Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial.

PURPOSE: To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab (FluCam) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS AND METHODS: A total of 36 patients were treated in this phase II study (median age, 61.47 years; mean number of prior chemotherapies, 2.6; Binet stage C, n = 28). After an initial dose escalation of alemtuzumab over 3 days, alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days. Treatment was repeated after 28 days for up to six cycles. Restaging (following National Cancer Institute criteria) was carried out after cycles 2 and 4 and 1 month after the end of treatment. RESULTS: The overall response rate was 83% (11 complete responses, 19 partial responses, one stable disease, and five progressive diseases). Two patients with progressive disease developed fungal pneumonias, and one patient died as a result of Escherichia coli sepsis. Two subclinical cytomegalovirus reactivations occurred. CONCLUSION: The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.     

Host Cell Entry and Neutralization Sensitivity of SARS-CoV-2 Lineages B.1.620 and R.1

The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) facilitates viral entry into host cells and is the key target for neutralizing antibodies. The SARS-CoV-2 lineage B.1.620 carries fifteen mutations in the S protein and is spread in Africa, the US and Europe, while lineage R.1 harbors four mutations in S and infections were observed in several countries, particularly Japan and the US. However, the impact of the mutations in B.1.620 and R.1 S proteins on antibody-mediated neutralization and host cell entry are largely unknown. Here, we report that these mutations are compatible with robust ACE2 binding and entry into cell lines, and they markedly reduce neutralization by vaccine-induced antibodies. Our results reveal evasion of neutralizing antibodies by B.1.620 and R.1, which might have contributed to the spread of these lineages.     

Long-Term Effects of an Oligoantigenic Diet in Children with Attention-Deficit/Hyperactivity Disorder (ADHD) on Core Symptomatology

In the early 1920s, it was discovered that nutrition is associated with what is known today as Attention-Deficit/Hyperactivity Disorder (ADHD) and that certain foods can worsen the symptoms. In previous studies, approximately 60% of the participants experience at least a 40% reduction in ADHD symptoms after an oligoantigenic diet (OD). The purpose of this study was to evaluate ADHD symptoms in children approximately 3.5 years after completing a 4-week oligoantigenic diet. Among 28 participants who completed the 4-week diet, 21 were re-assessed for this study after 3.5 years. The severity of ADHD symptoms was assessed with the ADHD-Rating-Scale-IV (ARS). Of 21 participants, 14 fulfilled the responder criterion, whereas 7 did not. At follow-up, 28% of the participants were taking medication. The mean ARS total score improved significantly from T1: M = 29.62 (SD = 9.80) to T2: M = 15.86 (SD = 8.56) between the time points before and after the diet (d = −1.91). There was also a lower ARS total score at the follow-up T5: M = 16.00 (SD = 10.52) compared to before the diet (d = −1.17). This study shows that individually adjusted nutrition significantly improved the ADHD symptomatology of the participants long-term. This suggests that an oligoantigenic diet with subsequent individual nutritional recommendations could become an additional treatment option for children with ADHD.     

Mechanisms of arachidonic acid-induced contractions of canine cerebral arteries

The effects of arachidonic acid in cerebral blood vessels has been examined using rings of canine cerebral arteries. Arachidonic acid produced dose-dependent contractions of this preparation even after mechanical removal of the endothelium. The contractions were not blocked by indomethacin or acetylsalicylic acid, both of which inhibit cyclooxygenase, but were inhibited by nordihydroguaiaretic acid which is a lipoxygenase inhibitor, BW 755c which blocks both pathways, and FPL 55712 which is an antagonist at leukotriene receptors. These data imply that arachidonic acid-induced contractions are mediated by products of the lipoxygenase pathway. Leukotrienes and cyclooxygenase products are generated by this preparation as shown by HPLC and radioimmunoassay and both LTC4 and LTD4 produce contractions in cerebral arteries lending further evidence in support of this suggestion.     

Troponin level and efficacy of abciximab in patients with acute coronary syndromes undergoing early intervention after clopidogrel pretreatment

Objective We investigated how does troponin level (TnT) affect the benefit achieved by abciximab in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with a high loading dose of clopidogrel. Methods The Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT 2) trial included 2,022 patients with non-ST elevation ACS undergoing PCI who were randomized to abciximab or placebo after pretreatment with 600 mg of clopidogrel. The patients were divided into groups with elevated TnT level (n = 1,049) and no elevated TnT level (n = 973). The primary end point of the trial was the composite of death, myocardial infarction and urgent reintervention at 30 days. Results In patients with elevated TnT level the incidence of the primary end point was 13.1% in the abciximab group Vs. 18.3% in the placebo group [relative risk (RR): 0.70; 95% confidence interval (CI), 0.52–0.95, P = 0.02]. The combined incidence of death or myocardial infarction was 12.9% in the abciximab group vs. 17.9% in the placebo group (RR: 0.71; 95% CI, 0.52–0.96, P = 0.03). In contrast, the incidence of the primary end point in patients with no elevated TnT level was identical in both treatment groups (4.6%). The risk of bleeding was not related to TnT level. Conclusions Baseline troponin level affects the benefit of abciximab in patients with ACS undergoing PCI after pretreatment with a high loading dose of clopidogrel. Abciximab reduces the risk of ischemic events only in patients with ACS and elevated troponin level.     

Sinusoidales Obstruktionssyndrom und venookklusive Lebererkrankung – Diagnose und Therapiemöglichkeiten

Die Gastroenterologie - Das sinusoidale Obstruktionssyndrom (SOS), auch als ?veno-occlusive disease“ (VOD) bezeichnet, ist eine seltene, potenziell letal verlaufende...     

Angeborene Herzfehler und Lippen-Kiefer-Gaumenspalten bei Zwillingen

Ohne Zusammenfassung Mit 8 Abbildungen (15 Einzelbildern) im Text.