Browsing by Subject "FAILURE"

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  • Tuohinen, Suvi Sirkku; Aula, Hanna; Skyttä, Tanja; Huhtala, Heini; Keski-Pukkila, Konsta; Nikus, Kjell; Virtanen, Vesa; Kellokumpu-Lehtinen, Pirkko-Liisa; Raatikainen, Pekka (2022)
    Background/Aim: Radiotherapy (RT) induces late changes in all cardiac structures. Most studies of early changes focus on individual parameters. Patients and Methods: Data from eighty early-stage breast cancer patients at baseline, post-RT and three-year follow-up visit were assessed prospectively. Changes in ten cardiac parameters were collected including electrocardiogram (ECG), echocardiography, and biomarkers. A percentage of abnormal changes was calculated. Results: The mean heart radiation dose (Dmean) was independently associated with the increased incidence of changes post-RT (?? =0.403, p
  • Drug-Induced Liver Injury Network; Int DILI Consortium iDILIC; Cirulli, Elizabeth T.; Nicoletti, Paola; Laitinen, Tarja (2019)
    BACKGROUND & AIMS: We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility. METHODS: We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry. We analyzed DNA from 113 Icelandic cases and 239,304 controls to validate our findings. RESULTS: We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that encodes a substitution of tryptophan with arginine in the protein tyrosine phosphatase, nonreceptor type 22 gene (PTPN22) (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.62; P = 1.2 x 10(-9) and replicated the finding in the validation set (OR 1.48; 95% CI 1.09-1.99; P =.01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32-1.98; P = 4.0 x 10(-6); allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21-1.56; P = 1.5 x 10(-6); allele frequency = 11.5%). Among amoxicillin-and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A* 02: 01 and DRB1* 15: 01. CONCLUSIONS: In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.
  • Koski, Tapio; Salmi, Heli; Keski-Nisula, Juho; Bille, Anders; Björnsson, Einar; Jessen, Casper; Forstholm, Ronnie; Lääperi, Mitja; Rautiainen, Paula (2022)
    Aim Early extubation after cardiac surgery shortens paediatric intensive care unit (PICU) length of stay (LOS) and decreases complications from mechanical ventilation (MV). We explored the duration of MV in Scandinavian paediatric heart centres. Methods We retrospectively reviewed the MV duration and PICU LOS of 696 children operated for atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy of Fallot (TOF) or total cavopulmonary connection (TCPC) in four Scandinavian centres in 2015-2016. Neonates (n = 90) were included regardless of heart surgery type. Results Patients with ASD were extubated at a median of 3.25 h (interquartile range [IQR] 2.00-4.83), followed by patients with TCPC (median 5.00 h, IQR 2.60-16.83), VSD (median 7.00 h, IQR 3.69-22.25) and TOF (median 18.08 h, IQR 6.00-41.38). Neonates were not extubated early (median 94.42 h, IQR 45.03-138.14). Although MV durations were reflected in PICU LOS, this was not as apparent among those extubated within 12 h. The Swedish centres had shortest MV durations and PICU LOS. Extubation failed in 24/696 (3.4%) of patients. Conclusion Scandinavian paediatric heart centres differed in the duration of postoperative MV. Deferring extubation up to 12 h postoperatively did not markedly prolong PICU LOS.
  • Wester, Tomas; Lilja, Helene Engstrand; Stenstrom, Pernilla; Pakarinen, Mikko (2017)
    Background. Serial transverse enteroplasty facilitates weaning from parenteral support in selected patients with short bowel syndrome, although repeated procedure is frequently required. Our aim was to evaluate the outcome of a series of patients after serial transverse enteroplasty and define predictors of repeated serial transverse enteroplasty and weaning off parenteral support. Methods. All children who underwent serial transverse enteroplasty at 4 Nordic pediatric surgery centers from 2004-2015 were included in this observational study. Data were collected from the patient records. The study was approved by the local ethics review boards. Results. Twenty-seven children with short bowel with initial median small bowel length of 26 cm (range, 10-100 cm) were included. Eleven patients had the ileocecal valve remaining. Serial transverse enteroplasty was performed at median age of 7.5 months (range, 0.9-224 months). Serial transverse enteroplasty made the small bowel 46% (0-233%) longer. Eleven patients (41 %) underwent a repeated serial transverse enteroplasty 12 months (1.0-72 months) later; 7 patients required additional operative procedures, but none were transplanted. At follow-up, 45.1 months (1.8-126 months) after the first serial transverse enteroplasty, 11 (41 %) patients needed parenteral support. The remaining 16 patients had been weaned off parenteral support. One patient had died. Absence of the ileocecal valve was the only factor, which predicted the need for a repeated serial transverse enteroplasty (odds ratio 16.7, 95 % confidence interval, 1.7-164.8, P =.007). No factor was identified predicting need for parenteral support at follow-up. Conclusion. A majority of children with short bowel syndrome can be weaned from parenteral support after serial transverse enteroplasty. The absence of the ileocecal valve predicts the need for a repeated serial transverse enteroplasty, which was required by 40% of the patients.
  • Vincenzi, Bruno; Napolitano, Andrea; Fiocco, Marta; Mir, Olivier; Rutkowski, Piotr; Blay, Jean-Yves; Reichardt, Peter; Joensuu, Heikki; Fumagalli, Elena; Gennatas, Spyridon; Hindi, Nadia; Nannini, Margherita; Ceruso, Mariella Spalato; Italiano, Antoine; Grignani, Giovanni; Brunello, Antonella; Gasperoni, Silvia; De Pas, Tommaso; Badalamenti, Giuseppe; Pantaleo, Maria A.; van Houdt, Winan J.; IJzerman, Nikki S.; Steeghs, Neeltje; Gelderblom, Hans; Desar, Ingrid M. E.; Falkenhorst, Johanna; Silletta, Marianna; Sbaraglia, Marta; Tonini, Giuseppe; Martin-Broto, Javier; Hohenberger, Peter; Le Cesne, Axel; Jones, Robin L.; Dei Tos, Angelo P.; Gronchi, Alessandro; Bauer, Sebastian; Casali, Paolo G. (2022)
    Purpose: The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9-mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopatho-logic variables with survival was evaluated in a large multi-institutional European cohort. Experimental Design: Data from 185 patients were retrospec-tively collected in 23 European GIST reference centers. Propen-sity score matching (PSM) and inverse-probability of treatment weighting (IPTW) were used to account for confounders. Uni-variate and multivariate unweighted and weighted Cox propor-tional hazard regression models were estimated for relapse-free survival (RFS), modified-RFS (mRFS) and imatinib failure-free survival (IFFS). Univariate Cox models were estimated for overall survival. Results: Of the 185 patients, 131 (70.8%) received a starting dose of 400 mg/d and the remaining 54 (29.2%) a dose of 800 mg/d. Baseline characteristics were partially unbalanced, suggesting a potential selection bias. PSM and IPTW analyses showed no advantage of imatinib 800 mg/d. In the weighted multivariate Cox models, high-dose imatinib was not associated with the survival outcomes [RFS: hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.79-1.94; mRFS: HR, 1.69; 95% CI, 0.92-3.10; IFFS: HR, 1.35; 95% CI, 0.79- 2.28]. The variables consistently associated with worse survival out-comes were high mitotic index and nongastric tumor location. Conclusions: In this retrospective series of patients with KIT exon 9-mutated GIST treated with adjuvant imatinib, a daily dose of 800 mg versus 400 mg did not show better results in terms of survival outcomes. Prospective evaluation of the more appropriate adjuvant treatment in this setting is warranted.
  • Penttila, Tero; Makynen, Heikki; Hartikainen, Juha; Hyppola, Harri; Lauri, Timo; Lehto, Mika; Lund, Juha; Raatikainen, M. J. Pekka; FinFib2 Investigators (2017)
    Background: Atrial fibrillation (AF) is a common arrhythmia that causes numerous visits to emergency departments (ED). The aim of the FinFib2 study was to evaluate whether treatment of patients with AF in ED is consistent with the contemporary European Society of Cardiology (ESC) management guidelines. Here we report the results of antiarrhythmic drug therapy (AAD) in ED. Methods: All patients within the two-week study period whose primary reason for the ED visit was symptomatic AF were included into this prospective multicentre study. Comprehensive data on factors contributing to the treatment of AF were collected, including a data of previous use of ADDs, and changes made for them during a visit in ED. Results: The study population consisted of 1013 consecutive patients (mean age 70 +/- 13 years, 47.6% female). The mean European Heart Rhythm Association (EHRA) symptom score was 2.2 +/- 0.8. Rhythm control strategy was opt for 498 (63.8%) and 140 (64.5%) patients with previously and newly diagnosed AF, respectively. In patients with previously diagnosed AF the most frequently used AAD was a beta blocker (80.9%). Prior use of class I (11.4%) and III (9.1%) AADs as well as start or adjustment of their dosage (7.4%) were uncommon. Most of the patients with newly diagnosed AF were prescribed a beta blocker (71.0%) or a calcium channel antagonist (24.0%), and only two of them received class I or class III AADs. Conclusions: Our data demonstrated that in patients presenting to the ED with recurrent symptomatic AF and aimed for rhythm control strategy, the use of class I and class III AADs was rare despite ESC guideline recommendations. It is possible that early adaptation of a more aggressive rhythm control strategy might improve a quality of life for symptomatic patients and alleviate the ED burden associated with AF. Beta blockers were used by majority of patients as rate control therapy both in rate and rhythm control groups.
  • Eriksson, M.; Reichardt, P.; Joensuu, H.; Krarup-Hansen, A.; Hagberg, O.; Hohenberger, P.; Hagberg, H.; Hansson, L.; Foukakis, T.; Pulkkanen, K.; Bauer, S.; Goplen, D.; Rossen, P. Blach; Hall, K. Sundby (2021)
    Background: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib. Patients and methods: Since all eligible patients had progressive disease, we preferred a non-randomized, phase II multicentre trial so that all patients could receive a potentially active drug. Patients had a progressive metastatic or locally advanced GIST and were >= 18 years of age, with a performance status of 0-2, and sufficient organ functions. The primary endpoint was disease control rate (defined as complete remission thorn partial remission thorn stable disease) at 12 weeks on pazopanib. A Simon's two-stage analysis was used with an interim analysis 12 weeks after enrollment of the first 22 patients, and if passed, there was a full enrolment of 72 patients. GIST mutational analysis was done, and most patients had pazopanib plasma concentration measured after 12 weeks. Results: Seventy-two patients were enrolled. The disease control rate after 12 weeks was 44%, and the median PFS was 19.6 weeks (95% confidence interval 12.6-23.4 weeks). Pazopanib-related toxicity was moderate and manageable. No statistically significant differences were found related to mutations. Plasma concentrations of pazopanib had a formal but weak correlation with outcome. Conclusion: Pazopanib given in the third line to patients with GIST progressing on both imatinib and sunitinib was beneficial for about half of the patients. The PAGIST trial confirms the results from the PAZOGIST trial, and the median PFS achieved seems comparable to the PFS achieved with regorafenib in the third-line setting.
  • Aro, Aapo Lauri Aleksi; Phan, Derek; Teodorescu, Carmen; Uy-Evanado, Audrey; Reinier, Kyndaron; Gunson, Karen; Jui, Jonathan; Huikuri, Heikki V.; Chugh, Sumeet S. (2017)
    Delayed QRS transition zone in the precordial leads of the 12-lead electrocardiogram (ECG) has been recently associated with increased risk of sudden cardiac death (SCD), but the underlying mechanisms are unknown. We correlated echocardiographic findings with ECG and clinical characteristics to investigate how alterations in cardiac structure and function contribute to this risk marker. From the ongoing population-based Oregon Sudden Unexpected Death Study (catchment population similar to 1 million), SCD cases with prior ECG available (n = 627) were compared with controls (n = 801). Subjects with delayed transition at V-5 or later were identified, and clinical and echocardiographic patterns associated with delayed transition were analysed. Delayed transition was present in 31% of the SCD cases and 17% of the controls. These subjects were older and more likely to have cardiovascular risk factors and history of myocardial infarction. Delayed transition was associated with increased left ventricular (LV) mass (122.7 +/- 40.2 vs. 102.9 +/- 33.7 g/m(2); P <0.001), larger LV diameter (53.3 +/- 10.4 vs. 49.2 +/- 8.0 mm; P <0.001), and lower LV ejection fraction (LVEF) (46.4 +/- 15.7 vs. 55.6 +/- 12.5%; P <0.001). In multivariate analysis, delayed transition was independently associated with myocardial infarction, reduced LVEF, and LV hypertrophy. The association between delayed transition and SCD was independent of the LVEF (OR 1.57; 95% CI 1.04-2.38; P = 0.032). The underpinnings of delayed QRS transition zone extend beyond previous myocardial infarction and reduced LVEF. Since the association with sudden death is independent of these factors, this novel marker of myocardial electrical remodelling should be explored as a potential risk predictor of SCD.
  • Raissadati, Alireza; Haukka, Jari; Pätilä, Tommi; Nieminen, Heta; Jokinen, Eero (2020)
    Background Postoperative morbidity is an increasingly important outcome measure of patients who have undergone congenital heart surgery (CHS). We examined late postoperative morbidity after CHS on the basis of patients' government-issued medical special reimbursement rights. Methods and Results Between 1953 and 2009, 10 635 patients underwent CHS at Conclusions Chronic cardiac and noncardiac sequelae are common after CHS regardless of the severity of the defect, underscoring the importance of long-term follow-up of all patients after CHS.
  • SICS Study Grp; Hiemstra, Bart; Eck, Ruben J.; Wiersema, Renske; Pettilä, Ville; van der Horst, Iwan C. C. (2019)
    Objectives: Caregivers use clinical examination to timely recognize deterioration of a patient, yet data on the prognostic value of clinical examination are inconsistent. In the Simple Intensive Care Studies-I, we evaluated the association of clinical examination findings with 90-day mortality in critically ill patients. Design: Prospective single-center cohort study. Setting: ICU of a single tertiary care level hospital between March 27, 2015, and July 22, 2017. Patients: All consecutive adults acutely admitted to the ICU and expected to stay for at least 24 hours. Interventions: A protocolized clinical examination of 19 clinical signs conducted within 24 hours of admission. Measurements Main Results: Independent predictors of 90-day mortality were identified using multivariable logistic regression analyses. Model performance was compared with established prognostic risk scores using area under the receiver operating characteristic curves. Robustness of our findings was tested by internal bootstrap validation and adjustment of the threshold for statistical significance. A total of 1,075 patients were included, of whom 298 patients (28%) had died at 90-day follow-up. Multivariable analyses adjusted for age and norepinephrine infusion rate demonstrated that the combination of higher respiratory rate, higher systolic blood pressure, lower central temperature, altered consciousness, and decreased urine output was independently associated with 90-day mortality (area under the receiver operating characteristic curves = 0.74; 95% CI, 0.71-0.78). Clinical examination had a similar discriminative value as compared with the Simplified Acute Physiology Score-II (area under the receiver operating characteristic curves = 0.76; 95% CI, 0.73-0.79; p = 0.29) and Acute Physiology and Chronic Health Evaluation-IV (using area under the receiver operating characteristic curves = 0.77; 95% CI, 0.74-0.80; p = 0.16) and was significantly better than the Sequential Organ Failure Assessment (using area under the receiver operating characteristic curves = 0.67; 95% CI, 0.64-0.71; p <0.001). Conclusions: Clinical examination has reasonable discriminative value for assessing 90-day mortality in acutely admitted ICU patients. In our study population, a single, protocolized clinical examination had similar prognostic abilities compared with the Simplified Acute Physiology Score-II and Acute Physiology and Chronic Health Evaluation-IV and outperformed the Sequential Organ Failure Assessment score.
  • Marttila, E.; Thoren, H.; Törnwall, J.; Viitikko, A.; Wilkman, T. (2018)
    The aim of this retrospective study was to analyse the incidence of complications and loss of flaps after primary reconstructions for oral cancer in 191 patients at our hospital over the five years 2005-2010. The patients' clinical and personal details, characteristics of the tumours, types of microvascular flap, complications, and outcomes were recorded. The soft tissue flaps used most often were the fasciocutaneous radial forearm free flap (RFFF) (n = 86, 45%) and the anterolateral thigh free flap (ALTFF) (n = 48, 25%) while the most commonly used osseous flap was the deep circumflex iliac artery flap (DCIA) (n = 25, 13%). There were postoperative complications that required intervention in a quarter of the patients, most often in the age group 41-50 years (p = 0.018). Older age was not associated with the development of complications. The overall survival of all free flaps was 181/191 (95%), and the only significant individual predictor of loss of a flap was reconstruction with a DCIA (p = 0.016), five of the 25 of which were lost. We conclude therefore that DCIA free flaps are associated with an increased risk of failure; the method of osseous reconstruction for maxillofacial reconstruction should be selected carefully; and carefully chosen older patients do not seem to be at increased risk of morbidity. (C) 2018 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
  • Huoponen, Saara; Aaltonen, Kalle J.; Viikinkoski, Jaana; Rutanen, Jarno; Relas, Heikki; Taimen, Kirsi; Puolakka, Kari; Nordström, Dan; Blom, Marja (2019)
    Objectives The objective of this study was to evaluate the cost-effectiveness of abatacept, tocilizumab, and tumor necrosis factor (TNF) inhibitors as compared with rituximab in Finnish rheumatoid arthritis patients, who have previously been treated with TNF inhibitors. Methods A patient-level simulation model was developed to predict costs and outcomes associated with four biological drugs (abatacept, tocilizumab, rituximab and TNF inhibitors) in the treatment of rheumatoid arthritis. Following lack of efficacy or adverse events, the patients were switched to another biological drug until all four options were exhausted. After that, the patients were assumed to receive a 6th line treatment until death. The patients' baseline characteristics and regression models used in the simulation were based on observational data from the National Register for Biological Treatments in Finland. Direct costs comprised drug costs, administration costs, costs of switching, and outpatient and inpatient care, while indirect costs included disability pension and sick leaves due to rheumatoid arthritis. Several subgroup and deterministic sensitivity analyses were conducted. Results Drug costs were the lowest for rituximab, but when administration costs and costs of switching were included, drug costs were the lowest for TNF inhibitors. Abatacept was associated with the highest drug costs, whereas rituximab was associated with the highest healthcare costs. In total, TNF inhibitors had the lowest direct costs, while rituximab had the highest direct costs. The amount of quality-adjusted life years (QALY) gained ranged from 9.405 for rituximab to 9.661 for TNF inhibitors. TNF inhibitors, abatacept, and tocilizumab were dominant in comparison to RTX. Conclusions TNF inhibitors, abatacept, and tocilizumab had lower costs and higher QALYs than rituximab, and therefore, they were dominant in comparison to rituximab. As TNF inhibitors had the lowest costs and highest QALYs, they were the most cost-effective treatment option.
  • Makela, Keijo T.; Matilainen, Markus; Pulkkinen, Pekka; Fenstad, Anne M.; Havelin, Leif I.; Engesaeter, Lars; Furnes, Ove; Overgaard, Soren; Pedersen, Alma B.; Kaerrholm, Johan; Malchau, Henrik; Garellick, Goeran; Ranstam, Jonas; Eskelinen, Antti (2014)
  • Pohjoismaki, Jaakko L. O.; Goffart, Steffi; Taylor, Robert W.; Turnbull, Douglas M.; Suomalainen, Anu; Jacobs, Howard T.; Karhunen, Pekka J. (2010)
  • Joensuu, Heikki; Blay, Jean-Yves; Comandone, Alessandro; Martin-Broto, Javier; Fumagalli, Elena; Grignani, Giovanni; Del Muro, Xavier Garcia; Adenis, Antoine; Valverde, Claudia; Pousa, Antonio Lopez; Olivier, Bouche; Italiano, Antoine; Bauer, Sebastian; Barone, Carlo; Weiss, Claudia; Crippa, Stefania; Camozzi, Maura; Castellana, Ramon; Le Cesne, Axel (2017)
    Background: This multicentre phase II trial (DOVIGIST) evaluated the antitumour activity of dovitinib as second-line treatment of patients with gastrointestinal stromal tumour (GIST) refractory to imatinib or who do not tolerate imatinib. Methods: Patients received oral dovitinib 500 mg day(-1), 5 days on/2 days off, until GIST progression or unacceptable toxicity, with an objective to evaluate efficacy, assessed as the disease control rate (DCR) at 12 weeks. Tumour assessment and response to dovitinib therapy were evaluated by Response Evaluation Criteria In Solid Tumours (RECIST v1.1) and the Choi criteria. Secondary objectives included assessment of progression-free survival (PFS), safety and tolerability, and DCR at the end of treatment. Results: Thirty-eight of the 39 patients enrolled had histologically confirmed GIST. The DCR at 12 weeks was 52.6% (90% confidence interval (CI), 38.2-66.7%) meeting the preset efficacy criterion for the primary end point. The objective response rate (complete response+partial response) was 2.6% (1 of 38; 90% CI, 0.1-11.9%), and 5.3% (n = 2; 90% CI, 0.9-15.7%) at the end of the study. The median PFS was 4.6 months (90% CI, 2.8-7.4 months). Dose interruption was required in 26 patients (66.7%), of which 18 (69.2%) were due to adverse events. The most frequently observed grade 3 adverse events included hypertension (n = 7), fatigue (n = 5), vomiting (n = 4), hypertriglyceridaemia (n = 4), and gamma-glutamyltransferase increase (n = 4). Conclusions: Dovitinib is an active treatment for patients with GIST who are intolerant to imatinib or whose GIST progresses on imatinib.
  • Björkman, P.; Weselius, E. -M.; Kokkonen, T.; Rauta, V.; Alback, A.; Venermo, M. (2019)
    Background and Aims: Stenosis due to intimal hyperplasia and restenosis after initially successful percutaneous angioplasty are common reasons for failing arteriovenous fistulas. The aim of this study was to evaluate the effect of drug-coated balloons in the treatment of arteriovenous fistula stenosis. Design: Single-center, parallel group, randomized controlled trial. Block randomized by sealed envelope 1:1. Materials and Methods: A total of 39 patients with primary or recurrent stenosis in a failing native arteriovenous fistulas were randomized to drug-coated balloon (n=19) or standard balloon angioplasty (n=20). Follow-up was 1year. Primary outcome measure was target lesion revascularization. Results: In all, 36 stenoses were analyzed; three patients were excluded due to technical failure after randomization. A total of 88.9% (16/18) in the drug-coated balloon group was revascularized or occluded within 1year, compared to 22.2% (4/18) of the stenoses in the balloon angioplasty group (relative risk for drug-coated balloon 7.09). Mean time-to- target lesion revascularization was 110 and 193days after the drug-coated balloon and balloon angioplasty, respectively (p=0.06). Conclusions: With 1-year follow-up, the target lesion revascularization-free survival after drug-coated balloon-treatment was clearly worse. The reason for this remains unknown, but it may be due to differences in the biological response to paclitaxel in the venous arteriovenous fistula-wall compared to its antiproliferative effect in the arterial wall after drug-coated balloon treatment of atherosclerotic occlusive lesions. Trial registration: ClinicalTrials.gov NCT03036241
  • Chan, Juliana C. N.; Paldanius, Päivi M.; Mathieu, Chantal; Stumvoll, Michael; Matthews, David R.; Del Prato, Stefano (2021)
    We analysed glycaemic durability (sustained glycaemic control) with early combination therapy (metformin plus vildagliptin) versus metformin monotherapy, among patients with type 2 diabetes diagnosed before (young-onset [YOD]) and after (late-onset [LOD]) the age of 40 years, enrolled in the VERIFY trial. The primary endpoint was time to initial treatment failure (TF), defined as HbA1c of 7.0% or higher at two consecutive scheduled visits after randomization. The time to secondary TF was assessed when both groups were receiving and failing on the combination. A total of 186 (9.3%) patients had YOD and 1815 (90.7%) had LOD with a mean age difference of 20.4 years. Compared with metformin monotherapy, early combination reduced the risk of time to initial TF for both YOD (48%,P<.0006) and LOD (46%,P<.0001). With early combination, risk for time to secondary TF was reduced by 48% (P<.0035) in YOD and 24% (P<.0009) in LOD. Both treatment approaches were well tolerated with no unexpected safety concerns. In treatment-naive patients with YOD (HbA1c 6.5%-7.5%), an early combination strategy improved attainment of the glycaemic target with durability and delayed treatment escalation compared with initial metformin monotherapy.
  • Törmänen, Suvi; Pörsti, Ilkka; Lakkisto, Päivi; Tikkanen, Ilkka; Niemelä, Onni; Paavonen, Timo; Mustonen, Jukka; Eräranta, Arttu (2017)
    Background: We studied whether endothelin receptor antagonist and calcimimetic treatments influence renal damage and kidney renin-angiotensin (RA) components in adenine-induced chronic renal insufficiency (CRI). Methods: Male Wistar rats (n = 80) were divided into 5 groups for 12 weeks: control (n = 12), 0.3% adenine (Ade; n = 20), Ade + 50 mg/kg/day sitaxentan (n = 16), Ade + 20 mg/kg/day cinacalcet (n = 16), and Ade + sitaxentan + cinacalcet (n = 16). Blood pressure (BP) was measured using tail-cuff, kidney histology was examined, and RA components measured using RT-qPCR. Results: Adenine caused tubulointerstitial damage with severe CRI, anemia, hyperphosphatemia, 1.8-fold increase in urinary calcium excretion, and 3.5-fold and 18-fold increases in plasma creatinine and PTH, respectively. Sitaxentan alleviated tubular atrophy, while sitaxentan + cinacalcet combination reduced interstitial inflammation, tubular dilatation and atrophy in adenine-rats. Adenine diet did not influence kidney angiotensin converting enzyme (ACE) and AT(4) receptor mRNA, but reduced mRNA of renin, AT(1a), AT(2), (pro) renin receptor and Mas to 40-60%, and suppressed ACE2 to 6% of that in controls. Sitaxentan reduced BP by 8 mmHg, creatinine, urea, and phosphate concentrations by 16-24%, and PTH by 42%. Cinacalcet did not influence BP or creatinine, but reduced PTH by 84%, and increased hemoglobin by 28% in adenine-rats. The treatments further reduced renin mRNA by 40%, while combined treatment normalized plasma PTH, urinary calcium, and increased ACE2 mRNA 2.5-fold versus the Ade group (p <0.001). Conclusions: In adenine-induced interstitial nephritis, sitaxentan improved renal function and tubular atrophy. Sitaxentan and cinacalcet reduced kidney renin mRNA by 40%, while their combination alleviated tubulointerstitial damage and urinary calcium loss, and increased kidney tissue ACE2 mRNA.
  • Nummi, Annu; Pätilä, Tommi; Mulari, Severi; Lampinen, Milla; Nieminen, Tuomo; Mäyränpää, Mikko; Vento, Antti; Harjula, Ari; Kankuri, Esko (2022)
    Objectives. Several approaches devised for clinical utilization of cell-based therapies for heart failure often suffer from complex and lengthy preparation stages. Epicardial delivery of autologous atrial appendage micrografts (AAMs) with a clinically used extracellular matrix (ECM) patch provides a straightforward therapy alternative. We evaluated the operative feasibility and the effect of micrografts on the patch-induced epicardial foreign body inflammatory response in a porcine model of myocardial infarction. Design. Right atrial appendages were harvested and mechanically processed into AAMs. The left anterior descending coronary artery was ligated to generate acute infarction. Patches of ECM matrix with or without AAMs were transplanted epicardially onto the infarcted area. Four pigs received the ECM and four received the AAMs patch. Cardiac function was studied by echocardiography both preoperatively and at 3-week follow-up. The primary outcome measures were safety and feasibility of the therapy administration, and the secondary outcome was the inflammatory response to ECM. Results. Neither AAMs nor ECM patch-related complications were detected during the follow-up time. AAMs patch preparation was feasible according to time and safety. Inflammation was greatly reduced in AAMs when compared with ECM patches as measured by the amount of infiltrated inflammatory cells and area of inflammation. Immunohistochemistry demonstrated an increased CD3+ cell density in the AAMs patch infiltrate. Conclusions. Epicardial AAMs transplantation demonstrated safety and clinical feasibility. The use of micrografts significantly inhibited ECM-induced foreign body inflammatory reactivity. Transplantation of AAMs shows good clinical applicability as adjuvant therapy to cardiac surgery and can suppress acute inflammatory reactivity.
  • Rentola, Raisa R.; Skrifvars, Markus B.; Heinonen, Erkki; Häggblom, Tom; Hästbacka, Johanna (2020)
    Background Controlling arterial carbon dioxide is paramount in mechanically ventilated patients, and an accurate and continuous noninvasive monitoring method would optimize management in dynamic situations. In this study, we validated and further refined formulas for estimating partial pressure of carbon dioxide with respiratory gas and pulse oximetry data in mechanically ventilated cardiac arrest patients. Methods A total of 4741 data sets were collected retrospectively from 233 resuscitated patients undergoing therapeutic hypothermia. The original formula used to analyze the data is PaCO2-est1 = PETCO2 + k[(PIO2 - PETCO2) - PaO2]. To achieve better accuracy, we further modified the formula to PaCO2-est2 = k(1)*PETCO2 + k(2)*(PIO2 - PETCO2) + k(3)*(100-SpO(2)). The coefficients were determined by identifying the minimal difference between the measured and calculated arterial carbon dioxide values in a development set. The accuracy of these two methods was compared with the estimation of the partial pressure of carbon dioxide using end-tidal carbon dioxide. Results With PaCO2-est1, the mean difference between the partial pressure of carbon dioxide, and the estimated carbon dioxide was 0.08 kPa (SE +/- 0.003); with PaCO2-est2 the difference was 0.036 kPa (SE +/- 0.009). The mean difference between the partial pressure of carbon dioxide and end-tidal carbon dioxide was 0.72 kPa (SE +/- 0.01). In a mixed linear model, there was a significant difference between the estimation using end-tidal carbon dioxide and PaCO2-est1 (P <.001) and PaCO2-est2 (P <.001) respectively. Conclusions This novel formula appears to provide an accurate, continuous, and noninvasive estimation of arterial carbon dioxide.