Immune checkpoint inhibitors versus second line chemotherapy for patients with lung cancer refractory to first line chemotherapy.

PURPOSE: Anti Programmed Death-ligand (PD1/PD-L1) directed immune-checkpoint-inhibitors (ICI) are widely used to treat patients with advanced non-small cell lung cancer (NSCLC) who progress after first line chemotherapy. The best strategy after early progression under first line has not been specifically studied. PATIENTS AND METHODS: We conducted a multicenter, retrospective study including all consecutive NSCLC patients progressing within the first 3 months following introduction of first-line chemotherapy and being treated with second line ICI monotherapy or chemotherapy between March 2010 and November 2017. We analysed the clinicopathological data and outcome under second line chemotherapy vs. second line ICI: objective response rate (ORR), progression-free survival (PFS), overall survival (OS. RESULTS: We identified 176 patients with refractory disease, 99 who received subsequent immunotherapy and 77 undergoing chemotherapy. The 2 populations were comparable regarding the main prognostic criteria, median age was 60, main histology was adenocarcimoma (68.2%). PFS was not significantly different between both treatments 1.9 [1.8-2.1] versus 1.6 month [1.4-2.0] (P=0.125). Compared to chemotherapy, ICI treated patients had a superior OS (P=0.03) (Median [95% CI] OS 4.6 [2.8-6.7] versus 4.2 months [3.4-5.9] and a non-significant improvement in ORR (17.2% versus 7.9%, respectively, P=0.072). Poor performance status (ECOG PS≥2) and a higher number of metastatic sites (≥3) were associated with poorer prognosis. KRAS-mutated patients did not seem to benefit more from ICI than chemotherapy. CONCLUSIONS: ICI appears to be the preferred second-line treatment for patients who are refractory to first line chemotherapy.

Myelin status is associated with change in functional mobility following slope walking in people with multiple sclerosis.

BACKGROUND: The level of myelin disruption in multiple sclerosis patients may impact the capacity for training-induced neuroplasticity and the magnitude of therapeutic response to rehabilitation interventions. Downslope walking has been shown to increase functional mobility in individuals with multiple sclerosis, but it is unclear if myelin status influences therapeutic response. OBJECTIVE: The current study aimed to examine the relationship between baseline myelin status and change in functional mobility after a walking intervention. METHODS: The Timed Up and Go test was used to measure functional mobility before and after completion of a repeated, six-session slope walking intervention in 16 participants with relapsing-remitting multiple sclerosis. Multi-component T2 relaxation imaging was used to index myelin water fraction of overall water content in brain tissue compartments. RESULTS: Results demonstrated that the ratio of the myelin water fraction in lesion to normal-appearing white matter (myelin water fraction ratio) significantly predicted 31% of the variance in change in Timed Up and Go score after the downslope walking intervention, where less myelin disruption was associated with greater intervention response. CONCLUSIONS: Myelin water content fraction ratio may offer a neural biomarker of myelin to identify potential responders to interventions targeting functional impairments in multiple sclerosis.

Establishing between-session reliability of TMS-conditioned soleus H-reflexes.

Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can be used to evaluate descending corticomotor influences on spinal reflex excitability through modulation of the Hoffman reflex (H-reflex). The purpose of this study was to characterize between-session reliability of cortical, spinal, and cortical-conditioned spinal excitability measures collected from the soleus muscle. Thirteen able-bodied young adult participants were tested over four sessions. Intraclass correlation coefficients were calculated to quantify between-session reliability of active motor threshold (AMT), unconditioned H-reflexes (expressed as a percentage of Mmax), and conditioned H-reflexes using short-latency facilitation (SLF) and long-latency facilitation (LLF). Pearson correlation coefficients were calculated to assess associations between H-reflex facilitation and unconditioned H-reflex amplitude. Between-session reliability for SLF (ICC=0.71) was higher than for LLF (ICC=0.45), was excellent for AMT (ICC=0.95), and was moderate for unconditioned H-reflexes (ICC=0.63). Our results suggest moderate-to-good reliability of SLF and LLF to evaluate cortical influences on spinal reflex excitability across multiple testing sessions in able-bodied individuals.

Electrical stimulation-evoked resistance exercise therapy improves arterial health after chronic spinal cord injury.

STUDY DESIGN: Repeated measures training intervention. OBJECTIVES: To evaluate the effects of neuromuscular electrical stimulation (NMES)-induced resistance exercise therapy on lower extremity arterial health in individuals with chronic, complete spinal cord injury (SCI). We define "arterial health" using three surrogate markers: (a) resting diameter, (b) flow-mediated dilation (FMD), and (c) arterial range. SETTING: Department of Kinesiology, University of Georgia, USA. METHODS: We assessed five 36+/-5-year-old male individuals with chronic, complete SCI before, during, and after 18 weeks of training. The quadriceps femoris muscle group of both legs were trained twice a week with 4 x 10 repetitions of unilateral, dynamic knee extensions. The health of the posterior tibial artery was assessed using a B-mode ultrasound unit equipped with a high-resolution video capture device. Proximal occlusion was used to evoke ischemia for 5 min and then for 10 min. FMD was calculated using the peak diameter change (above rest) following 5 min occlusion. Arterial range was calculated using minimum (during occlusion) and maximum diameters (post 10 min occlusion). Hierarchical linear modeling accounted for the nested (repeated measures) experimental design. RESULTS: FMD improved from 0.08+/-0.11 mm (2.7%) to 0.18+/-0.15 mm (6.6%) (P=0.004), and arterial range improved from 0.36+/-0.28 to 0.94+/-0.40 mm (P=0.001), after 18 weeks of training. Resting diameter did not significantly change. CONCLUSIONS: Home-based, self-administered NMES resistance exercise therapy consisting of 80 contractions/week improved FMD and arterial range. This provides evidence that resistance exercise therapy can improve arterial health after SCI, which may reduce the risk of future cardiovascular disease.

Electrically stimulated resistance training in SCI individuals increases muscle fatigue resistance but not femoral artery size or blood flow.

STUDY DESIGN: Longitudinal. OBJECTIVES: The purpose of this study was to evaluate the effect of lower extremity resistance training on quadriceps fatigability, femoral artery diameter, and femoral artery blood flow. SETTING: Academic Institution. METHODS: Five male chronic spinal cord injury (SCI) individuals (American Spinal Injury Association (ASIA): A complete; C5-T10; 36+/-5 years old) completed 18 weeks of home-based neuromuscular electrical stimulation (NMES) resistance training. Subjects trained the quadriceps muscle group twice a week with four sets of 10 dynamic knee extensions against resistance while in a seated position. All measurements were made before training and after 8, 12, and 18 weeks of training. Ultrasound was used to measure femoral artery diameter and blood flow. Blood flow was measured before and after 5 and 10 min of distal cuff occlusion, and during a 4-min isometric electrical stimulation fatigue protocol. RESULTS: Training resulted in significant increases in weight lifted and muscle mass, as well as a 60% reduction in muscle fatigue (P = 0.001). However, femoral arterial diameter did not increase. The range was 0.44+/-0.03 to 0.46+/-0.05 cm over the four time points (P = 0.70). Resting, reactive hyperemic, and exercise blood flow did not appear to change with training. CONCLUSION: NMES resistance training improved muscle size and fatigue despite an absence of response in the supplying vasculature. These results suggest that the decreases in arterial caliber and blood flow seen with SCI are not tightly linked to muscle mass and fatigue resistance. In addition, muscle fatigue in SCI patients can be improved without increases in arterial diameter or blood flow capacity.

Endoventricular patch reconstruction of ischemic failing ventricle. a single center with 20 years experience. advantages of magnetic resonance imaging assessment.

The left ventricular reconstruction (LVR) with endoventricular circular patch plasty (EVCPP) was reported in 1984 as a surgical method to rebuild left ventricular aneurysm or asynergy after myocardial infarction. Scarred LV wall can be dyskinetic or akinetic according to the type of infarction (transmural or not), and the progressive dilatation of LV (remodeling) depends on the size of the asynergic scar. Assessment of this extension and of LV volume and performances, is easy and reliable by magnetic resonance (CMR). The surgical technique is based on the insertion inside the ventricle on contractile myocardium, of a circular patch restoring curvature and physiological volume, and allowing exclusion of asynergic non resectable regions. The ventricular reconstruction method also has other components that include coronary revascularization (almost always), mitral repair (if needed) and endocardectomy when spontaneous or inducible ventricular tachycardia (VT) are present. The experience of the authors (> 1100 cases) and results obtained by other Centers, allows proposal of this technique as a way to treat the ischemic failing ventricle.

Ventricular arrhythmias after LV remodelling: surgical ventricular restoration or ICD?

UNLABELLED: Ventricular arrhythmias cause ~50% of deaths in remodeled ventricles after myocardial infarction, and the Multicenter Automatic Defibrillator Implantation Trial (MADIT II) showed that the Implantable Cardioverter Defibrillator (ICD) saved lives in high risk coronary patients with advanced left ventricular dysfunction. We studied 382 patients with remodeled hearts by preoperative Ventricular stimulation (PVS) to evaluate surgical ventricular restoration (SVR) that excludes scar and lower ventricular volume alters the early and late arrhythmia process without ICD utilization. METHODS: Clinical and hemodynamic results before and after SVR in post-infarction patients, are compared to contrast spontaneous and/or inducible ventricular tachycardia to patients without arrhythmias. Study arrhythmia groups included: Spontaneous in 87 patients with clinical documented ventricular arrhythmias and inducible or not inducible ventricular tachycardia: Inducible in 105 patients without clinical ventricular arrhythmias but PVS inducible ventricular tachycardia; and No arrhythmias in 190 patients without spontaneous or PVS inducible ventricular tachycardia. RESULTS: Preoperative LV end systolic volume index helped define preoperative arrythmia potential: Spontaneous > 120/m(2), inducible > 100 ml/m(2), and none < 100ml/m(2). Overall operative mortality rate was 7.6% (29/382). Sudden cardiac death rate was 2.5% causing 18.7% of all deaths. Surgical management reduced inducible ventricular tachycardia, from 41% preoperatively (144/352) to 8% (26/307) at early study, and 8% (14/177) one year later. Cardiac mortality was low at 5-years and not different between groups, despite use of only one late ICD device. CONCLUSIONS: Favorable electrical success rate and low mortality always included volume reduction to interrupt functional re-entry circuits, but also added endocardiectomy, cryoablation, CABG and mitral repair when needed. Overall SVR findings show volume and shape alteration limits ventricular arrhythmias that impair prognosis, and suggests ICD devices are not needed.

Mechanical synchrony: role of surgical ventricular restoration in correcting LV dyssynchrony during chamber rebuilding.

Cardiac failure is frequently complicated by intra and or interventricular conduction delay that results in dyssynchronized cardiac contraction and relaxation. In contrast to an electrical intervention by biventricular pacing, this study tests the capacity of geometric rebuilding by surgical ventricular restoration (SVR) to restore a more synchronous contractile pattern through mechanical reconstruction without exogenous pacing input. Thirty patients (58 +/- 8 years) undergoing SVR at the Cardiothoracic Center of Monaco were prospectively evaluated with a protocol which uses simultaneous measurements of ventricular volumes and pressure to construct pressure/volume (P/V) and pressure/length (P/L) loops. Mean QRS duration was within normal limits (100 +/- 17 ms) preoperatively. Preoperative LV contraction was highly asynchronous. Endocardial time motion was either early or delayed at the end-systolic phase, yielding P/L loops with abnormal in size, shape, and orientation. Postoperatively, SVR resulted in leftward shifting of P/V loops and increased area; endocardial time motion and P/L loops almost normalized. The hemodynamic consequences of SVR included improved ejection fraction; reduced end-diastolic and end-systolic volume index; more rapid peak filling rate; peak ejection rate and mechanical efficiency resulting in mechanical intraventricular resynchronization that improves LV performance.

Magnesium enrichment and distribution in plants.

Food products enriched with stable isotopes are used in nutrition to study the metabolic fate of nutrients in humans. This study reports on the labeling of green beans, white beans, soybeans and wheat with a stable isotope of magnesium (25Mg) obtained in greenhouse conditions for further studies on magnesium bioavailability. Soybean and green bean are the most efficient plant species to obtain large amounts of edible parts rapidly with a minimum loss of labeled Mg in other parts of the plants. The results obtained showed that a relatively high percentage of the magnesium found in seeds (grains/beans) can come from the redistribution of magnesium previously accumulated in other organs.

Concurrent cardiovascular and resistance training in healthy older adults.

PURPOSE: The recommendations for exercise training and physical activity for older adults include cardiovascular and resistance training components (CVT and RT, respectively). The purpose of the present investigation was to compare the fitness benefits of concurrent CVT and RT with those attained through an equivalent duration of CVT or RT alone. METHODS: Thirty-six participants (ages 60-84) were assigned to a control group or to one of three exercise treatment groups. The treatment groups exercised three times per week for 12 wk using RT (N = 11), CVT (N = 10), or CVT and RT (BOTH, N = 9). Pre- and post-training, participants performed a submaximal exercise test (GXT), five repetition-maximum strength tests (5RM), and the AAHPERD functional fitness test for older adults. RESULTS: All exercise treatment groups revealed lower resting heart rate and rate-pressure product; lower exercise diastolic blood pressure and rating of perceived exertion; increased GXT duration; increased leg, back, and shoulder 5RM scores; and improved AAHPERD flexibility, coordination, and cardiovascular endurance scores. The exercise treatment groups responded differently on the following: RT and BOTH enhanced arm and chest strength more than CVT; and BOTH enhanced AAHPERD strength and agility scores more than CVT or RT. CONCLUSIONS: Concurrent CVT and RT is as effective in eliciting improvements in cardiovascular fitness and 5RM performance as CVT or RT, respectively. Moreover, incorporating both CVT and RT in exercise programs for older adults may be more effective in optimizing aspects of functional fitness than programs that involve only one component.

Effects of the Dor procedure on left ventricular dimension and shape and geometric correlates of mitral regurgitation one year after surgery.

OBJECTIVES: In the present study we retrospectively analyzed ventriculographic data from symptomatic patients after myocardial infarction who underwent the Dor procedure (endoventricular circular patch plasty repair) to evaluate left ventricular shape 1 year after the operation and to analyze the geometric correlates of late mitral regurgitation. METHODS: Forty-four patients with previous transmural anterior myocardial infarction comprised the study group. Left ventricular volumes, global left ventricular systolic and diastolic sphericity, the extent of wall motion abnormalities, and the presence and degree of mitral regurgitation were analyzed before and 1 year after operation. RESULTS: Comparing preoperative diastole to systole within the cardiac cycle, left ventricular shape becomes more elliptical in systole than it was in diastole (eccentricity index closer to 1). The intervention leads to an increased diastolic sphericity, but for each cardiac cycle, the systolic shape is more elliptical relative to its diastolic counterpart in respect to basal conditions. Mitral regurgitation was detected after operations in 17 patients; 14 of them did not have mitral regurgitation before operations. Patients with late mitral regurgitation had greater preoperative volumes and more spherical chamber than did patients without late mitral regurgitation. CONCLUSIONS: Despite a more spherical postoperative left ventricular chamber, systolic pump function improves after the Dor procedure, mainly for the improvement in inferior wall shortening. The presence of late mitral regurgitation is relatively frequent in this series of patients, and this emphasizes the importance of a more accurate quantitative evaluation of preoperative functional mitral regurgitation to repair the valve when appropriate. Geometric correlates of late mitral regurgitation appeared to be greater chamber sphericity and larger ventricular volumes preoperatively.

Left ventricular reconstruction by endoventricular circular patch plasty repair: a 17-year experience.

The first experience with endoventricular circular patch plasty (EVCPP) was reported in 1984 as a surgical method to rebuild left ventricular (LV) geometry made more spheric after myocardial infarction. The consequence is dilated ischemic cardiomyopathy. In anterior infarction, the free LV wall and septum are scarred and become dyskinetic or akinetic. The fundamental approach excludes the noncontractile (asynergy) and nonresectable regions to restore more normal size and shape. The current experience of our group in 2001, includes 1,011 patients, and confirmation of our results by others, including an international team. The basic components are LV reconstruction, revascularization, and mitral repair (when needed), which form an integrated method of surgical management. Endocardiectomy and cryoablation are used with spontaneous and inducible ventricular arrhythmias. This article reviews these results and summarizes 10 important points concerning the surgical treatment of ischemic dilated cardiomyopathy that may provide guidelines for the future. These data indicate EVCPP, and its variations, form the central theme in surgical treatment of congestive heart failure.

Intermediate survival and predictors of death after surgical ventricular restoration.

This study examined the effects of Dor procedure on long-term survival in patients with previous transmural anterior myocardial infarction who were referred to a single experienced center for left ventricular reconstruction by endoventricular patch-plasty repair. Our aim was to evaluate the impact of this procedure on long-term survival and to assess the ability of preoperative, perioperative, and postoperative variables to predict late survival. Major indications for surgery were left ventricular dysfunction, angina, ventricular arrhythmias, or a combination of the three; 20 patients underwent urgent cardiac surgery. The total group was 245 patients, with 8.1% hospital mortality, and 19 patients lost to follow-up [corrected]. The study group comprised 207 patients. Many pre- and postoperative clinical, hemodynamic, and functional variables, as well as operative parameters, were studied by univariate analysis. During a mean follow-up period of 39+/-19 months, 30 end points were observed, including 27 deaths and 3 heart transplants. Event-free survival was 98%+/-1% at 1 year, 95.8%+/-1.4% at 2 years, and 82.1%+/-3.3% at 5 years. Cox regression analysis showed preoperative New York Heart Association functional class, ejection fraction, end systolic volume index, and remote asynergy as independent predictors of mortality. The procedure has a favorable impact on 5-year survival. Independent predictors of late survival are the preoperative functional status and the left ventricular systolic function.

Surgical ventricular restoration in patients with postinfarction coronary artery disease: effectiveness on spontaneous and inducible ventricular tachycardia.

Surgical ventricular reconstruction (SVR) involves resection of scar, septal exclusion, cavity reduction by endoventricular patch, and complete coronary grafting. At the Cardiothoracic Centre of Monaco, ventricular stimulation (PVS) is performed before SVR, unless contraindicated. In patients with spontaneous and/or inducible ventricular arrhythmias, nonguided endocardiectomy and cryosurgery are added. We report clinical and hemodynamic results after SVR in postinfarction patients, to compare management of patients with spontaneous and/or inducible ventricular tachycardia, with those without arrhythmias. The 3 subsets were: Group A, 87 patients with clinical documented ventricular arrhythmias and inducible or not inducible ventricular tachycardia (Spontaneous); Group B, 105 patients without clinical ventricular arrhythmias but with inducible ventricular tachycardia at PVS (Inducible); and Group C, 190 patients without spontaneous arrhythmias and not inducible ventricular tachycardia at PVS (No arrhythmias). Overall surgical mortality rate was 7.6% (29 of 382). Sudden death mortality was only 18.7% of all deaths. Surgical management caused marked reduction of inducible ventricular tachycardia, from 144 of 352 inducible ventricular tachycardia before surgery (41%), to 26 of 307 (8%) at early study, and 14 of 177 (8%) one year later. Cardiac mortality was low at 5 years, and not different among groups; this indicates that the surgical procedure limits the ventricular arrhythmias that normally impair prognosis in postinfarction dilated cardiomyopathy. We believe the favorable electrical success rate and low mortality are not linked to one aspect of the surgical procedure, but to an integrated approach that relieves ischemia (coronary bypass graft), and reduces left ventricular volumes (SVR) to improve pump function, and nonguided endocardiectomy plus cryoablation, to interrupt functional reentry circuits.

Effects of reconstructive surgery for left ventricular anterior aneurysm on ventriculoarterial coupling.

OBJECTIVE: To investigate left ventricular elastance (Emax) and effective arterial elastance (Ea) in postinfarction left ventricular aneurysm and evaluate their role in left ventricular function improvement after endoventricular circular patch plasty (EVCPP). Ventriculoarterial coupling has never been studied in these patients. PATIENTS: 22 consecutive patients (49 to 73 years) with left ventricular anterior aneurysm. METHODS: Haemodynamic studies were done before and two weeks after EVCPP. Ventriculography was performed during atrial pacing (100 beats/min). Pressure/volume loops were analysed and derived parameters measured. Emax was estimated by applying the "single beat" method. Ea was calculated as end systolic pressure/stroke volume. RESULTS: Left ventricular volumes and Ea decreased after surgery: end diastolic volume index from mean (SD) 155 (53) to 106 (29); end systolic volume index from 112 (51) to 62 (30) ml/m2 (both p < 0.0001); Ea from 1.65 (0.70) to 1.39 (0.41) mm Hg/ml (p = 0.04). Ejection fraction and Emax increased, without significant changes in stroke volume and work. The decrease in Ea was directly correlated with its preoperative value. The time interval between left ventricular pressure upstroke and peak systolic pressure decreased, from 237 (39) to 191 (41) ms (p < 0.0001), paralleling morphological changes in pressure tracings. CONCLUSIONS: After EVCPP, ventriculoarterial coupling improves because of the fall in Ea caused by end systolic pressure reduction. The improvement is related to aortic pressure waveform changes and improved relaxation.

Endoventricular patch reconstruction in large ischemic wall-motion abnormalities.

Endoventricular patch plasty (EVPP) has been used since 1984 to rebuild the left ventricle. The global experience of our group includes more than 835 cases. Large wall-motion abnormalities were detected by the center line method when > 60% of the circumference of the left ventricle was asynergic. In this series, 269 patients had an ejection fraction < 30%. Surgery for repair of large wall-motion abnormalities was conducted on the arrested heart with insertion within the left ventricle of a patch rebuilding the contractile area while leaving a residual volume between 50 and 70 cc/m2 of body surface. The global results of the technique of EVPP are analyzed on the last 700 operated patients. Three series of patients with large wall-motion abnormalities were examined. We conclude that this technique is appropriate in advanced stages of ischemic disease as an alternative to cardiac transplant. At an operative risk of approximately 12%, improvement is obtained in 80% of cases.

Endoventricular patch plasties with septal exclusion for repair of ischemic left ventricle: technique, results and indications from a series of 781 cases.

Most cases of left ventricular aneurysms undergo operation through resection of the exteriorized dyskinetic area with longitudinal suturing of the opening and this technique has been considered by cardiologists (Froehlich et al) to bring no improvement to the morphology and performance of the left ventricle. Some technical modifications have been adopted, such as the septal plicature (Cooley) or circular suturing of the opening (Jatene). Since 1984 our team has used an endoventricular patch, sutured over the contractile area and excluding the akinetic non-resectable scars, bringing a significant and calculable improvement to the left ventricular function. This technique of left ventricular reconstruction (LVR), called endoventricular circular patch plasty (EVCPP) has been already used on more than 750 patients (May 97). Clinical and echographic data for each case are completed by right catheterisation with measurement of the cardiac output, pulmonary arterial pressures (PAP) and programmed ventricular stimulation (PVS), in order to detect eventual ventricular tachycardia (IVT). During left heart catheterisation, the morphology of the left ventricle (LV) is studied on right and left anterior oblique incidences and the LV ejection fraction (EF) is checked globally (GEF) and especially in its contractile portion (CEF). After surgery, a hemodynamic study associated with a PVS, is carried out during the first post-operative month, and again after one year. Results were clinically satisfactory in more than 90% of cases (8.9% of NYHA III-IV), and in more than 90% of cases with ventricular arrhythmia with the hemodynamic persistent EF at one year, superior to the pre-operative CEF. Thus we have to propose the following indications: Elective: This ventricular reconstruction can be recommended for ventricular aneurysms or akinesias with angina, arrhythmias or attacks of cardiac insufficiency, when GEF > 30% and CEF > 40%. The operative mortality rate varies from 1,5 to 3%, which is better than allowing natural evolution. Mandatory: In emergency, when safe immediate circulatory assistance or a cardiac transplant is unavailable, LVR can give hope for survival to more than 80% of patients, whereas natural evolution is without hope. Finally the operative indication is uncertain in two contrasting circumstances: In asymptomatic patients when hemodynamic and angiographic examinations after myocardial infarction show left ventricular dyskinesia. If GEF is below 40% and CEF below 50%, it seems wise to propose LVR in order to prevent unfavourable evolution. In end-stage ischemic cardiomyopathies, if the EF is below 20%, CEF is below 30%, cardiac output is below 1.5 l, and the mean pulmonary pressure is above 25, then a cardiac transplant should be considered. EVCPP with septal exclusion is a safe technique and easily reproduced when associated with coronary revascularization as far as practicable, then EVCPP improves the ventricular function. When associated with sub-total endocardectomy, then EVCPP allows excellent control of VA.

Efficacy of endoventricular patch plasty in large postinfarction akinetic scar and severe left ventricular dysfunction: comparison with a series of large dyskinetic scars.

BACKGROUND: Many believe that dyskinesia is the only predictor of favorable surgical outcome after large myocardial infarction and that akinetic scars do not recover well in patients with globally depressed ventricular function. METHODS: This study evaluates clinical and hemodynamic results of endoventricular circular patch plasty in patients with either large akinetic scar (n = 51) or large dyskinetic scar (n = 49) and depressed left ventricular function (ejection fraction <30%). Groups were comparable for symptoms, indication for operation, and delay from myocardial infarction. Heart failure was a major indication for operation in both groups. Coronary grafting was performed in 98% of patients: 10 had mitral valve repair or replacement, and 47 patients with preoperative ventricular arrhythmias had cryotherapy. In-hospital mortality was 12% (five patients in the akinetic group [10%] and seven in the dyskinetic group [14%]). RESULTS: Results showed an early and late improvement in New York Heart Association functional class and ejection fraction (from 23% +/- 5% to 31% +/- 11% to 40% +/- 13% in akinetic patients and from 23% +/- 6% to 41% +/- 10% to 41% +/- 12% in dyskinetic patients). Ventricular tachycardia was reduced significantly in both groups early and late after the operation. CONCLUSION: We conclude that in patients with either large akinetic or dyskinetic scar and severe left ventricular dysfunction, endoventricular circular patch plasty associated with coronary grafting and cryotherapy, when indicated, provides surviving patients with significant improvement in cardiac function. This approach can be considered as an alternative to heart transplantation in patients with severe left ventricular dysfunction.

Report of the European DNA Profiling Group (EDNAP)--an investigation of the hypervariable STR loci ACTBP2, APOAI1 and D11S554 and the compound loci D12S391 and D1S1656.

This paper describes the results of three collaborative exercises which continues the EDNAP theme to explore whether uniformity of DNA profiling results could be achieved between European laboratories using STRs. In an earlier exercise, complex hypervariable AAAG-repeat STR loci were investigated, but reproducibility was found to be poor because of the variation of techniques used by participating laboratories. In the exercise reported here, an internal allelic ladder composed of ACTBP2 and D11S554 fragments was distributed. This ladder was used to size ACTBP2 analysed by a "singleplex" PCR amplification and D11S554 combined with APOAI1 in a separate "duplex" reaction. Laboratories were asked to test 7 blood stains, one of which was a known control, and to report the results to the co-ordinating laboratory. The exercise demonstrated that ACTBP2 showed good reproducibility between laboratories, whereas further testing would be needed to validate APOAI1 and D11S554 for interlaboratory comparisons. In separate exercises, the simple loci D12S391 and D1S1656 were tested; both of these showed excellent reproducibility between laboratories.