The incidence and management of slipped capital femoral epiphysis: a population-based study.

We aimed to investigate the national trends in the incidence and management of slipped capital femoral epiphysis (SCFE) and to report the need for reoperations. We included all <19-year-old patients hospitalised for SCFE in 2004-2014 in mainland Finland (n=159). Data from the Finnish Care Register for Health Care, Statistics Finland, and Turku University Hospital patient charts were analyse for the incidence of SCFE in 2004-2012, the length of stay, and the type of surgery with respect to age, gender, study year, and season. The reoperations and rehospitalisations in 2004-2014 for SCFE were analysed for 2-10 years after surgery. In 2004 to 2012, primary surgery for SCFE was performed for 126 children. The average annual incidence of SCFE was 1.06/100 000 (95% confidence interval [CI], 0.81-1.38) in girls and 1.35/100 000 (95% CI 1.07-1.70) in boys. The median age at surgery was lower in girls than in boys (11 and 13 years, respectively, p<0.0001). During the study period, there was no significant change in the incidence of SCFE (p=0.9330), the type of primary procedures performed (p=0.9988), or the length of stay after the primary procedure (p=0.2396). However, the length of stay after percutaneous screw fixation was shorter compared with open reduction and fixation (mean 3.4 and 7.9 days, respectively, p<0.0001). There was no significant difference in the rate of reoperations according to the type of primary surgery. In conclusion, the incidence of SCFE and the proportion of different primary surgeries have recently remained stable in Finland.

Population-based study of anastomotic stricture rates after minimally invasive and open oesophagectomy for cancer.

Background: The population-based incidence of anastomotic stricture after minimally invasive oesophagectomy (MIO) and open oesophagectomy (OO) is not known. The aim of this study was to compare rates of anastomotic stricture requiring dilatation after the two approaches in an unselected cohort using nationwide data from Finland and Sweden. Methods: All patients who had MIO or OO for oesophageal cancer between 2007 and 2014 were identified from nationwide registries in Finland and Sweden. Outcomes were the overall rate of anastomotic stricture and need for single or repeated (3 or more) dilatations for stricture within the first year after surgery. Multivariable Cox regression provided hazard ratios (HRs) with 95 per cent confidence intervals, adjusted for age, sex, co-morbidity, histology, stage, year, country, hospital volume, length of hospital stay and readmissions. Results: Some 239 patients underwent MIO and 1430 had an open procedure. The incidence of strictures requiring one dilatation was 16·7 per cent, and that for strictures requiring three or more dilatations was 6·6 per cent. The HR for strictures requiring one dilatation was not increased after MIO compared with that after OO (HR 1·19, 95 per cent c.i. 0·66 to 2·12), but was threefold higher for repeated dilatations (HR 3·25, 1·43 to 7·36). Of 18 strictures following MIO, 14 (78 per cent) occurred during the first 2 years after initiating this approach. Conclusion: The need for endoscopic anastomotic dilatation after oesophagectomy was common, and the need for repeated dilatation was higher after MIO than following OO. The increased risk after MIO may reflect a learning curve.

Antecedentes: Se desconoce la incidencia poblacional de estenosis anastomóticas tras esofaguectomía mínimamente invasiva (minimally invasive oesophagectomy, MIO) y esofaguectomía abierta (open oesophagectomy, OO). El objetivo de este estudio fue comparar las tasas de estenosis anastomótica que precisan dilataciones después de los dos abordajes de esofaguectomía en una cohorte no seleccionada utilizando los datos poblacionales de Finlandia y Suecia. Métodos: Todos los pacientes sometidos a MIO (n = 239) o OO (n = 1430) por cáncer de esófago entre 2007 y 2014 fueron identificados a partir de los registros nacionales en Finlandia y Suecia. Las variables de resultados fueron la incidencia global de estenosis anastomótica y la necesidad de una sola dilatación o dilataciones repetidas (≥ 3) para la estenosis durante el primer año de la cirugía. La regresión multivariable de Cox proporcionó los cocientes de riesgos instantáneos (hazard ratios, HRs) con los i.c. del 95% ajustados por edad, sexo, comorbilidad, histología, estadio, año, país, volumen del hospital, duración de la estancia hospitalaria y reingresos. Resultados: La incidencia de estenosis que precisaron una dilatación fue del 16,7%, y del 6,6% para estenosis que precisaron ≥ 3 dilataciones. El HR de estenosis que requirieron una dilatación no se incrementó tras MIO en comparación con OO (HR 1,19, i.c. del 95% 0,66­2,12), pero fue 3 veces más para dilataciones repetidas (≥ 3) (HR 3,25, i.c. del 95% 1,43­7,36). De las 18 estenosis tras MIO, 14 (78%) ocurrieron durante los primeros dos años en los que se inició este abordaje. Conclusión: La necesidad de dilatación endoscópica de la anastomosis tras esofaguectomía fue frecuente y la necesidad de dilataciones repetidas fue más alta tras MIO en comparación con OO. El riesgo aumentado tras MIO puede deberse a la curva de aprendizaje.

Effects of levosimendan in experimental acute coxsackievirus myocarditis.

BACKGROUND: Acute heart failure is a potentially fatal manifestation of viral myocarditis. Development of myocardial damage in myocarditis involves cardiomyocyte apoptosis. Levosimendan is a novel calcium sensitizing inotropic agent with anti-apoptotic properties. We studied the feasibility of inotropic treatment with levosimendan and its effects on apoptosis in experimental acute heart failure caused by coxsackievirus myocarditis. MATERIALS AND METHODS: Adolescent BALB/c mice were infected with myocarditic Woodruff variant of coxsackievirus B3 (2 x 10(4) plaque-forming units). Mice were randomized into those receiving levosimendan 0.33 mg kg(-1) (total dose 1 mg kg(-1) day(-1)) (n = 20) or vehicle (n = 19) given orally by gauge three times a day for 7 days after infection. Left ventricular function was evaluated by transthoracic echocardiography and the mice were euthanized on day 7. Histopathology, amount of virus in the heart (virus titration assay) and cardiomyocyte apoptosis (TUNEL assay) were studied. Uninfected untreated control mice were also studied. RESULTS: Infection resulted in histopathologically severe myocarditis and significant impairment of left ventricular function. Levosimendan treatment significantly improved ventricular function (fractional shortening 0.32 +/- 0.04 vs. 0.23 +/- 0.05, P = 0.005; contractility 0.60 +/- 0.12 vs. 0.39 +/- 0.14, P = 0.007 and myocardial performance index 0.36 +/- 0.06 vs. 0.62 +/- 0.15, P < 0.0001) compared with vehicle. Levosimendan also reduced cardiomyocyte apoptosis (0.26 +/- 0.08% vs. 0.44 +/- 0.15% in vehicle, P = 0.008), but did not have an effect on areas of myocardial necrosis or inflammation, or the amount of virus in the heart. Levosimendan treatment did not affect mortality (total mortality 63%). CONCLUSIONS; Levosimendan improves ventricular function and inhibits cardiomyocyte apoptosis; therefore, it is suggested as a potentially feasible therapy in acute heart failure caused by viral myocarditis.

Development of troponin autoantibodies in experimental coxsackievirus B3 myocarditis.

BACKGROUND: Autoantibodies against various endogenous proteins are found in myocarditis. Troponin autoantibodies are detected in patients with chronic dilated cardiomyopathy, but their presence in myocarditis remains unknown. We set out to study the presence of troponin autoantibodies in experimental viral myocarditis. MATERIALS AND METHODS: BALB/c mice infected with coxsackievirus B3 Nancy strain were followed-up at days 1-7 and 2, 4, 8 and 12 weeks after infection. Levels of circulating cardiac troponin I and circulating troponin autoantibodies were measured. Transthoracic echocardiography was performed. Myocarditis was histopathologically graded and cardiomyocyte apoptosis was quantified (TUNEL). RESULTS: Histopathologically relatively mild acute myocarditis followed by persistent cardiomyocyte damage was observed. Rate of cardiomyocyte apoptosis was the highest on day 5 (0.16 +/- 0.01% vs. 0.03 +/- 0.01% in controls, P < 0.001). Circulating troponin I levels were increased to day 5 (45.2 +/- 6.5 ng mL(-1), P < 0.005 vs. controls). Troponin autoantibodies were detected from 2 weeks after infection (20% of animals had autoantibodies at 2 weeks, 60% at 4 and 8 weeks and 20% at 12 weeks, P < 0.05 vs. controls). Fractional shortening remained decreased after acute myocarditis (0.36 +/- 0.02 at 4 weeks, 0.30 +/- 0.02 at 8 and 12 weeks vs. 0.41 +/- 0.01 before infection, P < 0.01) parallel to development of troponin autoantibodies. CONCLUSION: Troponin autoantibodies are formed in experimental virus induced myocarditis following troponin I release and cardiomyocyte apoptosis. The definite role of these autoantibodies remains to be further characterized.

Effects of levosimendan on cardiac remodeling and cardiomyocyte apoptosis in hypertensive Dahl/Rapp rats.

BACKGROUND AND PURPOSE: Progression of heart failure in hypertensive Dahl rats is associated with cardiac remodeling and increased cardiomyocyte apoptosis. This study was conducted to study whether treatment with a novel inotropic vasodilator compound, levosimendan, could prevent hypertension-induced cardiac remodeling and cardiomyocyte apoptosis. EXPERIMENTAL APPROACH: 6-week-old salt-sensitive Dahl/Rapp rats received levosimendan (0.3 mg kg(-1) and 3 mg kg(-1) via drinking fluid) and high salt diet (NaCl 7%) for 7 weeks, Dahl/Rapp rats on low-salt diet served as controls. Blood pressure, cardiac functions by echocardiography, cardiomyocyte apoptosis by TUNEL technique, tissue morphology, myocardial expression of calcium cycling proteins, and markers of neurohumoral activation were determined. KEY RESULTS: Untreated Dahl/Rapp rats on high salt diet developed severe hypertension, cardiac hypertrophy and moderate systolic dysfunction. 38% of Dahl/Rapp rats (9/24) survived the 7-week-follow-up period. Cardiomyocyte apoptosis was increased by 6-fold during high salt diet. Levosimendan improved survival (survival rates in low- and high-dose levosimendan groups 12/12 and 9/12, p<0.001 and p=0.05, respectively), increased cardiac function, and ameliorated cardiac hypertrophy. Levosimendan dose-dependently prevented cardiomyocyte apoptosis. Levosimendan normalized salt-induced increased expression of natriuretic peptide, and decreased urinary noradrenaline excretion. Levosimendan also corrected salt-induced decreases in myocardial SERCA2a protein expression and myocardial SERCA2a/NCX-ratio. CONCLUSIONS AND IMPLICATIONS: Improved survival by the novel inotropic vasodilator levosimendan in hypertensive Dahl/Rapp rats is mediated, at least in part, by amelioration of hypertension-induced cardiac remodeling and cardiomyocyte apoptosis.

Glutathione depletion and cardiomyocyte apoptosis in viral myocarditis.

BACKGROUND: The course of viral myocarditis is highly variable. Oxidative stress and Bcl-2 family genes may play a role in its pathogenesis by regulating the amount of cardiomyocyte apoptosis. Apoptosis is difficult to detect and quantify in vivo. Therefore, we set to look for indicators of this potentially preventable form of cell death during various phases of experimental murine coxsackievirus B3 myocarditis. METHODS: BALB/c mice were infected with the cardiotropic coxsackievirus B3 variant. Glutathione (HPLC), cardiomyocyte apoptosis (TUNEL and caspase-3 cleavage), Bax and Bcl-X(L) mRNA expression (real time RT-PCR), histopathology and viral replication (plaque assay and real time RT-PCR) were measured from day 3 to day 20 after infection. RESULTS: Infection caused severe myocarditis and led to progressive decrease of plasma glutathione levels. Myocardial mRNA levels of pro-apoptotic Bax and antiapoptotic Bcl-X(L) were significantly increased from day 3 onwards. Bax mRNA and ratio of Bax to Bcl-X(L) correlated with cardiomyocyte apoptosis (r = 0.77, P = < 0.001 and r 0.51, P < 0.01, respectively). Cardiomyocyte apoptosis was highest on day 5, coinciding with a rapid decline in plasma glutathione (r = -0.52, P = 0.003). CONCLUSIONS: Systemic oxidative stress as indicated by decreased plasma glutathione levels coincides with cardiomyocyte apoptosis in experimental coxsackievirus myocarditis. Decreased plasma glutathione levels and changes in cardiac Bax and Bcl-X(L) mRNA expression identify a phase of myocarditis in which the potentially preventable cardiomyocyte apoptosis is mostly observed.

Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes.

AIMS/HYPOTHESIS: Diabetes is known to reduce survival after myocardial infarction. Our aim was to examine whether diabetes is associated with enhanced cardiomyocyte apoptosis and thus interferes with the post-infarction remodelling process in myocardium in rat. METHODS: Four weeks after intravenous streptozotocin (diabetic groups) or citrate buffer (controls) injection, myocardial infarction was produced by ligation of left descending coronary artery. Level of cardiomyocyte apoptosis was quantified by TUNEL and caspase-3 methods. Collagen volume fraction and connective tissue growth factor were determined under microscope. Left ventricular dimensions were evaluated by echocardiography and planimetry. RESULTS: The number of apoptotic cardiomyocytes was equally high in diabetic and non-diabetic rats after 1 week from infarction. At 12 weeks after infarction the number of apoptotic cells was higher in the diabetic as compared to non-diabetic rats both in the border zone of infarction and in non-infarcted area. Correspondingly, left ventricular end diastolic diameter, relative cardiac weight, connective tissue growth factor-expression and fibrosis were increased in diabetic compared with non-diabetic rats with myocardial infarction. CONCLUSION/INTERPRETATION: Sustained cardiomyocyte apoptosis, left ventricular enlargement, increased cardiac fibrosis and enhanced profibrogenic connective tissue growth factor expression were detected after myocardial infarction in experimental diabetes. Apoptotic myocyte loss could be an important mechanism contributing to progressive dilatation of the heart and poor prognosis after myocardial infarction in diabetes.