Predictors of insufficient recanalization and portal hypertensive complications after treatment of non-cirrhotic, non-malignant portal vein thrombosis - a population-based study

Objectives In acute portal vein thrombosis (PVT), a six-month anticoagulation treatment achieves complete recanalization in only 35%-45% of patients, but the predictors of poor treatment responses are unclear. We examined treatment outcomes in PVT and aimed to identify predictors of incomplete recanalization and portal hypertensive complications. Materials and methods This retrospective study comprised patients diagnosed with PVT between 2006 and 2015. Key exclusion criteria were liver cirrhosis, malignancy, and age Results The final cohort comprised 145 patients, of whom 132 (92%) were primarily treated with anticoagulation. The 5-year cumulative incidence of complete recanalization was 42% and of portal hypertensive complications, 31%. Independent predictors of insufficient recanalization were sub-acute or chronic thrombosis (hazard ratio (HR) 3.1, 95% CI 1.6-5.8), while acute pancreatitis was a protective factor (HR 0.3, 95% CI 0.2 - 0.7). Independent predictors of incident portal hypertensive complications were as cites at baseline (HR 3.3, 95% CI 1.7-6.7), sub-acute or chronic thrombosis (HR 2.9, 95% CI 1.6-5.3), extension of thrombosis to the splenic or mesenteric vein (HR 2.6, 95% CI 1.2-5.7), myeloproliferative disease (HR 3.0, 95% CI 1.4-6.5), and anemia (HR 2.1, 95% 1.1-3.9), while acute pancreatitis was a protective factor (HR 0.1, 95% CI 0.03-0.5). Conclusions Etiology and age of thrombosis are associated with treatment responses in PVT. The presence of ascites at baseline, etiology, and extent of thrombosis, a non-acute thrombosis and anemia, are associated with the risk of portal hypertensive complications. Etiology and extent of thrombosis should be taken into account when determining the treatment (method) for PVT.Peer reviewe

Editor's Choice – Epidemiology, Diagnostics, and Outcomes of Acute Occlusive Arterial Mesenteric Ischaemia : A Population Based Study

Publisher Copyright: © 2022 The Author(s)Objective: The exact incidence and outcomes of acute occlusive arterial mesenteric ischaemia (AMI) are unclear as most studies include only patients diagnosed correctly while alive. The aim of this study was to assess the incidence, mortality, and diagnostics of AMI by also including patients diagnosed post-mortem. Methods: This retrospective study comprised patients diagnosed with AMI either alive or post-mortem between 2006 and 2015 within a healthcare district serving 1.6 million inhabitants. Key exclusion criteria were venous or non-obstructive ischaemia. Results: A total of 470 patients were included in the study of which 137 (29%) were diagnosed post-mortem. The most common misdiagnoses on those not diagnosed alive were unspecified infection (n = 19, 17%), gastrointestinal bleeding (n = 13, 11%), and ileus (n = 13, 11%). Of those diagnosed alive (n = 333), 187 (56%) underwent active surgical or endovascular treatment. During the 2006 – 2015 period, the overall incidence of AMI was 3.05 (95% CI 2.78 – 3.34)/100 000 person years and 26.66 (95% CI 24.07 – 29.45) for those aged 70 years or more. The mean autopsy rate during the study period was 29% for the overall population (32% during 2006 – 2010 and 25% during 2011 – 2015) and 18% for those aged 70 years or more. Overall, the 90-day mortality was 83% in all patients. The ninety day mortality decreased, being 87% during the first period (2006 – 2010) and 79% during the second period (2011 – 2015) (p = .029), while at the same time the proportion of patients diagnosed alive rose from 71% to 80% (p = .030) and the number of endovascular revascularisations rose from 1% to 5% (p = .022). Conclusion: A significant proportion of patients with AMI are not diagnosed alive, which is reflected in the mortality rates. Post-mortem examinations and autopsy rate data continue to be key factors in epidemiological studies on AMI.Peer reviewe

Ensimmäisen päivystyspisteen erikoisala vaikuttaa potilaan hoitotuloksiin akuutissa mesenteriaali-iskemiassa : lähetekäytäntöjen ja triagen tärkeys

Tutkimuksen tarkoitus: Äkillinen suoliston verenkiertovajaus (akuutti mesenteriaali-iskemia (AMI)) on edelleen, kehittyneistä hoitomuodoista huolimatta, korkean kuolleisuuden tauti. Yksi olennainen hoidon tuloksiin vaikuttava tekijä on viive ensimmäisestä terveydenhuollon pisteestä leikkaukseen (leikkausviive), mutta tämän viiveen syyt ovat huonosti tunnettuja. Tämän tutkimuksen tarkoitus oli etsiä viiveeseen vaikuttavia tekijöitä, erityisesti hoitoketjun osalta. Aineisto ja menetelmät: Kyseessä on retrospektiivinen tutkimus, jossa tutkittiin 2006- 2015 Meilahden sairaalassa leikattuja AMI-potilaita. Poissuljimme tutkimuksesta potilaat, joilla oli pitkäaikainen, puoliäkillinen, paksusuoleen rajoittunut, laskimoperäinen tai verisuonia tukkimaton mesenteriaali-iskemia. Potilaat jaettiin kahteen alaryhmään sen mukaan, oliko ensimmäinen terveydenhuollon piste, jonka he kohtasivat kirurginen päivystys (KP) vai ei-kirurginen päivystys (ei-KP). Ensisijainen päätemuuttuja oli leikkausviive ja toissijaiset päätemuuttujat olivat sairaalahoidon kesto ja 90-päivän kuolleisuus. Tulokset: Lopullisessa tutkimuspotilasjoukossa oli 81 potilasta. Ei-KP ensimmäisenä hoitokontaktina oli itsenäisesti yhteydessä yli 12 tunnin leikkausviiveeseen (OR 3.7 (95% luottamusväli 1.3-10.2), mediaani viive 15.2 tuntia (IQR 10.9-21.2) vs. 10.1 tuntia (IQR 6.9-18.5), p = 0.025). Sairaalahoidon kesto oli lyhyempi (mediaani 6.5 päivää (4.0-10.3) vs. 10.8 päivää (7.0-22.3), p = 0.045) ja 90-päivän kuolleisuus matalampi KP-ryhmässä (50.0% vs. 74.5%, p = 0.025). Johtopäätökset: Ensimmäinen erikoisala johon potilas lähetetään, vaikuttaa oleellisesti AMI-potilaan leikkausviiveeseen ja kuolleisuuteen. Hoitoketjun sujuvoittaminen niin, että potilas pääsee mahdollisimman nopeasti hoitoon vatsaelin- ja verisuonikirurgiseen yksikköön, voi parantaa AMI:n hoidon tuloksia. (200 sanaa

Porttilaskimotukos

Vertaisarvioitu.Porttilaskimotukoksen kliininen kuva vaihtelee oireettomasta sattumalöydöksestä akuuttiin vatsaan tai esimerkiksi suonikohjuvuodon taustalta todettavaan krooniseen tukokseen. Dopplerkaikukuvauksella voidaan päästä diagnoosiin. Tietokonetomografialla tarkennetaan tukoksen laajuus, tuoreus, paikalliset taustatekijät sekä suoli-iskemian merkit. Taustalla on usein monen riskitekijän yhdistelmä. Hoidon tavoitteena on tukoksen sulaminen ja laajenemisen esto, taustatekijöihin puuttuminen sekä komplikaatioiden kuten suoli-iskemian, portahypertension tai portaalisen biliopatian estäminen. Akuutin tukoksen antikoagulaatiohoito aloitetaan heti. Hoidon pituus ja kroonisen tukoksen osalta hoidon aihe arvioidaan tapauskohtaisesti ottaen huomioon yksilölliset vuoto- ja tukosriskitekijät. Seurannassa portahypertension komplikaatioita ilmenee jopa vajaalla puolella potilaista, mikä puoltaa aktiivisia varhaisia rekanalisaatioyrityksiä ja pitkäaikaista seurantaa. Voimakasoireisen laajan akuutin tukoksen endovaskulaarisia tromboosia hajottavia hoitoja voidaan harkita.Peer reviewe

Choice of First Emergency Room Affects the Fate of Patients With Acute Mesenteric lschaemia : The Importance of Referral Patterns and Triage

Objectives: Despite modern advances in diagnosis and treatment, acute arterial mesenteric ischaemia (AMI) remains a high mortality disease. One of the key modifiable factors in AMI is the first door to operation time, but the factors attributing to this parameter are largely unknown. The aim of this study was to evaluate the factors affecting delay, with special focus on the pathways to treatment. Methods: This was a single academic centre retrospective study. Patients undergoing intervention for AMI caused by thrombosis or embolism of the superior mesenteric artery between 2006 and 2015 were identified from electronic patient records. Patients not eligible for intervention or with chronic, subacute onset, colonic only, venous, or non-occlusive mesenteric ischaemia were excluded. Patients were divided into two groups according to the first speciality examining the patient (surgical emergency room [SER], surgeon examining the patient first or non-surgical emergency room [non-SER], internist examining the patient first). The primary endpoint was first door to operation time and secondary endpoints were length of stay and 90 day mortality. Results: Eighty-one patients with AMI were included. Fifty patients (62%) died during the first 30 days and 53 (65%) within 90 days. Presenting first in non-SER (vs. SER) was independently associated with a first door to operation time of over 12 h (OR 3.7 [95% CI 1.3-10.2], median time 15.2 h [IQR 10.9-21.2] vs. 10.1 h [IQR 6.9-18.5], respectively, p = .025). The length of stay was shorter (median 6.5 days [4.0-10.3] vs. 10.8 days [7.0-22.3], p = .045) and 90 day mortality was lower in the SER group (50.0% vs. 74.5%, p = .025). Conclusions: The first specialty that the patient encounters seems to be crucial for both delayed management and early survival of AMI. Developing fast/direct pathways to a unit with both gastrointestinal and vascular surgeons offers the possibility of improving the outcome of AMI.Peer reviewe

Akuutti mesenteriaali-iskemia - epidemiologia ja hoitotulokset

Background: Acute mesenteric ischemia (AMI) is a disease with high mortality. The exact incidence is still unclear as data mostly come from studies based on patient records. These do not include those that are not correctly diagnosed with AMI while alive. Mortality of AMI rises concomitantly with door to operation time, but the factors contributing to these delays remain largely unknown. Portal vein thrombosis (PVT) is usually treated with anticoagulation and only in a relatively small portion of patients the thrombus extends to the superior mesenteric vein (SMV) or splenic vein (SV) which may lead to the development of bowel ischemia. However, even without serious complications an untreated PVT can lead to portal hypertensive complications that can cause significant morbidity. The risk factors for insufficient recanalization and indicators for more invasive treatment methods for PVT are still unclear. Material and methods: This thesis included four original retrospective studies. The first three studies concerning AMI focused on arterial occlusive AMI, therefore, AMI caused by strangulation and non-occlusive, traumatic, and iatrogenic AMI were excluded. Study I included patients who were diagnosed with or died of AMI during 2006-2015 in the Hospital District of Helsinki and Uusimaa (HUS). The study also included AMI patients diagnosed postmortem. This data was collected from death certificates. Study II included patients treated for arterial AMI in Meilahti hospital during 2006-2015. Study III included patients who were diagnosed with arterial AMI between 2014 and April 2020 in the HUS area and were operated on in Meilahti. The patients were divided into pre-and postpathway groups according to the time of diagnosis in relation to the implementation of a treatment pathway and care bundle (from 2014 to 2017 and from May 2018 to April 2020). Study IV included patients diagnosed with non-cirrhotic and non-malignant PVT in the HUS area between 2006 and 2015. Results: In study I, 29% of patients were diagnosed postmortem (out of a total of 470). The overall incidence did not change during the study period, although some subgroups, such as the working age population, showed an increase. The overall incidence rate was 3.1/100 000 PY during the study period and 26.7 in those aged 70 years or more. Study II included 81 patients, of whom 65% died within 90 days of diagnosis. If the patient arrived first at a surgical emergency room (SER), first door to operation time was shorter (10h vs. 15h, p = .025), hospital stay was shorter (7 vs. 11 days, p = .045) and 90-day mortality lower (50% vs. 75%, p = .025). Study III included 145 patients who were divided into pre- and postgroups. The groups were comparable in disease acuity and baseline characteristics. In the postgroup, more patients were diagnosed with contrast enhanced CT (74% vs. 94%, p = .001), the in-hospital delay to operating room was shorter (7h vs. 3h, p = .023), more revascularizations were done (68% vs. 84%, p = .030), especially endovascular interventions (33% vs. 64%, p <.001) and 30-day mortality was lower (51% vs. 25% p = .001). In multivariate analysis belonging to the postgroup was a protective factor for 30-day mortality. Study IV included 145 patients with PVT, the majority of whom (92%) were treated primarily with anticoagulation. The 5-year cumulative incidence of complete recanalization was 42% and 31% for portal hypertensive complications (PHC). A non-acute thrombus was an independent risk factor for insufficient recanalization (HR 3.1, 95% CI 1.6-5.8) whereas acute pancreatitis was a protective factor (HR 0.3, 95% CI 0.2-0.7). Risk factors for PHC were non-acute thrombus (HR 2.9, 95% CI 1.6-5.3), ascites at baseline (HR 3.3, 95% CI 1.7-6.7), thrombus extending to the SMV or SV (HR 2.6, 95% CI 1.2-5.7), myeloproliferative disease (HR 3.0, 95% CI 1.4-6.5) and anemia (HR 2.1, 95% CI 1.1-3.9), whereas acute pancreatitis was a protective factor (HR 0.1, 95% CI 0.03-0.5). Conclusions: The overall incidence of AMI did not change during the study period, but there was an increase in the working age population. A third of patients were only diagnosed postmortem. The specialty of the first emergency room an AMI patient encounters crucially affects the delays in treatment as well as early survival. Delays were decreased by implementing a treatment pathway and care bundle, which also led to decreased mortality, as well as an increase in appropriate CT imaging and an increased rate of revascularizations. Thrombus etiology and age affected recanalization in PVT patients, whereas thrombus age, etiology and extent, ascites at baseline and anemia affected development of portal hypertensive complications. The age, extent and etiology of a PVT might be of use in determining which patients benefit from more invasive treatment options.Tausta: Akuutti mesenteriaali-iskemia (AMI) on korkean kuolleisuuden tauti, jonka yleisyys kasvaa iän myötä. Sen tarkka esiintyvyys on edelleen epäselvä. Diagnostiikka on haastava, eivätkä hoitotulokset ole merkittävästi muuttuneet kehittyneistä hoitomuodoista huolimatta. Oireiden alusta leikkaukseen kestävä aika vaikuttaa merkittävästi kuolleisuuteen, mutta viiveiden syyt ovat edelleen pitkälti tuntemattomat. Porttilaskimon tukos (PVT) hoidetaan yleensä antikoagulaatiolla. Tukos voi joskus levitä ylempään suolilievelaskimoon (SMV) tai pernalaskimoon (SV), altistaen suoli-iskemian kehittymiselle. Kuitenkin myös ilman vakavia komplikaatioita hoitamaton PVT voi johtaa porttilaskimon hypertensioon, jonka komplikaatiot aiheuttavat merkittävää sairastavuutta. Puutteellisen rekanalisaation riskitekijät ja kajoavampien hoitotoimenpiteiden indikaatiot ovat kuitenkin edelleen epäselviä. Materiaali ja menetelmät: Tämä työ sisältää neljä alkuperäistä retrospektiivistä aineistotutkimusta. Ensimmäiset kolme keskittyivät valtimoperäiseen AMIn. Osatyö I sisälsi vuosina 2006-2015 HUS-alueella diagnosoidut tai kuolleet AMI-potilaat. Tietoja kerättiin potilastietorekisterien lisäksi kuolinsyytodistuksista. Osatyö II sisälsi Meilahden sairaalassa akuutin valtimoperäisen AMIn vuoksi vuosina 2006-2015 hoidetut potilaat. Osatyö III sisälsi tammikuun 2014 ja huhtikuun 2020 välillä Helsingin yliopistollisen sairaalan (HUS) alueella diagnosoidut valtimoperäiset AMIt jotka operoitiin Meilahdessa. Potilaat jaettiin ennen ja jälkeen ryhmiin riippuen diagnoosin ajasta suhteessa hoitopolun käyttöönottoon (2014 – 2017 ja toukokuu 2018 – huhtikuu 2020). Osatyö IV sisälsi vuosien 2006 ja 2015 välillä HUS-alueella hoidetut ei-kirroottiset ja ei-malignit PVT-potilaat. Tulokset: Ensimmäisessä osatyössä 470:sta AMI-potilaasta 29 % diagnosoitiin ensimmäisen kerran obduktiossa. Esiintyvyys ei kokonaisuudessaan muuttunut tutkimusjakson aikana, mutta alaryhmissä – kuten työikäisellä väestöllä – havaittiin nousua. Kokonaisuudessaan esiintyvyys oli 3,1/100 000 henkilövuotta ja yli 70-vuotiailla 26,7. Osatyö II sisälsi 81 potilasta, joista 65 % kuoli 90 päivän sisällä diagnoosista. Jos potilas saapui ensin kirurgiseen päivystykseen (SER), saapumisesta leikkaukseen kuluva aika oli lyhyempi (10 h vs. 15 h, p = 0,025), samoin sairaalahoidon kesto (7 vs. 11 päivää, p = 0,045) ja 90-päivän kuolleisuus oli matalampi (50 vs. 75 %, p = 0,025). Osatyö III sisälsi 145 potilasta, jotka jaettiin ennen ja jälkeen ryhmiin, joiden välissä hoitoketju käynnistettiin. Ryhmät olivat sairauden kehittymisen ja taustamuuttujien osalta verrannollisia. Jälkeen-ryhmässä oli enemmän varjoaine-TT:llä diagnosoituja (74 % vs. 94 %, p = 0,001), lyhyempi viive leikkaukseen pääsyyn (7 h vs. 3 h, p = 0,023), enemmän revaskularisaatioita (68 % vs. 84 %, p = 0,030), etenkin endovaskulaarisia (33 % vs. 64 %, p <0,001) ja 30-päivän kuolleisuus oli matalampi (51 % vs. 25 % p = 0,001). Monimuuttuja-analyysissä jälkeen-ryhmään kuuluminen oli suojaava tekijä 30-päivän kuolleisuudelle. Osatyö IV sisälsi 145 PVT-potilasta, joista suurin osa (92 %) hoidettiin primääristi antikoagulaatiolla. 5-vuotinen kumulatiivinen insidenssi täydelle rekanalisaatiolle oli 42 % ja porttilaskimon hypertensiivisille komplikaatioille (PHC) 31 %. Ei-akuutti trombi oli itsenäinen riskitekijä puutteelliselle rekanalisaatiolle (HR 3,1, 95 % CI 1,6–5,8), kun taas akuutti pankreatiitti etiologiana oli suojaava tekijä (HR 0,3, 95 % CI 0,2–0,7). Riskitekijöitä PHC:lle olivat ei-akuutti trombi (HR 2,9, 95 % CI 1,6–5,3), askites lähtötilanteessa (HR 3,3, 95 % CI 1,7–6,7), SMV:n tai SV:n ylettyvä trombi (HR 2,6, 95 % CI 1,2–5,7), myeloproliferatiivinen sairaus (HR 3,0, 95 % CI 1,4–6,5) ja anemia (HR 2,1, 95 % CI 1,1–3,9). Akuutti pankreatiitti oli suojaava tekijä (HR 0,1, 95 % CI 0,03–0,5). Johtopäätökset: AMIn esiintyvyydessä ei kokonaisuudessaan tapahtunut muutoksia tutkimusajanjaksolla. Lähes kolmasosa potilaista diagnosoitiin vasta obduktiossa. AMI-potilaan ensimmäisenä kohtaaman päivystyspisteen erikoisala vaikuttaa oleellisesti sekä viiveisiin että alkuvaiheen kuolleisuuteen. Hoitoketjun käynnistäminen johti viiveiden vähenemiseen ja kuolleisuuden alenemiseen, sekä lisääntyneeseen adekvaattiin kuvaamiseen ja revaskularisaatioihin. PVT:n rekanalisaatioon vaikuttivat trombin etiologia ja ikä, joiden lisäksi PHC:n kehittymiseen vaikuttivat trombin laajuus, askites lähtötilanteessa ja anemia. Trombin etiologia, ikä ja laajuus voivat auttaa valikoimaan potilaita, jotka hyötyisivät kajoavammista hoitomuodoista

The implementation of a pathway and care bundle for the management of acute occlusive arterial mesenteric ischemia reduced mortality

BACKGROUND Acute mesenteric ischemia (AMI) is a disease with high mortality and requires a multidisciplinary approach for effective management. A pathway and care bundle were developed and implemented with the objective to reduce mortality. The aim of this retrospective comparative study was to analyze the effects of the pathway on patient management and outcome. METHODS All consecutive patients operated in a secondary and tertiary referral center because of occlusive arterial AMI were identified between 2014 and April 2020. The pathway aimed to increase overall awareness, and hasten and improve diagnostics and management. Patients treated before implementation of the pathway (pregroup, years 2014-2017) were compared with patients treated using the pathway (postgroup, May 2018 to April 2020). Univariate and multivariate analyses were used to compare the groups. RESULTS There were 78 patients in the pregroup and 67 patients in the postgroup with comparable baseline characteristics and disease acuity. The postgroup was more often diagnosed with contrast-enhanced computed tomography (58 [74%] vs. 63 [94%], p = 0.001) and had shorter mean in-hospital delay to operating room (7 hours [interquartile range, 3.5-12.5] vs. 3 hours [interquartile range, 2-11], p = 0.023). Revascularization was done more often in the postgroup (53 [68%] vs. 56 [84%], p = 0.030) especially using endovascular treatment (26 [33%] vs. 43 [64%], p < 0.001). Thirty-day mortality was lower in the postgroup (23 [51%] vs. 17 [25%], p = 0.001). Being managed in the postgroup remained as a protective factor (odds ratio, 0.32; 95% confidence interval, 0.14-0.75; p = 0.008) for 30-day mortality in the multivariate analysis. CONCLUSION Implementing a pathway and care bundle resulted in enhanced regional and in-hospital awareness of AMI, more appropriate computed tomography imaging, shorter in-hospital delays, increased number of revascularizations, and, hence, lower mortality.Peer reviewe

Potential for intestinal transplantation after acute mesenteric ischemia in patients aged less than 70 years : A population-based study

Background and objective: Acute mesenteric ischemia (AMI) has a high mortality rate due to the development of bowel necrosis. Patients are often ruled outside active care if a large proportion of small bowel is necrotic. With the development of treatment for short bowel syndrome (SBS) and intestinal transplantation methods, long-term survival is possible even after extensive small bowel resections. This study aims to assess the incidence of SBS and potentially suitable candidates for intestinal transplantation among patients treated for AMI. Methods: This population-based retrospective study comprised patients aged less than 70 years and diagnosed with AMI between January 2006 and October 2020 in Helsinki and Uusimaa health care district, Finland. Results: Altogether, AMI was diagnosed in 711 patients, of whom 133 (19%) were aged below 70. An intervention was performed in 110 (83%) patients. Of these 133 patients, 16 (12%) were ruled outside active treatment due to extensive small bowel necrosis at exploratory laparotomy, of whom 6 (5%) were potentially suitable for intestinal transplantation. Two patients were considered as potential candidates for intestinal transplantation at bowel resection but died of AMI. Nine (7%) patients needed parenteral nutrition after resection, and two of them (2%) developed SBS. Only one patient needed long-term parenteral nutrition after hospital discharge. This patient remained dependent on parenteral nutrition but died before evaluation of intestinal transplantation could be carried out while the other patient was able to return to enteral nutrition. Conclusions: A small number of patients with AMI below 70 years of age are potentially eligible for intestinal transplantation.Peer reviewe

Nuclear factor erythroid 2-related factors 1 and 2 are able to define the worst prognosis group among high-risk diffuse large B cell lymphomas treated with R-CHOEP

Abstract Aims: Oxidative stress markers and antioxidant enzymes have previously been shown to have prognostic value and associate with adverse outcome in patients with diffuse large B cell lymphoma (DLBCL). Nuclear factor erythroid 2-related factor 1 (Nrf1) and factor 2 (Nrf2) are among the principal inducers of antioxidant enzyme production. Kelch ECH associating protein 1 (Keap1) is a negative regulator of Nrf2, and BTB (BR-C, ttk and bab) domain and CNC homolog 1 (Bach1) represses the function of both factors. Their significance in DLBCL prognosis is unknown. Methods: Diagnostic biopsy samples of 76 patients with high-risk DLBCL were retrospectively stained with immunohistochemistry for Nrf1, Nrf2, Keap1 and Bach1, and correlated with clinical data and outcome. Results: Nuclear Nrf2 and nuclear Bach1 expression were associated with adverse clinical features (anaemia, advanced stage, high IPI, high risk of neutropaenic infections), whereas cytoplasmic Nrf1 and Nrf2 were associated with favourable clinical presentation (normal haemoglobin level, no B symptoms, limited stage). None of the evaluated factors could predict survival alone. However, when two of the following parameters were combined: high nuclear score of Nrf2, low nuclear score of Nrf1, high cytoplasmic score of Nrf1 and low cytoplasmic score of Keap1 were associated with significantly worse overall survival. Conclusions: Nrf1 and Nrf2 are relevant in disease presentation and overall survival in high-risk DLBCL. Low nuclear expression of Nrf1, high cytoplasmic expression of Nrf1, high nuclear expression of Nrf2 and low cytoplasmic expression of Keap1 are associated with adverse outcome in this patient group