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- Hasselgren, Kristina, et al.
(författare)
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ALPPS Improves Survival Compared With TSH in Patients Affected of CRLM Survival Analysis From the Randomized Controlled Trial LIGRO
- 2021
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 273:3, s. 442-448
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the oncological outcome for patients with colorectal liver metastases (CRLM) randomized to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH). Background: TSH with portal vein occlusion is an established method for patients with CRLM and a low volume of the future liver remnant (FLR). ALPPS is a less established method. The oncological outcome of these methods has not been previously compared in a randomized controlled trial. Methods: One hundred patients with CRLM and standardized FLR (sFLR) <30% were included and randomized to resection by ALPPS or TSH, with the option of rescue ALPPS in the TSH group, if the criteria for volume increase was not met. The first radiological follow-up was performed approximately 4 weeks postoperatively and then after 4, 8, 12, 18, and 24 months. At all the follow-ups, the remaining/recurrent tumor was noted. After the first follow-up, chemotherapy was administered, if indicated. Results: The resection rate, according to the intention-to-treat principle, was 92% (44 patients) for patients randomized to ALPPS compared with 80% (39 patients) for patients randomized to TSH (P = 0.091), including rescue ALPPS. At the first postoperative follow-up, 37 patients randomized to ALPPS were assessed as tumor free in the liver, and also 28 patients randomized to TSH (P = 0.028). The estimated median survival for patients randomized to ALPPS was 46 months compared with 26 months for patients randomized to TSH (P = 0.028). Conclusions: ALPPS seems to improve survival in patients with CRLM and sFLR <30% compared with TSH.
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- Robroek, Bjorn J. M., et al.
(författare)
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Microclimatological consequences for plant and microbial composition in Sphagnum-dominated peatlands
- 2014
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Ingår i: Boreal environment research. - Helsinki, Finland : Finnish Environment Institute. - 1239-6095 .- 1797-2469. ; 19:3, s. 195-208
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Tidskriftsartikel (refereegranskat)abstract
- In three Scandinavian peatlands we studied to what extent plant and microbial community compositions are governed by local-scale microhabitat, with a special interest in the effect of aspect (i.e. exposition of slopes). Despite differences in solar irradiance between the south- and north-facing slopes, maximum temperature was elevated in the south-facing slopes at the most northern site only. Pore-water nutrient concentrations were not affected by aspect, yet dissolved organic carbon concentrations were higher in the south-facing microhabitats. This was likely caused by higher vascular plant biomass. Plant and microbial community composition clearly differed among sites. In all three sites, microhabitat (i.e. prevailing water-table depth) affected the plant and microbial community compositions. Aspect, however, did not affect community composition, even though microclimate significantly differed between the south- and the north-facing aspects at the northernmost site. Our results highlight the complex link between plant community composition, microbial community and environmental conditions, which deserves much more attention than currently in order to fully understand the effects of climate change on peatland ecosystem function.
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- Sandström, Per, et al.
(författare)
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ALPPS Improves Resectability Compared with Conventional Two-stage Hepatectomy in Patients with Advanced Colorectal Liver Metastasis : Results from a Scandinavian Multicenter Randomized Controlled Trial (LIGRO Trial)
- 2018
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Ingår i: Annals of Surgery. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-4932 .- 1528-1140. ; 267:5, s. 833-840
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the study was to evaluate if associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) could increase resection rates (RRs) compared with two-stage hepatectomy (TSH) in a randomized controlled trial (RCT). Background: Radical liver metastasis resection offers the only chance of a cure for patients with metastatic colorectal cancer. Patients with colorectal liver metastasis (CRLM) and an insufficient future liver remnant (FLR) volume are traditionally treated with chemotherapy with portal vein embolization or ligation followed by hepatectomy (TSH). This treatment sometimes fails due to insufficient liver growth or tumor progression. Methods: A prospective, multicenter RCT was conducted between June 2014 and August 2016. It included 97 patients with CRLM and a standardized FLR (sFLR) of less than 30%. Primary outcome - RRs were measured as the percentages of patients completing both stages of the treatment. Secondary outcomes were complications, radicality, and 90-day mortality measured from the final intervention. Results: Baseline characteristics, besides body mass index, did not differ between the groups. The RR was 92% [95% confidence interval (CI) 84%-100%] (44/48) in the ALPPS arm compared with 57% (95% CI 43%-72%) (28/49) in the TSH arm [rate ratio 8.25 (95% CI 2.6-26.6); P < 0.0001]. No differences in complications (Clavien-Dindo ≥3a) [43% (19/44) vs 43% (12/28)] [1.01 (95% CI 0.4-2.6); P = 0.99], 90-day mortality [8.3% (4/48) vs 6.1% (3/49)] [1.39 [95% CI 0.3-6.6]; P = 0.68] or R0 RRs [77% (34/44) vs 57% (16/28)] [2.55 [95% CI 0.9-7.1]; P = 0.11)] were observed. Of the patients in the TSH arm that failed to reach an sFLR of 30%, 12 were successfully treated with ALPPS. Conclusion: ALPPS is superior to TSH in terms of RR, with comparable surgical margins, complications, and short-term mortality.
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- Ladds, Marcus J. G. W., et al.
(författare)
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A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.
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- Lebwohl, Benjamin, et al.
(författare)
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Risk of Severe Covid-19 in Patients with Celiac Disease : A Population-Based Cohort Study
- 2021
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Ingår i: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 13, s. 121-130
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with celiac disease (CeD) are at increased risk of certain viral infections and of pneumococcal pneumonia, raising concerns that they may be susceptible to severe coronavirus disease 2019 (Covid-19). We aimed to quantify the association between CeD and severe outcomes related to Covid-19.Methods: We performed a population-based cohort study, identifying individuals with CeD in Sweden, as defined by small intestinal villus atrophy diagnosed at all (n=28) Swedish pathology departments during the years spanning 1969-2017, and alive on February 1, 2020. We compared these patients to controls matched by sex, age, county, and calendar period. We performed Cox proportional hazards with follow-up through July 31, 2020, assessing risk of 1) hospital admission with a primary diagnosis of laboratory-confirmed Covid-19 (co-primary outcome); and 2) severe disease as defined by admission to intensive care unit and/or death attributed to Covid-19 (co-primary outcome).Results: Among patients with CeD (n=40,963) and controls (n=183,892), the risk of hospital admission for Covid-19 was 2.9 and 2.2 per 1000 person-years respectively. After adjusting for comorbidities, the risk of hospitalization for Covid-19 was not significantly increased in patients with CeD (HR 1.10; 95% CI 0.80-1.50), nor was the risk of severe Covid-19 increased (HR 0.97; 95% CI 0.59-1.59). Results were similarly null when we compared CeD patients to their non-CeD siblings with regard to these outcomes. Among all patients with CeD and controls hospitalized with a diagnosis of Covid-19 (n=58 and n=202, respectively), there was no significant difference in mortality (HR for CeD compared to controls 0.96; 95% CI 0.46-2.02).Conclusion: In this population-based study, CeD was not associated with an increased risk of hospitalization for Covid-19 or intensive care unit and/or death attributed to Covid-19.
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- Lundqvist, Pia, et al.
(författare)
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Development and psychometric properties of the Swedish ALPS-Neo pain and stress assessment scale for newborn infants
- 2014
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 103:8, s. 833-839
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To validate and evaluate the psychometric properties of the ALPS-Neo, a new pain assessment scale created for the continuous evaluation of pain and stress in preterm and sick term infants. Methods: A unidimensional scale for continuous pain, Astrid Lindgren Children's Hospital Pain Scale (ALPS 1), was developed further to assess continuous pain and stress in infants treated in the neonatal intensive care unit (NICU). The pain scale includes observations of five behaviours. A manual was created, clarifying the scoring criteria. An internal and an external panel assessed face validity. Psychometric properties were evaluated in three different steps. Inter-rater reliability was estimated from video-based assessments (n = 625) using weighted kappa statistics (test I). Inter-rater reliability was further evaluated in test II (n = 125) and test III (n = 96) by real-time assessments using the intraclass correlation coefficient (ICC) and Cronbach's alpha. Results: The final inter-rater reliability (test III) was assessed as good with ICC 0.91 for the total score and 0.62-0.81 for the five items. Cronbach's alpha showed 0.95 for the total score. Conclusion: ALPS-Neo is a new assessment tool for optimising the management of pain and stress in newborn infants in the NICU. It has proved easy to implement and user-friendly, permitting fast, reliable observations with high inter-rater reliability.
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