Tomas Svoboda

Coronary versus carotid blood flow and coronary perfusion pressure in a pig model of prolonged cardiac arrest treated by different modes of venoarterial ECMO and intraaortic balloon counterpulsation

IntroductionExtracorporeal membrane oxygenation (ECMO) is increasingly used in cardiac arrest (CA). Adequacy of carotid and coronary blood flows (CaBF, CoBF) and coronary perfusion pressure (CoPP) in ECMO treated CA is not well established. This study compares femoro-femoral (FF) to femoro-subclavian (FS) ECMO and intraaortic balloon counterpulsation (IABP) contribution based on CaBF, CoBF, CoPP, myocardial and brain oxygenation in experimental CA managed by ECMO.MethodsIn 11 female pigs (50.3 ± 3.4 kg), CA was randomly treated by FF versus FS ECMO ± IABP. Animals under general anesthesia had undergone 15 minutes of ventricular fibrillation (VF) with ECMO flow of 5 to 10 mL/kg/min simulating low-flow CA followed by continued VF with ECMO flow of 100 mL/kg/min. CaBF and CoBF were measured by a Doppler flow wire, cerebral and peripheral oxygenation by near infrared spectroscopy. CoPP, myocardial oxygen metabolism and resuscitability were determined.ResultsCaBF reached values > 80% of baseline in all regimens. CoBF > 80% was reached only by the FF ECMO, 90.0% (66.1, 98.6). Addition of IABP to FF ECMO decreased CoBF to 60.7% (55.1, 86.2) of baseline, P = 0.004. FS ECMO produced 70.0% (49.1, 113.2) of baseline CoBF, significantly lower than FF, P = 0.039. Addition of IABP to FS did not change the CoBF; however, it provided significantly higher flow, 76.7% (71.9, 111.2) of baseline, compared to FF + IABP, P = 0.026. Both brain and peripheral regional oxygen saturations decreased after induction of CA to 23% (15.0, 32.3) and 34% (23.5, 34.0), respectively, and normalized after ECMO institution. For brain saturations, all regimens reached values exceeding 80% of baseline, none of the comparisons between respective treatment approaches differed significantly. After a decline to 15 mmHg (9.5, 20.8) during CA, CoPP gradually rose with time to 68 mmHg (43.3, 84.0), P = 0 .003, with best recovery on FF ECMO. Resuscitability of the animals was high, both 5 and 60 minutes return of spontaneous circulation occured in eight animals (73%).ConclusionsIn a pig model of CA, both FF and FS ECMO assure adequate brain perfusion and oxygenation. FF ECMO offers better CoBF than FS ECMO. Addition of IABP to FF ECMO worsens CoBF. FF ECMO, more than FS ECMO, increases CoPP over time.

Mild therapeutic hypothermia is superior to controlled normothermia for the maintenance of blood pressure and cerebral oxygenation, prevention of organ damage and suppression of oxidative stress after cardiac arrest in a porcine model

BackgroundMild therapeutic hypothermia (HT) has been implemented in the management of post cardiac arrest (CA) syndrome after the publication of clinical trials comparing HT with common practice (ie, usually hyperthermia). Current evidence on the comparison between therapeutic HT and controlled normothermia (NT) in CA survivors, however, remains insufficient.MethodsEight female swine (sus scrofa domestica; body weight 45 kg) were randomly assigned to receive either mild therapeutic HT or controlled NT, with four animals per group. Veno-arterial extracorporeal membrane oxygenation (ECMO) was established and at minimal ECMO flow (0.5 L/min) ventricular fibrillation was induced by rapid ventricular pacing. After 20 min of CA, circulation was restored by increasing the ECMO flow to 4.5 L/min; 90 min of reperfusion followed. Target core temperatures (HT: 33°C; NT: 36.8°C) were maintained using the heat exchanger on the oxygenator. Invasive blood pressure was measured in the aortic arch, and cerebral oxygenation was assessed using near-infrared spectroscopy. After 60 min of reperfusion, up to three defibrillation attempts were performed. After 90 min of reperfusion, blood samples were drawn for the measurement of troponin I (TnI), myoglobin (MGB), creatine-phosphokinase (CPK), alanin-aminotransferase (ALT), neuron-specific enolase (NSE) and cystatin C (CysC) levels. Reactive oxygen metabolite (ROM) levels and biological antioxidant potential (BAP) were also measured.ResultsSignificantly higher blood pressure and cerebral oxygenation values were observed in the HT group (P<0.05). Sinus rhythm was restored in all of the HT animals and in one from the NT group. The levels of TnI, MGB, CPK, ALT, and ROM were significantly lower in the HT group (P<0.05); levels of NSE, CysC, and BAP were comparable in both groups.ConclusionsOur results from animal model of cardiac arrest indicate that HT may be superior to NT for the maintenance of blood pressure, cerebral oxygenation, organ protection and oxidative stress suppression following CA.

The Role of Molecular Testing in the Differential Diagnosis of Salivary Gland Carcinomas

Salivary gland neoplasms are a morphologically heterogenous group of lesions that are often diagnostically challenging. In recent years, considerable progress in salivary gland taxonomy has been reached by the discovery of tumor type-specific fusion oncogenes generated by chromosome translocations. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive genomic characteristics. Mammary analog secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion. Hyalinizing clear cell carcinoma is a low-grade tumor with infrequent nodal and distant metastasis, recently shown to harbor an EWSR1-ATF1 gene fusion. The CRTC1-MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low-grade and high-grade mucoepidermoid carcinomas associated with improved survival. A t(6;9)(q22-23;p23-34) translocation resulting in a MYB-NFIB gene fusion has been identified in the majority of adenoid cystic carcinomas. Polymorphous (low-grade) adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin are related entities with partly differing clinicopathologic and genomic profiles; they are the subject of an ongoing taxonomic debate. Polymorphous (low-grade) adenocarcinomas are characterized by hot spot point E710D mutations in the PRKD1 gene, whereas cribriform adenocarcinoma of (minor) salivary glands origin are characterized by translocations involving the PRKD1-3 genes. Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with morphologic and molecular features akin to invasive ductal carcinoma of the breast, including HER2 gene amplification, mutations of TP53, PIK3CA, and HRAS and loss or mutation of PTEN. Notably, a recurrent NCOA4-RET fusion has also been found in SDC. A subset of SDC with apocrine morphology is associated with overexpression of androgen receptors. As these genetic aberrations are recurrent they serve as powerful diagnostic tools in salivary gland tumor diagnosis, and therefore also in refinement of salivary gland cancer classification. Moreover, they are promising as prognostic biomarkers and targets of therapy.

P27 as a prognostic factor of early cervical carcinoma.

Objective The aim of this study was to clarify whether the evaluation of cell-cycle regulatory protein p27 can serve as a prognostic factor in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical carcinoma. Patients and Methods A retrospective study was performed on 130 surgically treated patients with FIGO stage IB cervical carcinoma with at least a 5-year follow-up. The expression of p27 was investigated independently by 2 experienced pathologists using immunohistochemistry. The prognostic significance of established prognostic factors and p27 expression were analyzed using univariate and multivariate analyses. Results In a univariate analysis, lymph node status, tumor diameter, Gynecologic Oncology Group (GOG) score, lymph vascular space invasion, and p27 expression were significant prognostic factors for overall survival (OS). We found a correlation between p27 expression and lymph node status, tumor diameter, invasion, and GOG score. The p27 expression was a statistically significant prognostic factor for OS in a univariate analysis (log-rank test, P = 0.03). In a multivariate analysis, only lymph node status and tumor diameter were statistically significant prognostic factors for OS. Conclusions This study demonstrated that a low p27 expression is associated with lymph node metastasis, deep stromal invasion, tumor diameter more than 20 mm, and high GOG score and had a prognostic influence on OS in a univariate analysis in a series of 130 women with FIGO stage IB cervical carcinoma. Lymph node status and the diameter of the tumor were the only statistically significant prognostic factors in multivariate analysis.

Ischemic Postconditioning and Nitric Oxide Administration Failed to Confer Protective Effects in a Porcine Model of Extracorporeal Cardiopulmonary Resuscitation.

The protective effects of ischemic postconditioning (IPC) and nitric oxide (NO) administration have been demonstrated in several ischemic scenarios. However, current evidence regarding the effect of IPC and NO in extracorporeal cardiopulmonary resuscitation remains lacking. Fifteen female swine (body weight 45 kg) underwent veno-arterial extracorporeal membrane oxygenation (ECMO) implantation; cardiac arrest-ventricular fibrillation was induced by rapid ventricular pacing. After 20 min of cardiac arrest, blood flow was restored by increasing the ECMO flow rate to 4.5 L/min. The animals (five per group) were then randomly assigned to receive IPC (three cycles of 3 min ischemia and reperfusion), NO (80 ppm via oxygenator), or mild hypothermia (HT; 33.0°C). Cerebral oximetry and aortic blood pressure were monitored continuously. After 90 min of reperfusion, blood samples were drawn for the measurement of troponin I, myoglobin, creatine-phosphokinase, alanine aminotransferase, neuron-specific enolase, cystatin C, and reactive oxygen metabolite (ROM) levels. Significantly higher blood pressure and cerebral oxygen saturation values were observed in the HT group compared with the IPC and NO groups (P < 0.05). The levels of troponin I, myoglobin, creatine phosphokinase, and alanine aminotransferase were significantly lower in the HT group (P < 0.05); levels of neuron-specific enolase, cystatin C, and ROM were not significantly different. IPC and NO were comparable in all monitored parameters. The results of the present study indicate that IPC and NO administration are not superior interventions to HT for the maintenance of blood pressure, cerebral oxygenation, organ protection, and suppression of oxidative stress following extracorporeal cardiopulmonary resuscitation.

No linguistic borders ahead? Looking beyond the knocked-down language barrier

The article deals with the concept of borders and barriers in considering scenarios where the linguistic barrier is eventually lifted by technology one day. It begins with reflections on the biblical narrative of the Tower of Babel as an ancient representation of the concept of linguistic barriers between language communities. It gives numerous examples of the uptake of this narrative, from Translation Studies, to project calls and the marketing statements of machine translation technology. In the following section, examples of existing technology are presented, which could be considered as a first generation of automatic translation/interpretation systems. In the main section, several trends are predicted for both the translators’ profession and general economic/business/political/societal developments. The consequences are anticipated of a situation where ordinary cross-language communication will eventually have been almost fully taken over by automated systems. The article points to both the technology’s positive potential and, by showing the eventual risks involved, it equally rejects an attitude of the technology’s uncritical uptake. The article closes by pointing to the ethical dimension of machine translation systems linked with their types of uses and the choices reserved for their users.

Renal Cell Carcinoma With Leiomyomatous Stroma: A Group of Tumors With Indistinguishable Histopathologic Features, But 2 Distinct Genetic Profiles

We have studied a cohort of renal cell carcinomas (RCCs) with smooth-muscle stroma (N=6), which lacked any of following genetic aberrations: mutations in the VHL-gene-coding sequence, loss of heterozygosity of chromosome 3p, or hypermethylation of VHL. Using targeted next-generation sequencing, no intronic VHL mutations or mutations in selected genes involved in angiogenesis and genes frequently mutated in clear cell RCC were identified. Tumors were also tested for the presence of hotspot mutations in the TCEB1 gene with negative results in all cases. We conclude that there exists a group of RCCs with abundant leiomyomatous stroma, where the epithelial component is indistinguishable from conventional clear cell RCC and distinct from clear cell (tubulo-) papillary RCC and that these tumors lack aberrations related to the function of the VHL gene, mutations in genes involved in angiogenesis, and hotspot mutations in the TCEB1 gene.

The Influence of Palliative Chemotherapy on the Quality of Life of Patients with Gastric Cancer

BACKGROUND Gastric cancer is a malignant disease with a poor prognosis. The incidence of gastric cancer in the Czech Republic in 2013 was 14.34 cases per 100,000 citizens. Unfortunately, most patients are dia-gnosed with advanced stage disease and therefore undergo palliative treatment. Some patients undergo surgery and a very small percentage undergo palliative chemotherapy. The five year survival rate for those with advanced gastric cancer ranges from 5-15%. METHODS This is a prospective study of patients undergoing chemotherapy for advanced gastric cancer. The aim was to assess the quality of life of those undergoing chemotherapy. RESULTS The results showed that chemotherapy reduced the quality of life for these patients. DISCUSSION Although palliative chemotherapy prolonged time to progression, it had little impact on overall survival. Conversely, chemotherapy reduced quality of life. Thus, clinicians and patients must decide whether to begin palliative chemotherapy. The final decision should be made by the patient after discussion with the treating clinician. CONCLUSION Treatment of patients with gastric cancer must be undertaken on an individual basis. Those undergoing palliative treatment must play an active role in the decision process regarding chemotherapy and assess the potential benefits and drawbacks. Because chemotherapy treatment has a detrimental effect on quality of life, the decision should be based on factors that predict the likely therapeutic effect of chemotherapy. A definitive decision can then be made as to whether chemotherapy is indicated. KEY WORDS gastric cancer - palliative chemotherapy - chemotherapy - quality of life - WHOQOL-BREFThis study was supported by grant of Internal Grant Agency of the Czech Ministry of Health No. NS14227-3.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 10. 1. 2016Accepted: 8. 6. 2016.