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Background. It has been unclear whether simple atrial septal defect (ASD) is an independent risk factor for infective endocarditis (IE). This study aimed to untangle the risk of endocarditis in a large nationwide cohort. Methods. We acquired data from the Finnish hospital discharge register on all individuals with ASD diagnosis from 1969 to 2019. Patients with complex congenital cardiac abnormalities were ruled out. Five individualized controls from the general population were matched to the ASD patient's birth year, sex, and residence at the index date. All the patients with ICD-8, -9, or -10 diagnosis codes for IE were gathered from the hospital discharge registry. Results. Altogether, 8322 patients with ASD and 39,237 individualized controls were enrolled in the study. Median follow-up was 21.6 years (IQR 11.8-36.9) from the first hospital contact. In total, 24 (16 male) cases of infective endocarditis among ASD patients and 10 (8 male) cases among controls were diagnosed during the follow-up. The incidence of endocarditis was 0.11 per 1000 person-years in the patients with ASD and 0.011 per 1000 person-years in the controls. The adjusted risk ratio for endocarditis was 13.51 (95% CI: 6.20-29.46) in patients with ASD compared to the control cohort. Patients with ASD and endocarditis had higher long-term mortality than individualized control patients (MRR 2.25, 95% CI: 1.23-4.11). Conclusions. The incidence of IE in patients with ASD was higher than in the general population. Mortality associated with IE was higher in patients with ASD compared to controls.
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Endocardite Bacteriana , Endocardite , Cardiopatias Congênitas , Comunicação Interatrial , Humanos , Masculino , Endocardite/diagnóstico , Endocardite/epidemiologia , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/epidemiologia , Comunicação Interatrial/complicações , Cardiopatias Congênitas/epidemiologia , Fatores de RiscoRESUMO
Until now, in clinical dentistry, antibacterial photodynamic therapy (aPDT) has been restricted to in-office treatments, which hampers repeated applications. This pilot study tested the benefit of a commercially available Lumoral® device designed for regular periodontal dual-light aPDT treatment at home. Seven patients with peri-implant disease applied dual-light aPDT daily in addition to their normal dental hygiene for four weeks. A single Lumoral® treatment includes an indocyanine green mouth rinse followed by 40 J/cm2 radiant exposure to a combination of 810 nm and 405 nm light. A point-of-care analysis of active-matrix metalloproteinase (aMMP-8), visible plaque index (VPI), bleeding on probing (BOP), and peri-implant pocket depth (PPD) measurements was performed on day 0, day 15, and day 30. Reductions in aMMP-8 (p = 0.047), VPI (p = 0.03), and BOP (p = 0.03) were observed, and PPD was measured as being 1 mm lower in the implant (p = ns). These results suggest a benefit of regular application of dual-light aPDT in peri-implantitis. Frequently repeated application can be a promising approach to diminishing the microbial burden and to lowering the tissue destructive proteolytic and inflammatory load around dental implants. Further studies in larger populations are warranted to show the long-term benefits.
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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.
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Apêndice Atrial , Oclusão Coronária , Corpos Estranhos , Animais , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Estudos de Viabilidade , Inflamação , SuínosRESUMO
BACKGROUND: Improvements in mortality after congenital heart surgery have necessitated a shift in focus to postoperative morbidity as an outcome measure. We examined late morbidity after congenital heart surgery based on prescription medication use. METHODS: Between 1953 and 2009, 10,635 patients underwent congenital heart surgery at <15 years of age in Finland. We obtained 4 age-, sex-, birth-time, and hospital district-matched controls per patient. The Social Insurance Institution of Finland provided data on all prescription medications obtained between 1999 and 2012 by patients and controls. Patients were assigned one diagnosis based on a hierarchical list of cardiac defects and dichotomised into simple and severe groups. Medications were divided into short- and long-term based on indication. Follow-up started at the first operation and ended at death, emigration, or 31 December, 2012. RESULTS: Totally, 8623 patients met inclusion criteria. Follow-up was 99.9%. In total, 8126 (94%) patients required prescription medications. Systemic anti-bacterials were the most common short-term prescriptions among patients (93%) and controls (88%). Patients required betablockers (simple hazard ratio 1.9, 95% confidence interval 1.7-2.1; severe hazard ratio 6.5, 95% confidence interval 5.3-8.1) and diuretics (simple hazard ratio 3.2, 95% CI 2.8-3.7; severe hazard ratio 38.8, 95% CI 27.5-54.7) more often than the general population. Both simple and severe defects required medication for cardiovascular, gastrointestinal, psychiatric, neurologic, metabolic, autoimmune, and infectious diseases more often than the general population. CONCLUSIONS: The significant risk for postoperative cardiovascular and non-cardiovascular disease warrants close long-term follow-up after congenital heart surgery for all defects.
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Cardiopatias Congênitas , Humanos , Cardiopatias Congênitas/diagnóstico , Período Pós-Operatório , Prescrições , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
INTRODUCTION: Active matrix metalloproteinase (aMMP)-8 utilized in point-of-care testing (POCT) is regarded as a potential biomarker for periodontal and peri-implant diseases. Various host and microbial factors eventually influence the expression, degranulation, levels and activation of aMMP-8. The type of oral fluids (saliva, mouthrinse, gingival crevicular, and peri-implant sulcular fluids [GCF/PISF], respectively) affect the analysis. AREAS COVERED: With this background, we aimed to review here the recent studies on practical, inexpensive, noninvasive and quantitative mouthrinse and GCF/PISF chair-side POCT lateral flow aMMP-8 immunoassays (PerioSafe and ImplantSafe/ORALyzer) and how they help to detect, predict, monitor the course, treatment and prevention of periodontitis and peri-implantitis. The correlations of aMMP-8 POCT to other independent and catalytic activity assays of MMP-8 are also addressed. EXPERT OPINION: The mouthrinse aMMP-8 POCT can also detect prediabetes/diabetes and tissue destructive oral side-effects due to the head and neck cancers' radiotherapy. Chlorhexidine and doxycycline can inhibit collagenolytic human neutrophil and GCF aMMP-8. Furthermore, by a set of case-series we demonstrate the potential of mouthrinse aMMP-8 POCT to real-time/online detect periodontitis as a potential risk disease for coronavirus disease 2019 (COVID-19). The clinical interdisciplinary utilization of aMMP-8 POCT requires additional oral, medical, and interdisciplinary studies.
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COVID-19/enzimologia , Metaloproteinase 8 da Matriz/metabolismo , Pandemias , SARS-CoV-2 , Biomarcadores/análise , Biomarcadores/metabolismo , COVID-19/complicações , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/enzimologia , Doxiciclina/uso terapêutico , Humanos , Imunoensaio/métodos , Metaloproteinase 8 da Matriz/análise , Antissépticos Bucais , Higiene Bucal , Peri-Implantite/diagnóstico , Peri-Implantite/enzimologia , Periodontite/complicações , Periodontite/diagnóstico , Periodontite/enzimologia , Testes Imediatos , Radioterapia/efeitos adversos , Fatores de Risco , Tratamento Farmacológico da COVID-19RESUMO
PURPOSE: During cancer treatment, oral mucositis due to radiotherapy or chemotherapy often leads to disruption of the oral mucosa, enabling microbes to invade bloodstream. Viridans streptococcal species are part of the healthy oral microbiota but can be frequently isolated from the blood of neutropenic patients. We have previously shown the antibacterial efficacy of dual-light, the combination of antibacterial blue light (aBL) and indocyanine green photodynamic therapy (aPDT). METHODS: Here, we investigated the dual-light antibacterial action against four-day Streptococcus oralis biofilm. In addition, while keeping the total radiant exposure constant at 100J/cm2, we investigated the effect of changing the different relative light energies of aBL and aPDT to the antibacterial potential. RESULTS: The dual-light had a significant antibacterial effect in all the tested combinations. CONCLUSION: Dual-light can be used as an effective disinfectant against S. oralis biofilm.
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Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Verde de Indocianina/uso terapêutico , Fotoquimioterapia/métodos , Streptococcus oralis/efeitos dos fármacos , Humanos , Estomatite/tratamento farmacológico , Estomatite/microbiologia , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologiaRESUMO
INTRODUCTION: Newborn infants with transposition of the great arteries (d-TGA) need immediate care for an optimal outcome. This study comprised a nationwide 11-year population-based cohort of d-TGA infants, and assessed whether the implementation of a nationwide systematic fetal screening program, or other perinatal, or perioperative factors, are associated with mortality or an increased need for hospital care. MATERIAL AND METHODS: The national cohort consisted of all live-born infants with simple d-TGA (TGA ± small ventricular septal defect, n = 127) born in Finland during 2004-2014. Data were collected from six national registries. Prenatal diagnosis and perinatal and perioperative factors associated with mortality and length of hospitalization were evaluated. RESULTS: Preoperative mortality was 7.9%, and the total mortality was 8.7%. The prenatal detection rate increased after introducing systematic fetal anomaly screening from 5.0% to 37.7% during the study period (P < .0001), but the total mortality rate remained unchanged. All prenatally diagnosed infants (n = 27) survived. Lower gestational age (odds ratio 0.68, P = .012) and higher maternal age at birth (odds ratio 1.16, P = .036) were associated with increased mortality in multivariable analysis. Older infant age at time of operation (P = .002), longer aortic clamp time (P < .001), and higher maternal body mass index (P = .027) were associated with longer initial hospital stay. An extended need for hospital care during the first year of life was multi-factorial. CONCLUSIONS: In our cohort, none of the prenatally diagnosed d-TGA infants died. As a result of the limited prenatal detection rates, however, the sample size was insufficient to reach statistical significance. The d-TGA infants born with lower gestational age and to older mothers had increased mortality.
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Hospitalização/estatística & dados numéricos , Obesidade Materna , Transposição dos Grandes Vasos , Índice de Massa Corporal , Estudos de Coortes , Feminino , Finlândia/epidemiologia , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Idade Materna , Triagem Neonatal/métodos , Obesidade Materna/diagnóstico , Obesidade Materna/epidemiologia , Gravidez , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/estatística & dados numéricos , Fatores de Risco , Transposição dos Grandes Vasos/diagnóstico , Transposição dos Grandes Vasos/mortalidade , Transposição dos Grandes Vasos/terapiaRESUMO
Thymic commitment of human FOXP3+ regulatory T cells begins at the double positive (DP) CD4+ CD8+ stage. In the current study we show that interleukin-2 promotes the development of FOXP3+ thymocytes and enhances their survival at the DP phase. IL-2 increases the frequency of FOXP3+ cells and promotes the Treg phenotype after TCR-mediated positive selection at the most mature DP stage. However, it has no effect on FOXP3+ cells at the earlier maturation steps before positive selection. DP FOXP3+ are highly susceptible to cell death but IL-2 promotes their survival. The anti-apoptotic protein BCL-2 (B Cell Lymphoma 2) is also upregulated by IL-2 at the most mature DP stage. In addition to IL-2, we identify IL-15 to have a significant role in the upregulating FOXP3 and survival of Tregs at the DP phase. IL-7 also increases the expression of BCL-2 in the DP FOXP3+ thymocytes. Our results indicate that common gamma chain cytokines IL-2, IL-7 and IL-15 promote the development of regulatory T cells at the most mature DP stage after TCR-mediated positive selection through suppressing cell death. This article is protected by copyright. All rights reserved.
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BACKGROUND: Postoperative pain after median sternotomy is usually treated with i.v. opioids. We hypothesized that continuous wound infusion of ropivacaine decreases postoperative morphine consumption and improves analgesia in children who undergo cardiac surgery. METHODS: This randomized, double-blind study comprised 49 children aged 1-9 years who underwent atrial septal defect (ASD) closure. Patients received continuous local anesthetic wound infiltration either with 0.2% ropivacaine, 0.3-0.4 mg·kg(-1) ·h(-1) (Group R) or with saline (Group C). Rescue morphine consumption, Objective Pain Scale (OPS), time to mobilization, time to enteral food intake, and time to discharge were recorded. RESULTS: There were no statistically significant differences in morphine consumption at 24, 48, and 72 h postsurgery between R and C groups. There was a weak evidence for a difference in the time to the first morphine administration after tracheal extubation to be longer for Group R than Group C (186.2 vs 81.0 min; 95% CI (-236.5, 26.2), P = 0.114). The incidence of nausea and vomiting were comparable between the groups. No signs or symptoms of local anesthetic toxicity were registered. CONCLUSIONS: Contrary to our hypothesis, continuous ropivacaine wound infusion did not reduce morphine consumption, pain score values, or nausea and vomiting in children who underwent ASD closure with median sternotomy and mediastinal drain.
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Amidas/administração & dosagem , Anestésicos Locais/administração & dosagem , Mediastino/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Esternotomia , Amidas/uso terapêutico , Anestésicos Locais/uso terapêutico , Criança , Pré-Escolar , Método Duplo-Cego , Drenagem , Feminino , Humanos , Lactente , Infusões Parenterais/métodos , Masculino , Estudos Prospectivos , Ropivacaina , Resultado do TratamentoRESUMO
Myocardial infarction causes scarring and loss of functional capacity of the heart, because the heart is itself unable to repair the damaged area. While the development of new forms of treatment for the repair of myocardial destruction has actually been investigated by introducing into the heart various stem cells present in an adult human, the efficacy of the treatments conducted in the studies has so far unfortunately been low. Embryonic stem cells and iPS cells are a highly significant research subject. Cardiomyocytes differentiated from stem cells are being studied also in drug testing, and they are expected to revolutionize drug development and safety tests of novel drugs as well as enable personalized medication in the future.
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Infarto do Miocárdio/terapia , Miócitos Cardíacos/citologia , Transplante de Células-Tronco/métodos , Diferenciação Celular/fisiologia , Células-Tronco Embrionárias/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Infarto do Miocárdio/fisiopatologia , Medicina de PrecisãoRESUMO
Bone marrow mononuclear cells (BMMCs) have been evaluated for their ability to improve cardiac repair and benefit patients with severe ischemic heart disease and heart failure. In our single-center trial in 2006-2011 we demonstrated the safety and efficacy of BMMCs injected intramyocardially in conjunction with coronary artery bypass surgery. The effect persisted in the follow-up study 5 years later. In this study, we investigated the efficacy of BMMC therapy beyond 10 years. A total of 18 patients (46%) died during over 10-years follow-up and 21 were contacted for participation. Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) and clinical evaluation were performed on 14 patients, seven from each group. CMRIs from the study baseline, 1-year and 5-years follow-ups were re-analyzed to enable comparison. The CMRI demonstrated a 2.1-fold larger reduction in the mass of late gadolinium enhancement values between the preoperative and the over 10-years follow-up, suggesting less scar or fibrosis after BMMC treatment (- 15.1%; 95% CI - 23 to - 6.7% vs. - 7.3%; 95% CI - 16 to 4.5%, p = 0.039), compared to placebo. No differences in mortality or morbidity were observed. Intramyocardially injected BMMCs may exert long-term benefits in patients with ischemic heart failure. This deserves further evaluation in patients who have received BMMCs in international clinical studies over two decades.
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Medula Óssea , Insuficiência Cardíaca , Humanos , Seguimentos , Meios de Contraste , Gadolínio , Transplante de Medula Óssea/métodos , Insuficiência Cardíaca/cirurgia , Transplante de Células , Resultado do TratamentoRESUMO
INTRODUCTION: When collected in a standardized fashion, oral fluid analysis can refine the diagnosis of periodontal and peri-implant disease. In practice, dental professionals can perform active matrix metalloproteinase (aMMP-8) analysis chairside. AREAS COVERED: Periodontal tissues are mainly made up of type I collagen, and collagen breakdown is one of the main events in periodontal and peri-implantitis destructive lesions. In addition to traditional measurements, their diagnosis can be refined with tests utilizing oral fluids. The active matrix metalloproteinase-8 (aMMP-8) is possible to be determined from the gingival crevicular fluid (GCF), peri-implant sulcus fluid (PISF), and other oral fluids such as mouth rinse and saliva. We also investigated the applicability of aMMP-8 chair-side test kits in the evaluation of oral health benefits of different adjunctive host-modulating periodontal therapies including fermented lingonberry mouthwash (FLJ) and antibacterial photodynamic therapy (aPDT). EXPERT OPINION: The aMMP-8 levels can more reliably detect early activation of periodontal and peri-implant disease as compared to traditional diagnostic methods that assess the experienced health status or past disease, rather than the present or future pathology. Novel therapies like, fermented lingonberry juice as a mouthrinse or aPDT, are potential host-modulating adjunctive treatments to reduce the signs of oral inflammation and infection.
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Peri-Implantite , Periodontite , Humanos , Peri-Implantite/diagnóstico , Peri-Implantite/terapia , Peri-Implantite/microbiologia , Sistemas Automatizados de Assistência Junto ao Leito , Periodontite/diagnóstico , Periodontite/tratamento farmacológico , Líquido do Sulco Gengival/metabolismoRESUMO
OBJECTIVES: Several studies have reported mortality risk factors associated with hypoplastic left heart syndrome (HLHS). However, these data are ambiguous and mainly focused on the independent effects of these factors. We examined both the independent and the cumulative effects of preoperative risk factors for poor outcome in patients undergoing the Norwood procedure. Moreover, we studied the risk factors associated with prolonged initial hospital stays in these patients. METHODS: We performed a retrospective national 18-year observational study of preoperative risk factors for 1 year, as well as total follow-up mortality or need for transplant in patients with HLHS (N = 99) born in Finland between 1 January 2004 and 31 December 2021. RESULTS: Overall, one-year survival was 85.6%. In a multivariable analysis, having a major extracardiac anomaly and being small for gestational age were significant predictors of one-year mortality or the need for a transplant. Aortic atresia was a predictor of total follow-up mortality. An analysis of the cumulative effect indicated that the presence of 2 risk factors was associated with higher mortality. CONCLUSIONS: HLHS remains the defect with the highest procedural risks for mortality in paediatric cardiac surgery. From a prognostic point of view, recognition of independent preoperative risk factors as well as the cumulative effect of risk factors for mortality is essential.The results of this study were presented orally at the 55th Annual Meeting of the Association for European Paediatric and Congenital Cardiology, Geneva, Switzerland, 28 May 2022.
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BACKGROUND: Previous studies have revealed the potential diagnostic utility of aMMP-8, an active form of MMP-8, in periodontal and peri-implant diseases. While non-invasive point-of-care (PoC) chairside aMMP-8 tests have shown promise in this regard, there is a dearth of literature on the evaluation of treatment response using these tests. The present study aimed to investigate treatment-related changes in aMMP-8 levels in individuals with Stage III/IV-Grade C periodontitis compared to a healthy control group, using a quantitative chairside PoC aMMP-8 test, and to determine its correlation with clinical parameters. METHODS: The study included 27 adult patients (13 smoker, 14 non-smoker) with stage III/IV-grade C periodontitis and 25 healthy adult subjects. Clinical periodontal measurements, real-time PoC aMMP-8, IFMA aMMP-8, and Western immunoblot analyses were performed before and 1 month after anti-infective scaling and root planing periodontal treatment. Time 0 measurements were taken from the healthy control group to test the consistency of the diagnostic test. RESULTS: Both PoC aMMP-8 and IFMA aMMP-8 tests showed a statistically significant decrease in aMMP-8 levels and improvement in periodontal clinical parameters following treatment (p < 0.05). The PoC aMMP-8 test had high diagnostic sensitivity (85.2%) and specificity (100.0%) for periodontitis and was not affected by smoking (p > 0.05). Treatment also reduced MMP-8 immunoreactivity and activation as demonstrated by Western immunoblot analysis. CONCLUSION: The PoC aMMP-8 test shows promise as a useful tool for the real-time diagnosis and monitoring of periodontal therapy.
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Active matrix metalloproteinase-8 (aMMP-8) is a promising biomarker candidate for the modern periodontal and peri-implant disease diagnostics utilizing the chairside/point-of-care oral fluid technologies. These rapid biomarker analysis technologies utilize gingival crevicular fluid (GCF), peri-implant sulcular fluid (PISF), or mouth rinse as the oral fluid matrices that can be collected patient-friendly and non-invasively without causing bacteremia. aMMP-8, but not total or latent proMMP-8, has been shown to be a relevant biomarker to be implemented to the latest 2017 classification system of periodontitis and peri-implantitis. Thus, aMMP-8 point-of-care-testing (POCT)-but not total or latent proMMP-8-can be conveniently used as an adjunctive and preventive diagnostic tool to identify and screen the developing and ongoing periodontal and peri-implant breakdown and disease as well as predict its episodic progression. Similarly, aMMP-8 POCT provides an important tool to monitor the treatment effect of these diseases, but also other diseases such as head and neck cancer, where it can identify and predict the rapid tissue destructive oral side-effects during and after the radiotherapy. Additionally, recent studies support aMMP-8 POCT benefitting the identification of periodontitis and diabetes as the escalating risk diseases for COVID-19 infection. Overall, aMMP-8 POCT has launched a new clinical field in oral medicine and dentistry, i.e., oral clinical chemistry.
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Good oral hygiene at home is the foundation for optimal treatment response and long-term periodontal disease control. Antibacterial photodynamic therapy (aPDT) provides a very potent adjunctive treatment for plaque control. However, the literature regarding repeated aPDT use is sparse. aPDT has been a modality applied mainly in the dental office environment, and when applied once a year or every few months, the results have been usually disappointing. Recently, LED development has brought aPDT for repeated and practical use at home. We present the very positive results and clinical outcome of daily applied dual-light aPDT-technology treatment in conjunction with mechanical cleaning of a 78-year-old male patient with severe periodontal disease (Stage IV and Grade B).
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A single-site, randomized clinical trial was designed to determine the efficacy of regular home use of Lumoral® dual-light antibacterial aPDT in periodontitis patients. For the study, 200 patients were randomized to receive non-surgical periodontal treatment (NSPT), including standardized hygiene instructions and electric toothbrush, scaling and root planing, or NSPT with adjunctive Lumoral® treatment. A complete clinical intraoral examination was conducted in the beginning, at three months, and at six months. This report presents the three-month results of the first 59 consecutive randomized subjects. At three months, bleeding on probing (BOP) was lower in the NSPT + Lumoral®-group than in the NSPT group (p = 0.045), and more patients in the NSPT + Lumoral®-group had their BOP below 10% (54% vs. 22%, respectively, p = 0.008). In addition, patients in the NSPT + Lumoral®-group improved their oral hygiene by visible-plaque-index (p = 0.0003), while the NSPT group showed no statistical improvement compared to the baseline. Both groups significantly reduced the number of deep periodontal pockets, but more patients with a reduction in their deep pocket number were found in the NSPT + Lumoral® group (92% vs. 63%, p = 0.02). Patients whose number of deep pockets was reduced by 50% or more were also more frequent in the NSPT + Lumoral®-group (71% vs. 33%, p = 0.01). Patients with initially less than ten deep pockets had fewer deep pockets at the three-month follow-up in the Lumoral® group (p = 0.01). In conclusion, adjunctive use of Lumoral® in NSPT results in improved treatment outcomes at three months post-therapy.
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BACKGROUND: Myoblast sheet transplantation is a promising novel treatment for ischemic heart failure. The aim of this study was to test the hypothesis that heat shock (HS) pre-treatment affects the angiogenic properties of myoblast sheets in vivo and in vitro. MATERIAL/METHODS: We studied HS preconditioning of L6 myoblast sheets in relation to their apoptosis, proliferation, and vascular endothelial growth factor (VEGF)-associated responses under normoxia and under hypoxia in vitro. In vivo evaluation of their therapeutic effect was performed with 60 male Wistar rats divided into 3 groups (20 each): sole left anterior descending (LAD) ligation (control); LAD ligation and non-conditioned sheet transplantation (L6 No-Shock); and LAD ligation and L6-heat shock conditioned sheet transplantation (L6 Heat-Shock). Left ventricular function was evaluated by echocardiography after 3, 10, and 28 days. RESULTS: Expression of HSP70/72 was strongly induced 24 hours after HS, and thereafter it decreased notably during 72 hours in hypoxia. Under normal growth conditions, HSP70/72 expression remained stable. HS delayed apoptosis-associated caspase-3 expression during 24-hour hypoxia compared to non-treated controls. However, VEGF expression reduced significantly in the heat shock pretreated sheets. Ejection fraction of the L6-myoblast HS pre-treatment group (L6 Heat-Shock) decreased gradually during follow-up, in the same pattern as the controls. However, these functional parameters improved in the L6-myoblast normal sheet group (L6 No-Shock) at the tenth day and remained significantly better. CONCLUSIONS: HS protects myoblast sheets from hypoxia-associated apoptosis in vitro, but reduces VEGF expression of the sheet, leading to lower therapeutic effect in heart failure.
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Técnicas de Cultura de Células/métodos , Insuficiência Cardíaca/terapia , Resposta ao Choque Térmico , Mioblastos/metabolismo , Mioblastos/transplante , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Apoptose , Caspase 3/metabolismo , Hipóxia Celular , Linhagem Celular , Proliferação de Células , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP72/metabolismo , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Masculino , Mioblastos/patologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Estresse Oxidativo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Wistar , Volume Sistólico , Resultado do Tratamento , UltrassonografiaRESUMO
Background: Cardiopulmonary bypass (CPB) may lead to tissue hypoxia, inflammatory response, and risk for acute kidney injury (AKI). We evaluated the prevalence of AKI and inflammatory response in neonates undergoing heart surgery requiring CPB with or without antegrade cerebral perfusion (ACP). Methods: Forty neonates were enrolled. The patients were divided into two groups depending on the use of ACP. AKI was classified based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Inflammatory response was measured using plasma concentrations of interleukins 6 (IL-6) and 10 (IL-10), white blood cell count (WBC), and C-reactive protein (CRP). Results: Eight patients (20%) experienced AKI: five (29%) in the ACP group and three (13%) in the non-ACP group (P = 0.25). Postoperative peak plasma creatinine and urine neutrophil gelatinase-associated lipocalin were significantly higher in the ACP group than in the non-ACP group [46.0 (35.0-60.5) vs 37.5 (33.0-42.5), P = 0.044 and 118.0 (55.4-223.7) vs 29.8 (8.1-109.2), P = 0.02, respectively]. Four patients in the ACP group and one in the non-ACP group required peritoneal dialysis (P = 0.003). Postoperative plasma IL-6, IL-10, and CRP increased significantly in both groups. There were no significant differences between the ACP and non-ACP groups in any of the inflammatory parameters measured. Conclusions: No significant difference in the AKI occurrence or inflammatory response related to CPB modality could be found. In our study population, inflammation was not the key factor leading to AKI. Due to the limited number of patients, these findings should be interpreted with caution.