Correlation of Hypertension and Proteinuria with Outcome in Elderly Bevacizumab-Treated Patients with Metastatic Colorectal Cancer

Background

Studies suggest a relationship between hypertension and outcome in bevacizumab-treated patients with metastatic colorectal cancer (mCRC). We performed a retrospective analysis of two phase II studies (BECA and BECOX) to determine if hypertension and proteinuria predict outcome in elderly patients with mCRC treated with bevacizumab.

Patients and Methods

Patients ≥70 years of age received either capecitabine 1250 mg/m² bid days 1–14 + bevacizumab 7.5 mg/kg day 1 every 21 days (BECA study) or capecitabine 1000 mg/m² bid days 1–14 with bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m² day 1 (BECOX study). The primary objective was to correlate hypertension and proteinuria with overall response rate (ORR), time to progression (TTP) and overall survival (OS). Secondary objectives included identification of risk factors associated with the development of hypertension and proteinuria and determining whether development of hypertension or proteinuria in the first 2 cycles was related to ORR, disease-control rate (DCR), TTP or OS.

Results

In total, 127 patients (median age 75.5 years) were included in the study. Hypertension correlated with DCR and OS; proteinuria correlated with ORR and DCR. Proteinuria or hypertension in the first 2 cycles did not correlate with efficacy. Risk factors for hypertension were female gender (odds ratio [OR] 0.241; P = 0.011) and more bevacizumab cycles (OR 1.112; P = 0.002); risk factors for proteinuria were diabetes (OR 3.869; P = 0.006) and more bevacizumab cycles (OR 1.181; P<0.0001). Multivariate analysis identified as having prognostic value: baseline lactate dehydrogenase, haemoglobin, number of metastatic lesions and DCR.

Conclusion

This analysis of two phase II studies suggests that hypertension is significantly correlated with OS but not with ORR and TTP, whereas proteinuria is correlated with ORR but not with OS and TTP. Both hypertension and proteinuria are associated with the duration of bevacizumab treatment and do not represent an independent prognostic factor.     

Polymorphisms in ABC Transporter Genes and Concentrations of Mercury in Newborns – Evidence from Two Mediterranean Birth Cohorts

Background

The genetic background may influence methylmercury (MeHg) metabolism and neurotoxicity. ATP binding cassette (ABC) transporters actively transport various xenobiotics across biological membranes.

Objective

To investigate the role of ABC polymorphisms as modifiers of prenatal exposure to MeHg.

Methods

The study population consisted of participants (n = 1651) in two birth cohorts, one in Italy and Greece (PHIME) and the other in Spain (INMA). Women were recruited during pregnancy in Italy and Spain, and during the perinatal period in Greece. Total mercury concentrations were measured in cord blood samples by atomic absorption spectrometry. Maternal fish intake during pregnancy was determined from questionnaires. Polymorphisms (n = 5) in the ABC genes ABCA1, ABCB1, ABCC1 and ABCC2 were analysed in both cohorts.

Results

ABCB1 rs2032582, ABCC1 rs11075290, and ABCC2 rs2273697 modified the associations between maternal fish intake and cord blood mercury concentrations. The overall interaction coefficient between rs2032582 and log2-transformed fish intake was negative for carriers of GT (β = −0.29, 95%CI −0.47, −0.12) and TT (β = −0.49, 95%CI −0.71, −0.26) versus GG, meaning that for a doubling in fish intake of the mothers, children with the rs2032582 GG genotype accumulated 35% more mercury than children with TT. For rs11075290, the interaction coefficient was negative for carriers of TC (β = −0.12, 95%CI −0.33, 0.09), and TT (β = −0.28, 95%CI −0.51, −0.06) versus CC. For rs2273697, the interaction coefficient was positive when combining GA+AA (β = 0.16, 95%CI 0.01, 0.32) versus GG.

Conclusion

The ABC transporters appear to play a role in accumulation of MeHg during early development.     

Motion analysis of the glenohumeral joint during activities of daily living

The shoulder complex has a larger range of motion (ROM) than any other joint complex in the human body, leaving it prone to numerous injuries. Objective kinematic analysis could yield useful functional insights that may assist clinical practice. Non-invasive optoelectronic motion analysis techniques have been used to assess the shoulders of five healthy subjects performing ROM tasks and 10 functional tasks of daily living. The four most demanding tasks – touching the side and back of the head, brushing the opposite side of the head, lifting an object to shoulder height and lifting an object to head height, required 78%, 60%, 61% and 71%, respectively, of the glenohumeral elevation necessary for full abduction in the scapular plane for the 10 shoulders. This has implications for clinical practice where maximum arm elevation is commonly used to determine a patient's ability to return to work and other everyday activities.     

Ethnicity,region and nation: Valencian identity and the Spanish nation-state

In the exploration of the relationships between ethnicity, national identity, and symbolic building of the region, this article deals with a key issue: the achievements and limitations of the assimilation of culturally heterogeneous populations by European nation-states. The modern Spanish national identity (at times shown as purely political) has included and still includes cultural elements (above all, the spread of the Spanish language). This meant that the ethnicity of the Valencians (a population with autonomous political structures until their violent destruction in 1707) had to be redefined as a regional identity in order to avoid coming into conflict with national identity. This re-working excluded the Catalan language, spoken by most of the inhabitants of the region, from the political sphere. In the long term, this cultural characteristic became stigmatized, which favoured its undercommunication to the extent that a process of language shift was initiated. This case study highlights the historical analysis of ethnic identity and the instability of its integration into national structures.     

Shiga Toxin 2-Encoding Bacteriophages in Human Fecal Samples from Healthy Individuals

Shiga toxin-converting bacteriophages (Stx phages) carry the stx gene and convert nonpathogenic bacterial strains into Shiga toxin-producing bacteria. Previous studies have shown that high densities of free and infectious Stx phages are found in environments polluted with feces and also in food samples. Taken together, these two findings suggest that Stx phages could be excreted through feces, but this has not been tested to date. In this study, we purified Stx phages from 100 fecal samples from 100 healthy individuals showing no enteric symptoms. The phages retrieved from each sample were then quantified by quantitative PCR (qPCR). In total, 62% of the samples carried Stx phages, with an average value of 2.6 × 10⁴ Stx phages/g. This result confirms the excretion of free Stx phages by healthy humans. Moreover, the Stx phages from feces were able to propagate in enrichment cultures of stx-negative Escherichia coli (strains C600 and O157:H7) and in Shigella sonnei, indicating that at least a fraction of the Stx phages present were infective. Plaque blot hybridization revealed lysis by Stx phages from feces. Our results confirm the presence of infectious free Stx phages in feces from healthy persons, possibly explaining the environmental prevalence observed in previous studies. It cannot be ruled out, therefore, that some positive stx results obtained during the molecular diagnosis of Shiga toxin-producing Escherichia coli (STEC)-related diseases using stool samples are due to the presence of Stx phages.     

Microbial inoculum production for biocrust restoration: testing the effects of a common substrate versus native soils on yield and community composition

Human activities are causing unprecedented disturbances in terrestrial ecosystems across the globe. To reverse soil deterioration in drylands, a promising tool is the ex situ cultivation of biological soil crusts, topsoil geobiological assemblages that provide key ecosystem services. One approach is to transplant biocrusts cultivated in greenhouse nursery facilities into degraded sites to accelerate recovery. Lichen‐ and moss‐dominated biocrusts have been successfully grown using a common, sandy soil. We compared the use of a common, sandy soil versus native soils as a substrate for the cultivation of cyanobacteria‐dominated biocrusts. In greenhouse experiments, we inoculated natural biocrusts collected from three Southwestern USA dryland sites on to either a common, sandy soil or on their respective native soils. The common substrate resulted in a moderate enhancement of growth yield relative to native soils. While changes in bacterial phyla composition remained low in all cases, the use of a common substrate introduced larger shifts in cyanobacterial community composition than did using native soils. The shift increase attributable to the common, sandy soil was not catastrophic—and typical cyanobacteria of field biocrusts remained dominant—unless textural differences between the common substrate and native soils were marked. Because collecting native soils adds a significant effort to growing cyanobacterial biocrusts in greenhouses for restoration purposes, the use of a common, sandy substrate may be considered by land managers as a standard practice. But we recommend to regularly monitor the composition of the grown biomass.     

Inoculation and habitat amelioration efforts in biological soil crust recovery vary by desert and soil texture

As dryland degradation continues, it is increasingly important to understand how to effectively restore biocrust communities. Potential techniques include the addition of biocrust inoculum to accelerate biocrust recovery. Enhanced erosion typical of degraded environments creates a challenge for these approaches, due to loss by wind or water and burial by saltating particles. To retain and protect added inoculum, the inclusion of habitat‐amelioration techniques can improve recovery rates. This study tested three different types of inoculum (field‐collected, greenhouse‐cultivated, and laboratory‐cultivated biocrust) coupled with two treatments to augment soil stability and ameliorate habitat limitations: soil surface polyacrylamide additions and installation of straw barriers. This was done across two deserts (Great Basin and Chihuahuan) and separated into generally coarse‐ or finer‐textured soils in each desert, with results monitored for 3 years (2015, 2016, 2017). While the inoculum type, coupled with habitat ameliorations, occasionally enhanced biocrust growth across years and treatments, in other cases, it made no difference compared to natural recovery rates. Rather, the desert location and soil texture groupings were the most prominent factors in determining recovery trajectories. Recovery proportions were similar in the finer‐textured sites in both the Great Basin and the Chihuahuan deserts, while the coarser‐textured site in the Great Basin did show some recovery over time and the Chihuahuan coarser‐textured site did not. This study demonstrates the importance of understanding site potential and identifying key limitations to biocrust recovery for successful restoration projects.