve better results in xenogeneic cell transplantation.


Assuntos
Transplante de Células/métodos , Implantes Experimentais , Neovascularização Fisiológica , Transplante Heterólogo/métodos , Animais , Composição de Medicamentos/métodos , Células HEK293 , Humanos , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismo
19.
Ann Thorac Surg ; 109(4): 1104-1111, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31891695

RESUMO

BACKGROUND: Current knowledge about sex-related differences states that pain is generally more frequent and intense in women. Because severe postthoracotomy pain is associated with complications, sufficient pain control is essential. Data on sex-related aspects in the context of pain after thoracotomy are scarce. The study attempted to determine whether sex significantly affects pain and pain treatment after thoracotomy. METHODS: This retrospective study assessed visual analogue scale (VAS) scores and analgesic consumption (opioids and diclofenac) during the first 5 days after surgery and the point in time when analgesics were changed from the intravenous to the oral route in patients who had open lung surgery. The influences of sex, PCEA (patient-controlled epidural analgesia), age, and surgical factors were evaluated with mixed-model analysis. RESULTS: The study was able to include 344 patients (130 female, 214 male). The VAS scores model did not consider sex as relevant. The opioid model showed a PCEA-time-sex interaction with increasing opioid demand after day 3 that predominantly affected male patients (P < .001). Diclofenac doses where significantly higher in an interaction of female sex and small extent of surgery (P = .007). Posterolateral thoracotomy led to significantly higher VAS scores (P < .001) and higher demand for opioids (P = .007) and diclofenac (P = .012). CONCLUSIONS: The study concluded that there are no general sex-related differences in pain intensity and analgesic requirement after thoracotomy. Anterolateral thoracotomy was the less painful surgical approach. PCEA had favorable results, although there seemed to a rebound pain phenomenon after epidural catheter removal on postoperative day 3 that mainly affected male patients.


Assuntos
Dor Pós-Operatória/epidemiologia , Toracotomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgesia Controlada pelo Paciente , Analgésicos/uso terapêutico , Feminino , Humanos , Pneumopatias/patologia , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico , Pneumonectomia/efeitos adversos , Estudos Retrospectivos , Fatores Sexuais , Adulto Jovem
20.
Comput Biol Med ; 122: 103831, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32658732

RESUMO

In this paper, we present an approach for multi-channel lung sound classification, exploiting spectral, temporal and spatial information. In particular, we propose a frame-wise classification framework to process full breathing cycles of multi-channel lung sound recordings with a convolutional recurrent neural network. With our recently developed 16-channel lung sound recording device, we collect lung sound recordings from lung-healthy subjects and patients with idiopathic pulmonary fibrosis (IPF), within a clinical trial. From the lung sound recordings, we extract spectrogram features and compare different deep neural network architectures for binary classification, i.e. healthy vs. pathological. Our proposed classification framework with the convolutional recurrent neural network outperforms the other networks by achieving an F-score of F1≈92%. Together with our multi-channel lung sound recording device, we present a holistic approach to multi-channel lung sound analysis.


Assuntos
Redes Neurais de Computação , Sons Respiratórios , Humanos , Pulmão/diagnóstico por imagem , Respiração
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