Morphologic dysplasia in de novo acute myeloid leukemia (AML) is related to unfavorable cytogenetics but has no independent prognostic relevance under the conditions of intensive induction therapy: results of a multiparameter analysis from the German AML Cooperative Group studies.

PURPOSE: On the basis of cytomorphology according to the French-American-British (FAB) classification, we evaluated the prognostic impact of dysplastic features and other parameters in de novo acute myeloid leukemia (AML). We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification. PATIENTS AND METHODS: We analyzed prospectively 614 patients with de novo AML, all of whom were diagnosed by central morphologic analysis and treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute promyalocytic leukemia study. RESULTS: Patients with AML M3, M3v, or M4eo demonstrated a better outcome compared with all other FAB subtypes (P <.001); no prognostic difference was observed among other FAB subtypes. The presence or absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic markers, such as age, cytogenetics, presence of Auer rods, and lactate dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall and event-free survival in univariate analyses (P <.001 for all parameters tested). However, in a multivariate analysis, only cytogenetics (unfavorable or favorable), age, and high LDH maintained their prognostic impact. Dysplasia was not found to be an independent prognostic parameter, but the detection of trilineage dysplasia correlated with unfavorable cytogenetics. CONCLUSION: Our results indicate that cytomorphology and classification according to FAB criteria are still necessary for the diagnosis of AML but have no relevance for prognosis in addition to cytogenetics. Our results suggest that the WHO classification should be further developed by using cytogenetics as the main determinant of biology. Dysplastic features, in particular, have no additional impact on predicting prognosis when cytogenetics are taken into account.     

Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer.

PURPOSE: Multiple chromosome abnormalities, including gain of chromosome20q, have been detected frequently in human pancreatic cancers. Overexpression of the STK15/BTAK/Aurora A gene located on chromosome 20q13, which encodes a centrosome-associated serine/threonine kinase, has been shown to induce chromosomal instability, leading to aneuploidy and cell transformation in multiple in vitro experimental systems. The purpose of this study was to investigate the expression and copy number alteration of STK15 in pancreatic cancer. EXPERIMENTAL DESIGN: STK15 expression at both the mRNA and protein levels together with the copy number of STK15 gene was measured in nine pancreatic carcinoma cell lines: (a) HPAF-II; (b) Aspc-1; (c) Panc-1; (d) Panc-3; (e) Panc-28; (f) Panc-48; (g) HS766T; (h) MIAPaCa-2; and (i) BxPc3. STK15 protein expression was also examined in normal pancreatic tissues and tumors by Western blotting and immunohistochemistry. RESULTS: STK15 was overexpressed in all of the nine cell lines examined, but gene amplification was infrequent. Western Blot analysis of primary tumor tissues revealed 2-10 times overexpression of STK15 protein compared with normal adjacent tissues from pancreatic cancer patients. Concurrent overexpression of cdc20, an STK15-associated protein, and reduced expression of cdc25, a mitosis-activating protein phosphatase, were detected in the same tumor samples. Elevated STK15 protein expression was detected in 22 of 38 tumor sections (58%) from pancreatic cancer patients. The extent of STK15 expression was not significantly correlated with the size, degree of differentiation, and metastasis status of the tumors. CONCLUSIONS: These results show that STK15 is overexpressed in pancreatic tumors and carcinoma cell lines and suggest that overexpression of STK15 may play a role in pancreatic carcinogenesis.     

High-dose ara-C and etoposide in refractory or relapsing acute leukemia

Summary A total of 32 patients (15 men and 17 women) presenting with relapsing or refractory acute leukemia were treated with a 3-h infusion of 3 g/m² cytosine arabinoside (ara-C) twice daily on days 1–6 and a 1-h infusion of 100 mg/m² etoposide on days 1–5. In all, 6 subjects had acute lymphocytic leukemia (ALL); 25 had acute myeloid leukemia (AML) of types M1 (n=6), M2 (n=10), M4 (n=5), and M5 (n=4); and 1 had mixed-type leukemia. The median age was 35 years (ranges, 16–62 years). Of the patients presenting with AML, 11 were primarily refractory and 3 became refractory after their first relapse. Six subjects had an early first relapse following a complete remission (CR) that lasted <6 months and five, a second relapse. Another patient underwent a primary relapse after >6 months but had been heavily pretreated. In all, 5 subjects with refractory AML achieved a CR [36%; 95% confidence interval (CI), 10%–62%) as did 7 patients exhibiting relapsing AML (58%; CI, 30%–86%). Three patients who had relapsing or resistant ALL achieved a CR. Side effects consisted of severe hematotoxicity associated with granulocytopenia of <500/mm³ that lasted for a mean of 23.6 days and thrombocytopenia of <20,000/mm³ whose mean duration was 20.8 days. Marked gastrointestinal toxicity and infections were also prevalent. Cutaneous and ocular toxicity as well as allergic, pulmonary and cerebellar side effects were observed in a few cases. We conclude that the combination of high-dose ara-C and etoposide is a powerful but toxic induction regimen for refractory or relapsed acute leukemia.     

Strengthening Process by Electron Beam to Carbon Fiber for Impact Strength Enhancement of Interlayered Thermoplastic-Polypropylene Carbon Fiber Composite

Strong adhesion between recyclable thermoplastic (TP) polymer and carbon fiber (CF) has always been highly sought after. Therefore, for an interlayered CF reinforced TP polypropylene (CFRTPP) composite composed of 3 sized CF plies, alternating between 4 PP sheets, designated [PP]₄[CF]₃, a process of activating CF plies directly on both sides with homogeneous low energy electron beam irradiation (EBI) under N₂ gas, prior to lamination assembly and hot press of 4.0 MPa at 493 K for 3 min was carried out. Experimental results showed EBI dose of 43.2, 129, or 216 kGy significantly raised Charpy impact values, a_uc at all fracture probabilities, P_f. The 129 kGy dose appeared to be at or near optimum increasing a_uc 103%, 83%, and 65% at low-, median-, and high-P_f = 0.07, 0.50, and 0.93; while raising statistically lowest impact value, a_s at P_f = 0 calculated by 3-dimensional Weibull equation about 110%, indicating increased safety and reliability. It is assumed dangling bonds generated by the EBI rapidly form covalent bonds CF:C:O:C:PP and CF:C:C:PP at the interface, along with cross-linking in the PP near the CF. This is by charge transfer from CF to PP.     

Non-arteritic anterior ischemic optic neuropathy (NA-AION) after intravitreal injection of bevacizumab (Avastin®) for treatment of angoid streaks in pseudoxanthoma elasticum

Background

To report a case of nonarteritic anterior ischemic optic neuropathy (NA-AION) following intravitreal injection of bevacizumab (Avastin®).

Methods

Interventional case report with an 18-month follow-up.

Results

A 51-year-old male with pseudoxanthoma elasticum presented with NA-AION 2 weeks after treatment with intravitreal of bevazicumab (Avastin®) for choroidal neovascularisation secondary to angioid streaks. Except from a small optic disc without cupping he did not show further risk factors.

Discussion

Risk of NA-AION should be taken into consideration when deciding for intravitreal application of drugs including anti-vascular endothelial growth factors (VEGF) agents like bevacizumab (Avastin®) in the treatment of retinal vascular diseases.

     

White matter brain structure predicts language performance and learning success

Individual differences in the ability to process language have long been discussed. Much of the neural basis of these, however, is yet unknown. Here we investigated the relationship between long‐range white matter connectivity of the brain, as revealed by diffusion tractography, and the ability to process syntactically complex sentences in the participants'' native language as well as the improvement thereof by multiday training. We identified specific network motifs by singular value decomposition that indeed related white matter structural connectivity to individual language processing performance. First, for two such motifs, one in the left and one in the right hemisphere, their individual prevalence significantly predicted the individual language performance, suggesting an anatomical predisposition for the individual ability to process syntactically complex sentences. Both motifs comprise a number of cortical regions, but seem to be dominated by areas known for the involvement in working memory rather than the classical language network itself. Second, we identified another left hemispheric network motif, whose change of prevalence over the training period significantly correlated with the individual change in performance, thus reflecting training induced white matter plasticity. This motif comprises diverse cortical areas including regions known for their involvement in language processing, working memory and motor functions. The present findings suggest that individual differences in language processing and learning can be explained, in part, by individual differences in the brain''s white matter structure. Brain structure may be a crucial factor to be considered when discussing variations in human cognitive performance, more generally.     

Artificial intelligence in colonoscopy ‐ Now on the market. What's next?

Adoption of artificial intelligence (AI) in clinical medicine is revolutionizing daily practice. In the field of colonoscopy, major endoscopy manufacturers have already launched their own AI products on the market with regulatory approval in Europe and Asia. This commercialization is strongly supported by positive evidence that has been recently established through rigorously designed prospective trials and randomized controlled trials. According to some of the trials, AI tools possibly increase the adenoma detection rate by roughly 50% and contribute to a 7–20% reduction of colonoscopy‐related costs. Given that reliable evidence is emerging, together with active commercialization, this seems to be a good time for us to review and discuss the current status of AI in colonoscopy from a clinical perspective. In this review, we introduce the advantages and possible drawbacks of AI tools and explore their future potential including the possibility of obtaining reimbursement.     

Beiträge zur Kenntnis der Kupfersulfatvergiftung

Zusammenfassung Es werden zunächst einige Vergiftungsfälle aus der Literatur der letzten Jahre angeführt und dann 2 tödliche medizinale Kupfersulfatvergiftungen, die sich durch Verwechslung von zur Magenausheberung verwendeter Coffeinreizlösung mit Kupfersulfatlösung ereignet haben, eingehender beschrieben. Die Verteilung des Kupfers im Körper und seine Ausscheidung konnte vonSchubert durch experimentelle Verwendung von Badiokupfer einwandfrei geklärt werden. Nach diesen Untersuchungen weist die Leber zu allen Zeiten den weitaus größten Kupfergehalt auf. Die Kupferausscheidung vollzieht sich im wesentlichen über das Gallengangsystem in bedeutend geringerem Ausmaße durch die Nieren. Kupfer wirkt außer auf den peripheren Kreislauf hauptsächlich auf die roten Blutkörperchen im Sinne einer Hämolyse. Bei länger dauernder Vergiftungszeit findet sich ein ganz ähnliches Blutbild wie bei der perniziösen Anämie. Auf Grund der hier beschriebenen Vergiftungsfälle spielt für den Verlauf der Vergiftung außer der zugeführten Kupfersulfatlösung (Menge und Konzentration) dem Alter und der Konstitution, sicher auch die Temperatur der Lösung und der Zustand der Magenschleimhaut eine wesentliche Rolle. Schließlich wird noch gutachtlich zu diesen Fällen Stellung genommen.     

Eine systematische Untersuchung der Geschmacksschwellen

Ohne ZusammenfassungIII. abschließende Mitteilung.