Antitumor vaccination of patients with glioblastoma multiforme: a pilot study to assess feasibility, safety, and clinical benefit.

PURPOSE: Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. PATIENTS AND METHODS: In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. RESULTS: Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P = .024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P < .001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (> or = 3 years). Ninety-one percent of vaccinated patients survived 1 year, 39% survived 2 years, and 4% were long-term survivors. In the vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8(+) tumor-infiltrating T-lymphocytes in secondary tumors. CONCLUSION: Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas. This could be substantiated by the observed antitumor immune response.     

Cystatin C: efficacy as screening test for reduced glomerular filtration rate

Serum cystatin C, a cysteine proteinase inhibitor, has been proposed as a marker of glomerular filtration rate (GFR). Serum cystatin C, serum creatinine and creatinine clearance were measured in 226 patients with various nephropathies, covering the entire range of renal function, to evaluate the efficacy of cystatin C as a screening test to detect reduced creatinine clearance in comparison to creatinine. Subgroups of 53 patients with glomerular and 26 patients with tubular impairment were compared to assess whether cystatin C performed differently in either glomerular or tubular impairment. Cystatin C detected reduced creatinine clearance with higher sensitivity (97 vs. 83%), and higher negative predictive value (96 vs. 87%) compared to creatinine. In parallel, 95% sensitivity of cystatin C as derived from receiver-operating characteristic plot was significantly higher (p < 0.05). In the subgroups with glomerular or tubular impairment, cystatin C and creatinine did not significantly differ with regard to efficacy. Serum cystatin C is as efficacious as serum creatinine to detect reduced GFR as measured by creatinine clearance. The efficacy of cystatin C as a screening test may even be superior compared to creatinine. In addition, the efficacy of cystatin C is independent of either glomerular or tubular impairment.     

Mukormykose als Ursache einer nekrotisierenden Enterokolitis

Zusammenfassung Die gastrointestinale Mukormykose ist ein seltenes Krankheitsbild. Betroffene Frühgeborene fallen durch eine Perforation im Magen-Darm-Trakt oder eine nekrotisierende Enterokolitis auf. Wir stellen ein Frühgeborenes der 24. SSW mit einer Darmperforation vor, bei dem eine Mukormykose des Darms sowohl durch die Kultur als auch im histologischen Pr?parat nachgewiesen wurde. Im Gegensatz zur „klassischen” nekrotisierenden Enterokolitis lag keine Pneumatosis intestinalis vor, es kam sehr früh zu einer Darmperforation, und der Dünndarm zeigte eine ausgepr?gte Minderperfusion. Diese Punkte k?nnten die Differenzierung zwischen gastrointestinaler Mukormykose und typischer nekrotisierender Enterokolitis erleichtern, was von Bedeutung ist, da nur die frühzeitige Diagnosestellung einen raschen Therapiebeginn (chirurgische Sanierung, Amphotericin B) und damit eine Verbesserung der schlechten Prognose erm?glicht.      

Rapid genotyping of newborn gene mutant mice

One important aspect of utilizing transgenic mice is the need to genotype them in order to distinguish mice that carry a disrupted gene or a transgene from mice that do not. Current methods for genotyping include isolation of genomic DNA from tail biopsies followed by PCR amplification. Particularly, both digestion of tail tissue using proteinase K as well as resuspension of purified DNA are time-consuming and were usually carried out overnight. Here, we describe a rapid and robust method for the genotyping of bdnf targeted mice which allows us to determine the genotype of newborn mice at the day of birth within 6 h. After a freezing–thawing step tail tissue is digested in less than 2 h, and the DNA is precipitated, resuspended and ready for PCR in about 60 min. The method could be easily adapted to a variety of different mutant mice and especially should benefit neuroscientists interested in using animals with known genotype very early in postnatal development.     

Subgroups in the treatment of nasal polyposis with dupilumab: A retrospective study

Dupilumab has been shown to be safe and effective in treating chronic rhinosinusitis with polyposis (CRSwNP). There is to this date no published data whether subgroups like patients with aspirin exacerbated respiratory disease (AERD), increased histologic eosinophilia or elevated blood eosinophil or IgE-levels benefit greater from dupilumab therapy. Moreover, there is no data comparing the efficacy of functional endoscopic sinus surgery (FESS) with dupilumab therapy. We conducted a retrospective chart review of all patients that were treated at a tertiary referral center for CRswNP with dupilumab. We also contacted the patients with a questionnaire to evaluate the efficacy of previous surgeries and dupilumab therapy by visual analogue scale (VAS) and the glasgow benefit inventory (GBI) as well as report on side effects. Overall, 75 patients were included in the study at hand that reported back 138 times. While dupilumab treatment was efficient, we found no systematic evidence of greater efficacy of dupilumab in patients with AERD, histologic eosinophilia or increased blood eosinophil or IgE-levels. All patients showed a considerable decrease in subjective burden of disease, objective smell tests and endoscopic findings. From the patients point of view, dupilumab therapy showed greater efficacy both in the VAS and the GBI overall and all subcategories but “social support.” Dupilumab is efficient in treating CRSwNP; this effect is independent from disease characteristics like AERD, histologic eosinophilia, serum IgE-levels or eosinophil counts. There seems to be a group of patients that benefit greater from dupilumab therapy compared to FESS.     

Serum and Urine Metabolites in Healthy Men after Consumption of Acidified Milk and Yogurt

The identification of molecular biomarkers that can be used to quantitatively link dietary intake to phenotypic traits in humans is a key theme in modern nutritional research. Although dairy products (with and without fermentation) represent a major food group, the identification of markers of their intake lags behind that of other food groups. Here, we report the results from an analysis of the metabolites in postprandial serum and urine samples from a randomized crossover study with 14 healthy men who ingested acidified milk, yogurt, and a non-dairy meal. Our study confirms the potential of lactose and its metabolites as markers of lactose-containing dairy foods and the dependence of their combined profiles on the fermentation status of the consumed products. Furthermore, indole-3-lactic acid and 3-phenyllactic acid are two products of fermentation whose postprandial behaviour strongly discriminates yogurt from milk intake. Our study also provides evidence of the ability of milk fermentation to increase the acute delivery of free amino acids to humans. Notably, 3,5-dimethyloctan-2-one also proves to be a specific marker for milk and yogurt consumption, as well as for cheese consumption (previously published data). These molecules deserve future characterisation in human interventional and observational studies.