Browsing by Subject "REPAIR"

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  • Aho, Joonas; Helenius, Mikko; Vattulainen-Collanus, Sanna; Alastalo, Tero-Pekka; Koskenvuo, Juha (2016)
    Cell damage can lead to rapid release of ATP to extracellular space resulting in dramatic change in local ATP concentration. Evolutionary, this has been considered as a danger signal leading to adaptive responses in adjacent cells. Our aim was to demonstrate that elevated extracellular ATP or inhibition of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1/CD39) activity could be used to increase tolerance against DNA-damaging conditions. Human endothelial cells, with increased extracellular ATP concentration in cell proximity, were more resistant to irradiation or chemically induced DNA damage evaluated with the DNA damage markers gamma H2AX and phosphorylated p53. In our rat models of DNA damage, inhibiting CD39-driven ATP hydrolysis with POM-1 protected the heart and lung tissues against chemically induced DNA damage. Interestingly, the phenomenon could not be replicated in cancer cells. Our results show that transient increase in extracellular ATP can promote resistance to DNA damage.
  • Nietosvaara, Yrjana; Grahn, Petra; Sommarhem, Antti (2019)
  • Kiiski, Johanna; Fagerholm, Rainer; Tervasmaki, Anna; Pelttari, Liisa M.; Khan, Sofia; Jamshidi, Maral; Mantere, Tuomo; Pylkas, Katri; Bartek, Jiri; Bartkova, Jirina; Mannermaa, Arto; Tengstrom, Maria; Kosma, Veli-Matti; Winqvist, Robert; Kallioniemi, Anne; Aittomäki, Kristiina; Blomqvist, Carl; Nevanlinna, Heli (2016)
    Breast cancer (BC) is a heterogeneous disease, and different tumor characteristics and genetic variation may affect the clinical outcome. The FANCM c.5101C> T nonsense mutation in the Finnish population associates with increased risk of breast cancer, especially for triple-negative breast cancer patients. To investigate the association of the mutation with disease prognosis, we studied tumor phenotype, treatment outcome, and patient survival in 3,933 invasive breast cancer patients, including 101 FANCM c.5101C> T mutation carriers and 3,832 non-carriers. We also examined association of the mutation with nuclear immunohistochemical staining of DNA repair markers in 1,240 breast tumors. The FANCM c.5101C>T mutation associated with poor 10-year breast cancer-specific survival (hazard ratio (HR) 51.66, 95% confidence interval (CI) 1.09-2.52, p=0.018), with a more pronounced survival effect among familial cases (HR=2.93, 95% CI 1.5-5.76, p=1.80 x 10 23). Poor disease outcome of the carriers was also found among the estrogen receptor (ER) positive subgroup of patients (HR=1.8, 95% CI 1.09-2.98, p=0.021). Reduced survival was seen especially among patients who had not received radiotherapy (HR=3.43, 95% CI 1.6-7.34, p=1.50x10(-3)) but not among radiotherapy treated patients (HR=1.35, 95% CI 0.82-2.23, p=0.237). Significant interaction was found between the mutation and radiotherapy (p=0.040). Immunohistochemical analyses show that c.5101C> T carriers have reduced PAR-activity. Our results suggest that FANCM c.5101C>T nonsense mutation carriers have a reduced breast cancer survival but postoperative radiotherapy may diminish this survival disadvantage.
  • Laine, Matti T.; Bjoerck, Martin; Beiles, C. Barry; Szeberin, Zoltan; Thomson, Ian; Altreuther, Martin; Debus, E. Sebastian; Mani, Kevin; Menyhei, Gabor; Venermo, Maarit (2017)
    Objective: This study investigated the diameter of internal iliac artery (IIA) aneurysms (IIAAs) at the time of rupture to evaluate whether the current threshold diameter for elective repair of 3 cmis reasonable. The prevalence of concomitant aneurysms and results of surgical treatment were also investigated. Methods: This was a retrospective analysis of patients with ruptured IIAA from seven countries. The patients were collected from vascular registries and patient records of 28 vascular centers. Computed tomography images taken at the time of rupture were analyzed, and maximal diameters of the ruptured IIA and other aortoiliac arteries were measured. Data on the type of surgical treatment, mortality at 30 days, and follow-up were collected. Results: Sixty-three patients (55 men and 8 women) were identified, operated on from 2002 to 2015. The patients were a mean age of 76.6 years (standard deviation, 9.0; range 48-93 years). A concomitant common iliac artery aneurysm was present in 65.0%, 41.7% had a concomitant abdominal aortic aneurysm, and 36.7% had both. IIAA was isolated in 30.0%. The mean maximal diameter of the ruptured artery was 68.4mm(standard deviation, 20.5 mm; median, 67.0 mm; range, 25-116 mm). One rupture occurred at <3 cm and four at <4 cm (6.3% of all ruptures). All patients were treated, 73.0% by open repair and 27.0% by endovascular repair. The 30-day mortality was 12.7%. Median follow-up was 18.3 months (interquartile range, 2.0-48.3 months). The 1-year Kaplan-Meier estimate for survival was 74.5% (standard error, 5.7%). Conclusions: IIAA is an uncommon condition and mostly coexists with other aortoiliac aneurysms. Follow-up until a diameter of 4 cm seems justified, at least in elderly men, although lack of surveillance data precludes firm conclusions. The mortality was low compared with previously published figures and lower than mortality in patients with ruptured abdominal aortic aneurysm.
  • Chang, Hae Ryung; Cho, Sung Yoon; Lee, Jae Hoon; Lee, Eunkyung; Seo, Jieun; Lee, Hye Ran; Cavalcanti, Denise P.; Mäkitie, Outi; Valta, Helena; Girisha, Katta M.; Lee, Chung; Neethukrishna, Kausthubham; Bhavani, Gandham S.; Shukla, Anju; Nampoothiri, Sheela; Phadkei, Shubha R.; Park, Mi Jung; Ikegawa, Shiro; Wang, Zheng; Higgs, Martin R.; Stewart, Grant S.; Jung, Eunyoung; Lee, Myeong-Sok; Park, Jong Hoon; Lee, Eun A.; Kim, Hongtae; Myung, Kyungjae; Jeon, Woosung; Lee, Kyoungyeul; Kim, Dongsup; Kim, Ok-Hwa; Choi, Murim; Lee, Han-Woong; Kim, Yonghwan; Cho, Tae-Joon (2019)
    SPONASTRIME dysplasia is a rare, recessive skeletal dysplasia characterized by short stature, facial dysmorphism, and aberrant radiographic findings of the spine and long bone metaphysis. No causative genetic alterations for SPONASTRIME dysplasia have yet been determined. Using whole-exome sequencing (WES), we identified bi-allelic TONSL mutations in 10 of 13 individuals with SPONASTRIME dysplasia. TONSL is a multi-domain scaffold protein that interacts with DNA replication and repair factors and which plays critical roles in resistance to replication stress and the maintenance of genome integrity. We show here that cellular defects in dermal fibroblasts from affected individuals are complemented by the expression of wild-type TONSL. In addition, in vitro cell-based as-says and in silico analyses of TONSL structure support the pathogenicity of those TONSL variants. Intriguingly, a knock-in (KI) Tonsl mouse model leads to embryonic lethality, implying the physiological importance of TONSL. Overall, these findings indicate that genetic variants resulting in reduced function of TONSL cause SPONASTRIME dysplasia and highlight the importance of TONSL in embryonic development and postnatal growth.
  • Nikunen, Matti; Rajantie, Hanna; Marttila, Emilia; Snäll, Johanna (2021)
    The aim of the study was to assess factors leading to revision surgery and implant position of primary orbital fracture reconstructions. A retrospective cohort included patients who underwent orbital floor and/or medial wall fracture reconstruction for recent trauma. Demographics, fracture type, surgery and implant-related variables, and postoperative implant position were analyzed. The overall revision surgery rate was 6.5% (15 of 232 surgeries). The rate was highest in combined midfacial fractures with rim involvement (14.0%), lower in zygomatico-orbital fractures (8.7%), and lowest in isolated blowout fractures (3.8%). Fracture type, orbital rim fixation and implant malposition predicted revision. The best positioning was achieved with patient-specific milled titanium implants (mtPSI) and resorbable materials, whereas the poorest with preformed three-dimensional titanium plates. Combined midfacial fractures with rim involvement in particular have a high risk for orbital revision surgery. Within the limitations of the present study, mtPSIs should be preferred in the reconstruction of primary orbital fractures if possible. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery.
  • Puhakka, Jani; Afara, Isaac O.; Paatela, Teemu; Sormaala, Markus J.; Timonen, Matti A.; Viren, Tuomas; Jurvelin, Jukka S.; Toyras, Juha; Kiviranta, Ilkka (2016)
    Objective. Accurate arthroscopic evaluation of cartilage lesions could significantly improve the outcome of repair surgery. In this study, we investigated for the first time the potential of intra-articular ultrasound as an arthroscopic tool for grading cartilage defects in the human shoulder joint in vivo and compared the outcome to results from arthroscopic evaluation and magnetic resonance imaging findings. Design. A total of 26 sites from 9 patients undergoing routine shoulder arthroscopy were quantitatively evaluated with a clinical intravascular (40MHz) ultrasound imaging system, using the regular arthroscopy portals. Reflection coefficient (R), integrated reflection coefficient (IRC), apparent integrated backscattering (AIB), and ultrasound roughness index (URI) were calculated, and high-resolution ultrasound images were obtained per site. Each site was visually graded according to the International Cartilage Repair Society (ICRS) system. "Ultrasound scores" corresponding to the ICRS system were determined from the ultrasound images. Magnetic resonance imaging was conducted and cartilage integrity at each site was classified into 5 grades (0 = normal, 4 = severely abnormal) by a radiologist. Results. R and IRC were lower at sites with damaged cartilage surface (P = 0.033 and P = 0.043, respectively) and correlated with arthroscopic ICRS grades (r (s) = -0.444, P = 0.023 and r (s) = -0.426, P = 0.03, respectively). Arthroscopic ICRS grades and ultrasound scores were significantly correlated (rs = 0.472, P = 0.015), but no significant correlation was found between magnetic resonance imaging data and other parameters. Conclusion. The results suggest that ultrasound arthroscopy could facilitate quantitative clinical appraisal of articular cartilage integrity in the shoulder joint and provide information on cartilage lesion depth and severity for quantitative diagnostics in surgery.
  • Lagus, Heli; Kankuri, Esko; Nuutila, Kristo; Juteau, Susanna; Sarlomo-Rikala, Maarit; Vuola, Jyrki (2018)
    Cellular grafts used for skin repair require rapid integration with the host tissue to remain viable and especially to nourish the epidermal cells. Here, we evaluated the responses in the split-thickness skin grafts (STSGs) grafted on three differently treated wound beds: directly on excised wound bed (EX), on an artificial dermal template (DT) and on granulation tissue (GT) induced by cellulose sponge. In ten burn patients, after excision, a test area was divided into three sections: One transplanted with STSG instantaneously and two sections had a pre-treatment for 2 weeks with either DT or a cellulose sponge inducing granulation tissue formation and thereafter grafted with STSGs. One week after grafting, the STSGs on GT demonstrated most endothelial CD31(+) staining, largest average vessel diameters as well as most CD163(+) staining of M2-like macrophages and most MIB1(+) proliferating epidermal cells, suggesting an active regenerative environment. STSGs on DT had smallest vessel diameters and the least CD163(+) macrophages. STSGs on EX had the least CD31(+) cells and the least MIB1(+) proliferating cells. After 3 months, this reactivity in STSGs had subsided, except increased dermal cell proliferation was observed in STSGs on EX. Results show that pre-treatment of wound bed and induction of granulation tissue formation can accelerate host-graft interaction by stimulating graft vasculature and inducing cell proliferation.
  • Ahonen-Siirtola, Mirella; Nevala, Terhi; Vironen, Jaana; Kössi, Jyrki; Pinta, Tarja; Niemeläinen, Susanna; Keränen, Ulla; Ward, Jaana; Vento, Pälvi; Karvonen, Jukka; Ohtonen, Pasi; Mäkelä, Jyrki; Rautio, Tero (2020)
    Purpose Laparoscopic incisional ventral hernia repair (LIVHR) is often followed by seroma formation, bulging and failure to restore abdominal wall function. These outcomes are risk factors for hernia recurrence, chronic pain and poor quality of life (QoL). We aimed to evaluate whether LIVHR combined with defect closure (hybrid) follows as a diminished seroma formation and thereby has a lower rate of hernia recurrence and chronic pain compared to standard LIVHR. Methods This study is a multicentre randomised controlled clinical trial. From November 2012 to May 2015, 193 patients undergoing LIVHR for primary incisional hernia with fascial defect size from 2 to 7 cm were recruited in 11 Finnish hospitals. Patients were randomised to either a laparoscopic (LG) or a hybrid (HG) repair group. The main outcome measure was hernia recurrence, evaluated clinically and radiologically at a 1-year follow-up visit. At the same time, chronic pain scores and QoL were also measured. Results At the 1-year-control visit, we found no difference in hernia recurrence between the study groups. Altogether, 11 recurrent hernias were found in ultrasound examination, producing a recurrence rate of 6.4%. Of these recurrences, 6 (6.7%) were in the LG group and 5 (6.1%) were in the HG group (p > 0.90). The visual analogue scores for pain were low in both groups; the mean visual analogue scale (VAS) was 1.5 in LG and 1.4 in HG (p = 0.50). QoL improved significantly comparing preoperative status to 1 year after operation in both groups since the bodily pain score increased by 7.8 points (p <0.001) and physical functioning by 4.3 points (p = 0.014). Conclusion Long-term follow-up is needed to demonstrate the potential advantage of a hybrid operation with fascial defect closure. Both techniques had low hernia recurrence rates 1 year after operation. LIVHR reduces chronic pain and physical impairment and improves QoL. Trial Registry: Clinical trial number NCT02542085.
  • Ahonen-Siirtola, M.; Nevala, T.; Vironen, J.; Kössi, J.; Pinta, T.; Niemeläinen, S.; Keränen, U.; Ward, J.; Vento, P.; Karvonen, J.; Ohtonen, P.; Mäkelä, J.; Rautio, T. (2018)
    PurposeThe seroma rate following laparoscopic incisional ventral hernia repair (LIVHR) is up to 78%. LIVHR is connected to a relatively rare but dangerous complication, enterotomy, especially in cases with complex adhesiolysis. Closure of the fascial defect and extirpation of the hernia sack may reduce the risk of seromas and other hernia-site events. Our aim was to evaluate whether hybrid operation has a lower rate of the early complications compared to the standard LIVHR.MethodsThis is a multicenter randomized-controlled clinical trial. From November 2012 to May 2015, 193 patients undergoing LIVHR for primary incisional hernia with fascial defect size from 2 to 7cm were recruited in 11 Finnish hospitals. Patients were randomized to either a laparoscopic (LG) or to a hybrid (HG) repair group. The outcome measures were the incidence of clinically and radiologically detected seromas and their extent 1month after surgery, peri/postoperative complications, and pain.ResultsBulging was observed by clinical evaluation in 46 (49%) LG patients and in 27 (31%) HG patients (p=0.022). Ultrasound examination detected more seromas (67 vs. 45%, p=0.004) and larger seromas (471 vs. 112cm(3), p=0.025) after LG than after HG. In LG, there were 5 (5.3%) enterotomies compared to 1 (1.1%) in HG (p=0.108). Adhesiolysis was more complex in LG than in HG (26.6 vs. 13.3%, p=0.028). Patients in HG had higher pain scores on the first postoperative day (VAS 5.2 vs. 4.3, p=0.019).ConclusionClosure of the fascial defect and extirpation of the hernia sack reduce seroma formation. In hybrid operations, the risk of enterotomy seems to be lower than in laparoscopic repair, which should be considered in cases with complex adhesions.Clinical trial numberNCT02542085.
  • Jormalainen, Mikko; Raivio, Peter; Biancari, Fausto; Mustonen, Caius; Honkanen, Hannu-Pekka; Venermo, Maarit; Vento, Antti; Juvonen, Tatu (2020)
    The aim of this study was to evaluate all-cause mortality and aortic reoperations after surgery for Stanford type A aortic dissection (TAAD). We evaluated the late outcome of patients who underwent surgery for acute TAAD from January 2005 to December 2017 at the Helsinki University Hospital, Finland. We studied 309 patients (DeBakey type I TAAD: 89.3%) who underwent repair of TAAD. Aortic root repair was performed in 94 patients (30.4%), hemiarch repair in 264 patients (85.4%) and partial/total aortic arch repair in 32 patients (10.4%). Hospital mortality was 13.6%. At 10 years, all-cause mortality was 34.9%, and the cumulative incidence of aortic reoperation or late aortic-related death was 15.6%, of any aortic reoperation 14.6%, reoperation on the aortic root 6.6%, on the aortic arch, descending thoracic and/or abdominal aorta 8.7%, on the descending thoracic and/or abdominal aorta 6.4%, and on the abdominal aorta 3.8%. At 10 years, cumulative incidence of reoperation on the distal aorta was higher in patients with a diameter of the descending thoracic aorta >= 35 mm at primary surgery (cumulative incidence in the overall series: 13.2% vs. 4.0%, SHR 3.993, 95%CI 1.316-12.120; DeBakey type I aortic dissection: 13.6% vs. 4.5%, SHR 3.610, 95%CI 1.193-10.913; patients with dissected descending thoracic aorta: 15.8% vs. 5.9%, SHR 3.211, 95%CI 1.067-9.664). In conclusion, surgical repair of TAAD limited to the aortic segments involved by the intimal tear was associated with favorable survival and a low rate of aortic reoperations. However, patients with enlarged descending thoracic aorta at primary surgery had higher risk of late reoperation. Half of the distal aortic reinterventions were performed on the abdominal aorta.
  • Kyrklund, Kristiina; Pakarinen, Mikko P.; Rintala, Risto J. (2017)
    Anorectal malformations are an important group of congenital anomalies that vary widely in their anatomical characteristics and complexity. Understanding the long-term functional outcomes after modern treatments, and how these compare to the general population, are essential for ensuring that patients receive optimal, evidence-based care. With increasing appreciation of the wider impact of the illness on patients and their families, minimizing social disability from fecal incontinence and enabling normal social integration from the outset are key management concerns. This review summarizes the current knowledge on the functional outcomes by type of malformation, reflecting on the literature, and our institutional experience over a follow-up period of nearly 30 years. (C) 2017 Elsevier Inc. All rights reserved.
  • Koivusalo, Antti I.; Sistonen, Saara J.; Lindahl, Harry G.; Rintala, Risto J.; Pakarinen, Mikko P. (2017)
    Purpose: Because of an extended gap between esophageal pouches a variety of methods are employed to treat oesophageal atresia (OA) without (type A) or with (type B) proximal tracheooesophageal fistula. This retrospective observational study describes their single centre long-term outcomes from 1947 to 2014. Methods: Of 693 patients treated for OA 68 (9.7%) had type A (n = 58, 8.3%) or B (n = 10, 1.4%). Hospital records were reviewed. Main outcome measures were survival and oral intake. Results: Nine (13%) patients had early and 10 (15%) delayed primary anastomosis, 30 (44%) underwent reconstruction including colonic interposition (n = 13), reversed gastric tube (n = 11) and jejunum interposition (n = 6), whereas19 (28%) had died without a definite repair. Median follow up was 35 (interquartile range, 7.4-40) years. Thirty-one (63%) of 49 patients with definitive repair survived long term. Survival was 22% for early and 80% for delayed primary anastomosis, 57% for colon interposition, 82% for gastric tube and 84% for jejunum interposition. Gastrooesophageal reflux was most common after gastric tube (80%), dysphagia after colon interposition (50%), and 3 (60%) of 5 survivors with jejunum interposition had permanent feeding ostomy because of neurological disorder. Endoscopic follow-up disclosed no oesophageal cancer or dysplasia. Repair in the most recent patients from 1985 to 2014 (n = 14) included delayed primary anastomosis (n = 7), jejunum interposition (n = 6) and gastric tube (n = 1) with 93% long-term survival. Conclusion: Morbidity among long-term survivors of type A or B OA is high. With modern management survival is, however, excellent and patients without neurological disorder achieve full oral intake either after primary anastomosis or reconstruction. (C) 2017 Elsevier Inc. All rights reserved.
  • Landry, M. R.; DuRoss, A. N.; Neufeld, M. J.; Hahn, L.; Sahay, G.; Luxenhofer, R.; Sun, C. (2020)
    Multimodal therapy is often used in oncology to overcome dosing limitations and chemoresistance. Recently, combination immunoradiotherapy has shown great promise in a select subset of patients with colorectal cancer (CRC). Furthermore, molecularly targeted agents delivered in tandem with immunotherapy regimens have been suggested to improve treatment outcomes and expand the population of responding patients. In this study, radiation-sensitizing small molecules niraparib (PARP inhibitor) and HS-173 (PI3K inhibitor) are identified as a novel combination that synergistically enhance toxicity and induce immunogenic cell death both in vitro and in vivo in a CRC model. These inhibitors were co-encapsulated in a polymer micelle to overcome solubility limitations while minimizing off-target toxicity. Mice bearing syngeneic colorectal tumors (CT26) were administered these therapeutic micelles in combination with X-ray irradiation and anti-CTLA-4 immunotherapy. This combination led to enhanced efficacy demonstrated by improved tumor control and increased tumor infiltrating lymphocytes. This report represents the first investigation of DNA damage repair inhibition combined with radiation to potentiate anti-CTLA-4 immunotherapy in a CRC model.
  • Houssari, Mahmoud; Dumesnil, Anais; Tardif, Virginie; Kivela, Riikka; Pizzinat, Nathalie; Boukhalfa, Ines; Godefroy, David; Schapman, Damien; Hemanthakumar, Karthik A.; Bizou, Mathilde; Henry, Jean-Paul; Renet, Sylvanie; Riou, Gaetan; Rondeaux, Julie; Anouar, Youssef; Adriouch, Sahil; Fraineau, Sylvain; Alitalo, Kari; Richard, Vincent; Mulder, Paul; Brakenhielm, Ebba (2020)
    Objective: Lymphatics play an essential pathophysiological role in promoting fluid and immune cell tissue clearance. Conversely, immune cells may influence lymphatic function and remodeling. Recently, cardiac lymphangiogenesis has been proposed as a therapeutic target to prevent heart failure after myocardial infarction (MI). We investigated the effects of gene therapy to modulate cardiac lymphangiogenesis post-MI in rodents. Second, we determined the impact of cardiac-infiltrating T cells on lymphatic remodeling in the heart. Approach and Results: Comparing adenoviral versus adeno-associated viral gene delivery in mice, we found that only sustained VEGF (vascular endothelial growth factor)-C(C156S)therapy, achieved by adeno-associated viral vectors, increased cardiac lymphangiogenesis, and led to reduced cardiac inflammation and dysfunction by 3 weeks post-MI. Conversely, inhibition of VEGF-C/-D signaling, through adeno-associated viral delivery of soluble VEGFR3 (vascular endothelial growth factor receptor 3), limited infarct lymphangiogenesis. Unexpectedly, this treatment improved cardiac function post-MI in both mice and rats, linked to reduced infarct thinning due to acute suppression of T-cell infiltration. Finally, using pharmacological, genetic, and antibody-mediated prevention of cardiac T-cell recruitment in mice, we discovered that both CD4(+)and CD8(+)T cells potently suppress, in part through interferon-gamma, cardiac lymphangiogenesis post-MI. Conclusions: We show that resolution of cardiac inflammation after MI may be accelerated by therapeutic lymphangiogenesis based on adeno-associated viral gene delivery of VEGF-C-C156S. Conversely, our work uncovers a major negative role of cardiac-recruited T cells on lymphatic remodeling. Our results give new insight into the interconnection between immune cells and lymphatics in orchestration of cardiac repair after injury.
  • Kesävuori, Risto; Vento, Antti; Lundbom, Nina; Schramko, Alexey; Jokinen, Janne J.; Raivio, Peter (2019)
    Introduction: A minimal volume ventilation method for robotically assisted mitral valve surgery is described in this study. In an attempt to reduce postoperative pulmonary dysfunction, 40 of 174 patients undergoing robotically assisted mitral valve surgery were ventilated with a small tidal volume during cardiopulmonary bypass. Methods: After propensity score matching, 31 patients with minimal volume ventilation were compared with 54 patients with no ventilation. Total ventilation time, PaO2/FiO(2) ratio, arterial lactate concentration, and the rate of unilateral pulmonary edema in the matched minimal ventilation and standard treatment groups were evaluated. Results: Patients in the minimal ventilation group had shorter ventilation times, 12.0 (interquartile range: 9.9-15.0) versus 14.0 (interquartile range: 12.0-16.3) hours (p = 0.036), and lower postoperative arterial lactate levels, 0.99 (interquartile range: 0.81-1.39) versus 1.28 (interquartile range: 0.99-1.86) mmol/L (p = 0.01), in comparison to patients in the standard treatment group. There was no difference in postoperative PaO2/FiO(2) ratio levels or in the rate of unilateral pulmonary edema between the groups. Conclusion: Minimal ventilation appeared beneficial in terms of total ventilation time and blood lactatemia, while there was no improvement in arterial blood gas measurements or in the rate of unilateral pulmonary edema. The lower postoperative arterial lactate levels may suggest improved lung perfusion among patients in the minimal volume ventilation group. The differences in the ventilation times were in fact small, and further studies are required to confirm the possible advantages of the minimal volume ventilation method in robotically assisted cardiac surgery.
  • Talman, Virpi; Teppo, Jaakko Sakari; Pöhö, Päivi Anneli; Movahedi, Parisa; Vaikkinen, Anu; Karhu, Suvi Tuuli; Trošt, Kajetan; Suvitaival, Tommi; Heikkonen, Jukka; Pahikkala, Tapio; Kotiaho, Ahti Antti Tapio; Kostiainen, Risto Kalervo; Varjosalo, Markku Tapio; Ruskoaho, Heikki Juhani (2018)
    Background The molecular mechanisms mediating postnatal loss of cardiac regeneration in mammals are not fully understood. We aimed to provide an integrated resource of mRNA, protein, and metabolite changes in the neonatal heart for identification of metabolism‐related mechanisms associated with cardiac regeneration. Methods and Results Methods and results Mouse ventricular tissue samples taken on postnatal day 1 (P01), P04, P09, and P23 were analyzed with RNA sequencing and global proteomics and metabolomics. Gene ontology analysis, KEGG pathway analysis, and fuzzy c‐means clustering were used to identify up‐ or downregulated biological processes and metabolic pathways on all 3 levels, and Ingenuity pathway analysis (Qiagen) was used to identify upstream regulators. Differential expression was observed for 8547 mRNAs and for 1199 of 2285 quantified proteins. Furthermore, 151 metabolites with significant changes were identified. Differentially regulated metabolic pathways include branched chain amino acid degradation (upregulated at P23), fatty acid metabolism (upregulated at P04 and P09; downregulated at P23) as well as the HMGCS (HMG‐CoA [hydroxymethylglutaryl‐coenzyme A] synthase)–mediated mevalonate pathway and ketogenesis (transiently activated). Pharmacological inhibition of HMGCS in primary neonatal cardiomyocytes reduced the percentage of BrdU‐positive cardiomyocytes, providing evidence that the mevalonate and ketogenesis routes may participate in regulating the cardiomyocyte cell cycle. Conclusions This study is the first systems‐level resource combining data from genomewide transcriptomics with global quantitative proteomics and untargeted metabolomics analyses in the mouse heart throughout the early postnatal period. These integrated data of molecular changes associated with the loss of cardiac regeneration may open up new possibilities for the development of regenerative therapies
  • Bourgery, Matthieu; Ekholm, Erika; Fagerlund, Katja; Hiltunen, Ari; Puolakkainen, Tero; Pursiheimo, Juha-Pekka; Heino, Terhi; Määttä, Jorma; Heinonen, Jussi; Yatkin, Emrah; Laitala, Tiina; Säämänen, Anna-Marja (2021)
    Long-bone fracture is a common injury and its healing process at the fracture site involves several overlapping phases, including inflammation, migration of mesenchymal progenitors into the fracture site, endochondral ossification, angiogenesis and finally bone remodelling. Increasing evidence shows that small noncoding RNAs are important regulators of chondrogenesis, osteogenesis and fracture healing. MicroRNAs are small singlestranded, non-coding RNA-molecules intervening in most physiological and biological processes, including fracture healing. Angiogenin-cleaved 5' tRNA halves, also called as tiRNAs (stress-induced RNAs) have been shown to repress protein translation. In order to gain further understanding on the role of small noncoding RNAs in fracture healing, genome wide expression profiles of tiRNAs, miRNAs and mRNAs were followed up to 14 days after fracture in callus tissue of an in vivo mouse model with closed tibial fracture and, compared to intact bone and articular cartilage at 2 months of age. Total tiRNA expression level in cartilage was only approximately one third of that observed in control D0 bone. In callus tissue, 11 mature 5 ' end tiRNAs out of 191 tiRNAs were highly expressed, and seven of them were differentially expressed during fracture healing. When comparing the control tissues, 25 miRNAs characteristic to bone and 29 miRNAs characteristic to cartilage tissue homeostasis were identified. Further, a total of 54 out of 806 miRNAs and 5420 out of 18,700 mRNAs were differentially expressed (DE) in callus tissue during fracture healing and, in comparison to control bone. They were associated to gene ontology processes related to mesenchymal tissue development and differentiation. A total of 581 miRNA-mRNA interactions were identified for these 54 DE miRNAs by literature searches in PubMed, thereby linking by Spearman correlation analysis 14 downregulated and 28 upregulated miRNAs to 164 negatively correlating and 168 positively correlating miRNA-mRNA pairs with chondrogenic and osteogenic phases of fracture healing. These data indicated that tiRNAs and miRNAs were differentially expressed in fracture callus tissue, suggesting them important physiological functions during fracture healing. Hence, the data provided by this study may contribute to future clinical applications, such as potential use as biomarkers or as tools in the development of novel therapeutic approaches for fracture healing.
  • Cederqvist, Sanna; Flinkkilä, Tapio; Sormaala, Markus; Ylinen, Jari; Kautiainen, Hannu; Irmola, Tero; Lehtokangas, Heidi; Liukkonen, Juho; Pamilo, Konsta; Ridanpää, Tero; Sirnio, Kai; Leppilahti, Juhana; Kiviranta, Ilkka; Paloneva, Juha (2021)
    Background Rotator cuff disease (RCD) causes prolonged shoulder pain and disability in adults. RCD is a continuum ranging from tendinopathy to full-thickness tendon tear. Recent studies have shown that subacromial decompression and non-surgical treatments provide equivalent results in RCD without a full-thickness tendon lesion. However, the importance of surgery for full-thickness tendon tears remains unclear. Methods In a pragmatic, randomised, controlled trial, 417 patients with subacromial pain underwent 3-month initial rehabilitation and MRI arthrography (MRA) for the diagnosis of RCD. Of these, 190 shoulders remained symptomatic and were randomised to non-surgical or surgical treatments. The primary outcomes were the mean changes in the Visual Analogue Scale for pain and the Constant Murley Score for shoulder function at the 2-year follow-up. Results At the 2-year follow-up, both non-surgical and surgical treatments for RCD reduced pain and improved shoulder function. The scores differed between groups by 4 (95% CI -3 to 10, p=0.25) for pain and 3.4 (95% CI -0.4 to 7.1, p=0.077) for function. Among patients with full-thickness ruptures, the reduction in pain (13, 95% CI 5 to 22, p=0.002) and improvement in function (7.0, 95% CI 1.8 to 12.2, p=0.008) favoured surgery. Conclusions Non-surgical and surgical treatments for RCD provided equivalent improvements in pain and function. Therefore, we recommend non-surgical treatment as the primary choice for patients with RCD. However, surgery yielded superior improvement in pain and function for full-thickness rotator cuff rupture. Therefore, rotator cuff repair may be suggested after failed non-surgical treatment.
  • Huhtamäki, Martina; Lindström, Jan; Londen, Anne-Marie (2020)
    This study examines other-repetitions in Finland Swedish talk-in-interaction: their sequential trajectories, prosodic design, and lexicogrammatical features. The key objective is to explore how prosody can contribute to the action conveyed by a repetition turn, that is, whether it deals with a problem of hearing or understanding, a problem of expectation, or just registers receipt of information. The analysis shows that large and upgraded prosodic features (higher onset, wider pitch span than the previous turn) co-occur with repair- and expectation-oriented repetitions, whereas small, downgraded prosody (lower onset, narrower pitch span than the previous turn) is characteristic of registering. However, the distinguishing strength of prosody is mostly gradient (rather than discrete), and because of this, other concomitant cues, most notably the speakers’ epistemic positions in relation to the repeated item, are also of importance for ascribing a certain pragmatic function to a repetition.