Early Repolarization Syndrome: Electrocardiographic Signs and Clinical Implications

Early repolarization syndrome (ERS) was previously considered as a benign variant, but it has recently emerged as a risk marker for idiopathic ventricular fibrillation (VF) and sudden death. As measured by electrocardiogram (ECG), early repolarization is characterized by an elevation of the J point and/or ST segment from the baseline by at least 0.1 mV in at least two adjoining leads. In particular, early repolarization detected by inferior ECG leads was found to be associated with idiopathic VF and has been termed as ERS. This condition is mainly observed in young men, athletes, and blacks. Also, it has become evident that electrocardiographic territory, degree of J‐point elevation, and ST‐segment morphology are associated with different levels of risk for subsequent ventricular arrhythmia. However, it is unclear whether J waves are more strongly associated with a depolarization abnormality rather than a repolarization abnormality. Several clinical entities can cause ST‐segment elevation. Therefore, clinical and ECG data are essential for differential diagnosis. At present, the data set is insufficient to allow risk stratification in asymptomatic individuals. ERS, idiopathic VF, and Brugada syndrome (known as J‐wave syndromes) are three clinical conditions that share many common ECG features; however, their clinical consequences are remarkably different. This review summarizes the current electrocardiographic data concerning ERS with clinical implications.     

Identification of a novel genetic locus associated with immune-mediated thrombotic thrombocytopenic purpura

Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare, life-threatening disorder, mediated through severe ADAMTS13 deficiency causing multi-system micro-thrombi formation, and has specific human leukocyte antigen associations. We undertook a large genome-wide association study to investigate additional genetically distinct associations in iTTP. We compared two iTTP patient cohorts with controls, following standardized genome-wide quality control procedures for single-nucleotide polymorphisms and imputed HLA types. Associations were functionally investigated using expression quantitative trait loci (eQTL), and motif binding prediction software. Independent associations consistent with previous findings in iTTP were detected at the HLA locus and in addition a novel association was detected on chromosome 3 (rs9884090, P=5.22x10^-10, odds ratio 0.40) in the UK discovery cohort. Meta-analysis, including the French replication cohort, strengthened the associations. The haploblock containing rs9884090 is associated with reduced protein O-glycosyltransferase 1 (POGLUT1) expression (eQTL P<0.05), and functional annotation suggested a potential causative variant (rs71767581). This work implicates POGLUT1 in iTTP pathophysiology and suggests altered post-translational modification of its targets may influence disease susceptibility.     

Die chirurgische Behandlung von Lungenmetastasen extrapulmonaler Prim?rtumoren - eine retrospektive Analyse von 1982-1995

Zusammenfassung Aufgrund kontroverser Diskussionen, gerade mit Vertretern konservativer Fachrichtungen, war das Ziel unserer Studie, die Chirurgie der Lungenmetastasen durch niedrige Mortalität und Morbidität, befriedigende Überlebensraten und verbesserte Lebensqualität zu begründen.¶ Methoden: Von Januar 1982 bis Mai 1995 erfaßten wir retrospektiv alle Patienten, die an Lungenmetastasen operiert wurden und führten Follow-up-Untersuchungen bis Mai 1995 durch, so daß auch bei den am Ende des Erfassungszeitraums operierten Patienten ein Verlauf über mindestens 3 Jahre dokumentiert werden konnte. Neben der Erhebung peri- und postoperativer Daten führten wir zur Bestimmung prognostischer Faktoren eine Multivarianzanalyse durch und bestimmten die Überlebensraten.¶ Ergebnisse: Im Erfassungszeitraum wurden 73 Patienten wegen Lungenmetastasen operiert. Im Follow-up konnten wir 48 Patienten (21 Frauen, 27 Männer) einbeziehen. Das mittlere Alter betrug 47,4 Jahre. Als häufigste Primärtumore fanden sich Adenokarzinome des Colons (n=9), Nierenzellkarzinome (n=9), Melanome (n=6), Osteosarkome (n=5) und Uteruskarzinome (n=5). Bei den 48 Patienten führten wir 61 Operationen durch, 93,4% als laterale Thorakotomie und 6,6% über eine mediane Sternotomie. Bei 67,2% wurde eine atypische Keilresektion und bei 31,2% eine anatomische Resektion vorgenommen. 62,5% aller Patienten zeigten solitäre Metastasen, 22,9% 2-4 und 14,6% multiple Metastasen. Das mediane tumorfreie Intervall (TI) aller Patienten betrug 24 Monate. Die Frühmortalität (30 Tage) lag bei 1,1%, die Morbidität bei 3,3%, die mediane Behandlungsdauer bei 11 Tagen. Die 3-Jahres-Überlebensrate aller Patienten betrug 37,5%. Als prognostisch relevante Faktoren wurden ermittelt: Art des Primärtumors (p<0,05), Anzahl der Metastasen (p<0,05) und die Dauer des TI (p<0,05). Signifikante Unterschiede ergaben sich in der 3-Jahres-Überlebensrate bei Kolonkarzinomen (55,6%) und Osteosarkomen (0%), bei multiplen (14,3%) und solitären Metastasen (50%), so wie einem TI <2 Jahre (29,2%) und >2 Jahre (45,5%). Die Operationstechnik ergab keine Unterschiede im Hinblick auf die Prognose.¶ Schlußfolgerungen: Geringe Mortalität und Morbidität, ebenso befriedigende Langzeitergebnisse bei fehlenden oder unbefriedigenden konservativen Therapieansätzen favorisieren die chirurgische Therapie von Lungenmetastasen. Bei häufig dringendem Therapiewunsch der Patienten stellt die chirurgische Intervention eine prognostisch gesicherte Indikation dar. Summary Background: Because of the controversial discussion, even with conservative specialities, the aim of the study was to show that the surgical treatment of pulmonary metastasis is an adequate therapy with low morbidity and mortality, good survival rates and an increasing quality of life.¶ Methods: From January 1982 until May 1992 we retrospectively reviewed all patients with pulmonary metastasis and completed follow-up until May 1995. Beside peri- and postoperative data we made a multivariant analysis to find the relevant prognostic factors and to define the survival rates.¶ Results: Over a period of 10 years 73 patients underwent an operation for pulmonary metastasis. Follow-up was completed in 48 patients (21 female, 27 male). Median age was 47.4 years. Most primary tumors were adenocarcinoma of the colon (n=9), renal-cell-carcinoma (n=9), melanoma (n=6), osteosarcoma (n=5), and uterus carcinoma (n=5). There were 61 operations nessecary in the 48 patients. The procedure was a lateral thoracotomy in 93.4% and a median sternotomy in 6.6%. The surgical technique was a wedge resection in 67.2% and an anatomic resection in 31.2%. 62.5% of the patients had solitary metastasis, 22.9% had 2-4, and 14.6% had multiple metastasis. The median disease-free interval (DFI) of all patients was 24 months. 30 day-mortality was 1.1%; morbidity was 3.3%. Mean hospitalization time was 11 days. The 3-year-survival of all patients was 37.5%. The following relevant prognostic factors were found: site of primary tumor (p>0.05), number of metastasis (p<0.05), duration of DFI (p<0.05). There were significant differences in the 3-year-survival for adenocarcinomas of the colon (55.6%) and osteosarcoma (0%), in multiple (14.3%) and solitary metastasis (50%) as well as a DFI <2 years (29.2%) and >2 years (45.5%). There were no differences in spite of the surgical technique.¶ Conclusions: Because of low mortality and morbidity, as well as good long-term results and without satisfying conservative treatments, the surgical treatment should be favored in pulmonary metastasis. It is a safe and sure therapy for the treatment of pulmonary metastasis.     

Nervenläsionen der unteren Extremitäten nach peripherer Gefäßrevaskularisation

Purpose: Discussion in the literature of peripheral nerve lesions after surgical treatment is based mainly on orthopedic surgery or on ischemic syndromes. There is no information about the frequency of nerve lesions after revascularization of the lower limb. Methods: Between 1992 and 1996, 436 patients underwent peripheral arterial revascularization, including 147 cases of deep revascularization, 127 supra-genicular femoro-popliteal bypasses, 116 infra-genicular femoro-popliteal bypasses and 56 femoro-crural bypasses. Mean patient age was 70.5±5.8 years; 182 patients were female and 254 were male. There was a 38% rate (166/436) of reoperation. All patients were examined based on anamnestic information and a detailed clinical neurological investigation, including the methods of Weber and Moberg. Results: We found eleven patients (4%) with peripheral nerve lesions after the primary operation. After the reoperation 55 patients (33%) had nerve lesions. Conclusions: Peripheral nerve lesions with sensory disturbance were present in 15% of our patients on discharge from hospital. They had mainly dysesthesia and hypesthesia but no kind of motor dysfunction. In our opinion, detailed preoperative information is very important because of the risk of sensitive nerve lesions.     

Ischaemic complications with intra-aortic balloon counter-pulsation: incidence and management

The most important limitation of the use of the intra-aortic balloon pump is the risk of vascular complications. The aim of this study was to identify risk factors and aspects of diagnosis and management that may decrease the risk of vascular morbidity associated with intra-aortic balloon pumps. Risk factors, surgical techniques, complications and other variables were retrospectively evaluated in 524 patients who had an intra-aortic balloon pump inserted between January 1988 and December 1998. Of the total, 140 (26.7%) patients with an intra-aortic balloon pump had ischaemic complications that needed surgery. The mean age was 65.2 +/-12.3 years (66.7% men and 27.5% women). The mortality rate was 28.1%. The mortality for patients with ischaemic vascular complications was significantly higher than in those patients without (59.6 versus 30.1%, P = 0.001). One-hundred and eight (77.2%) ischaemic complications occurred during therapy with an intra-aortic balloon pump and 32 (22.8%) complications after intra-aortic balloon pumping had been stopped. Thromboembolectomy was required in 71 (50.7%) patients. Associated surgical procedures were performed in 69 (49.3%) patients. A history of peripheral vascular disease (43.6 versus 23.6%, P < 0.05) and the presence of diabetes mellitus (49.2 versus 16.9%, P < 0.05) increased the risk of limb ischaemia significantly. Limb ischaemia remains the major complication after intra-aortic balloon pump insertion. Independent predictors for vascular complications included peripheral vascular disease and diabetes. Intra-aortic balloon pump removal and thrombectomy is usually sufficient to provide revascularization. Identification of subclinical disease may aid in the management of subsequent acute limb ischaemia.     

Spleen stiffness measurement using Fibroscan for the noninvasive assessment of esophageal varices in liver cirrhosis patients

Background and Aim: Splenomegaly in a common finding in liver cirrhosis that should determine changes in the spleen's density because of portal and splenic congestion and/or because of tissue hyperplasia and fibrosis. These changes might be quantified by elastography, so the aim of the study was to investigate whether spleen stiffness measured by transient elastography varies as liver disease progresses and whether this would be a suitable method for the noninvasive evaluation of the presence of esophageal varices. Patients and Methods: One hundred and ninety‐one patients (135 liver cirrhosis, 39 chronic hepatitis and 17 healthy controls) were evaluated by transient elastography for measurements of spleen and liver stiffness. Cirrhotic patients also underwent upper endoscopy for the diagnosis of esophageal varices. Results: Spleen stiffness showed higher values in liver cirrhosis patients as compared with chronic hepatitis and with controls: 60.96 vs 34.49 vs 22.01 KPa (P < 0.0001). In the case of liver cirrhosis, spleen stiffness was significantly higher in patients with varices as compared with those without (63.69 vs 47.78 KPa, P < 0.0001), 52.5 KPa being the best cut‐off value, with an area under the receiver operating characteristic of 0.74. Using both liver and spleen stiffness measurement we correctly predicted the presence of esophageal varices with 89.95% diagnostic accuracy. Conclusion: Spleen stiffness can be assessed using transient elastography, its value increasing as the liver disease progresses. In liver cirrhosis patients spleen stiffness can predict the presence, but not the grade of esophageal varices. Esophageal varices' presence can be better predicted if both spleen and liver stiffness measurements are used.