Rise In CK Research Articles

Testicular toxicity in cisplatin-treated Wistar rats is mitigated by Daflon and associated with modulation of Nrf2/HO-1 and TLR4/NF-kB signaling

BackgroundTesticular toxicity is a complication of cisplatin therapy and it limits its use. Since cisplatin-induced testicular damage is mediated by inflammation and oxidative stress, evaluation of the protective role of antioxidant and anti-inflammatory molecules such as micronized purified flavonoid fraction (Daflon®) is pertinent. Aim: Therefore, this study investigated the mitigating effect of daflon against cisplatin-induced testicular toxicity. Also, the impact of daflon on Nrf2/HO-1 and TLR4/NF-kB pathways, which are key pathways in cisplatin toxicity, was explored. Materials and methods: After 2 weeks of acclimatization, 20 male albino Wistar rats were allotted at random into 4 equal groups; control, daflon-treated, cisplatin-treated, and cisplatin+daflon-treated. Results: Daflon significantly restored cisplatin-induced reductions in body weight (112.20±9.01 vs. 129.60±5.68, P= 0.0175), body weight gain (-39.80±9.52 vs. −16.80±16.53, P= 0.0154), and testicular weight (1.69±0.08 vs. 1.95±0.13, P= 0.0980) and alterations in testicular histology. In addition, daflon abrogated cisplatin-induced rise in testicular CK (55.53±2.77 vs. 37.40±3.29, P< 0.0001) and LDH (74.52±3.20 vs. 65.89±2.08, P= 0.0009) activities, and lactate content (180.50±4.19 vs. 166.20±2.78, P< 0.0001). Also, daflon alleviated cisplatin-induced suppression of GnRH (5.09±0.60 vs. 10.17±0.51, P< 0.0001), LH (1.33±0.07 vs. 2.77±0.13, P< 0.0001), FSH (0.51±0.10 vs. 1.82±0.09, P< 0.0001), and testosterone (2.39±0.11 vs. 4.70±0.33, P< 0.001) as well as lowered sperm quality. More so, daflon attenuated cisplatin-induced testicular oxidative stress, inflammation, and apoptosis evidenced by daflon-driven suppression of MDA (14.16±0.66 vs. 9.22±0.52, P< 0.0001), TNF-α (79.42±5.66 vs. 54.13±3.56, P< 0.0001), IL-1β (8.63±0.41 vs. 3.37±0.43, P< 0.0001), IL-6 (6.87±0.48 vs. 3.67±0.32, P< 0.0001), and caspase 3 activity (4.20±0.26 vs. 0.72±0.23, P< 0.0001) and DNA fragmentation (34.60±3.05 vs. 17.20±3.19, P< 0.0001), and upregulation of GSH level (0.07±0.03 vs. 0.36±0.03, P< 0.0001), and GPx (5.96±0.46 vs. 11.88±1.05, P< 0.0001), GST (5.16±0.71 vs. 11.50±0.81, P< 0.0001), SOD (1.29±0.15 vs. 2.81±0.29, P< 0.0001), and catalase activities (6.18±0.69 vs. 10.71±0.74, P< 0.0001). Furthermore, daflon upregulated testicular Nrf2 expression (40.25±2.65 vs. 66.62±4.01, P< 0.0001) and HO-1 (4.18±0.56 vs. 8.79±0.55, P< 0.0001) activity but downregulated TLR4 (11.63±0.89 vs. 7.23±0.43, P< 0.0001) and NF-kB levels (113.20±3.36 vs. 78.22±3.90, P< 0.0001) in cisplatin-treated rats. Conclusion: Collectively, the ameliorative effect of daflon on cisplatin-induced testicular toxicity is associated with inhibition of oxidative stress and TLR4/NF-kB-mediated inflammatory pathways and activation of Nrf2/HO-1 signaling.

Whole-Body Electromyostimulation Impacts Physiological Responses During Aerobic Running: A Randomized Trial

ABSTRACTObjective: The aim of the current study was to evaluate the physiological and metabolic responses to running with whole-body electromyostimulation (wbEMS) compared to running without electromyostimulation (control, CG). Methods: Twenty healthy participants (9 male/11 female, age 42 ±7 years) conducted an incremental step test with respiratory gas analysis until exhaustion. Trials were conducted as wbEMS and CG in a random order. As outcome measures, (A) objective total exhaustion, (B) athletic responses (max. time and velocity) and (C) physiological and metabolic responses (V’O2/ kg, V’E, EE, RER, lactate) were compared. (D) The impact on the skeletal muscle was assessed prior, 48 h & 72 h after trial. Results: During both trials, participants (A) ran until total exhaustion. Nonetheless, (B) time and velocity till exhaustion as well as (C) RER prior to the first lactate threshold and V’E were reduced with wbEMS. All other correlates did not differ significantly between wbEMS and CG. Following 48 h and 72 h after the trial with wbEMS, (D) the impact on the skeletal muscle was 7- to 9-fold higher compared to baseline values. Values differed significantly to those after running without wbEMS. Conclusion: With the additional stimulation during voluntary activation, wbEMS induces earlier fatigue and a shift in energy metabolism toward fat utilization. Even during aerobic endurance tasks, a great impact on the skeletal muscle indicated by the rise in CK could be observed which promotes wbEMS as an alternative training stimulus that is easy-to-apply and effective during endurance training.

Longitudinal Changes of Serum Creatine Kinase and Acute Kidney Injury among Patients with Severe COVID-19.

Background Acute kidney injury (AKI) is a common complication of COVID-19. Several etiologies have been identified, including pigment deposition likely associated with myopathic damage. Nevertheless, the relationship between longitudinal creatine-kinase trends and renal outcomes is uncertain. Aim To correlate longitudinal changes in serum creatine-kinase levels with hospital-acquired AKI (beyond 48 h of hospital admission) in severe COVID-19 patients. Methods This is a retrospective cohort study, and creatine-kinase levels were assessed over time in 1551 hospitalized patients with normal renal function at the time of hospital admission. Results In subjects who developed hospital-acquired AKI (n = 126, 8.1%), the serum creatine-kinase concentration before AKI onset was not different when compared to patients without AKI (slope of log creatine-kinase/day = −0.09 [95% CI −0.17 to +0.19] vs. +0.03 [95% CI −0.1 to +0.1]). After AKI diagnosis, serum creatine-kinase levels showed a significantly ascendent slope (slope of log creatine-kinase/day after AKI diagnosis = +0.14; 95% CI + 0.05 to +0.3). The AKI evolution was the main factor associated with the creatine-kinase trend. Subjects with persistent AKI (n = 40, 32%) had rising creatine-kinase levels during hospitalization (slope of log creatine-kinase/day = +0.30 95% CI + 0.19 to +0.51). A rising creatine-kinase trend (n = 114, 8%) was associated with a 1.89-fold higher risk of in-hospital death (95% CI 1.14 to 3.16). Nevertheless, this association disappeared after adjusting AKI evolution and LDH baseline levels. Conclusion In severe COVID-19 patients, a slight increase in creatine-kinase levels was observed after AKI occurrence but not before. Our results show that, at least for the appearance of hospital-acquired AKI, the CK rise does not meet the temporality criterion of causality regarding the occurrence of AKI. Rising creatine-kinase trends were associated with a higher risk of mortality, but this association was modified by AKI evolution and inflammation. There is a limited efficiency for AKI prognosis in the serial follow-up of CK levels in severe COVID-19 patients with normal renal function.

What happens &amp;gt;10 years after percutaneous septal ablation for hypertrophic obstructive cardiomyopathy? Ultra long-term follow-up of 120 patients

Abstract Introduction and methods Recent registry analyses including the European multicenter registry (Euro-ASA) documented a favourable long-term outcome of septal ablation (ASA/PTSMA) competitive to surgical myectomy. There is no information about the period beyond 10 years. We therefore analyzed the outcome in 120 HOCM patients (pts., mean age @ index intervention: 62±13 years) treated with ASA who survived &amp;gt;10 years. Results Mean CK rise during the index intervention was 537±258 U/l (reference: &amp;lt;80). A DDD-pacemaker (DDD-PM) had to be implanted in 26 pts. (22%) for procedure-related AV conduction problems. A re-intervention for residual or recurrent outflow obstruction (LVOTO) had to be performed in 12 pts. (10%; re-PTSMA: 10 pts.; myectomy: 2 pts). These cases included, at their last follow-up visit 107 pts. (89%) were in functional class I or II. During follow-up (159±33 [range: 122–264] months), 12 pts. (8%) died, of these 6 (4%) from non-cardiac, and 6 (4%) from cardiovascular causes including one sudden death. Furthermore, 4 (3%) ICDs were implanted (1 for secondary, 3 for primary prevention of sudden cardiac death). The most frequent clinical problem was atrial fibrillation which occurred in 27 pts. (23%), and which was refractory to rhythm control attempts in 21 pts. (18%). Conclusions The procedure-related DDD-PM rate in this septal ablation cohort including the early learning curve more than doubled the current one. Nevertheless, during ultra long-term follow up a durable clinical improvement was observed with mortality rates around 1%/year, nearly equivalent to that of 0.8% observed in normal populations. Atrial fibrillation is a frequent problem in this elderly, formerly obstructive HCM population. Funding Acknowledgement Type of funding source: None

8. Myositis as an idiosyncratic drug reaction to leflunomide

IntroductionMyositis is a broad diagnosis with a number of potential causes. There are numerous drugs that can lead to myotoxicity. We discuss a case of a patient with known rheumatoid arthritis who developed myositis with no evidence of an additional autoimmune condition and where the most likely cause seems to be leflunomide.Case descriptionA 46-year-old Asian lady with a background of seropositive rheumatoid arthritis and overactive bladder developed increasing muscle weakness. Disease activity was well-controlled on leflunomide which had been started four years ago after an initial trial of methotrexate proved ineffective. Other regular medications include tolterodine and rigevidon (combined oral contraceptive pill), paracetamol and co-codamol. She presented to her GP in February with generalised muscle weakness, fatigue, dry mouth, hair loss and occasional shortness of breath on exertion. Blood tests showed elevated CK at 1132 u/l, ALT 57 u/l (AST normal), LDH 302 u/L, CRP 4 mg/l and ESR 25mm/h.Further tests were subsequently arranged following rheumatology review including ANA and ENA (both negative), an extended myositis panel and HMGCoAR antibodies (also negative). MRI of her lower limbs showed bilateral oedema within the anterior and lateral muscle compartments of her thighs, worse on the left, and in keeping with myositis. Given the possibility of leflunomide being the cause of her symptoms it was stopped. Her CK one month after stopping leflunomide had decreased to 819 u/l and then 389 u/l after four months. The patient reported improvement in her muscle weakness, CK is currently being monitored, and she is awaiting an EMG. A muscle biopsy has been discussed with her previously and although she had refused initially, in view of persistent mild elevation in CK, the biopsy and leflunomide washout will be discussed again with her again. As she is clinically asymptomatic and not keen to try new medications, further immunosuppression has not been started.DiscussionMyositis is seen in a wide range of conditions with numerous possible causes. It can be drug-induced, secondary to viral infections or caused by autoimmune conditions including overlap conditions and idiopathic inflammatory myopathies. Drug-induced myositis is most commonly associated with statins, but has been seen with many different medications.Leflunomide is a disease-modifying anti rheumatic drug used particularly in the treatment of inflammatory arthritis but has also been used in treatment resistant dermatomyositis. It inhibits the mitochondrial enzyme, dihydroorotate dehydrogenase to reduce the reproduction of rapidly dividing cells. A rise in CK is considered a common side effect. We have only found one other case report where leflunomide was suspected to have induced polymyositis, also in a patient with rheumatoid arthritis. Both biochemical and clinical improvement following cessation of leflunomide, with no other inventions raises the likelihood of this being a leflunomide-induced myositis.Key learning pointsWhen faced with a patient with rheumatoid arthritis presenting with symptoms suggestive of myositis, whilst an overlap autoimmune condition is a possibility, it is important to consider potential drug causes. Numerous drugs have been implicated through both direct myotoxicity and immunologically mediated myotoxicity. Importantly for rheumatologists these can include glucocorticoids, antimalarial drugs, colchicine and tumour necrosis factor inhibitors. According to the summary of product characteristics a rise in CK is commonly seen with leflunomide but clinical myositis has only been reported rarely.Conflicts of interestThe authors have declared no conflicts of interest.

2. Pregnancy and myositis

2. Pregnancy and myositis

408. Inflammatory myositis in pregnancy. The value of early diagnosis and aggressive treatment: A case series

Introduction Inflammatory myositis’ (IM) encompasses multi-systemic autoimmune conditions including dermatomyositis (DM), polymyositis (PM) and myositis-overlaps. Diagnostic delays reflect the rarity of IM (1–6 per 1,000,000), the varying presentations associated and a dismissal of symptoms as ‘normal for pregnancy’. Immunosuppression is often withheld unduly. Objectives We aim to increase the awareness of this aggressive yet treatable condition. Methods We describe 4 cases of IM treated in pregnancy. 31 yr multigravida: Known autoimmune disease (hypothyroidism and type-1-diabetes) presents with varying symptoms throughout pregnancy: fatigue and proximal myopathy (12/40), shawl rash (22/40), pneumonia requiring intubation (25/40) and pre-eclampsia (PET) necessitating caesarean section (CS) (26/40). Post-partum, ECMO was required for a progressive organising pneumonia. The unifying diagnosis was DM, treated with IV methylprednisolone (IVMP), rituximab and cyclosporine. 35 yr multigravida: Complicated by gestational diabetes, unexplained transaminitis and proteinuria presented 38/40 with an intrauterine death. Post-partum a photosensitive rash (2/52), inflammatory arthritis (4/52) and organising pneumonia (11/52) developed. CK was normal. MDA-5 (amyopathic) DM was diagnosed and treated with IVMP, cyclophosphamide and methotrexate. 39 yr primip: Known RNA-polymerase diffuse systemic sclerosis (SSc) presented with dyspnoea and orthopnoea, requiring intubation (7/40). CK, troponin and BNP were elevated and myositis-overlap SSc with cardiac, proximal muscle and gastrointestinal involvement diagnosed. Treatment included IVMP and intravenous immunoglobulin. Steroid-sparing agents (azathioprine and rituximab) were instituted to avoid a renal-crisis. She remains pregnant. 30 yr primip: Known anti-SRP (necrotising) myositis, presented with proximal myopathy, respiratory muscle weakness and CK rise (12/40) following discontinuation of maintenance therapy. Re-treated with IVMP and rituximab at 16/40. Emergency CS (32 + 4/40) was performed for placenta praevia. Results Despite extreme presentations of IM peri-partum, all 4 patients were treated aggressively with complete resolution of symptoms. Obstetric outcomes were less favourable. Discussion Rituximab is effective and safe in early pregnancy. Pregnancy should not be a barrier to early diagnosis or treatment.

GRADE III CORONARY PERFORATION: OBSERVING THE INCIDENCE, RISK FACTORS, MANAGEMENT AND OUTCOMES FROM A CANADIAN PROVINCIAL PERSPECTIVE

The aim of the study was to evaluate the incidence, risk factors, outcomes and management of grade III coronary perforations within a provincial centre following percutaneous coronary intervention. We then sought to define a Canada-wide strategy, through the distribution of a national survey, in order to formulate a consensual management strategy for this life threatening complication. Coronary perforation is a rare but serious complication that can occur during percutaneous coronary intervention and is associated with a high risk of morbidity and mortality. In an era were PCI practice has evolved, the data for coronary perforations and a consensus as to the best management practice remains limited. We performed a retrospective analysis of 6816 patients undergoing PCI from 1st April 2012 to 22nd September 2015. Fifty-four patients suffered grade III perforation. Adverse outcomes following coronary perforation were defined as: in-hospital mortality, cardiac tamponade, post-procedure CABG, cardiac arrest, unanticipated rise in CK> 200. Most lesions were complex: type C 40.7%, type B2 22.2%, CTO 27.8%. In-hosp mortality was 7.4%; which was comparable to other studies. Coronary perforation tended to occur predominantly during post-dilatation 20.4%. Following perforation, protamine was used in almost half of the cases (44.4%); coil embolization 1.9%, pericardiocentesis 5.6%, micro-catheter suction 3.7%, fat embolization 3.7%. In hospital death occurred in 7.4% with a one-year mortality of 9.3%. The target lesion revascularisation was 1.9% with a target vessel revascularisation of 1.9%. Worse outcomes were associated with Ellis class 3, NSTEMI/ unstable angina, three vessel disease. Coronary perforation is associated with complex lesions with adverse outcomes being associated with acute coronary syndromes and three-vessel disease, with protamine remaining a useful adjunct in achieving haemostasis.

Resveratrol Does Not Protect from Ischemia-Induced Acute Kidney Injury in an in Vivo Rat Model

Background/Aims: The natural polyphenol resveratrol (RSV) has been shown to ameliorate ischemia/reperfusion (I/R)-induced damage. Therefore, a rat model of I/R-induced AKI equipped with intensive monitoring was utilized to examine direct renal protection by RSV in vivo. Methods: AKI was induced by bilateral renal clamping (45 min) followed by reperfusion (3 h). Solvent-free RSV was continuously infused intravenously (0.056 and 0.28 mg/kg) in a total volume of 7 ml/kg/h starting from 30 min before renal clamping. At a mean arterial blood pressure below 70 mmHg for more than 5 min, bolus injections of 0.5 ml 0.9% NaCl solution were administered repetitively (max. 5 ml/kg/h). Results: No differences could be found between normoxic control groups with/without RSV. Bilateral renal clamping and subsequent reperfusion caused a progressive rise in creatinine, cystatin C, and CK, a decrease in cellular ATP content and diuresis. Infusion of RSV increased sirtuin 1 expression after ischemia/reperfusion and was associated with decreased blood pressure during ischemia and early reperfusion accompanied by an increased requirement of bolus injections as well as with increased expression of TNFα. Conclusion: RSV did not exert protective effects on I/R-induced AKI in the present short-term in vivo rat model. The lack of protection is potentially connected to aggravation of blood pressure instability.

Rosuvastatin safety: An experimental study of myotoxic effects and mitochondrial alterations in rats

Myopathy is the most commonly reported adverse effect of statins. All statins are associated with myopathy, though with different rates. Rosuvastatin is a potent statin reported to induce myopathy comparable to earlier statins. However, in clinical practice most patients could tolerate rosuvastatin over other statins. This study aimed to evaluate the myopathic pattern of rosuvastatin in rats using biochemical, functional and histopathological examinations. The possible deleterious effects of rosuvastatin on muscle mitochondria were also examined. The obtained results were compared to myopathy induced by atorvastatin in equimolar dose. Results showed that rosuvastatin induced a rise in CK, a slight increase in myoglobin level together with mild muscle necrosis. Motor activity, assessed by rotarod, showed that rosuvastatin decreased rats’ performance. All these manifestations were obviously mild compared to the prominent effects of atorvastatin. Parallel results were obtained in mitochondrial dysfunction parameters. Rosuvastatin only induced a slight increase in LDH and a minor decrease in ATP (∼14%) and pAkt (∼12%). On the other hand, atorvastatin induced an increase in LDH, lactate/pyruvate ratio and a pronounced decline in ATP (∼80%) and pAkt (∼65%). These findings showed that rosuvastatin was associated with mild myotoxic effects in rats, especially when compared to atorvastatin.

P.191 - Rituximab for the treatment of anti-HMGCR necrotizing autoimmune myopathy

The effectiveness of rituximab in refractory myositis has been suggested by case reports and case series. Recently, anti-HMGCR, a new autoantibody associated with necrotizing autoimmune myopathy and related to statin exposure was discovered. Our objective was to address the effectiveness of rituximab in the subgroup of anti-HMGCR necrotizing autoimmune myopathy. We identified 4 patients with anti-HMGCR necrotizing autoimmune myopathy that were treated with rituximab. Medical records were reviewed to assess their clinical presentation, muscle testing, serum CK levels, corticosteroid doses and associated immunosuppressant agents while receiving rituximab, and their evolution at last follow-up. Only one patient had previous statin exposure. Two patients had a slowly-progressive dystrophic-like presentation over 20 years. All patients had a relapsing disease and needed multiple therapy trials and combination to maintain remission. Two patients were resistant to rituximab and clearly IVIg-dependent, requiring long-term treatment with IVIg to maintain remission. One patient had a thrombotic event while on IVIg and was successfully switched to rituximab. Another patient experienced a biological flare with an isolated CK rise following IVIg discontinuation yet subsequent slowly-progressive CK lowering with rituximab re-infusion and introduction of methotrexate. At last follow-up all patients were in clinical remission. Two of them were still on IVIg with low-dose prednisone +/− azathioprine. Two patients were adequately controlled with rituximab and low-dose prednisone +/− methotrexate. Our patients with anti-HMGCR necrotizing autoimmune myopathy had a refractory disease with multiple relapses. Larger prospective trials are needed to confirm potential efficacy of rituximab in this subgroup of patients.

Rare form of basal ballooning without reduction of left ventricular function in takotsubo cardiomyopathy

Fig. 1. Basal ballooning of a well-contracting left ventricle with an EF of 60%. A 54-year old female patientwas admitted to the hospital because of chest pain and dyspnoea together with arterial hypertension, diabetes mellitus type II and a weight of 110 kg. Severe episodes of stressrelated events were in the past history of the patient. ECGwasnormal under two controls. Troponinwas slightly increased but CK and CK-MB was normal. Echocardiography showed a well contracting left ventricle with inferior hypokinesia. Coronary angiography revealed normal coronary arteries with a dominant right coronary artery. Left ventricular angiography showed normal sized, hypertrophied left ventricular function with basal ballooning resembling takotsuko cardiomyopathy (Fig. 1). In conclusion, this is a very rare case of basal ballooning in stressrelated takotsubo cardiomyopathy with a frequency with about 1% [1]. Apical ballooning in takotsubo cardiomyopathy accounts for 85% and mid-ventricular ballooning for about 14%. Sometimes there is a mixture with apical and mid-ventricular ballooning in the sense of inferoapical contraction impairment [2]. The slight increase of troponin without CK and CK-MB rise is a diagnostic marker of takotsubo cardiomyopathy.

Abstract 9297: Incidence and Implications of Aborted Myocardial Infarction in STREAM

Background: Timely and effective reperfusion therapy in patients (pts) with ST-segment elevation myocardial infarction (STEMI) may avoid significant necrosis. Aborted MI (AbMI) was a pre-specified (previously unreported) endpoint in the STREAM (STrategic Reperfusion therapy Early After MI) trial comparing a pharmacoinvasive strategy (Gp A) vs. primary PCI (Gp B) in STEMI pts presenting within 3 hours of symptom onset. Methods: 1754 pts with interpretable electrocardiograms (ECGs) and sequential biomarkers were included. AbMI was defined by successful reperfusion i.e. core laboratory assessed worst lead ST-elevation resolution ≥50% (90-min post-tenecteplase (TNK) in Gp A or 30-min post-PCI in Gp B), and minimal rise in biomarkers (≤2 times ULN rise in CK or CKMB) or if unavailable, ≤5xULN rise in troponin. All pts received heparin and clopidogrel at first medical contact. Results: In Gp A, 11.1% (n=99) had AbMI vs. 6.9% (n=59) in Gp B (p&lt; 0.01). AbMI pts were younger, more often had prior MI, exhibited Killip I, had less baseline ΣST-deviation, and fewer Q waves within their acute infarct zone (Table). Within Gp A, AbMI pts had faster time to TNK and a lower all-cause death/shock/congestive heart failure (CHF)/re-MI than non-AbMI pts; this distinction was not evident in Gp B. Total ischemic time was 100 minutes longer in Gp B AbMI pts. Forty-five pts (i.e. 2.5%; evenly distributed by treatment) had masquerading MI with minimal biomarker elevation and persistent ST-elevation in sequential ECGs related to left ventricular hypertrophy, pericarditis, or early repolarization. Conclusions: These data demonstrate that fibrinolysis coupled with anti-thrombotic and antiplatelet therapy more frequently aborts MI: such pts have more favorable outcomes compared to non-AbMIs. Diligent review of ECG evolution in STEMI is necessary to distinguish AbMI from infarct masquerade.

Predictors of 30-Day Mortality After Percutaneous Coronary Intervention: Establishment of a PCI Risk Model

symptoms, significant ECG changes, and/or rise in CK or troponin-I >3× upper limit of normal [or above baseline values in acute coronary syndromes (ACS)], and distinct fromthe indexevent) in14,584 consecutivePCIprocedures from April 2004 to September 2009. Results: Patients with PPMI (n= 184; 1.3%) compared to those without PPMI (n= 14,400) were older (67± 13 vs. 64± 12 years), had lower left ventricular ejection fraction (LVEF) (49± 14 vs. 53± 12%), and greater incidence of pre-existing heart failure and chronic lung disease (all p 70% of models) and chronic lung disease (predictive in >50% of models) increased the ROC to 90.7%; H-LÝ=Ý1.09 (pÝ=Ý0.78) and 91.6%; H-LÝ=Ý0.78 (pÝ=Ý0.94), respectively. Conclusion: CS, eGFR, OHCA and EF independently predicted 30-day mortality in unselected PCI cases with excellent statistical discrimination and calibration. This validated, simple clinical risk model may be useful in risk assessment prior to PCI. represent a high-risk cohort with considerably higher 30-day mortality, suggesting increased vigilance postprocedure is warranted. doi:10.1016/j.hlc.2011.05.354

A Patient with Inclusion Body Myositis suffering from Left Thalamic Hemorrhage

We report a case of a 74-year-old man with dual disabilities. The patient suffered from inclusion body myositis for 13 years, and then suddenly developed right hemiplegia due to a left thalamic hemorrhage, and was transferred to our department for further rehabilitation after undergoing conservative treatment at the acute stage. Although his hemiplegia considerably improved at admission(Brunnstrom stage V/V), he experienced a severe disturbance when standing up and walking because of muscle weakness in the pelvic girdle and upper thighs, and sensory disturbance in his right lower extremity, and therefore had to wear a waist belt for assistance during standing up and a plastic Ankle Foot Orthosis(AFO)with a solid ankle on the right side for stability during walking. To improve his impairment, he underwent muscle strengthening training for the pelvic girdle and lower extremities as much as an ordinary hemiplegic patient, and his muscle strength increased without any muscle pain or blood CK rise. After 12 weeks of the training, he could stand up and walk independently 80m with a tripod cane and AFO, requiring no assistance. In conclusion, this patient with dual disabilities was able to improve his ability to stand up and walk in spite of mild hemiplegia, and the muscle strengthening training he underwent was not harmful even though the patient also suffered from inclusion body myositis.

Interleukin-6 Mediated Non-ischemic Injury To Cardiac Myocytes During Marathon Running

Since the fatal collapse of the legendary Pheidippides in 490 BC, mechanisms contributing to sudden cardiac death as shown to occur in 1 per 50,000 marathon runners during races are poorly understood. PURPOSE To explore the role of an acute inflammatory response to exertional rhabdomyolysis in the triggering of acute cardiac events. METHODS measurement of total creatine kinase, interleukin (IL)-6, C reactive protein (CRP), creatine kinase MB (CK-MB), cardiac troponin T (cTnT) and ischemia modified albumin (IMATM) by the albumin cobalt binding ACB ± TM Test in 46 asymptomatic middle-aged marathon runners before and sequentially after the 2001–02 Boston Marathons. RESULTS A 15-fold post-race rise in CK was accompanied by 40- and 20- fold increases in IL-6 and C-reactive protein respectively. There was a transient increase in cTnT to diagnostically indeterminate levels with no change in IMA by the ACB Test despite a 14-fold increase in CK-MB (Table 1).TableCONCLUSIONS These findings are consistent with non-ischemic injury to cardiomyocytes without necrosis perhaps due to IL-6 mediated leakage of cytosolic cTnT. Strategies for primary prevention of exertional cardiac events including the Pheidippides factor and the diagnostic assessment of such runners for acute coronary syndromes are considered. Supported by NIH Grants PO1- DA14528, K05-DA00101, K05-DA0064.

Interleukin-6 Mediated Non-ischemic Injury To Cardiac Myocytes During Marathon Running

Since the fatal collapse of the legendary Pheidippides in 490 BC, mechanisms contributing to sudden cardiac death as shown to occur in 1 per 50,000 marathon runners during races are poorly understood. PURPOSE To explore the role of an acute inflammatory response to exertional rhabdomyolysis in the triggering of acute cardiac events. METHODS measurement of total creatine kinase, interleukin (IL)-6, C reactive protein (CRP), creatine kinase MB (CK-MB), cardiac troponin T (cTnT) and ischemia modified albumin (IMATM) by the albumin cobalt binding ACB ± TM Test in 46 asymptomatic middle-aged marathon runners before and sequentially after the 2001–02 Boston Marathons. RESULTS A 15-fold post-race rise in CK was accompanied by 40- and 20- fold increases in IL-6 and C-reactive protein respectively. There was a transient increase in cTnT to diagnostically indeterminate levels with no change in IMA by the ACB Test despite a 14-fold increase in CK-MB (Table 1).TableCONCLUSIONS These findings are consistent with non-ischemic injury to cardiomyocytes without necrosis perhaps due to IL-6 mediated leakage of cytosolic cTnT. Strategies for primary prevention of exertional cardiac events including the Pheidippides factor and the diagnostic assessment of such runners for acute coronary syndromes are considered. Supported by NIH Grants PO1- DA14528, K05-DA00101, K05-DA0064.

Ein-Jahresverlauf nach echokardiographisch geführter perkutaner Septumablation bei hypertropher obstruktiver Kardiomyopathie

Percutaneous transluminal septal myocardial ablation by alcohol-induced septal branch occlusion was introduced as a new treatment option in symptomatic patients with hypertrophic obstructive cardiomyopathy. Echocardiographic monitoring of the procedure resulted in improvement of acute results. In this study we analyzed the follow-up after echocardiographic guided septal ablation. 100 consecutive symptomatic patients (50 men; age 52.7 +/- 15.7 years; NYHA class 2.8 +/- 0.6) underwent percutaneous septal ablation with echocardiographic monitoring. All patients had clinical and non-invasive 3-months and 1 year follow-up. Acute reduction of the left ventricular outflow tract gradient was achieved in 99 patients from 76 +/- 37 to 19 +/- 21 mm Hg at rest, from 104 +/- 34 to 43 +/- 31 mm Hg during Valsalva maneuver, and from 146 +/- 45 to 59 +/- 42 mm Hg post extrasystole (p < 0.0001, each). Mean CK rise was 570 +/- 236 U/l. One patient died at day 2 due to fulminant pulmonary embolism following deep venous thrombosis, and 8 patients required a permanent DDD-pacemaker due to postinterventional complete heart block. During follow-up no further patient died. All living 99 patients showed clinical improvement to NYHA-class 1.4 +/- 0.6 after 3 months and 1.5 +/- 0.6 after 1 year (p < 0.0001, each). Non-invasive follow-up studies observed ongoing outflow tract gradient reduction, decrease of septal and left ventricular posterior wall thickness, and improvement of exercise capacity and time. Percutaneous septal ablation is an effective treatment of symptomatic patients with hypertrophic obstructive cardiomyopathy. During one-year follow-up remodeling after induced therapeutic septal infarction resulted in improvement of acute gradient reduction with ongoing symptomatic and objective improvement and without significant complications and side-effects.

Effects of prior exercise on eccentric exercise-induced neutrophilia and enzyme release

The purpose of this study was to determine the effects of prior exercise on changes in circulating neutrophils, neutrophil activation, and myocellular enzymes following a standardized bout of eccentric exercise. Twenty-four male volunteers were randomized into three groups (N = 8). Group C performed 10 sets of 10 eccentric contractions of the quadriceps muscles with both legs (100% of the concentric IRM). Group D and Group F exercised for 2 h at 56%VO2max on a cycle ergometer followed by a similar bout of eccentric contractions. Group F also received 7.5 mL x kg(-1) of a carbohydrate-electrolyte beverage every 30 min during the submaximal exercise, whereas group D received no fluid. Body weight remained unchanged in groups C and F and decreased in group D by 1.56 +/- 0.34 kg. Ultrastructural Z-Band damage increased three-fold following exercise and remained elevated 3 d after exercise but was not different among groups. Circulating neutrophils were elevated more in group D compared with those in group C immediately after the exercise or rest period, and this difference persisted 3 h after the eccentric exercise. Serum lactoferrin concentrations increased 3.3-fold after exercise in all groups (P < 0.01). Creatine kinase levels (CK) rose in all subjects, with subjects in Group F and D having a significantly greater rise in CK after exercise compared with those in group C. These data indicate that submaximal exercise followed by a bout of eccentric exercise results in similar amounts of myofibrillar injury with a larger neutrophil response and CK release.

Guiding of Percutaneous Transcoronary Septal Myocardial Ablation in Hypertrophic Obstructive Cardiomyopathy by Myocardial Contrast Echocardiography:

Percutaneous transluminal septal myocardial ablation (PTSMA) by alcohol injection into septal branches (SB) of the left coronary artery has evolved as a promising therapeutic option for selected patients with obstructive hypertrophic cardiomyopathy (HOCM). Originally, probatory balloon occlusion of the target vessel was considered to be predictive for definitive reduction of left ventricular outflow gradients (LVOTG). The need for additional information regarding the exact site and extension of the therapeutic septal infarction is demonstrated by a case report. In this patient, myocardial contrast echocardiography (MCE) was performed prior to alcohol injection and showed that the septal area corresponding to LVOTG formation was supplied by a SB originating atypically from an intermediate branch. PTSMA guided by MCE led to complete LVOTG elimination without sustained rhythm disturbances and with a minimum CK rise.