No description available.

L’hémorragie sous-arachnoïdienne (HSA) est une pathologie redoutable résultant fréquemment de la rupture d’un anévrisme intracrânien. Elle est associée à une mortalité élevée et d’importants déficits neurologiques. Le saignement entraîne l’augmentation de la pression intracrânienne, la diminution du flux cérébral sanguin, l’apparition de l’inflammation cérébrale et la mort neuronale. Ces évènements de la phase d’insulte cérébrale précoce (72 premières heures) conditionnent le devenir du patient. Le vasospasme était initialement considéré comme la cause principale des ischémies cérébrales retardées (DCI), mais sa diminution pharmacologique n’a montré aucun bénéfice pour les patients. Cependant, l’infiltration rapide des leucocytes dans le SNC suivant le saignement semble impliquée dans le développement des DCI. Notre hypothèse est que l’activation précoce du système immunitaire à la suite de l’HSA est responsable de la mort neuronale retardée et de la survenue des déficits constatés chez les patients souffrant d’HSA. Nos buts étaient de caractériser la contribution des leucocytes dans l’inflammation cérébrale et la mort neuronale dans un modèle murin d’HSA, de moduler cette inflammation par l’utilisation de la protéine MFG-E8, une protéine anti-inflammatoire favorisant la clairance apoptotique, et de confirmer la présence d’une signature immunologique comparable chez les patients HSA. Notre modèle murin nous a permis d’induire chirurgicalement l’HSA et d’injecter par voie intrapéritonéale la protéine MFG-E8. La composition cellulaire du sang (humain et murin) et du cerveau des souris a été analysée par cytométrie en flux. Le plasma (humain et murin) et le liquide céphalo-rachidien (LCR) des patients ont été analysés par dosage cytokinique. Certains cerveaux de souris étaient inclus en paraffine pour l’imagerie par microscopie confocale. La lignée cellulaire de microglie nous a permis d’étudier la modulation de la capacité de phagocytose et de production de ROS par l’exposition au sérum ou au LCR de patients HSA. Dans une première étude, nous avons démontré le rôle de l’inflammation cérébrale précoce dans le développement de la mort neuronale et des symptômes chez les souris HSA. Nous avons également caractérisé la présence de marqueurs inflammatoires systémiques chez les patients HSA. Dans une deuxième étude, nous avons montré que le traitement par la protéine MFG-E8 chez les souris HSA entraînait la diminution de l’inflammation périphérique ainsi que de la présence des marqueurs M1, de l’activation des astrocytes et de la mort neuronale dans le cerveau aboutissant à la diminution de la sévérité des symptômes. L’étude de l’activation immunitaire chez les patients HSA, nous a permis d’observer une signature immunologique similaire à notre modèle murin. Nous avons montré que les patients HSA présentaient une augmentation des cellules immunitaires innées et une immunodépression lymphocytaire en comparaison avec des donneurs sains. Nous avons également décrit l’importance du grade et du genre des patients par la caractérisation d’un profil inflammatoire plus sévère chez les patients hauts gradés et chez les hommes. Finalement, nos résultats confirment l’existence d’une signature immunologique similaire entre les patients HSA et notre modèle murin aboutissant, dans les deux cas, à l’augmentation de l’activation de l’inflammation systémique et cérébrale. Cette signature immunologique est dépendante du sexe et du grade des patients. La diminution de la gravité des symptômes par le traitement avec la protéine MFG-E8 dans notre modèle souris confirme l’implication incontestable de l’inflammation dans l’apparition des déficits moteurs secondaires à la mort neuronale, et le potentiel thérapeutique de cette protéine MFG-E8 dans le développement de nouvelles thérapies. / Subarachnoid hemorrhage (SAH) is a redoubtable pathology resulting frequently from the rupture of an intracranial aneurysm. It is associated to an important mortality and severe neurologic deficits. The bleeding leads to an increase in the intracranial pressure, to a decrease in cerebral blood flow, to the development of cerebral inflammation and to neuronal death. These events of early brain injury (first 72 hours) determine the patient’s prognosis. The vasospasm was first thought to be the main cause of delayed cerebral ischemia (DCI), but its pharmacological decrease was not being associated to any benefits for the patients. However, rapid leucocytic infiltration in the CNS secondary to the bleeding seems implicated in the development of DCI. Our hypothesis is that the early immune system activation in SAH is responsible for delayed neuronal death and for the onset of symptoms in SAH patients. Our goals were to characterize the contribution of leucocytes in cerebral inflammation and neuronal death in our SAH mice model, to modulate the inflammation by using MFG-E8 protein, an anti-inflammatory protein promoting the apoptotic clearance, and to confirm this similar immunologic signature in SAH patients. Our mouse model allows us to surgically induce SAH and to inject the MFG-E8 protein by intraperitoneal injection. The cellular composition of blood (human and mouse) and of mouse brains were analyzed by flow cytometry. The plasma (human and mouse) and the cerebrospinal fluid (CSF) were analyzed by cytokine assay. Some mice brains were paraffin-embedded for confocal microscopy imaging. Microglia cell lines allowed us to evaluate the modulation of phagocytosis and reactive oxygen species (ROS) production secondary to the exposition to SAH patients’ serum and CSF. In the first study, we have demonstrated the impact of early cerebral inflammation on neuronal death and the occurrence of symptoms in SAH mice. We also have characterized the presence of systemic inflammatory markers in SAH patients. In the second study, we have shown that MFG-E8 protein treatment in our SAH mice model is linked to a decrease in peripheric inflammation as well as to a decrease of M1 markers, astrocytic activation and neuronal death in the brain leading to a decrease of symptoms severity. iv The study of immune activation in SAH patients allowed us to observe an immune signature like in our mouse model. We have revealed that SAH patients have an increase in innate immune cells and in lymphocytic immunosuppression in comparison to healthy donors. We have also described the importance of gender and SAH grade by the characterization of a more severe inflammatory profile in high-grade and in male patients. To conclude, our results confirm the existence of a similar immune signature between SAH patients and our mouse model leading in both cases to an increase in systemic and cerebral inflammation. This immunologic signature depends on the patients’ gender and on the grade of SAH. The decrease of symptom severity with MFG-E8 protein treatment in our mice model confirms the unquestionable implication of inflammation in the occurrence of motor deficits secondary to neuronal death and the therapeutic potential of MFG-E8 for the development of new therapies.

<p>U savremenoj hirurgiji imperativ je da hirur&scaron;ka procedura bude efikasna, ali i da obezbedi kvalitetan i brz oporavak. Najbitniji segment operativnog lečenja je obezbediti maksimalan učinak kako bi se osobi omogućio brz i potpun povratak aktivnostima dnevnog života. Posebno je pojačano&nbsp;&nbsp; interesovanje za rekonstrukciju prednjeg ukr&scaron;tenog ligamenta kod mlađe i sporsko aktivne populacije. Trendovi u medicini kao i u ortopedskoj hirurgiji idu u pravcu smanjenja postoperativnog krvarenja, bola i skraćenja postoperativnog oporavka. Supstancija sa antifibrinolitičkim delovanjem, kao &scaron;to je traneksamična kiselina, svakako je na&scaron;la svoje mesto u smanjenju postoperativnog krvarenja. Ciljevi istraživanja su se odnosili na utvrđivanje uticaja lokalno aplikovane traneksamične kiseline tokom rekonstrukcije prednjeg ukr&scaron;tenog ligamenta kolena na postoperativno krvarenje, posmatrane laboratorijske parametre, mere obima kolena, učestalosti postoperativnih komplikacija i kvaliteta postoperativnog oporavka između dve grupe ispitanika (ispitivana i kontrolna grupa). Studija je bila eksprimentalnog karaktera i sprovedena je u Kliničkom centru Vojvodine u Novom Sadu uz odobrenje etičke komisije. U istraživanje, metodom slučajnog izbora, bila su uključena 124 ispitanika oba pola raspoređena u dve grupe (ispitivana i kontrolna), a kod kojih je indikovana operativno zbrinjavanje prekida prednjeg ukr&scaron;tenog ligamenta kolena i koji su dali pristanak da budu uključeni u studiju. Svi prikupljeni podaci su beleženi u protokol, koji je za ovo istraživanje posebno dizajniran. Ispitanici su bili podvrgnuti operativnom zahvatu, uz primenu op&scaron;te ili spinalne anestezije, sa postavljenom pneumatskom poveskom na operisanom ekstremitetu. Ispitivanoj grupi bilo je lokalno aplikovano 20 ml traneksamične kiseline, dok je u kontolnoj grupi na isti način aplikovano 20 ml NaCl 0,9 % rastvora. Postoperativni gubici krvi su praćeni i beleženi tokom 24 h od operacije, dok su laboratorijki nalazi uzorkovani preoperativno i sedmog postoperativnog dana. U posmatranom periodu (preoperativno, sedmog postoperativnog dana, treće i &scaron;este postoperativne nedelje) kod ispitanika je praćen obim kolena i pojava komplikacija (hematom, hemartroza). Nakon sprovedenog istraživanje, prikupljeni podaci su dokumentovani i statistički obrađeni. Rezultati istraživanja jasno ukazuju da postoji statistički značajna razlika (t=7.181, p&lt;0.001) u količni postoperativnog krvarenja između grupa. Prosečno postoperativno krvarenje u ispitivanoj grupi je bilo 71.29&plusmn;40.76 ml, u odnosu na kontrolnu grupu gde je postoperativno krvarenje iznosilo 154.35&plusmn;81.45 ml. U kontrolnoj grupi, postoperativno se beleže niže vrednosti hemoglobina (t=9.608, p&lt;0.001) i hematokrita (t=8.325, p&lt;0.001), i vi&scaron;e vrednosti trombocita (t=2.201, p=0.032) nego u ispitivanoj grupi. Podaci o postoperativnom bolu ispitanika govore u prilog statistički značajnoj razlici u jačini bola prve nedelje nakon operacije između ispitivane i kontrolne grupe (t=2.405, p=0.018) i treće nedelje nakon operacije (t=3.700, p&lt;0.001). U ispitivanoj grupi zabeležena je ređa pojava hematoma 6.45% (n=4), dok je u kontrolnoj grupi 19.35% (n=12). Svi pacijenti u uzorku su popunili upitnik o postoperativnom kvalitetu oporavka. Nije zabeležena statistički značajna razlika u kvalitetu postoperativnog oporavka nakon operacije između dve analizirane grupe ispitanika. Dobijeni rezultati o postoperativnom krvarenju, nakon aplikovane traneksamične kiseline, ukazuju na efikasnost leka i pri lokalnoj primeni tokom rekonstrukcije prednjeg ukr&scaron;tenog ligamenta kolena. S obzirom na insuficijentnost podataka, ovo ispitivanje stvara &scaron;iru osnovu za dalja istraživanja.</p> / <p>In modern surgery, we need an effective surgical procedure, which provides quality and rapid recovery. The most important segment of surgical treatment is to provide maximum impact to allow a person to return quickly and fully to the activities of daily living. There has been particular interest in the reconstruction of the anterior cruciate ligament in the younger and sport active population. Trends in medicine, as well as in orthopedic surgery, are heading towards reducing postoperative bleeding, pain, and postoperative recovery. A substance with antifibrinolytic activity, such as tranexamic acid, has certainly found its place in reducing postoperative bleeding. The objectives of the study were to determine the effect of locally applied tranexamic acid during the reconstruction of the anterior cruciate knee ligament on postoperative bleeding, observed laboratory parameters, measures of knee circumference, frequency of postoperative complications, and quality of postoperative recovery between the two groups of subjects (study and control group). The study was prospective, conducted at the Clinical Center of Vojvodina in Novi Sad with the approval of the ethics committee. The study, by random selection method, included 124 subjects of both sexes, divided into two groups (tested and control), which indicated operative management of the anterior cruciate ligament rupture and gave informed consent for inclusion in the study. All data collected were recorded in a protocol, which was specifically designed for this research. Subjects underwent surgery, with general or spinal anesthesia, with pneumatic attachment placed on the extremity undergoing surgery. The test group was given topically 20 ml of tranexamic acid, while the control group was administered 20 ml in the same way. NaCl 0.9% solution. Postoperative blood losses were monitored and recorded within 24 h of surgery, while laboratory findings were sampled preoperatively and on the seventh postoperative day. During the observed period (preoperatively, on the seventh postoperative day, on the third and sixth postoperative weeks), the knee volume and the occurrence of complications (hematoma, hemarthrosis) were monitored in the subjects. Following the survey, the data collected were documented and statistically processed. The study results indicate that there was a statistically significant difference (t = 7.181, p &lt;0.001) in the amount of postoperative bleeding between groups. The mean postoperative bleeding in the study group was 71.29 &plusmn; 40.76 ml, compared to the control group where postoperative bleeding was 154.35 &plusmn; 81.45ml. In the control group, lower hemoglobin values (t = 9.608, p &lt;0.001) and hematocrit (t = 8.325, p &lt;0.001) were observed postoperatively, and higher platelet counts (t = 2.201, p = 0.032) than in the study group. The data on the postoperative pain of the respondents support a statistically significant difference in the severity of pain on the first week after surgery between the study and the control group (t = 2.405, p = 0.018) and the third week after surgery (t = 3.700, p &lt;0.001). In the study group, the incidence of hematoma was less than 6.45% (n = 4), while in the control group it was 19.35% (n = 12). All patients in the sample completed a questionnaire on postoperative quality of recovery. There was no statistically significant difference in the quality of postoperative recovery after surgery between the two analyzed groups of subjects. The results of post-operative bleeding, after administrated tranexamic acid, indicate the efficacy of the drug and at a local application during the reconstruction of the anterior cruciate ligament. Due to the insufficiency of data, this study creates a broad basis for further research.</p>

Einleitung: Die schnelle Detektion und genaue Beurteilbarkeit (Charakterisierung) von rupturierten, zerebralen Aneurysmen ist entscheidend für die Wahl der adäquaten endovaskulären oder neurochirurgischen Intervention (Therapie), um Patienten mit akuter Subarachnoidalblutung (SAB) eine möglichst gute Prognose zu verschaffen. Es war das Ziel der Studie zu untersuchen, ob und wie weit die Knochensubtraktions-CT-Angiografie (CT-DSA), bereits mit einem relativ alten 16-Kanal-MSCT in der Lage ist die invasive Digitale Subtraktionsangiografie (DSA; Goldstandard) hinsichtlich der Detektion, morphologischer Charakterisierung und letztendlich Therapieentscheidung zu ersetzen und damit den klinischen Pfad dieser Patienten zu beeinflussen. Methodik: Zu diesem Zweck untersuchten wir 116 Patienten mit akuter SAB vor der intrakraniellen Aneurysmatherapie. Die SAB Patienten wurden jeweils erst mit 16-Kanal-MSCT Angiografie und verbesserter, automatisierter Knochensubtraktion untersucht. Der verbesserte CT-DSA Algorithmus beinhaltet eine block- oder scheibenweise Patienten Bewegungskorrektur und eine lokal adaptierbare 3D dilatierte Knochenmaske. Die lokale Adaption der Maske wurde für eine präzisere Knochensubtraktion an der Grenze von Gefäß zu Knochen entwickelt. Danach wurde die konventionelle DSA angewandt. Zwei erfahrene Neuroradiologen beurteilten die CT-DSA und die DSA Daten unabhängig voneinander. Es wurde die Genauigkeit der verbesserten CT-DSA Methode für die Detektion, morphologische Charakterisierung sowie die Vermessung der Aneurysmadimensionen bestimmt. Im Fall von Uneinigkeit wurde ein Ergebnis im Konsens ermittelt. Zudem wurde die Röntgendosis beider Methoden für die Diagnostik von Aneurysmen verglichen. Ergebnisse: Mit der DSA wurden in 71 Patienten 74 Aneurysmen entdeckt. Achtundsechzig Patienten hatten 1 und 3 Patienten zwei Aneurysmen. Mit den CT-DSA Daten konnten 73 der 74 in der DSA delektierten Aneurysmen gefunden werden. Hier hatten 66 Patienten 1 und 4 Patienten 2 Aneurysmen. Mit der CT-DSA wurde noch ein weiteres kleines Aneurysma detektiert. Die Auswertung per Aneurysma, für die Sensitivität, Spezifität, den negativen und positiven Vorhersagewert, zeigte für die CT-DSA jeweils 99% und 100%, sowie 100% und 98%. Für kleine Aneurysmen, ≤3,0 mm betrug die Sensitivität 94%, mit einem 95%-Konfidenzintervall zwischen 73%–99%. Längenmessungen mit der CT-DSA waren ebenso genau wie bei der DSA und stimmten bei kleineren Messungen sogar noch besser überein als bei größeren. Die CT-DSA Fundus/Hals-Verhältnisse lagen mit 0,03 (ca. 2%) unter denen der DSA. Das Dosis-Längen-Produkt für die CT-DSA lag bei 565 mGy × cm ±201 [SD] und für die DSA bei 1.609 mGy × cm ±1.300 [SD]. Diskussion: Die CT-Angiografie mit 16-Kanal-MSCT und modernen Knochen-subraktionsalgorithmen ist für die Detektion von zerebralen Aneurysmen bei Patienten mit akuter SAB ebenso genau wie die DSA. Sie erzielt ähnliche Ergebnisse für die Aneurysmamorphologie und -abmessungen. Diese gilt selbst für schädelbasisnahe und kleine Aneurysmen oder bei Patientenbewegung. In Fällen, in denen die erste CT-DSA die Ursache der SAB nicht zeigt, ist es nicht mehr zwingend notwendig eine DSA durchzuführen. Eine zweite CT-DSA ist ausreichend. Weiterhin benötigt die CT-DSA bis zu 65% weniger Röntgendosis für die Diagnose als die DSA. Zudem ist die Diagnose mit der CT-DSA in kürzerer Zeit und für den Patienten risikoärmer, weil nichtinvasiv. Schlussfolgerung: Die CT-DSA mit einem verbesserten Algorithmus, der Bewegungsartefakte und artifizielle Stenosen an der Grenze von Gefäß zu Knochen minimierte, zeigt in Verbindung mit einem 16-Kanal-MSCT eine diagnostische Äquivalenz zur DSA. Diese Tatsache und die zusätzlich deutlich geringere Röntgenstrahlenbelastung sprechen dafür, die DSA Diagnostik bei Patienten mit spontaner SAB durch die schnellere und schonendere CT-DSA zu ersetzten. Damit kann die CT-DSA Therapieentscheidungen schneller, schonender, kostengünstiger und zielgerichteter herbeiführen. Bei der Einführung dieses Verfahrens ist weniger auf die eingesetzte CT-Technologie (16-, 64-, 320-Zeilen oder Zwei-Röhren MSCT) als auf den Einsatz der aktuellsten Knochensubtraktions-Technologie sowie ein angemessenes Training (Erfahrung) des Befunders zu achten.:1 Einleitung 1 1.1 Ätiologie der Subarachnoidalblutung (SAB) 1 1.2 SAB Pathogenese 2 1.3 SAB Epidemiologie 4 1.4 SAB Risikofaktoren 4 1.5 SAB Grading 5 1.6 SAB Letalität 5 1.7 SAB Diagnostik 6 1.7.1 Invasive Digitale Subtraktionsangiografie (DSA) 6 1.7.2 Nichtinvasive Mehrschicht-Computertomografie (CT) 10 1.8 Aneurysma Therapie 15 1.9 Zielsetzung 17 2 Patienten und Methoden 20 2.1 Patienten 20 2.2 Ein – und Ausschlusskriterien 20 2.3 Nativ-CT und CT-DSA 22 2.3.1 Nativ-CT Technik 22 2.3.2 CT-DSA Technik 22 2.3.3 Prototypische, automatisierte CT-DSA Auswertung 24 2.4 Digitale Subtraktionsangiografie (DSA) 27 2.5 Vermessung der Aneurysmen 27 2.6 Vergleich der Messmethoden 29 2.7 Befundungsqualität der Untersucher 29 2.8 Beurteilung der Ergebnisse 29 2.9 Beurteilung der Strahlenbelastung 30 2.10 Statistische Methoden 31 2.10.1 Fallzahlplanung 32 2.10.2 Diagnostische Genauigkeit 33 2.10.3 Methodenvergleich 34 2.10.4 Inter- und Intraobserver-Variabilität 35 3 Ergebnisse 36 3.1 Patienten 36 3.2 Nativ-CT 36 3.3 CT-DSA 36 3.4 DSA - Referenz für die Aneurysmadetektion 42 3.5 Vergleich CT-DSA mit DSA 45 3.5.1 CT-DSA Genauigkeit 45 3.5.1.1 Basierend auf prospektiver DSA 45 3.5.1.2 Basierend auf retrospektiver DSA 47 3.5.2 Aneurysma-Messergebnisse 49 3.5.3 Untersucher und Aneurysma-Konfiguration 59 3.5.4 Röntgendosis 59 3.5.5 Bildinterpretationszeiten 60 4 Diskussion 61 4.1 CT-DSA Genauigkeit für den Aneurysmanachweis 61 4.1.1 Besonderheiten der CT-DSA Anwendung 63 4.1.2 Besonderheit der CT-DSA Prototypen Software 63 4.2. CT-DSA Informationen als alleinige Planungsbasis für neurochirurgische oder endovaskuläre Eingriffe 64 4.3 Robustheit und Reproduzierbarkeit 67 / Background and purpose: Detection and evaluation of ruptured aneurysms is critical for choosing an appropriate endovascular or neurosurgical intervention (therapy) in patients with acute subarachnoid hemorrhage (SAH). Our aim was to assess whether 16-detector row multislice CT (MSCT) bone-subtraction CTA is capable of guiding treatment for cerebral aneurysms in patients with acute SAH and could replace DSA – the current reference standard. Materials and methods: In a prospective study, 116 consecutive patients with SAH were examined with 16–detector row MSCT with an advanced bone-subtraction CTA prototype and DSA before intracranial aneurysm treatment. The advancements of the prototype CT-DSA algorithm were a slab-based patient motion correction and a locally optimized 3D dilated bonemask. The local adaption of the bone mask was designed for more precise bone subtraction at bone-to-vessel interfaces. Two independent neuroradiologists reviewed the bone-subtraction CTA blinded to DSA. The accuracy of the advanced bone-subtraction CTA for aneurysm detection, morphological characterization and the measurement of aneurysm dimensions were determined. In case of disagreement the result was attained in consensus. Additionally the radiation doses of the 2 diagnostic imaging modalities compared. Results: Seventy-one patients (61%) had 74 aneurysms on DSA. Sixty-eight patients had 1 and 3 patients 2 aneurysms. Bone-subtraction CTA detected 73 of these aneurysms. With CT-DSA 66 patients had 1 and 4 patients 2 aneurysms. CT-DSA discovered an additional small aneurysm. On a per-aneurysm basis, sensitivity, specificity, and positive and negative predictive values for bone-subtraction CTA were 99%, 100%, and 100% and 98%, respectively. For aneurysms of ≤3 mm, sensitivity was 94% (95% CI, 73%–99%). Length measurements with bone-subtraction CTA were as exact as the DSA measurements and agreed even better for small measurements than for larger ones. CT-DSA dome-to-neck ratios were on average 0.03 smaller (2%) than with DSA. Dose-length product was 565 mGy × cm ±201 [SD] for bone-subtraction CTA and 1.609 mGy × cm ±1.300 [SD ]for DSA.   Discussion: 16–detector row MSCT with advanced bone-subtraction CTA is as accurate as DSA in detecting cerebral aneurysms after SAH, provides similar information about aneurysm configuration and measures. This is even true for small aneurysms adjacent to bony structures (e.g. the base of the scull) or under patient motion. In SAB patients in whom the initial CT-DSA doesn’t show the root cause of the SAH, a DSA is not imperative any longer. In this case a second CT-DSA is sufficient. Additionally the CT-DSA reduces the average effective radiation dose for vascular diagnostics by 65%. Furthermore the CT-DSA-based diagnosis can be performed in shorter time and at less patient risk due to its non-invasive nature. Conclusion: The advanced CT-DSA algorithm - that minimized patient motion and artificial stenosis at the bone-to-vessel interfaces - in combination with commonly available 16-detector row MSCT demonstrated diagnostic equivalence in comparison to the DSA reference. Diagnostic equivalence in association with dose reduction suggests replacing DSA with the faster and more patient friendly bone-subtraction CTA in the diagnostic work-up of spontaneous SAH. Thus CT-DSA can accelerate targeted therapy decisions more cost effective and at less risk for the patient. Using the latest and appropriate subtraction technology and ensuring adequate training (reader experience) is more relevant than the used CT-technology (16-, 64-, 320-detector row or dual source MSCT) when introducing CT-DSA protocols.:1 Einleitung 1 1.1 Ätiologie der Subarachnoidalblutung (SAB) 1 1.2 SAB Pathogenese 2 1.3 SAB Epidemiologie 4 1.4 SAB Risikofaktoren 4 1.5 SAB Grading 5 1.6 SAB Letalität 5 1.7 SAB Diagnostik 6 1.7.1 Invasive Digitale Subtraktionsangiografie (DSA) 6 1.7.2 Nichtinvasive Mehrschicht-Computertomografie (CT) 10 1.8 Aneurysma Therapie 15 1.9 Zielsetzung 17 2 Patienten und Methoden 20 2.1 Patienten 20 2.2 Ein – und Ausschlusskriterien 20 2.3 Nativ-CT und CT-DSA 22 2.3.1 Nativ-CT Technik 22 2.3.2 CT-DSA Technik 22 2.3.3 Prototypische, automatisierte CT-DSA Auswertung 24 2.4 Digitale Subtraktionsangiografie (DSA) 27 2.5 Vermessung der Aneurysmen 27 2.6 Vergleich der Messmethoden 29 2.7 Befundungsqualität der Untersucher 29 2.8 Beurteilung der Ergebnisse 29 2.9 Beurteilung der Strahlenbelastung 30 2.10 Statistische Methoden 31 2.10.1 Fallzahlplanung 32 2.10.2 Diagnostische Genauigkeit 33 2.10.3 Methodenvergleich 34 2.10.4 Inter- und Intraobserver-Variabilität 35 3 Ergebnisse 36 3.1 Patienten 36 3.2 Nativ-CT 36 3.3 CT-DSA 36 3.4 DSA - Referenz für die Aneurysmadetektion 42 3.5 Vergleich CT-DSA mit DSA 45 3.5.1 CT-DSA Genauigkeit 45 3.5.1.1 Basierend auf prospektiver DSA 45 3.5.1.2 Basierend auf retrospektiver DSA 47 3.5.2 Aneurysma-Messergebnisse 49 3.5.3 Untersucher und Aneurysma-Konfiguration 59 3.5.4 Röntgendosis 59 3.5.5 Bildinterpretationszeiten 60 4 Diskussion 61 4.1 CT-DSA Genauigkeit für den Aneurysmanachweis 61 4.1.1 Besonderheiten der CT-DSA Anwendung 63 4.1.2 Besonderheit der CT-DSA Prototypen Software 63 4.2. CT-DSA Informationen als alleinige Planungsbasis für neurochirurgische oder endovaskuläre Eingriffe 64 4.3 Robustheit und Reproduzierbarkeit 67

No description available.

O objetivo do presente estudo foi avaliar a diferença de resultados maternos e neonatais em gestações complicadas por trombofilias hereditárias em pacientes com e sem tromboembolismo venoso. Apesar do aumento de evidências, na literatura, sobre a associação de trombofilias congênitas e resultados obstétricos adversos, há ainda dúvida se pacientes trombofílicas com tromboembolismo venoso apresentam resultados maternos e neonatais piores que as pacientes trombofílicas sem tromboembolismo venoso. O estudo analisou 66 gestantes com trombofilias hereditárias, de forma retrospectiva observacional e comparativa, das quais 33 apresentavam tromboembolismo venoso e 36 o não apresentavam. Os principais desfechos relacionados a resultados maternos e neonatais adversos foram: pré-eclâmpsia grave, descolamento prematuro de placenta, restrição de crescimento fetal, natimortalidade, prematuridade e complicações hemorrágicas maternas. As trombofilias congênitas incluídas no estudo foram o fator V de Leiden (FVL), mutação da protrombina G20210A, mutação C677T do gene da 5,10-metilenotetrahidrofolato redutase (MTHFR), deficiência de proteína S, deficiência de proteína C e deficiência de antitrombina. Ambos os grupos apresentaram características populacionais similares. A ocorrência de complicações maternas e fetais/neonatais foi similar nos dois grupos: pré-eclâmpsia grave (P=0,097), descolamento prematuro de placenta (P=0,478), restrição de crescimento fetal (P=0,868), natimortalidade (P=0,359), prematuridade (P=0,441) e complicações hemorrágicas maternas (P=0,478). Este estudo concluiu que a presença de tromboembolismo venoso em gestantes com trombofilia hereditária apresenta resultados maternos e neonatais semelhantes àquelas com trombofilias hereditárias sem tromboembolismo venoso. / The aim of this study was to evaluate differences in maternal and neonatal outcomes in pregnancies complicated by inherited thrombophilias between patients with and without venous thromboembolism. Despite increasing evidence in the literature indicating an association between inherited thrombophilias and adverse obstetric outcomes, doubts remain whether thrombophilic patients with venous thromboembolism present poorer maternal and neonatal outcomes than thrombophilic patients without venous thromboembolism. In this retrospective, observational and comparative study, 66 pregnant women with inherited thrombophilias, including 33 with venous thromboembolism and 36 without thromboembolism, were investigated. The main end-points analyzed were severe pre-eclampsia, placental abruption, fetal growth restriction, stillbirth, preterm delivery, and maternal hemorrhagic complications. The congenital thrombophilias included in this study were factor V Leiden (FVL), prothrombin G20210A mutation, C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, protein S deficiency, protein C deficiency, and antithrombin deficiency. The two groups were similar in terms of population characteristics. The frequency of maternal and fetal/neonatal complications was similar in the two groups: severe pre-eclampsia (P=0.097), placental abruption (P=0.478), fetal growth restriction (P=0.868), stillbirth (P=0.359), preterm delivery (P=0.441), and maternal hemorrhagic complications (P=0.478). This study concluded that venous thromboembolism in thrombophilic patients does not worsen maternal or neonatal outcomes when compared to thrombophilic patients without venous thromboembolism.

Introdução: A fluidoterapia é o tratamento de primeira linha para pacientes em choque hemorrágico ou choque séptico para restauração do volume circulante e da perfusão tecidual, mas diversas questões relacionadas a este tópico permanecem em debate, particularmente em relação às metas de ressuscitação representadas por variáveis fisiológicas a serem atingidas. A variação de pressão de pulso (VPP) já foi proposta como índice confiável para predição de fluido-responsividade em pacientes sob ventilação mecânica, mas requer avaliação complementar em variadas condições fisiopatológicas. Objetivo: O propósito do presente estudo foi comparar, em um modelo experimental de choque hemorrágico agudo com endotoxemia, uma estratégia de ressuscitação volêmica aguda guiada por VPP e pressão arterial média (PAM) a outra baseada em metas de ressuscitação convencionalmente empregadas envolvendo pressão venosa central (PVC), PAM e saturação venosa mista de oxigênio (SvO2). O modelo experimental foi desenvolvido para esta finalidade e cada variável empregada como meta foi adicionalmente avaliada quanto à capacidade de predição de fluido-responsividade. Métodos: Cinquenta e um porcos foram anestesiados, mecanicamente ventilados e, após preparo, aleatoriamente divididos em seis grupos: controle (Sham, n=8); infusão intravenosa de endotoxina em doses decrescentes (LPS, n=8); choque hemorrágico obtido por meio da retirada de 50% da volemia estimada em 20 minutos (Hemo, n=8); choque hemorrágico com endotoxemia conforme protocolos dos grupos LPS e Hemo (Hemo+LPS, n=9); choque hemorrágico com endotoxemia e, após 60 minutos, ressuscitação com cristalóides para atingir metas: PVC 12-15 mmHg, PAM &#8805; 65 mmHg e SvO2 &#8805; 65% (Conv, n=9); choque hemorrágico com endotoxemia e, após 60 minutos, ressuscitação com cristalóides para atingir as metas VPP &#8804; 13% e PAM &#8805; 65 mmHg (dPP, n=9). Tratamentos foram realizados por três horas. Além da avaliação hemodinâmica incluindo termodiluição e ecocardiografia transesofágica, foram realizadas gasometria arterial com mensuração de eletrólitos e lactato, gasometria venosa mista e tonometria intestinal. Ventilação regional foi avaliada por tomografia por impedância elétrica. Mensuração de citocinas séricas e exames histopatológicos pulmonares também foram efetuados. Resultados: Todos os animais dos quatro grupos que receberam a endotoxina desenvolveram hipertensão pulmonar e lesão pulmonar aguda ao longo do experimento. O grupo Hemo+LPS apresentou alta mortalidade (56%), com alterações hemodinâmicas mais acentuadas do que as observadas nos grupos Hemo e LPS. Os grupos Conv e dPP apresentaram o mesmo grau de comprometimento hemodinâmico observado inicialmente no grupo Hemo+LPS, mas houve rápida recuperação em reposta ao tratamento e todos sobreviveram. Entre os grupos tratados não houve diferenças significantes em relação ao volume de cristalóides administrado (volume total, P=0,066) ou ao débito urinário, mas a PVC no grupo Conv foi significantemente superior à dos grupos dPP (P=0,031) e Sham (P=0,048) ao final do protocolo. Entre as variáveis utilizadas como metas, áreas sob as curvas de características operacionais para predição de fluido-responsividade foram maiores para PVC (0,77; IC95%, 0,68-0,86) e VPP (0,74; IC95%, 0,65-0,83), sendo ambas estas variáveis selecionadas por regressão logística múltipla como variáveis independentes para predição de não-responsividade ao desafio volêmico (PVC: P=0,001, razão de chances, 1,7; IC95%, 1,25-2,32 e VPP: P=0,01, razão de chances, 0,91; IC95%, 0,84-0,98). O melhor valor de corte para VPP para maximização de sua função preditiva foi 15%, com sensibilidade 0,75 (IC95%, 0,63-0,85) e especificidade 0,64 (IC95% 0,49-0,77%). Resultados falso-positivos para VPP foram observados em condições de pressão arterial pulmonar média &#8805; 27 mmHg e gradiente transpulmonar &#8805; 14 mmHg, acompanhados de índice de resistência vascular pulmonar médio &gt; 3 unidades Wood. Resultados falso-negativos também foram constatados. Conclusões: O presente modelo experimental de choque hemorrágico agudo com endotoxemia produziu intenso comprometimento hemodinâmico, hipertensão pulmonar, lesão pulmonar aguda e, na ausência de tratamento, alta mortalidade. Nestas condições, a ressuscitação aguda com cristalóides guiada por VPP e PAM não produziu resultados inferiores à estratégia guiada por metas de ressuscitação convencionalmente estabelecidas, com base em PVC, PAM e SvO2. A principal diferença em desfecho entre as estratégias de ressuscitação foi indução de uma PVC significantemente maior no segundo grupo, ao final do protocolo. Apesar de seus desempenhos individuais terem sido considerados limitados em relação à predição de fluido-responsividade, PVC e VPP foram preditoras independentes de não-responsividade ao desafio volêmico, de modo que sua aplicação em conjunto deva ser investigada. VPP é proposta como uma variável adicional para auxiliar no monitoramento de pacientes, sendo o conhecimento de suas limitações indispensável. / Introduction: Fluid therapy is first-line treatment for patients in hemorrhagic or septic shock for the restoration of circulating volume and tissue perfusion, but several issues remain under debate, particularly regarding resuscitation goals represented by physiological variables to be achieved. Pulse pressure variation (PPV) has been proposed as a reliable index for the prediction of fluid responsiveness in mechanically ventilated patients, but further evaluation for its use in diverse conditions is required. Objective: To compare acute fluid resuscitation guided by PPV and mean arterial pressure (MAP) to another strategy consisting of conventionally-established goals, based on central venous pressure (CVP), MAP and mixed-venous oxygen saturation (SvO2), during experimental acute hemorrhagic shock with endotoxemia. An experimental model was developed to this end and each variable used as resuscitation goal was evaluated additionally for its ability to predict fluid-responsiveness. Methods: Fifty-one pigs were anesthetized, mechanically ventilated and, after preparation, randomized into six groups: control (Sham, n=8); intravenous infusion of endotoxin in decreasing doses (LPS, n=8); hemorrhagic shock of 50% the estimated blood volume in 20 minutes (Hemo, n=8); hemorrhagic shock with endotoxemia in accordance with protocols in groups LPS and Hemo (Hemo+LPS, n=9); hemorrhagic shock with endotoxemia followed by resuscitation with crystalloids, after 60 minutes, to achieve and maintain CVP 12-15 mmHg, MAP &#8805; 65 mmHg and SvO2 &#8805; 65% (Conv, n=9); hemorrhagic shock with endotoxemia followed by resuscitation with crystalloids, after 60 minutes, to achieve and maintain PPV &#8804; 13% and MAP &#8805; 65 mmHg (dPP, n=9). Treatments lasted for three hours. In addition to hemodynamic assessment including thermodilution and transesophageal echocardiography, arterial blood-gases with measurement of electrolytes and lactate, mixed-venous blood-gases and intestinal tonometry were performed. Regional ventilation was evaluated by electrical impedance tomography. Lung histopathology and measurement of serum cytokines were performed as well. Results: All animals from the four groups submitted to endotoxemia developed pulmonary hypertension and acute lung injury over the experimental period. Group Hemo+LPS presented with a high mortality rate (56%) and hemodynamic impairment which was more intense than that observed in groups Hemo or LPS. Groups Conv and dPP developed the same degree of hemodynamic compromise observed in group Hemo+LPS initially, but there was quick recovery in response to treatment and all pigs survived. Between treated groups there were no significant differences in amounts of crystalloids infused (total volume, P=0.066) or in urinary output, but CVP in group Conv was significantly higher than in groups dPP (P=0.031) and Sham (P=0.048) at the end of the study period. Among variables used as goals, areas under the receiver-operator characteristic curves regarding prediction of fluid-responsiveness were larger for CVP (0.77; 95%CI, 0.68-0.86) and PPV (0.74; 95%CI, 0.65-0.83), and both these variables were selected by multiple logistic regression as independent predictors of non-responsiveness to fluid challenge (CVP: P=0.001, odds ratio, 1.7; 95%CI, 1.25-2.32 and PPV: P=0.010, odds ratio, 0.91; 95%CI, 0.84-0.98). Best cutoff value to maximize the predictive function of PPV was 15%, with sensitivity 0.75 (95%CI, 0.63-0.85) and specificity 0.64 (95%CI 0.49-0.77). False positive results for PPV were observed at mean arterial pressure &#8805; 27 mmHg and transpulmonary gradient &#8805; 14 mmHg, with mean pulmonary vascular resistance index &gt; 3 Wood units. False negative results were also detected. Conclusions: This model of acute hemorrhagic shock with endotoxemia produced severe hemodynamic compromise, pulmonary hypertension, acute lung injury and, in the absence of treatment, a high mortality rate. In this setting, acute resuscitation with crystalloids guided by PPV and MAP was not inferior to the strategy guided by conventionally-established goals, based on CVP, MAP and SvO2. The main difference in outcome between resuscitation strategies was the induction of a significantly higher CVP in the second group, at the end of protocol. Although their individual performances were considered limited for the prediction of fluid-responsiveness, CVP and PPV were independent predictors of non-responsiveness to fluid challenge, so that their combined use should be investigated further. PPV is proposed as an additional variable to aid in patient monitoring, but awareness of its limitations is indispensable.

O objetivo do presente estudo foi avaliar a diferença de resultados maternos e neonatais em gestações complicadas por trombofilias hereditárias em pacientes com e sem tromboembolismo venoso. Apesar do aumento de evidências, na literatura, sobre a associação de trombofilias congênitas e resultados obstétricos adversos, há ainda dúvida se pacientes trombofílicas com tromboembolismo venoso apresentam resultados maternos e neonatais piores que as pacientes trombofílicas sem tromboembolismo venoso. O estudo analisou 66 gestantes com trombofilias hereditárias, de forma retrospectiva observacional e comparativa, das quais 33 apresentavam tromboembolismo venoso e 36 o não apresentavam. Os principais desfechos relacionados a resultados maternos e neonatais adversos foram: pré-eclâmpsia grave, descolamento prematuro de placenta, restrição de crescimento fetal, natimortalidade, prematuridade e complicações hemorrágicas maternas. As trombofilias congênitas incluídas no estudo foram o fator V de Leiden (FVL), mutação da protrombina G20210A, mutação C677T do gene da 5,10-metilenotetrahidrofolato redutase (MTHFR), deficiência de proteína S, deficiência de proteína C e deficiência de antitrombina. Ambos os grupos apresentaram características populacionais similares. A ocorrência de complicações maternas e fetais/neonatais foi similar nos dois grupos: pré-eclâmpsia grave (P=0,097), descolamento prematuro de placenta (P=0,478), restrição de crescimento fetal (P=0,868), natimortalidade (P=0,359), prematuridade (P=0,441) e complicações hemorrágicas maternas (P=0,478). Este estudo concluiu que a presença de tromboembolismo venoso em gestantes com trombofilia hereditária apresenta resultados maternos e neonatais semelhantes àquelas com trombofilias hereditárias sem tromboembolismo venoso. / The aim of this study was to evaluate differences in maternal and neonatal outcomes in pregnancies complicated by inherited thrombophilias between patients with and without venous thromboembolism. Despite increasing evidence in the literature indicating an association between inherited thrombophilias and adverse obstetric outcomes, doubts remain whether thrombophilic patients with venous thromboembolism present poorer maternal and neonatal outcomes than thrombophilic patients without venous thromboembolism. In this retrospective, observational and comparative study, 66 pregnant women with inherited thrombophilias, including 33 with venous thromboembolism and 36 without thromboembolism, were investigated. The main end-points analyzed were severe pre-eclampsia, placental abruption, fetal growth restriction, stillbirth, preterm delivery, and maternal hemorrhagic complications. The congenital thrombophilias included in this study were factor V Leiden (FVL), prothrombin G20210A mutation, C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, protein S deficiency, protein C deficiency, and antithrombin deficiency. The two groups were similar in terms of population characteristics. The frequency of maternal and fetal/neonatal complications was similar in the two groups: severe pre-eclampsia (P=0.097), placental abruption (P=0.478), fetal growth restriction (P=0.868), stillbirth (P=0.359), preterm delivery (P=0.441), and maternal hemorrhagic complications (P=0.478). This study concluded that venous thromboembolism in thrombophilic patients does not worsen maternal or neonatal outcomes when compared to thrombophilic patients without venous thromboembolism.

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