The feasibility of a randomised control trial to assess physiotherapy against surgery for recurrent patellar instability.

BACKGROUND: Patellar instability is a relatively common condition that leads to disability and restriction of activities. People with recurrent instability may be given the option of physiotherapy or surgery though this is largely driven by clinician preference rather than by a strong evidence base. We sought to determine the feasibility of conducting a definitive trial comparing physiotherapy with surgical treatment for people with recurrent patellar instability. METHODS: This was a pragmatic, open-label, two-arm feasibility randomised control trial (RCT) with an embedded interview component recruiting across three NHS sites comparing surgical treatment to a package of best conservative care; 'Personalised Knee Therapy' (PKT). The primary feasibility outcome was the recruitment rate per centre (expected rate 1 to 1.5 participants recruited each month). Secondary outcomes included the rate of follow-up (over 80% expected at 12 months) and a series of participant-reported outcomes taken at 3, 6 and 12 months following randomisation, including the Norwich Patellar Instability Score (NPIS), the Kujala Patellofemoral Disorder Score (KPDS), EuroQol-5D-5L, self-reported global assessment of change, satisfaction at each time point and resources use. RESULTS: We recruited 19 participants. Of these, 18 participants (95%) were followed-up at 12 months and 1 (5%) withdrew. One centre recruited at just over one case per month, one centre was unable to recruit, and one centre recruited at over one case per month after a change in participant screening approach. Ten participants were allocated into the PKT arm, with nine to the surgical arm. Mean Norwich Patellar Instability Score improved from 40.6 (standard deviation 22.1) to 28.2 (SD 25.4) from baseline to 12 months. CONCLUSION: This feasibility trial identified a number of challenges and required a series of changes to ensure adequate recruitment and follow-up. These changes helped achieve a sufficient recruitment and follow-up rate. The revised trial design is feasible to be conducted as a definitive trial to answer this important clinical question for people with chronic patellar instability. TRIAL REGISTRATION: The trial was prospectively registered on the International Standard Randomised Controlled Trial Number registry on the 22/12/2016 (reference number: ISRCTN14950321). http://www.isrctn.com/ISRCTN14950321.

Hypoxic reoxygenation during initial reperfusion attenuates cardiac dysfunction and limits ischemia-reperfusion injury after cardioplegic arrest in a porcine model.

OBJECTIVE: In clinical practice, reperfusion of ischemic myocardium usually occurs under high arterial oxygen levels. However, this might aggravate cardiac ischemia-reperfusion injury caused by excessive oxidative stress. In an experimental in vivo study, the cardioprotective role of hypoxic reoxygenation during initial reperfusion was assessed. METHODS: Twenty-one adult pigs were started on cardiopulmonary bypass with aortic crossclamping (90 minutes) and cardioplegic arrest. During initial reperfusion, 10 pigs underwent standard hypoxic reoxygenation (Pa(O(2)), 250-350 mm Hg), whereas gradual reoxygenation (Pa(O(2)), 40-90 mm Hg) was performed in 11 pigs. Cardiac function was analyzed by means of the thermodilution method and conductance catheter technique. RESULTS: In both groups cardiac index was decreased 10 minutes after cardiopulmonary bypass compared with preoperative values. Sixty minutes after cardiopulmonary bypass, cardiac index improved significantly after gradual reoxygenation compared with that after hypoxic reoxygenation (3.2 +/- 0.6 vs 2.5 +/- 0.5 L min(-1) m(-2), P = .04). Correspondingly, end-systolic pressure-volume relationship and peak left ventricular pressure increase were significantly less decreased in the gradual reoxygenation group. During and after reperfusion, malondialdehyde and troponin T values within the coronary sinus were significantly lower after gradual reoxygenation (60 minutes after declamping: malondialdehyde, 7.6 +/- 0.8 vs 4.6 +/- 0.5 micromol/L [P = .007]; troponin, 0.12 +/- 0.02 vs 0.41 +/- 0.12 ng/mL [P = .02]). CONCLUSION: Hypoxic reoxygenation at the onset of reperfusion attenuates myocardial ischemia-reperfusion injury and helps to preserve cardiac performance after myocardial ischemia in a pig model.

A giant rhabdomyoma with left ventricular inflow occlusion and univentricular physiology.

During a routine prenatal ultrasound a huge tumor was diagnosed located in the left ventricle and left atrium with complete obstruction of the left ventricular inflow tract. On the first day of life, urgent surgical intervention was necessary because of progressive heart failure with univentricular physiology. Intraoperatively, the tumor mass was found to originate from the left ventricular wall, reaching into the left atrium. Histological examination revealed a rhabdomyoma.

Effects of Manduca allatotropin and localization of Manduca allatotropin-immunoreactive cells in earwigs.

Manduca sexta allatotropin (Manse-AT) was first isolated on the basis of its ability to stimulate production of juvenile hormone in that insect. We examined whether this neuropeptide affects corpus allatum activity and visceral muscle contraction in adult females of the earwig, Euborellia annulipes. We also assessed the presence of allatotropin-like material in tissues using immunocytochemistry. Manse-AT at 1 nM to 10 muM stimulated juvenile hormone production in vitro by glands of low activity from 2-day virgin females. In glands of high activity from 12-day mated females, 1 and 100 nM allatotropin were effective, but 10 muM was not. Similarly, hindguts of 2-day and 12-day females significantly increased in motility in vitro in response to Manse-AT. A monoclonal antibody to Manse-AT was used to demonstrate allatotropin-like material throughout the nervous system of 2-day, virgin females. Immunoreactivity was most pronounced within varicosities of the corpora cardiaca and perisympathetic organs. No immunofluorescence was observed in gut tissue. Lastly, we showed that extract of retrocerebral complexes also enhanced in vitro hindgut motility from 2-day virgin females, in a dose-dependent manner. These results indicate material similar to M. sexta allatotropin in female earwigs and that such peptides may modulate juvenile hormone biosynthesis and visceral muscle contractions. Sensitivity to the peptides may change with physiological stage.

Cardiopulmonary bypass impairs left ventricular function determined by conductance catheter measurement.

OBJECTIVE: Postoperative cardiac depression is attributed to ischemia and the effects of cardiopulmonary bypass (CPB). To evaluate the effect of CPB alone on postoperative left ventricular (LV) dysfunction, we used a conductance catheter to determine the LV performance by pressure-volume relation before and after CPB. METHODS: Twenty-two 3-week-old piglets underwent sternotomy and normothermic CPB for one hour. A conductance catheter was placed in the LV cavity. End-systolic pressure-volume relationships (ESPVR), left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance (SVR) were measured under steady-state conditions before and 15 min after weaning from CPB in group A (n = 11). Group B included 11 piglets without CPB and served as control. RESULTS: There was no difference between groups before initiating CPB. As an indication of depressed LV function, the ESPVR slope (mmHg/ml) was significantly lower in group A after weaning from CPB than in group B (1.69 +/- 0.5 vs. 1.86 +/- 0.55; p = 0.008). In group A, peak dP/dt (max index) (mmHg/s/m (2)) decreased markedly (1596 +/- 339 vs. 2045 +/- 206; p = 0.03), while LVEDP (mmHg) was significantly increased (11.7 +/- 2.6 vs. 5.4 +/- 0.9; p < 0.0001). In addition, SVR (index) (dyn x s x cm (-5)/m (2)) in group A was significantly lower (1407 +/- 176 vs. 1677 +/- 313; p < 0.0001) than in group B. CONCLUSION: Using the very sensitive conductance catheter technique in a pig model, we could show that CPB leads to a significant depression of LV contractility and elastance even without ischemic arrest.

Human brain wave activity during exposure to radiofrequency field emissions from mobile phones.

The aim of this study was to determine whether there is an effect of mobile phone electromagnetic field emissions on the human electroencephalograph (EEG). EEG recordings from ten awake subjects were taken during exposure to radiofrequency (RF) emissions from a mobile phone positioned behind the head. Two experimental trials were conducted. In the first trial, RF exposures were generated by a GSM mobile phone with the speaker disabled and configured to transmit at full-radiated power. During the second trial, exposures were generated by a non-modified GSM mobile phone in active standby mode. For each trial, subjects were exposed in five minute intervals to a randomized, interrupted sequence of five active and five sham exposures. The experiment was conducted under single-blind conditions. The average EEG band power in active exposure recordings was compared to corresponding sham recordings. Statistical tests indicated significant difference in the full-power mode trial within the EEG alpha (8-13 Hz) and beta (13-32 Hz) bands. A subsequent statistical analysis of median spectral power in discrete EEG rhythms revealed significant differences in 7 of the 32 distinct frequencies overall. In conclusion, the results of this study lend support to EEG effects from mobile phones activated in talk-mode.

Biventricular pacing for successful weaning from extracorporal circulation in an infant with complex tetralogy of fallot.

Biventricular pacing therapy is an innovative therapy for improving cardiac output in adult patients with severe heart failure. However, this technique is not yet used in infants with congenital heart disease. We present a six month old infant with tetralogy of fallot and atresia of the left pulmonary artery in which biventricular stimulation led to improved left ventricular function and successful weaning from extracorporeal circulation.

Correction of simple congenital heart defects in infants and children through a minithoracotomy.

BACKGROUND: Minimally invasive surgical techniques in pediatric cardiac surgery have evolved throughout the last 10 years. Advantages of minimally invasive procedures include excellent cosmetic results and superior postoperative outcome. However, safety of minimally invasive techniques has to be proven. METHODS: In 21 female infants and children, a right anterolateral thoracotomy was performed. Mean age was 7.1 years (0.5 to 16.6 years) and mean body weight was 20.8 kg (8.3 to 56 kg). The following defects were repaired: atrial septum defect type II (n = 14); partial atrioventricular septum defect (n = 3); partial anomalous pulmonary venous connection (n = 2); ventricular septum defect (n = 2); mitral valve insufficiency (n = 1); and resection of an embolized atrial septum defect occluder (n = 1). In two cases, aortic cross-clamping was performed by using a transthoracic clamp. In 5 patients, femoral cannulation was performed. Skin incisions were limited to 4 to 7 cm. RESULTS: There was no operative or late mortality. Mean operation time, bypass time, and aortic cross-clamp time were 138 (95 to 275), 72 (32 to 179), and 35 (12 to 120) minutes, respectively. Mean postoperative mechanical ventilation time, mean intensive care unit stay, and mean hospital stay were 3.9 hours (1 to 12 hours), 1.4 days (1 to 3 days), and 12 days (8 to 18 days), respectively. Postoperative complications included hemorrhage in 1 patient requiring surgical intervention. Mean follow-up period was 13.3 months (1 to 36 months). All patients were in New York Heart Association class I postoperatively. Trivial mitral insufficiency was evident in 1 patient operated for partial atrioventricular septum defect. CONCLUSIONS: A small right anterolateral thoracotomy as a minimally invasive technique in pediatric cardiac surgery is a safe and suitable alternative in the operative management of simple congenital heart defects. Cosmetic results are superior, however, improved postoperative outcome has to be proven.

Leukocyte filtration in the early reperfusion phase on cardiopulmonary bypass reduces myocardial injury.

Improved myocardial protection and cardiopulmonary bypass (CPB) have limited, but not abolished, intraoperative myocardial damage due to surgical reperfusion injury after release of the aortic crossclamp. In this double-blind, randomized study, we evaluated whether short-term leukocyte filtration during reperfusion may further reduce myocardial damage. Thirty-eight patients with coronary artery disease were randomly assigned to CPB with (group I; n = 19) or without leukocyte filtration (group II; n = 19). There was no difference in bypass time or crossclamp time between the groups. No patient in group I required catecholamines, whereas three patients in group II were supported with adrenaline or dobutamine on the first and second postoperative day. In addition, troponin T plasma levels were lower in group I (p < 0.05), whereas other markers for tissue injury (CK, CK-MB, LDH, S-GOT and S100B) did not differ. In conclusion, leukocyte filtration during reperfusion may further improve CPB by reducing myocardial damage.

Uncontrolled reoxygenation by initiating cardiopulmonary bypass is associated with higher protein S100 in cyanotic versus acyanotic patients.

BACKGROUND: The systemic reoxygenation injury produced by initiating cardiopulmonary bypass (CPB) in infants with cyanotic heart disease may be associated with cerebral dysfunction and injury. Increased protein S100 (S100) serum levels may indicate cerebral and blood brain barrier damage as well as inflammatory changes, therefore serving to quantify these changes. The present clinical study assessed S100 in cyanotic patients undergoing CPB with normoxic versus hyperoxic paO2 in acyanotic cases and in controls without CPB. METHODS: 43 patients with congenital heart disease aged 5 days to 15 years (mean 4.4 years) were enrolled consecutively and divided in four groups: (1) Cyanotic infants undergoing controlled normoxic reoxygenation on CPB (n = 12), (2) cyanotic infants undergoing uncontrolled hyperoxic reoxygenation on CPB (n = 9), (3) acyanotic infants operated with CPB (n = 16) and (4) patients operated without CPB (n = 6). Blood samples were collected after induction of anesthesia (A), up to 4 hours after surgery (B) and at postoperative day one (C). RESULTS: Preoperative S100 serum levels [microg/l] in all groups were below clinical relevance. S100 increased markedly after surgery in groups 1 and 2. Differences in postoperative S100 levels were significant between groups 1 (0.45 +/- 0.13) and 3 (0.35 +/- 0.09; p = 0.018), between groups 2 (1.41 +/- 0.47) and 3 (p = 0.01), and between groups 2 and 4 (0.29 +/- 0.09; p = 0.045). There were no significant differences in postoperative S100 levels (B) between groups 1 and 2 (p = 0.05), groups 1 and 4 (p = 0.05), or groups 3 and 4 (p = 0.93). CONCLUSION: Uncontrolled hyperoxic reoxygenation on CPB for surgical correction of congenital heart defects is associated with higher S100 levels in cyanotic infants as compared to acyanotic patients undergoing comparable operations.

Synthetic protein treated versus heparin coated cardiopulmonary bypass surfaces: similar clinical results and minor biochemical differences.

OBJECTIVE: Complications associated with cardiopulmonary bypass (CPB) have gained more attention due to increased interest in coronary artery bypass grafting without CPB. The impact of heparin coating of CPB circuits has been discussed controversially. The present study examines if the treatment of the oxygenator surface with a synthetic protein may serve as an alternative to a completely heparin coated circuit. METHODS: Fifty-eight patients undergoing coronary artery bypass grafting with CPB were randomly assigned to completely heparin coated circuits or synthetic protein treated oxygenators in a double blind protocol, focussing on the inflammatory reaction resulting in membrane damage, coagulation changes and markers of cerebral injury or dysfunction. Treatment groups did not differ as to preoperative demographics, and intraoperative clinical data. Patients with any neurologic disease or risk factors for cerebral dysfunction were not included in the study. RESULTS: Postoperative clinical data did not differ between groups. Both surface treatments resulted in similar coagulation activation, hyperfibrinolysis and disseminated intravascular coagulation. Platelet count displayed a difference in favour of the heparin coated group (P = 0.029). Increased leukocyte activation reflected by rising myeloperoxidase concentrations on CPB was present in both synthetic protein and heparin coating groups. Interleukins 6 and 8 reacted similarly, but interleukin 8 increased significantly more (P = 0.0061) at the end of surgery in patients treated with protein treated oxygenators. The same pattern was observed for complement activation as determined by total complement complex (P = 0.006). Both surface changes resulted in moderately increased S-100B protein and neuron specific enolase, without difference between groups. Both markers did not reach concentrations associated with clinical manifestation of cerebral injury. CONCLUSIONS: These results in routine patients with short bypass time, imply that protein treated oxygenators are associated with a limited increase of biochemical markers similar to heparin coating. However, significantly lower interleukin 8 release and complement activation can be achieved by heparin coating. The protein treatment is a standard feature of the oxygenator examined in both groups. It is not associated with additional cost and therefore appropriate for use in routine patients.