PROGNOSTIC VALUE OF ANGIOGENESIS IN OPERABLE NON-SMALL CELL LUNG CANCER

Tumour angiogenesis is an important factor for tumour growth and metastasis. Although some recent reports suggest that microvessel counts in non-small cell lung cancer are related to a poor disease outcome, the results were not conclusive and were not compared with other molecular prognostic markers. In the present study, the vascular grade was assessed in 107 (T1,2–N0,1) operable non-small cell lung carcinomas, using the JC70 monoclonal antibody to CD31. Three vascular grades were defined with appraisal by eye and by Chalkley counting: high (Chalkley score 7–12), medium (5–6), and low (2–4). There was a significant correlation between eye appraisal and Chalkley counting ( P <0·0001). Vascular grade was not related to histology, grade, proliferation index (Ki67), or EGFR or p53 expression. Tumours from younger patients had a higher grade of angiogenesis ( P =0·05). Apart from the vascular grade, none of the other factors examined was statistically related to lymph node metastasis ( P <0·0001). A univariate analysis of survival showed that vascular grade was the most significant prognostic factor ( P =0·0004), followed by N-stage ( P =0·001). In a multivariate analysis, N-stage and vascular grade were not found to be independent prognostic factors, since they were strongly related to each other. Excluding N-stage, vascular grade was the only independent prognostic factor ( P =0·007). Kaplan–Meier survival curves showed a statistically significant worse prognosis for patients with high vascular grade, but no difference was observed between low and medium vascular grade. These data suggest that angiogenesis in operable non-small cell lung cancer is a major prognostic factor for survival and, among the parameters tested, is the only factor related to cancer cell migration to lymph nodes. The integration of vascular grading in clinical trials on adjuvant chemotherapy and/or radiotherapy could substantially contribute in defining groups of operable patients who might benefit from cytotoxic treatment.     

Coeliac disease,epilepsy, and cerebral calcifications: association with TG6 autoantibodies

A 4‐year‐old boy presented with occipital seizures but normal initial neuroimaging and proved refractory to antiepileptic medications. On repeat neuroimaging after 1 year, he had developed bi‐occipital calcification and was then found to have positive coeliac serology. He was diagnosed with coeliac disease, epilepsy, and cerebral calcifications (CEC) and became seizure free after starting the gluten‐free diet. Positive antibody binding to neurons and glia was demonstrated on indirect immunofluorescence. High levels of immunoglobulin‐A directed against transglutaminase isoenzyme 6 (TG6) were found in the patient’s serum. The positive response to the diet, TG6 antibodies, and neuronal antibody binding suggest that CEC might be autoimmune in nature, as in other extra‐intestinal manifestations of gluten‐related diseases, such as gluten ataxia.     

Apoptosis of Hodgkin–Reed–Sternberg cells in classical Hodgkin lymphoma revisited

Benharroch D, Einav I, Feldman A, Levy A, Ariad S, Gopas J. Apoptosis of Hodgkin–Reed–Sternberg cells in classical Hodgkin lymphoma revisited. APMIS 2010; 118: 339–45. We scrutinized the role of apoptosis of the Hodgkin–Reed–Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) and critically reviewed its features in the light of conflicting evidence. In this study, we found that tumor cells in this neoplasm showed inhibition of apoptosis in 55% of the 217 cHL cases only. It is also suggested that the two factors considered responsible for apoptosis inhibition in HRS cells, nuclear factor‐κB and the latent membrane protein‐1 of the Epstein–Barr virus, do not correlate with apoptosis inhibition, in contrast with the findings in the consensual pathogenetic scheme. The most significant association of HRS cell apoptosis was with p53, the negative expression of which related with a high apoptotic index (p = 0.001). These findings support our contention that the role of apoptosis in the HRS cells of Hodgkin lymphoma has not been completely elucidated and is at variance with that in the consensus.     

Video-assisted thoracoscopic surgery for right middle lobectomy in children

This case-control study was designed to evaluate the potential advantages and disadvantages of video-assisted thoracoscopic surgery for right middle lobectomy in children. Ten children (6.1±3.0 yr, mean±SD) who underwent right middle lobectomy under videoscopy were compared with 10 controls matched for age (6.8±3.5 yr) and operated by thoracotomy (muscle-sparing technique) during the same period by the same surgeon. Operating time was significantly longer in the videoscopy group than in the thoracotomy group (146±28 mn vs 100±27 mn, P<0.001). Minimum oxygen saturation values were significantly higher in the videoscopy group whereas oxygen requirements did not differ between groups. Incidence of postoperative respiratory complications (mainly atelectasis) was similar in the two groups. No difference in postoperative analgesic requirements in the postoperative period was demonstrated. No real benefit or disadvantage of videoscopy over standard thoracotomy could be observed in this retrospective case-control study.     

Angiographic Markers of Restenosis after Drug‐Eluting Stent Implantation: Surrogates for Late Clinical Outcomes?

Introduction: Although angiographic measures of restenosis, including late lumen loss, binary angiographic restenosis, and follow‐up percent diameter stenosis have value in determining the efficacy of new drug‐eluting stents (DES) designs, their ability to predict clinical events, including death, myocardial infarction, and target lesion revascularization (TLR) has been questioned. Methods: We reviewed the available literature and recent DES clinical trials to determine the relationship between clinical and angiographic markers of restenosis and late clinical outcomes after stent use. Results: Angiographic markers are useful surrogates for predicting differences in TLR between bare metal and DES. Due to the curvilinear relationship between late lumen loss and TLR and the skewedness of the late lumen loss distribution, late lumen loss as a single index has been less effective at predicting clinical differences between different DES when the absolute values of late lumen loss are low. Beyond predicting clinical restenosis, follow‐up angiographic indices have been less predictive of other late clinical events, such as very late stent thrombosis or aneurysm formation. Conclusions: Angiographic markers of restenosis may be a useful surrogate for TLR in pilot studies of patients treated with DES, but their use as a surrogate marker for all clinical events after stent placement, including death, myocardial infarction, and stent thrombosis, may be confounded by the progression of atherosclerosis at remote sites and vagaries of the distribution of late lumen loss in patients treated with DES.     

Outcomes of Patients with Coronary Artery Perforation Complicating Percutaneous Coronary Intervention and Correlations with the Type of Adjunctive Antithrombotic Therapy: Pooled Analysis from REPLACE-2, ACUITY, and HORIZONS-AMI Trials

Background: The lack of a specific counteragent to bivalirudin may complicate the management of patients with coronary artery (CA) perforation during percutaneous coronary intervention (PCI).
Aim: Assess outcomes of patients with CA perforation from three PCI trials comparing intravenous bivalirudin with provisional glycoprotein (GP) IIb/IIIa inhibition versus unfractionated heparin (UFH) plus GP IIb/IIIa.
Methods: A pooled analysis of patients treated with PCI in three randomized trials including REPLACE-2, ACUITY, and HORIZONS-AMI.
Results: Among a total of 12,921 patients, CA perforation occurred in 35 patients (0.27%). By multivariable analysis, baseline creatinine clearance was the only independent predictor of CA perforation (per 10 mL/min decrease, odds ratio [95% confidence interval]= 1.28 [1.11, 1.47], P = 0.0007). At 30 days, patients with versus without CA perforation had significantly (all P values ≤0.001) higher rates of 30-day mortality (11.4% vs. 1.0%), myocardial infarction (MI) [Q wave: 22.9% vs. 5.7%; non-Q wave: 17.1% vs. 4.9%], target vessel revascularization (TVR) [20.1% vs. 1.8%], and composite end-point of death/MI/TVR (31.4% vs. 7.8%). Patients assigned to bivalirudin versus UFH plus a GP IIb/IIIa inhibitor had nonsignificantly lower rates of death (0% vs. 18.8%, P = 0.08), similar rates of MI (26.7% vs. 25.0%, P = 0.92), significantly lower rates of TVR (6.7% vs. 37.5%, P = 0.04), and similar rates of the composite end-point of death/MI/TVR (35.5% vs. 26.7%, P = 0.54).
Conclusion: In three PCI trials, treatment of patients experiencing CA perforation with adjunctive antithrombotic therapy of bivalirudin monotherapy was not associated with worse outcomes compared to treatment with UFH plus GP IIb/IIIa inhibitors.     

Lysine deficiency reduces transcription activity and concentration of chromatin proteins reversibly in rat liver

The reversible effect of dietary lysine deficiency was studied in young adult rats. During 6 days on a lysine deficient diet the rats maintained the same body weight. During 2 days of recovery body weight gain was that of the controls. Liver nuclei were isolated, incubated with micrococcus nuclease and chromatin fractionated into a 2000 ×g pellet. 102 000 ×g pellet and supernatant fraction. Chromatin-bound RNA polymerase I plus III activity decreased by 15% per mg of fractional and nuclear DNA and by 30% per total liver. The corresponding decrease of RNA polymerase II activity was 30% and 40%. Recovery from lysine deficiency was complete after 2 days of refeeding the amino acid. Chromatin proteins of the 102000 ×g pellet were characterized by polyacrylamide gel electrophoresis in sodium dodecylsulfate and by 2-dimensional gel electrophoresis. Quantitative but no qualitative differences between the proteins of the dietary groups were observed. Relative to DNA the non-histone proteins decreased in the lysine deficient group by 43% and histones by 10%. It is concluded that RNA synthesis is restored to its original level within 2 days of refeeding lysine after 6 days of lysine deficiency.     

Wrist actigraphic scoring for sleep laboratory patients: algorithm development

Wrist actigraphy is employed increasingly in sleep research and clinical sleep medicine. Critical evaluation of the performance of new actigraphs and software is needed. Actigraphic sleep–wake estimation was compared with polysomnographic (PSG) scoring as the standard in a clinical sleep laboratory. A convenience sample of 116 patients undergoing clinical sleep recordings volunteered to participate. Actiwatch‐L recordings were obtained from 98 participants, along with 18 recordings using the newer Spectrum model (Philips Electronics), but some of the actigraphic recordings could not be adequately aligned with the simultaneous PSGs. Of satisfactory alignments, 40 Actiwatch recordings were used as a training set to empirically develop a new Scripps Clinic algorithm for sleep–wake scoring. The Scripps Clinic algorithm was then prospectively evaluated in 39 Actiwatch recordings and 16 Spectrum recordings, producing epoch‐by‐epoch sleep–wake agreements of 85–87% and kappa statistics averaging 0.52 (indicating moderate agreement). Wake was underestimated by the scoring algorithm. The correlations of PSG versus actigraphic wake percentage estimates were r = 0.6690 for the Actiwatch and r = 0.2197 for the Spectrum. In general, using a different weighting of activity counts from previous and subsequent epochs, the Scripps Clinic algorithm discriminated sleep–wake more successfully than the manufacturer’s Actiware algorithms. Neither algorithm had fully satisfactory agreement with PSG. Further evaluations of algorithms for these actigraphs are needed, along with controlled comparisons of different actigraphic designs and software.