Tumor-M2-Pyruvatkinase beim Nierenzellkarzinom Untersuchungen im Plasma von Patienten

Tumor cell metabolism is characterized by a high rate of aerobic glycolysis. The metabolic differences require changes in glycolytic enzyme activities and isoenzyme patterns. The inactive form of the M2 pyruvate kinase (Tu M2-PK) is specifically expressed in tumor cells and has been detected immunohistochemically in tumor tissue but also in peripheral blood of patients with different malignant tumors. In this study, Tu M2-PK in the plasma of patients with renal cell carcinoma (RCC) was compared with healthy volunteers. Tu M2-PK was quantified with a commercially available enzyme linked immunosorbent assay (ELISA) kit. Using the ELISA kit, plasma probes of 57 healthy individuals were compared to 63 patients with RCC (51 patients with non-metastatic RCC, 12 patients with metastatic RCC). Statistical analysis was performed with the non-parametric ANOVA test according to Kruskal-Wallis. In patients with renal cell carcinoma, Tu M2-PK was significantly higher than in healthy volunteers. For organ-defined, non-metastatic tumors, sensitivity was only 27.5%, if the 95% reference values of the control group were used for discrimination. The differences were more pronounced in patients with metastatic disease. Tu M2-PK was significantly enhanced compared to healthy controls, but also to the group with non-metastatic disease, the sensitivity was 66.7%. Our data show that Tu M2-PK has no impact as an unspecific marker for the diagnosis of renal cell carcinoma. This is especially relevant to organ-defined, non-metastatic RCC. In advanced metastatic disease, a potential importance as a parameter for treatment control in palliative therapeutic approaches can be assumed, and warrants further investigations.     

Circulating growth factor levels are associated with tumorigenesis in neurofibromatosis type 1.

PURPOSE: Neurofibromatosis type 1 (NF1) is characterized by systemic development of neurofibromas. Early clinical diagnosis can be ambiguous, and genetic diagnosis can be prohibitively difficult. Dysregulation of a number of growth factors has been suggested to be a mechanism of pathogenesis. This study was performed to assess the contribution of circulating growth factors for diffuse tumorigenesis and the diagnostic value of circulating growth factor identification in serum. EXPERIMENTAL DESIGN: The growth stimulation of neurofibroma-derived cells by serum from NF1 patients was tested, and serum growth factor levels in a cohort of NF1 patients (n = 39) between the ages of 7 and 70 years were analyzed. RESULTS: Concentrations of midkine (MK) and stem cell factor, but not epidermal growth factor, were substantially increased in serum of NF1 patients when compared with healthy controls. Within the NF1 group, MK levels increased dramatically at puberty from an average of 0.79 ng/mL in patients <18 years to 1.18 ng/mL in patients >18 years old. Stem cell factor and MK concentrations above a defined threshold in serum of NF1 patients are of diagnostic benefit for 96% of patients in the cohort tested. Furthermore, serum from NF1 patients enhanced proliferation of human neurofibroma-derived primary Schwann cells and endothelial cells substantially better than normal serum. CONCLUSIONS: Enhanced circulating growth factor levels contribute to diffuse tumorigenesis in NF1 and may provide the basis for molecular diagnosis.     

Juvenile Parodontopathie bei Ehlers-Danlos-Syndrom Typ VIII

Zusammenfassung Wir berichten über eine 15j?hrige Patientin mit einer frühzeitig einsetzenden Parodontopathie, die auch bei weiteren Familienmitgliedern vorgelegen hat. Weiterhin waren eine erh?hte Vulnerabilit?t der Haut mit verz?gerter und atypischer Wundheilung sowie eine überstreckbarkeit der Gelenke vorhanden. Auff?llig war au?erdem eine Voralterung, v.a. im Gesicht. Anhand des klinischen Bilds sowie der Familienanamnese konnte ein Ehlers-Danlos-Syndrom Typ VIII diagnostiziert werden, welches autosomal-dominant vererbt wird. Die genetischen und biochemischen Grundlagen dieser Erkrankung sind bisher nicht bekannt. Diskussion: Eine Parodontopathie im Rahmen eines Ehlers-Danlos-Syndroms kann als charakteristisch für den Typ VIII angesehen werden, w?hrend sie nur selten ein Symptom des Typs VI darstellt. Die beim Ehlers-Danlos-Syndrom nur zum Teil auftretende Voralterung kann zur Fehldiagnose eines Progeriesyndroms führen. Aufgrund der Parodontopathie sollte eine frühzeitige zahn?rztliche Betreuung erfolgen, um das Auftreten von Zahnverlusten m?glichst zu verz?gern.      

Diaphysäre Femurpseudarthrosen – nur ein technisches Problem?

Between 1981 and 1994 at the Bergmannsheil Ruhr University Hospital in Bochum, Germany, we treated 145 patients with femoral diaphyseal nonunions following initial operative treatment. Of these patients, 138 received this initial operative treatment at an outside institution. The primary reconstructions for the fractures utilized plates in 112 cases, reamed nails in 24 cases and external fixators in 9 cases. The average age of the patients was 35 years and the mean time from the initial operative treatment was 2 years. Twenty-seven patients (19%) presented with a hypertrophic nonunion and 118 (81%) with an atrophic nonunion. There was a significant correlation between primary "classic" plating and development of an atrophic nonunion (chi 2-test: P < 0.01). We observed 34 wound infections (23%) with no significant correlation to the type of primary osteosynthesis. We determined that 73 of the pseudarthroses were due to improper osteosynthesis techniques. Of these cases, 41% involved the use of plates, 83% involved the use of reamed nails, and 78% involved the use of external fixators. Fracture location near the diaphyseal-metaphyseal junctions was common in this problematic group. Ninety-two percent of all plates led to atrophic nonunions. There were 21 open fractures and of these 90% (n = 19) developed an atrophic pseudarthrosis and 29% (n = 6) developed a wound infection. Fifty-seven (39%) of all patients had additional injuries, but we found that did not increase the risk of disturbed bone healing. Our revision operations focused on the elimination of wound infections, refreshment of bone healing, and improvement in fragment stability. Only 28% of all "classic" plates and 11% of all external fixators were changed to an intramedullary implant at the time of the first revision surgery. Hypertrophic nonunions required a mean of 1.3 revision operations to achieve bone healing whereas a mean of 2 revision operations were necessary to fuse atrophic bone ends (P < 0.05). In cases of diaphyseal pseudarthrosis healing time was not affected by the type of osteosynthesis used for primary reconstructions. Since lack of fracture healing can often already be observed directly from postoperative X-rays, we recommend that revision procedures be performed early. The prolonged length of time to care for femoral nonunions underlines the importance of appropriate primary fracture treatment. That takes into consideration both the biomechanical and the biological aspects of bone healing.     

An acquired G-CSF receptor mutation results in increased proliferation of CMML cells from a patient with severe congenital neutropenia.

Severe congenital neutropenia (CN) is characterized by a maturation arrest of myelopoiesis at the promyelocyte stage. Treatment with pharmacological doses of recombinant human granulocyte colony-stimulating factor (rh-G-CSF) stimulates neutrophil production and decreases the risk of major infectious complications. However, approximately 15% of CN patients develop myeloid malignancies that have been associated with somatic mutations in the G-CSF receptor (G-CSFR) and RAS genes as well as with acquired monosomy 7. We report a CN patient with chronic myelomonocytic leukemia (CMML) who never received rh-G-CSF. Molecular analysis demonstrated a somatic G-CSFR mutation (C2390T), which led to expression of a truncated G-CSFR protein in the CMML. Normal G-CSFR expression was unexpectedly absent in primary and cultured CMML. In addition, CMML cells showed monosomy 7 and an oncogenic NRAS mutation. In vitro culture revealed a G-CSF-dependent proliferation of CMML cells, which subsequently differentiated along the monocytic/macrophage lineage. Our results provide direct evidence for the in vivo expression of a truncated G-CSFR in leukemic cells, which emerged in the absence of rh-G-CSF treatment and transduces proliferative signals.     

Efficacy of the Sentinox Spray in Reducing Viral Load in Mild COVID-19 and Its Virucidal Activity against Other Respiratory Viruses: Results of a Randomized Controlled Trial and an In Vitro Study

Sentinox (STX) is an acid-oxidizing solution containing hypochlorous acid in spray whose virucidal activity against SARS-CoV-2 has been demonstrated. In this paper, results of a randomized controlled trial (RCT) on the efficacy of STX in reducing viral load in mild COVID-19 patients ({"type":"clinical-trial","attrs":{"text":"NCT04909996","term_id":"NCT04909996"}}NCT04909996) and a complementary in vitro study on its activity against different respiratory viruses are reported. In the RCT, 57 patients were randomized (1:1:1) to receive STX three (STX-3) or five (STX-5) times/day plus standard therapy or standard therapy only (controls). Compared with controls, the log₁₀ load reduction in groups STX-3 and STX-5 was 1.02 (p = 0.14) and 0.18 (p = 0.80), respectively. These results were likely driven by outliers with extreme baseline viral loads. When considering subjects with baseline cycle threshold values of 20–30, STX-3 showed a significant (p = 0.016) 2.01 log₁₀ reduction. The proportion of subjects that turned negative by the end of treatment (day 5) was significantly higher in the STX-3 group than in controls, suggesting a shorter virus clearance time. STX was safe and well-tolerated. In the in vitro study, ≥99.9% reduction in titers against common respiratory viruses was observed. STX is a safe device with large virucidal spectrum and may reduce viral loads in mild COVID-19 patients.     

Sex-Dependent Effects of the Intake of NOVA Classified Ultra-Processed Foods on Syndrome Metabolic Components in Brazilian Adults

Longitudinal studies evaluating the relationship between UPF consumption and the incidence of Metabolic Syndrome (MetS) and its components are still scarce. This study aimed to evaluate the effect of UPF consumption on the incidence of MetS and its components in adults. A prospective study was conducted with 896 participants from the 1978/79 Ribeirão Preto cohort, São Paulo, Brazil. UPF consumption was evaluated in %kcal and %g at ages 23–25 years. Incidence of MetS and its components were estimated at ages 37–39 years, according to the Joint Interim Statement criteria. Poisson regression was used to assess associations, and interactions with sex were investigated. UPF consumption had no association with MetS (%kcal Adjusted PR: 1.00; 95% CI: 0.99–1.01; %g Adjusted PR: 1.00; 95% CI: 0.99–1.01). However, women with higher UPF consumption, in %kcal and %g, had a higher risk of abdominal obesity (%kcal: p = 0.030; %g: p = 0.003); and women with higher UPF consumption, in %g, had a higher risk of low HDL-cholesterol (p = 0.041). For the other components of MetS, no significant associations were observed in either sex. These findings suggest evidence of no association between UPF consumption and MetS; however, consumption of UPF was associated with increased WC and low HDL-c, but only in women.