Validation of prognostic scores for survival in cancer patients beyond first-line therapy

Background

DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples.

Methods

SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH.

Results

A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the SHOX2 gene showed no difference.

Conclusions

Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples.     

Paragonimiasis in Cameroon: molecular identification, serodiagnosis and clinical manifestations

Paragonimiasis is a common parasitic zoonosis in Cameroon and neighbouring countries in Western Africa. Serum, sputum and faecal samples were collected in an endemic area of South West Province, Cameroon, after administration of a questionnaire to identify individuals with appropriate symptoms and histories. Microscopic examination revealed eggs in sputum from 16 people, but none in any faecal sample. These 16 were among the 25 and 26 people, respectively, positive by ELISA and by immunoblot using Paragonimus africanus crude antigens. Copro-DNA detection was attempted using 23 faecal samples (18 from sputum egg-negative and five from sputum egg-positive individuals). Copro-DNA was detected in four of the five sputum egg-positive individuals. These results strongly suggest that: (1) serology is much more sensitive than sputum examination for diagnosis of paragonimiasis; and (2) a copro-DNA test may be more sensitive than a microscopic search for eggs in faeces. Molecular sequence data from ITS2 and cox1 genes confirmed that adult worms experimentally raised in cats were P. africanus and that eggs from sputum or other worm products from human faeces also belonged to this species. Based on these results, 26 of 168 persons (15.5%) were diagnosed as suffering from paragonimiasis.     

A cross-sectional assessment of frailty,falls and perceptions of ageing in people living with HIV using an mHealth platform

Objective

To evaluate frailty, falls and perceptions of ageing among clinically stable individuals with HIV, engaged with remote healthcare delivered via a novel smartphone application.

Methods

This was a multi-centre European cross-sectional, questionnaire-based sub-study of EmERGE participants. Frailty was assessed using the five-item FRAIL scale. Present criteria were summed and categorized as follows: 0, robust; 1–2, pre-frail; 3–5, frail. Falls history and EQ-5D-5L quality of life measure were completed. Participants were asked their felt age and personal satisfaction with ageing.

Results

A total of 1373 participated, with a mean age of 45 (± 9.8) years. Frailty was uncommon at 2%; 12.4% fell in the previous year, 58.8% of these recurrently. Mood symptoms and pain were prevalent, at 43.3% and 31.8%, respectively. Ageing satisfaction was high at 76.4%, with 74.6% feeling younger than their chronological age; the mean felt age was 39.3 years. In multivariable analysis, mood symptoms and pain were positively associated with frailty, falls and ageing dissatisfaction. An increase in pain severity and mood symptoms were respectively associated with 34% and 63% increased odds of pre-frailty/frailty. An increment in pain symptoms was associated with a 71% increase in odds of falling. Pain was associated with ageing poorly, as were mood symptoms, with odds of dissatisfaction increasing by 34% per increment in severity.

Conclusions

Although uncommon, frailty, falls and ageing dissatisfaction were seen in a younger cohort with medically stable HIV infection using a remote care model, promoting screening as advocated by European guidelines. These were more common in those with pain or mood symptoms, which should be proactively managed in clinical care and explored further in future research.     

Ataxia with vitamin E deficiency and severe dystonia: report of a case

Mutation of the gene for alpha-tocopherol transfer protein causes ataxia with isolated vitamin E deficiency, a disorder usually stabilized or improved after vitamin E supplementation. Dystonia has rarely been described in ataxia with isolated vitamin E deficiency (AVED) patients. We present the case of a young boy with AVED, whose neurological and extra-neurological cardinal symptoms of the disease improved after vitamin E supplementation but who progressively developed generalized dystonia.     

A Fumonisin Prevention Tool for Targeting and Ranking Agroclimatic Conditions Favoring Exposure in French Maize-Growing Areas

The levels of fumonisins (FUMO)—mycotoxins produced by Fusarium verticillioides—in maize for food and feed are subject to European Union regulations. Compliance with the regulations requires the targeting of, among others, the agroclimatic factors influencing fungal contamination and FUMO production. Arvalis-Institut du végétal has created a national, multiyear database for maize, based on field survey data collected since 2003. This database contains information about agricultural practices, climatic conditions and FUMO concentrations at harvest for 738 maize fields distributed throughout French maize-growing regions. A linear mixed model approach highlights the presence of borers and the use of a late variety, high temperatures in July and October, and a water deficit during the maize cycle as creating conditions favoring maize contamination with Fusarium verticillioides. It is thus possible to target a combination of risk factors, consisting of this climatic sequence associated with agricultural practices of interest. The effects of the various possible agroclimatic combinations can be compared, grouped and classified as promoting very low to high FUMO concentrations, possibly exceeding the regulatory threshold. These findings should facilitate the creation of a national, informative and easy-to-use prevention tool for producers and agricultural cooperatives to manage the sanitary quality of their harvest.     

Emergence of Mutations in the K13 Propeller Gene of Plasmodium falciparum Isolates from Dakar,Senegal, in 2013-2014

The kelch 13 (K13) propeller gene is associated with artemisinin resistance. In a previous work, there were no mutations found in 138 Plasmodium falciparum isolates collected in 2012 and 2013 from patients residing in Dakar, Senegal (M. Torrentino-Madamet et al., Malar J 13:472, 2014, http://dx.doi.org/10.1186/1475-2875-13-472). However, the N554H, Q613H, and V637I mutations were identified in the propeller region of K13 in 92 (5.5%) isolates in 2013 and 2014. There were five polymorphisms identified in the Plasmodium/Apicomplexa-specific domain (K123R, N137S, N142NN/NNN, T149S, and K189T/N).     

Urgent desensitization in patients bridged to heart transplantation under extracorporeal membrane oxygenation support: A preliminary experience

Antihuman leukocyte antigen (HLA) antibodies restrict the access to cardiac allografts. Desensitization therapy is a major challenge in patients with cardiogenic shock waiting for urgent heart transplantation (HT). We retrospectively reviewed six patients (mean age of 37.5 years [16–70]) who underwent plasmapheresis (PP) under extracorporeal membrane oxygenation (ECMO) before transplant between January 2017 and September 2018. The average duration of follow‐up was 25 months [20–32]. Mean fluorescence intensity (MFI) of HLA‐specific antibodies was reported as follows: score 4 for MFI < 1000, score 6 for 1000 < MFI < 3000 and score 8 for MFI > 3000. The mean duration of ECMO support was 29 days [1–74] and 6.8 [1–29] PP sessions were performed per patient before transplant. The mean number of HLA‐specific antibodies before HT was 9.6 for score 6 [4–13] and 5.8 for score 8 [1–12]. Four patients had major complications after transplantation (2 hemorrhagic shocks, 5 infectious events). Mean MFI reduction rate was 94% [79–100] for Class I and 44.2% for Class II [0–83]. Hospital survival was 100%, and early antibody‐mediated rejection was diagnosed in one patient at 7 days after HT. Plasmapheresis under ECMO support was associated with favorable early outcomes in highly sensitized candidates for urgent heart transplantation.