Browsing by Subject "TRANSPLANTATION"

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  • Eskelund, Christian W.; Kolstad, Arne; Jerkeman, Mats; Räty, Riikka; Laurell, Anna; Eloranta, Sandra; Smedby, Karin E.; Husby, Simon; Pedersen, Lone B.; Andersen, Niels S.; Eriksson, Mikael; Kimby, Eva; Bentzen, Hans; Kuittinen, Outi; Lauritzsen, Grete F.; Nilsson-Ehle, Herman; Ralfkiaer, Elisabeth; Ehinger, Mats; Sundstrom, Christer; Delabie, Jan; Karjalainen-Lindsberg, Marja-Liisa; Workman, Christopher T.; Garde, Christian; Elonen, Erkki; Brown, Peter; Gronbaek, Kirsten; Geisler, Christian H. (2016)
    In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 114years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 127 and 85years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.
  • Vakkilainen, Svetlana; Taskinen, Mervi; Klemetti, Paula; Pukkala, Eero; Mäkitie, Outi (2019)
    Cartilage-hair hypoplasia (CHH) is a skeletal dysplasia with combined immunodeficiency, variable clinical course and increased risk of malignancy. Management of CHH is complicated by a paucity of long-term follow-up data, as well as knowledge on prognostic factors. We assessed clinical course and risk factors for mortality in a prospective cohort study of 80 patients with CHH recruited in 1985-1991 and followed up until 2016. For all patients we collected additional health information from health records and from the national Medical Databases and Cause-of-death Registry. The primary outcome was immunodeficiency-related death, including death from infections, lung disease and malignancy. Standardized mortality ratios (SMRs) were calculated using national mortality rates as reference. Half of the patients (57%, n = 46) manifested no symptoms of immunodeficiency during follow-up while 19% (n = 15) and 24% (n = 19) demonstrated symptoms of humoral or combined immunodeficiency, including six cases of adult-onset immunodeficiency. In a significant proportion of patients (17/79, 22%), clinical features of immunodeficiency progressed over time. Of the 15 patients with non-skin cancer, eight had no preceding clinical symptoms of immunodeficiency. Altogether 20 patients had deceased (SMR = 7.0, 95% CI = 4.3-11); most commonly from malignancy (n = 7, SMR = 10, 95% CI = 4.1-21) and lung disease (n = 4, SMR = 46, 95% CI = 9.5-130). Mortality associated with birth length below-4 standard deviation (compared to normal, SMR/SMR ratio = 5.4, 95% CI = 1.5-20), symptoms of combined immunodeficiency (compared to asymptomatic, SMR/SMR ratio= 3.9, 95% CI = 1.3-11), Hirschsprung disease (odds ratio (OR) 7.2, 95% CI = 1.04-55), pneumonia in the first year of life or recurrently in adulthood (OR = 7.6/19, 95% CI = 1.3-43/2.6-140) and autoimmunity in adulthood (OR = 39, 95% CI = 3.5-430). In conclusion, patients with CHH may develop adult-onset immunodeficiency or malignancy without preceding clinical symptoms of immune defect, warranting careful follow-up. Variable disease course and risk factors for mortality should be acknowledged.
  • Ydreborg, Magdalena; Lisovskaja, Vera; Lagging, Martin; Christensen, Peer Brehm; Langeland, Nina; Buhl, Mads Rauning; Pedersen, Court; Morch, Kristine; Wejstal, Rune; Norkrans, Gunnar; Lindh, Magnus; Farkkila, Martti; Westin, Johan (2014)
  • Sanz-Garcia, Andres; Sodupe-Ortega, Enrique; Pernia-Espinoza, Alpha; Shimizu, Tatsuya; Escobedo-Lucea, Carmen (2020)
    Three-dimensional (3D) bioprinting promises to be essential in tissue engineering for solving the rising demand for organs and tissues. Some bioprinters are commercially available, but their impact on the field of Tissue engineering (TE) is still limited due to their cost or difficulty to tune. Herein, we present a low-cost easy-to-build printhead for microextrusion-based bioprinting (MEBB) that can be installed in many desktop 3D printers to transform them into 3D bioprinters. We can extrude bioinks with precise control of print temperature between 2-60 degrees C. We validated the versatility of the printhead, by assembling it in three low-cost open-source desktop 3D printers. Multiple units of the printhead can also be easily put together in a single printer carriage for building a multi-material 3D bioprinter. Print resolution was evaluated by creating representative calibration models at different temperatures using natural hydrogels such as gelatin and alginate, and synthetic ones like poloxamer. Using one of the three modified low-cost 3D printers, we successfully printed cell-laden lattice constructs with cell viabilities higher than 90% after 24-h post printing. Controlling temperature and pressure according to the rheological properties of the bioinks was essential in achieving optimal printability and great cell viability. The cost per unit of our device, which can be used with syringes of different volume, is less expensive than any other commercially available product. These data demonstrate an affordable open-source printhead with the potential to become a reliable alternative to commercial bioprinters for any laboratory.
  • Holster, Savanne; Hooiveld, Guido J.; Repsilber, Dirk; de Vos, Willem M.; Brummer, Robert J.; König, Julia (2019)
    Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe-host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.
  • Lankelma, Jacqueline M.; Belzer, Clara; Hoogendijk, Arie J.; de Vos, Alex F.; de Vos, Willem M.; van der Poll, Tom; Wiersinga, W. Joost (2016)
    OBJECTIVES: Broad-spectrum antibiotics disrupt the intestinal microbiota. The microbiota is essential for physiological processes, such as the development of the gut immune system. Recent murine data suggest that the intestinal microbiota also modulates systemic innate immune responses; however, evidence in humans is lacking. METHODS: Twelve healthy young men were given oral broad-spectrum antibiotics (ciprofloxacin 500 mg bid, vancomycin 500 mg tid and metronidazole 500 mg tid) for 7 days. At baseline, 1 day, and 6 weeks after antibiotics, blood and feces were sampled. Whole blood and isolated mononuclear cells were stimulated with selected Toll-like receptor agonists and heat-killed bacteria. Microbiota diversity and composition was determined using bacterial 16S rDNA sequencing. RESULTS: One day after the antibiotic course, microbial diversity was significantly lower compared with baseline. After antibiotic therapy, systemic mononuclear cells produced lower levels of tumor necrosis factor (TNF)-alpha after ex vivo stimulation with lipopolysaccharide (LPS). This diminished capacity to produce TNF-alpha was restored 6 weeks after cessation of antibiotic therapy. In whole blood, a reduced capacity to release interleukin (IL)-1 beta and IL-6 was observed after LPS stimulation. Antibiotic treatment did not impact on differential leukocyte counts, phagocytosis, and cell surface markers of neutrophils and monocytes. CONCLUSIONS: In this proof-of-principle study of healthy subjects, microbiota disruption by broad-spectrum antibiotics is reversibly associated with decreased systemic cellular responsiveness towards LPS. The implications of these findings in a clinical setting remain to be determined.
  • Paatela, Teemu; Vasara, Anna; Nurmi, Heikki; Kautiainen, Hannu; Kiviranta, Ilkka (2020)
    The International Cartilage Repair Society (ICRS) score and the Oswestry Arthroscopic Score (OAS) have been validated to evaluate repair tissue quality. However, the performance of these scores has not been studied in typical patients undergoing cartilage repair and who have lesions of varying sizes. In this study, we compared the performance of the ICRS and the OAS scores and analyzed the effect of lesion characteristics on the performance of these two scores. Cartilage repair quality was assessed in a total of 104 arthroscopic observations of cartilage repair sites of the knee in 62 patients after autologous chondrocyte implantation. Two observers scored the repair areas independently with the ICRS and the OAS scores. The performance of both scores was evaluated according to internal consistency and inter-rater reliability and correlation between the scores. The frequency and proportion of disagreements were analyzed according to the repair site area and the given score. The correlation between the scores was good (r = 0.91, 95% confidence interval [CI]: 0.87-0.94). Both scores showed moderate internal consistency and inter-rater reliability. Cronbach's alpha was 0.88 (95% CI: 0.80-0.92) for the ICRS score and 0.79 (95% CI: 0.70-0.86) for the OAS score. The intraclass correlation coefficient was 0.89 (95% CI: 0.84-0.92) for the ICRS and 0.81 (95% CI: 0.74-0.87) for the OAS scores. The frequency and proportion of disagreements were higher in larger repair sites. In arthroscopic use, both ICRS and OAS scores perform similarly, however, their reliability deteriorates as the lesion size increases. (c) 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
  • Zheng, GQ; Sundquist, K; Sundquist, J; Forsti, A; Hemminki, O; Hemminki, K (2021)
    Background Previous population-based studies on second primary cancers (SPCs) in urothelial cancers have focused on known risk factors in bladder cancer patients without data on other urothelial sites of the renal pelvis or ureter. Aims To estimate sex-specific risks for any SPCs after urothelial cancers, and in reverse order, for urothelial cancers as SPCs after any cancer. Such two-way analysis may help interpret the results. Methods We employed standardized incidence ratios (SIRs) to estimate bidirectional relative risks of subsequent cancer associated with urothelial cancers. Patient data were obtained from the Swedish Cancer Registry from years 1990 through 2015. Results We identified 46 234 urinary bladder cancers (75% male), 940 ureteral cancers (60% male), and 2410 renal pelvic cancers (57% male). After male bladder cancer, SIRs significantly increased for 9 SPCs, most for ureteral (SIR 41.9) and renal pelvic (17.2) cancers. In the reversed order (bladder cancer as SPC), 10 individual FPCs were associated with an increased risk; highest associations were noted after renal pelvic (21.0) and ureteral (20.9) cancers. After female bladder cancer, SIRs of four SPCs were significantly increased, most for ureteral (87.8) and pelvic (35.7) cancers. Female bladder, ureteral, and pelvic cancers associated are with endometrial cancer. Conclusions The risks of recurrent urothelial cancers were very high, and, at most sites, female risks were twice over the male risks. Risks persisted often to follow-up periods of >5 years, motivating an extended patient follow-up. Lynch syndrome-related cancers were associated with particularly female urothelial cancers, calling for clinical vigilance.
  • Kosola, Silja; Culnane, Evelyn; Loftus, Hayley; Tornivuori, Anna; Kallio, Mira; Telfer, Michelle; Miettinen, Päivi J.; Kolho, Kaija-Leena; Aalto, Kristiina; Raivio, Taneli; Sawyer, Susan (2021)
    Introduction More than 10% of adolescents live with a chronic disease or disability that requires regular medical follow-up as they mature into adulthood. During the first 2 years after adolescents with chronic conditions are transferred to adult hospitals, non-adherence rates approach 70% and emergency visits and hospitalisation rates significantly increase. The purpose of the Bridge study is to prospectively examine associations of transition readiness and care experiences with transition success: young patients' health, health-related quality of life (HRQoL) and adherence to medical appointments as well as costs of care. In addition, we will track patients' growing independence and educational and employment pathways during the transition process. Methods and analysis Bridge is an international, prospective, observational cohort study. Study participants are adolescents with a chronic health condition or disability and their parents/guardians who attended the New Children's Hospital in Helsinki, Finland, or the Royal Children's Hospital (RCH) in Melbourne, Australia. Baseline assessment took place approximately 6 months prior to the transfer of care and follow-up data will be collected 1 year and 2 years after the transfer of care. Data will be collected from patients' hospital records and from questionnaires completed by the patient and their parent/guardian at each time point. The primary outcomes of this study are adherence to medical appointments, clinical health status and HRQoL and costs of care. Secondary outcome measures are educational and employment outcomes. Ethics and dissemination The Ethics Committee for Women's and Children's Health and Psychiatry at the Helsinki University Hospital (HUS/1547/2017) and the RCH Human Research Ethics Committee (38035) have approved the Bridge study protocol. Results will be published in international peer-reviewed journals and summaries will be provided to the funders of the study as well as patients and their parents/guardians.
  • Eich, Torsten; Stahle, Magnus; Gustafsson, Bengt; Horneland, Rune; Lempinen, Marko; Lundgren, Torbjörn; Rafael, Ehab; Tufveson, Gunnar; von Zur-Mühlen, Bengt; Olerud, Johan; Scholz, Hanne; Korsgren, Olle (2018)
    Background: Effective digestive enzymes are crucial for successful islet isolation. Supplemental proteases are essential because they synergize with collagenase for effective pancreatic digestion. The activity of these enzymes is critically dependent on the presence of Ca2+ ions at a concentration of 5-10 mM. The present study aimed to determine the Ca2+ concentration during human islet isolation and to ascertain whether the addition of supplementary Ca2+ is required to maintain an optimal Ca2+ concentration during the various phases of the islet isolation process. Methods: Human islets were isolated according to standard methods and isolation parameters. Islet quality control and the number of isolations fulfilling standard transplantation criteria were evaluated. Ca2+ was determined by using standard clinical chemistry routines. Islet isolation was performed with or without addition of supplementary Ca2+ to reach a Ca2+ of 5 mM. Results: Ca2+ concentration was markedly reduced in bicarbonate-based buffers, especially if additional bicarbonate was used to adjust the pH as recommended by the Clinical Islet Transplantation Consortium. A major reduction in Ca2+ concentration was also observed during pancreatic enzyme perfusion, digestion, and harvest. Additional Ca2+ supplementation of media used for dissolving the enzymes and during digestion, perfusion, and harvest was necessary in order to obtain the concentration recommended for optimal enzyme activity and efficient liberation of a large number of islets from the human pancreas. Conclusions: Ca2+ is to a large extent consumed during clinical islet isolation, and in the absence of supplementation, the concentration fell below that recommended for optimal enzyme activity. Ca2+ supplementation of the media used during human pancreas digestion is necessary to maintain the concentration recommended for optimal enzyme activity. Addition of Ca2+ to the enzyme blend has been implemented in the standard isolation protocols in the Nordic Network for Clinical Islet Transplantation.
  • Hruskova, Zdenka; Pippias, Maria; Stel, Vianda S.; Abad-Diez, Jose M.; Sanchez, Manuel Benitez; Caskey, Fergus J.; Collart, Frederic; De Meester, Johan; Finne, Patrik; Heaf, James G.; Magaz, Angela; Palsson, Runolfur; Reisaeter, Anna Varberg; Salama, Alan D.; Segelmark, Mårten; Traynor, Jamie P.; Massy, Ziad A.; Jager, Kitty J.; Tesar, Vladimir (2019)
    Rationale & Objective: Data for outcomes of patients with end-stage renal disease (ESRD) secondary to systemic sclerosis (scleroderma) requiring renal replacement therapy (RRT) are limited. We examined the incidence and prevalence of ESRD due to scleroderma in Europe and the outcomes among these patients following initiation of RRT. Study Design: Registry study of incidence and prevalence and a matched cohort study of clinical outcomes. Setting & Participants: Patients represented in any of 19 renal registries that provided data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry between 2002 and 2013. Predictor: Scleroderma as the identified cause of ESRD. Outcomes: Incidence and prevalence of ESRD from scleroderma. Recovery from RRT dependence, patient survival after ESRD, and graft survival after kidney transplantation. Analytical Approach: Incidence and prevalence were calculated using population data from the European Union and standardized to population characteristics in 2005. Patient and graft survival were compared with 2 age- and sex-matched control groups without scleroderma: (1) diabetes mellitus as the cause of ESRD and (2) conditions other than diabetes mellitus as the cause of ESRD. Survival analyses were performed using Kaplan-Meier analysis and Cox regression. Results: 342 patients with scleroderma (0.14% of all incident RRT patients) were included. Between 2002 and 2013, the range of adjusted annual incidence and prevalence rates of RRT for ESRD due to scleroderma were 0.11 to 0.26 and 0.73 to 0.95 per million population, respectively. Recovery of independent kidney function was greatest in the scleroderma group (7.6% vs 0.7% in diabetes mellitus and 2.0% in other primary kidney diseases control group patients, both P Limitations: No data for extrarenal manifestations, treatment, or recurrence. Conclusions: Survival of patients with scleroderma who receive dialysis for more than 90 days was worse than for those with other causes of ESRD. Patient survival after transplantation was similar to that observed among patients with ESRD due to other conditions. Patients with scleroderma had a higher rate of recovery from RRT dependence than controls.
  • Karihtala, Kristiina; Leivonen, Suvi-Katri; Karjalainen-Lindsberg, Marja-Liisa; Chan, Fong Chun; Steidl, Christian; Pellinen, Teijo; Leppä, Sirpa (2022)
    Emerging evidence indicates a major impact for the tumor microenvironment (TME) and immune escape in the pathogenesis and clinical course of classical Hodgkin lymphoma (cHL). We used gene expression profiling (n = 88), CIBERSORT, and multiplex immunohistochemistry (n = 131) to characterize the immunoprofile of cHL TME and correlated the findings with survival. Gene expression analysis divided tumors into subgroups with T cell-inflamed and -noninflamed TME. Several macrophage-related genes were upregulated in samples with the non-T cell-inflamed TME, and based on the immune cell proportions, the samples clustered according to the content of T cells and macrophages. A cluster with high proportions of checkpoint protein (programmed cell death protein 1, PD-1 ligands, indoleamine 2,3 dioxygenase 1, lymphocyte-activation gene 3, and T-cell immunoglobulin and mucin domain containing protein 3) positive immune cells translated to unfavorable overall survival (OS) (5-year OS 76% vs 96%; P = .010) and remained an independent prognostic factor for OS in multivariable analysis (HR, 4.34; 95% CI, 1.05-17.91; P = .043). cHL samples with high proportions of checkpoint proteins overexpressed genes coding for cytolytic factors, proposing paradoxically that they were immunologically active. This checkpoint molecule gene signature translated to inferior survival in a validation cohort of 290 diagnostic cHL samples (P < .001) and in an expan-sion cohort of 84 cHL relapse samples (P = .048). Our findings demonstrate the impact of T cell-and macrophage-mediated checkpoint system on the survival of patients with cHL.
  • Pätilä , Tommi; Miyagawa, Shigeru; Imanishi, Yukiko; Fukushima, Satsuki; Siltanen, Antti; Mervaala, Eero; Kankuri, Esko; Harjula, Ari; Sawa, Yoshiki (2015)
    Although cell therapy of the failing heart by intramyocardial injections of myoblasts to results in regenerative benefit, it has also been associated with undesired and prospectively fatal arrhythmias. We hypothesized that intramyocardial injections of myoblasts could enhance inflammatory reactivity and facilitate electrical cardiac abnormalities that can be reduced by epicardial myoblast sheet delivery. In a rat model of ischemic heart failure, myoblast therapy either by intramyocardial injections or epicardial cell sheets was given 2 weeks after occlusion of the coronary artery. Ventricular premature contractions (VPCs) were assessed, using an implanted three-lead electrocardiograph at 1, 7, and 14 days after therapy, and 16-point epicardial electropotential mapping (EEPM) was used to evaluate ventricular arrhythmogenicity under isoproterenol stress. Cardiac functioning was assessed by echocardiography. Both transplantation groups showed therapeutic benefit over sham therapy. However, VPCs were more frequent in the Injection group on day 1 and day 14 after therapy than in animals receiving epicardial or sham therapy (p <0.05 and p <0.01, respectively). EEPM under isoproterenol stress showed macroreentry at the infarct border area, leading to ventricular tachycardias in the Injection group, but not in the myoblast sheet- or sham-treated groups (p = 0.045). Both transplantation types modified the myocardial cytokine expression profile. In animals receiving epicardial myoblast therapy, selective reductions in the expressions of interferon gamma, interleukin (IL)-1 beta and IL12 were observed, accompanied by reduced infiltration of inflammatory CD11b- and CD68-positive leukocytes, compared with animals receiving myoblasts as intramyocardial injections. Intramyocardial myoblast delivery was associated with enhanced inflammatory and immunomodulatory reactivity and increased frequency of VPCs. In comparison to intramyocardial injection, the epicardial route may serve as the preferred method of skeletal myoblast transplantation to treat heart failure.
  • Koenig, J.; Siebenhaar, A.; Hoegenauer, C.; Arkkila, P.; Nieuwdorp, M.; Noren, T.; Ponsioen, C. Y.; Rosien, U.; Rossen, N. G.; Satokari, R.; Stallmach, A.; de Vos, W.; Keller, J.; Brummer, R. J. (2017)
    Background Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication. Aim To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT. Methods Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors. Results Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings. Conclusions Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.
  • Braun, Oscar Ö.; Nilsson, Johan; Gustafsson, Finn; Dellgren, Göran; Fiane, Arnt E.; Lemström, Karl; Hubbert, Laila; Hellgren, Laila; Lund, Lars H. (2019)
    Objectives: The purpose of this study was to assess complications and mortality and its predictors, with continuous-flow left ventricular assist devices (CF-LVADs) in the Nordic Countries. Design: This was a retrospective, international, multicenter cohort study. Results: Between 1993 and 2013, 442 surgically implanted long-term mechanical assist devices were used among 8 centers in the Nordic countries. Of those, 238 were CF-LVADs (HVAD or HeartMate II) implanted in patients >18 years with complete data. Postoperative complications and survival were compared and Cox proportion hazard regression analysis was used to identify predictors of mortality. The overall Kaplan-Meier survival rate was 75% at 1 year, 69% at 2 years and 63% at 3 years. A planned strategy of destination therapy had poorer survival compared to a strategy of bridge to transplantation or decision (2-year survival of 41% vs. 76%, p <.001). The most common complications were non-driveline infections (excluding sepsis) (44%), driveline infection (27%), need for continuous renal replacement therapy (25%) and right heart failure (24%). In a multivariate model age and left ventricular diastolic dimension was left as independent risk factors for mortality with a hazard ratio of 1.35 (95% confidence interval (CI) [1.01-1.80], p = .046) per 10 years and 0.88 (95% CI [0.72-0.99], p = .044) per 5 mm, respectively. Conclusion: Outcome with CF LVAD in the Nordic countries was comparable to other cohorts. Higher age and destination therapy require particularly stringent selection.
  • Holster, S.; Repsilber, D.; Geng, D.; Hyotylainen, T.; Salonen, A.; Lindqvist, C. M.; Rajan, S. K.; de Vos, W. M.; Brummer, R. J.; König, J. (2021)
    Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.
  • Varmavuo, Ville; Silvennoinen, Raija; Anttila, Pekka; Saily, Marjaana; Sankelo, Marja; Putkonen, Mervi; Ahonen, Jouni; Mahlamaki, Eija; Mantymaa, Pentti; Savolainen, Eeva-Riitta; Remes, Kari; Jantunen, Esa (2016)
    Upfront autologous stem cell transplantation (ASCT) is the standard therapy for younger multiple myeloma (MM) patients. MM patients usually undergo stem cell mobilization with cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF), or with G-CSF alone. A limited number of randomized studies are available comparing costs of different mobilization strategies. Eighty transplant-eligible patients aged up to 70 years with untreated MM were included in this prospective study. The patients were treated with RVD induction for three 21-day cycles and randomized 1: 1 at inclusion into one of the two mobilization arms CY 2 g/m(2) + G-CSF [arm A] vs. G-CSF alone [arm B]. Plerixafor was given according to a specific algorithm if needed. Sixty-nine patients who received mobilization followed by blood graft collection were included in the cost analysis. The median total costs of the mobilization phase were significantly higher in arm A than in arm B (3855 (sic) vs. 772 (sic), p
  • Kantola, Taru; Mäklin, Suvi; Koivusalo, Anna-Maria; Räsänen, Pirjo; Rissanen, Anne; Roine, Risto; Sintonen, Harri; Höckerstedt, Krister; Isoniemi, Helena (2010)
  • Poganitsch-Korhonen, M.; Masliukaite, I.; Nurmio, M.; Lahteenmaki, P.; van Wely, M.; van Pelt, A. M. M.; Jahnukainen, K.; Stukenborg, J-B (2017)
  • Achiron, Asaf; Yahalomi, Tal; Hecht, Idan; Stanescu, Nir; Noy, Romi Achiron; Burgansky-Eliash, Zvia; Avizemer, Haggai; Tuuminen, Raimo; Spierer, Oriel (2022)
    Purpose. It is controversial whether donor-recipient sex mismatch is a risk factor associated with corneal graft failure. The purpose of this study was to investigate the effect of sex mismatch on corneal graft failure in high-risk and non-high-risk patients. Design. A retrospective study. Methods. The medical charts of patients who underwent corneal transplantations by one surgeon between 2012 and 2017 were reviewed. Patients were defined as high-risk for failure if they had glaucoma, ocular surface disease, or corneal vascularization. Graft failure rates were compared using the Kaplan-Meier survival curves between sex matched and mismatched subjects and between male-to-female grafting and other patients. Results. One hundred and thirteen patients with a minimum follow-up of 18 months were included. In 62 non-high-risk patients, graft failure rates were similar between the sex mismatched and the sex matched recipients (p=0.645, log-rank) and in male donor to female recipient transplantations and in the other transplantations (p=0.496, log-rank). Analysis of fifty-one eyes of 51 high-risk graft recipients (mean age of 73.4 +/- 12.7 years, N = 26 females) showed that graft failure rates were significantly higher in the sex mismatched than sex matched recipients (p=0.022, log-rank) and in male donor to female recipient transplantations than in the other transplantations (p=0.002, log-rank). Conclusions. Sex matching for every patient bares logistic difficulties; however, in patients who are at high-risk for graft failure, it may be a simple way to improve outcomes and better utilize corneal grafts.