Pulmonary hypertension is a group of diseases characterized by elevated pulmonary artery pressure and pulmonary vascular resistance with significant morbidity and mortality. The most prevalent type is pulmonary hypertension secondary to left heart disease (PH-LHD). The available experimental models of PH-LHD use partial pulmonary clamping by technically nontrivial open-chest surgery with lengthy recovery. We present a simple model in which the reduction of the cross-sectional area of the ascending aorta is achieved not by external clamping but by partial intravascular obstruction without opening the chest. In anesthetized rats, a blind polyethylene tubing was advanced from the right carotid artery to just above the aortic valve. The procedure is quick and easy to learn. Three weeks after the procedure, left heart pressure overload was confirmed by measuring left ventricular end-diastolic pressure by puncture (1.3 ± 0.2 vs. 0.4 ± 0.3 mmHg in controls, mean ± SD, P < 0.0001). The presence of pulmonary hypertension was documented by measuring pulmonary artery pressure by catheterization (22.3 ± 2.3 vs. 16.9 ± 2.7 mmHg, P = 0.0282) and by detecting right ventricular hypertrophy and increased muscularization of peripheral pulmonary vessels. Contributions of a precapillary vascular segment and vasoconstriction to the increased pulmonary vascular resistance were demonstrated, respectively, by arterial occlusion technique and by normalization of resistance by a vasodilator, sodium nitroprusside, in isolated lungs. These changes were comparable, but not additive, to those induced by an established pulmonary hypertension model, chronic hypoxic exposure. Intravascular partial aortic obstruction offers an easy model of pulmonary hypertension induced by left heart disease that has a vasoconstrictor and precapillary component.NEW & NOTEWORTHY We present a new, simple model of a clinically important type of pulmonary hypertension, that induced by left heart failure. Left ventricular pressure overload is induced in rats by inserting a blinded cannula into the ascending aorta via carotid artery access. This partial intravascular aortic obstruction, which does not require opening of the chest and prolonged recovery, causes pulmonary hypertension, which has a precapillary and vasoconstrictor as well as a vascular remodeling component.

• MeSH
• aorta * patofyziologie   patologie   MeSH
• arteria pulmonalis patofyziologie   patologie   MeSH
• cévní rezistence MeSH
• hypertrofie pravé komory srdeční patofyziologie   etiologie   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech * MeSH
• plicní hypertenze * patofyziologie   etiologie   MeSH
• potkani Sprague-Dawley MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Kombinovaná chemoterapie na bázi platiny zůstává standardní léčbou uroteliálního karcinomu. Pembrolizumab ve studii KEYNOTE-045 byl spojen s významně delším celkovým přežitím a s nižší mírou nežádoucích účinků souvisejících s léčbou než chemoterapie, a to jako terapie druhé linie pokročilého uroteliálního karcinomu refrakterního na platinu.

Platinum-based combination chemotherapy remains the standard treatment in urothelial cancer. Pembrolizumab in KEYNOTE-045 study was associated with significantly longer overall survival and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma.

• Klíčová slova
• pembrolizumab, studie KEYNOTE-045,
• MeSH
• acinární karcinom chirurgie   MeSH
• adjuvantní chemoterapie MeSH
• analýza přežití MeSH
• aorta patologie   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   terapeutické užití   MeSH
• indukce remise MeSH
• karcinom z přechodných buněk chirurgie   diagnóza   farmakoterapie   patologie   MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• nádory močovodu chirurgie   diagnóza   farmakoterapie   patologie   MeSH
• nádory prostaty chirurgie   MeSH
• nefroureterektomie MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH

The most common reason for ascending aorta resection is an aneurysm or dissection. Aortic dissection is a life-threatening condition in which an aneurysm is a crucial risk factor. The essential criteria for aneurysm resection include the diameter, genetic predisposition, and aortic valve disease. This study aimed to compare the histological findings in aneurysms and dissections and correlate them with clinical parameters to determine whether histopathological findings correspond with the current clinical approach. A total of 160 ascending aorta surgical specimens, separate or with an aortic valve, were collected and divided into four groups: aneurysm-tricuspid (n = 40; median 67 y), aneurysm-malformed (n = 68; median 50 y), dissection-tricuspid (n = 48; median 65.5 y), and dissection-malformed (n = 4; median 52.5 y). Male preponderance was observed in all groups; the youngest patients were in the aneurysm-malformed group. None of the specimens showed normal aortic histology. The most common finding in the aortic samples was medial degeneration, which was the most severe and most common in dissection. The mildest findings were found in the aneurysm-malformed group. Atherosclerosis was predominant and most severe in the aneurysm-tricuspid group, while only mild in both dissection groups, suggesting its protective effect against this complication. Chronic aortitis was the least common pathology, found only in the aneurysm-tricuspid group. The aortic valve was resected and examined simultaneously with the ascending aorta in 76 cases, most commonly in the aneurysm-malformed group (n = 53). Myxoid degeneration was the major finding in the tricuspid aortic valves, with calcifications in the malformed. Comparing the histopathological results with the clinical aspects, aneurysms with a malformed aortic valve seem to be managed appropriately, with the findings not reaching the severity as in patients with a tricuspid valve. In contrast, in patients with a tricuspid valve, there were more dissections than aneurysms, with a significant subset of aneurysms showing histological findings almost identical to those of dissections. Supported by histological findings, patients with a diseased ascending aorta and tricuspid aortic valve represent an underdiagnosed risk group that would benefit from earlier diagnosis and intervention to prevent dissection. There is a need to find a marker for dissection risk other than the aortic diameter.

• MeSH
• aorta * patologie   MeSH
• aortální chlopeň patologie   MeSH
• disekce aorty * MeSH
• genetická predispozice k nemoci MeSH
• lidé MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Diagnóza mobilního trombu na neaneurysmatické aortě je vzácná jednotka. Odhalena bývá zpravidla při embolických komplikacích, které jsou většinou fatální či výrazně devastující. Referovány jsou případy embolizace do periferie končetin, do renálních arterií s postižením renálních funkcí, infarkty myokardu, cévní mozkové příhody či makroembolizace s kritickou končetinovou či viscerální ischemií. Vzhledem k nízkému výskytu aortálních trombů a retrospektivní povaze studií není jasně stanovena jednotná strategie léčby. Při volbě optimální terapie hraje významnou roli charakter embolizace, lokalizace trombu a pacientův klinický stav. U našeho pacienta byl plán léčby určen po diskusi multidisciplinárního týmu a vyvíjel se podle klinické situace.

The presence of a mobile thrombus in a nonaneurysmal aorta is a rare clinical entity that is usually discovered after embolic, mostly fatal or devastating, complications. Cases have been reported of peripheral limb ischemia, renal dysfunction due to embolism into the renal arteries, myocardial infarction, stroke, or macroembolism with critical limb or visceral ischemia. Due to the low incidence of mobile thrombus, there is no uniform treatment strategy. The characteristics of embolization, thrombus location, and patient's clinical status all play a key role in choosing the optimal approach. In the case reported here, the therapeutic plan was established after consulting with the multidisciplinary team, and changed according to the current clinical situation.

• MeSH
• aorta diagnostické zobrazování   patologie   MeSH
• echokardiografie transezofageální MeSH
• heparin nízkomolekulární aplikace a dávkování   terapeutické užití   MeSH
• ischemická cévní mozková příhoda * etiologie   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• počítačová rentgenová tomografie metody   MeSH
• recidiva MeSH
• trombóza * diagnostické zobrazování   farmakoterapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• přehledy MeSH

• MeSH
• aorta patologie   MeSH
• ateroskleróza * etiologie   patologie   MeSH
• Hodgkinova nemoc * komplikace   patologie   radioterapie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• přežívající MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• Publikační typ
• dopisy MeSH

Medial degeneration is the most common histological finding in ascending aortic aneurysms with lesser but significant involvement by atherosclerosis. The overall extent and severity can be potentially underrated because of their uneven distribution and macroscopic inconspicuousness of medial degeneration. This study aims to compare the distribution of degenerative and atherosclerotic lesions around ascending aorta circumference, also considering aortic valve cuspidity. We evaluated 88 cases of resected ascending aortae, 25 with a tricuspid aortic valve and 63 with a malformed aortic valve, oriented by a cardiac surgeon and sent for pathological examination. We applied the consensus documents from 2015 and 2016 for microscopic evaluation of aortic specimens. The medial degeneration and atherosclerosis were graded semi-quantitatively for each aortic quadrant: convexity, anterior wall, concavity, and posterior wall. Nearly all quadrants showed at least mild medial degeneration; more severe findings of medial degeneration and atherosclerosis were in the aneurysms associated with the tricuspid valve. In the aneurysms with the tricuspid aortic valve, there was more frequent and more severe atherosclerosis at the concavity than at the anterior wall (p = .046); the frequency and severity of medial degeneration did not differ significantly. The aneurysms with a malformed aortic valve showed more severe medial degeneration at the concavity compared to the convexity (p = .011); atherosclerosis was less common and did not show any significant differences. More than half of the samples also revealed at least a one-grade (mostly one-grade) difference among the quadrants in individual cases for both atherosclerosis and medial degeneration. Extreme differences were rare except for atherosclerosis in the tricuspid group. The results revealed only slight overall differences around the aortic circumference, with concavity being the most susceptible. Still, thanks to occurring inter- and intraindividual variability, the examination of all quadrants seems meaningful not to miss the most severe changes and to underscore the findings.

• MeSH
• aorta patologie   MeSH
• aortální aneurysma * komplikace   patologie   MeSH
• aortální chlopeň patologie   MeSH
• ateroskleróza * komplikace   patologie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• aorta anatomie a histologie   patologie   MeSH
• aortální aneurysma diagnóza   patologie   terapie   MeSH
• disekce aorty diagnóza   patologie   terapie   MeSH
• lidé MeSH
• nemoci aorty * diagnóza   klasifikace   patologie   terapie   MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Akutní disekce aorty je život ohrožující stav, při kterém krev proniká trhlinou v tunica intima do cévní stěny, kterou podélně rozštěpuje, a vytváří nepravé lumen. Ačkoli tento stav postihuje zpravidla pacienty v 5. a 6. deceniu, vzácně se může vyskytnout i v mladém věku. V souvislosti s hemodynamickými a hormonálními změnami v těhotenství tvoří až polovinu případů akutní disekce aorty u žen mladších 40 let právě ženy gravidní. Mezi rizikové faktory akutní disekce aorty patří arteriální hypertenze, některé geneticky podmíněné syndromy asociované s méněcenností aortální stěny či vývojové vady aortální chlopně. V tomto kazuistickém sdělení prezentujeme případ neočekávaného úmrtí 34leté ženy ve 3. trimestru gravidity, u které pitva odhalila akutní disekci aorty.

Acute aortic dissection is a relatively rare life-threatening condition in which blood penetrates through a tear in the tunica intima into the vessel wall, splits it longitudinally and forms a false lumen. Although this condition usually affects patients in the 5th and 6th decade, it can rarely occur at a young age. Due to hemodynamic and hormonal changes in pregnancy, up to half of dissections in women younger than 40 years occur just during pregnancy. Risk factors for acute aortic dissection include arterial hypertension, genetic syndromes associated with connective tissue disorders, or developmental defects of the aortic valve. In this case report, we present a case of unexpected death of a 34-year-old woman in the third trimester of gravidity in whom the autopsy revealed an acute aortic dissection. This woman suffered from hypertension, which is one of the main risk factors for acute aortic dissection. Although histological examination of the aorta did not clearly show chronic changes in the vessel wall, it can be assumed, based on the current literature data, that hypertension combined with hemodynamic and hormonal changes during gravidity was the cause of this fatal condition. Concomitant use of triptans and selective serotonin reuptake inhibitors (SSRI) may have contributed to the decompensation of hypertension. However, clinical data on the use of these drugs were found out a long time after the autopsy and it was not possible to perform toxicological examination to confirm this suspicion.

• MeSH
• aorta anatomie a histologie   patologie   MeSH
• disekce aorty * diagnóza   mortalita   patofyziologie   MeSH
• dospělí MeSH
• hypertenze MeSH
• lidé MeSH
• náhlá smrt MeSH
• pitva MeSH
• rizikové faktory MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Herein we present a single institution 5-year experience with ascending aorta dissection biopsies depicting the clinicopathological features of 62 cases. To detect microscopic abnormalities in the aortic wall beside the dissection itself, we applied a new histopathological classification scheme from the consensus documents issued by The Society for Cardiovascular Pathology and The Association for the European Cardiovascular Pathology in 2015 and 2016. The most common finding was medial degeneration (MD) - 61 cases (98.4%); atherosclerosis (AS) was found in 19 aortae (30.6%), and chronic aortitis- giant cell pattern described in one aorta (1.6%). The medial degeneration constituents included mucoid matrix accumulation, smooth muscle cells and elastic fibers abnormalities, and medial fibrosis. The consensus document application led to increased MD reporting compared to older studies and to our previous experience, probably due to assessing more subtle and focal changes such as intralamellar fibrosis, intralamellar mucoid matrix accumulation, and loss of smooth muscle cell nuclei- these changes being also the most common MD abnormalities we are reporting. We have compared the results in patients with bicuspid (n = 7; 11.3%) versus tricuspid (n = 55; 88.7%) aortic valve, suggesting no significant differences except for translamellar fibrosis, which appeared to be more severe in the bicuspid valve group (p = 0.0397). The results might imply similar histopathological findings regardless of the aortic valve cuspidity in aortic dissection. These findings are in contrast to ascending aorta dilation (aneurysm), where more severe medial degeneration changes have been described in patients with the tricuspid aortic valve.

• MeSH
• aorta patologie   MeSH
• aortální chlopeň patologie   MeSH
• ateroskleróza patologie   MeSH
• disekce aorty patologie   MeSH
• disekce MeSH
• lidé středního věku MeSH
• lidé MeSH
• myocyty hladké svaloviny patologie   MeSH
• nemoci aorty patologie   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Valsartan has the potential to attenuate neointimal hyperplasia and to suppress the inflammatory response. This study aimed to evaluate the role of valsartan in neointimal hyperplasia and the toll-like receptor 4 (TLR4)-nitric oxide synthase (NOS) pathway in the balloon-injured rat aorta.Forty-eight Wistar rats were randomly allocated to three groups: sham control (control), balloon-injured group (surgery), and balloon-injured+valsartan-treated group (valsartan). Rats were killed at 14 and 28 days after balloon-injury, and then the aortic tissues were collected for morphometric analysis as well as for measurements of the mRNA or protein expression of angiotensin II, angiotensin II type 1 (AT1) receptor, angiotensin II type 2 (AT2) receptor, TLR4, endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), serine/arginine-rich splicing factor 1(SRSF1) and extracellular signal regulated kinase (ERK). Valsartan at a dose of 20 mg/kg/day markedly decreased neointimal hyperplasia in the aorta of balloon-injured rats, and significantly reduced the mRNA or protein expression of TLR4, AT1 receptor, SRSF1 and phosphorylated-ERK (p-ERK) as well as the aortic levels of iNOS (all p < 0.05). Moreover, valsartan increased the eNOS level and AT2 receptor mRNA and protein expression levels (all p < 0.05). Valsartan prevented neointimal hyperplasia and inhibited SRSF1 expression and the TLR4-iNOS-ERK-AT1 receptor pathway in the balloon-injured rat aorta.

• MeSH
• aorta účinky léků   enzymologie   patologie   MeSH
• blokátory receptoru 1 pro angiotenzin II farmakologie   MeSH
• extracelulárním signálem regulované MAP kinasy metabolismus   MeSH
• fosforylace MeSH
• hyperplazie MeSH
• modely nemocí na zvířatech MeSH
• nemoci aorty farmakoterapie   enzymologie   genetika   patologie   MeSH
• neointima * MeSH
• poranění cév farmakoterapie   enzymologie   genetika   patologie   MeSH
• potkani Wistar MeSH
• receptor angiotensinu typ 1 genetika   metabolismus   MeSH
• serin-arginin sestřihové faktory metabolismus   MeSH
• signální transdukce MeSH
• synthasa oxidu dusnatého, typ II metabolismus   MeSH
• toll-like receptor 4 genetika   metabolismus   MeSH
• valsartan farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH