FOLFCIS Treatment and Genomic Correlates of Response in Advanced Anal Squamous Cell Cancer

Background

Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Assessment of toxicity using dehydrogenases activity and mathematical modeling

Dehydrogenase activity is frequently used to assess the general condition of microorganisms in soil and activated sludge. Many studies have investigated the inhibition of dehydrogenase activity by various compounds, including heavy metal ions. However, the time after which the measurements are carried out is often chosen arbitrarily. Thus, it can be difficult to estimate how the toxic effects of compounds vary during the reaction and when the maximum of the effect would be reached. Hence, the aim of this study was to create simple and useful mathematical model describing changes in dehydrogenase activity during exposure to substances that inactivate enzymes. Our model is based on the Lagergrens pseudo-first-order equation, the rate of chemical reactions, enzyme activity, and inactivation and was created to describe short-term changes in dehydrogenase activity. The main assumption of our model is that toxic substances cause irreversible inactivation of enzyme units. The model is able to predict the maximum direct toxic effect (MDTE) and the time to reach this maximum (T_MDTE). In order to validate our model, we present two examples: inactivation of dehydrogenase in microorganisms in soil and activated sludge. The model was applied successfully for cadmium and copper ions. Our results indicate that the predicted MDTE and T_MDTE are more appropriate than EC₅₀ and IC₅₀ for toxicity assessments, except for long exposure times.     

Reoperation rates and risk factors for revision 4 years after dynamic stabilization of the lumbar spine

Background Context

The concept of dynamic stabilization (DS) of the lumbar spine for treatment of degenerative instability has been introduced almost two decades ago. Dynamic stabilization follows the principle of controlling movement in the coronal plane by providing load transfer of the spinal segment without fusion and, at the same time, reducing side effects such as adjacent segment disease (ASD). So far, only little is known about revision rates after DS due to ASD and screw loosening (SL).

Fixator-assisted nailing of tibial fractures: New surgical technique and presentation of first 30 cases

Background

Intramedullary nailing is considered a “gold standard” for treatment of tibial shaft fractures. However, some types of fractures are typically considered as “difficult for nailing”. This group includes the periarticular fractures, fractures of both bones at the same level, comminuted and segmental fractures of the tibia. Fixator-assisted nailing (FAN) is an effective method treatment of these types of fractures. The main requirements for the ideal reduction device are an ease of its installation and an ability of multiplanar fracture reduction. Fixator-assisted nailing (FAN) with the use of two perpendicular to each other monolateral tubular frames perfectly meets these requirements. In this study we present this new surgical technique and the analysis of first 30 cases.

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

Cognitive effects attributed to angiotensin II may result from its conversion to angiotensin IV.

This study tests the hypothesis that the facilitation of learning and improvement of memory observed after an intracerebroventricular (i.c.v.) injection of angiotensin II (Ang II) is, in fact, caused by its derivative angiotensin IV (Ang IV). We ran two memory tests as well as an auxiliary test assessing motor performance in rats injected (i.c.v., 1 nmol in 2 microl saline) with Ang II or Ang IV. There were separate groups receiving peptide or saline five, 10 and 15 minutes before testing. Ang IV significantly increased step-through latencies in a passive avoidance paradigm as well as improved discrimination between familiar and unfamiliar objects in an object recognition test in all groups showing better retrieval of memory of aversive as well as appetitive stimuli in the peptide-treated groups regardless of the time of its injection. In contrast, rats treated with Ang II demonstrated significant improvement of memory of aversive and appetitive stimuli in the same tests only 15 minutes after its i.c.v. injection, with no effect in the groups injected five minutes before testing and slight efficacy in those injected 10 minutes before the test. Numbers of crossings, rearings and bar approaches in an open field were similar both in the peptide-treated and control groups making it unlikely that changes in motor performance affected the memory tests. In line with the present views on the intracellular metabolism of Ang II, these results suggest degradation to Ang IV by aminopeptidases A and N is necessary before the cognitive effects can occur.