Background
Fibroblast growth factor receptor (FGFR2) has been proposed as a target in gastric cancer. However, appropriate methods to select patients for anti-FGFR2 therapies have not yet been ...established.
Methods
We used in situ techniques to investigate FGFR2 mRNA expression and gene amplification in a large cohort of 1036 Japanese gastric cancer patients. FGFR2 mRNA expression was determined by RNAscope. FGFR2 gene amplification was determined by dual-color in situ hybridization (DISH).
Results
We successfully analyzed 578 and 718 samples by DISH and RNAscope, respectively; 2% (12/578) showed strong
FGFR2
gene amplification (FGFR2:CEN10 >10); moderate
FGFR2
gene amplification (FGFR2:CEN10 <10; ≥2) was detected in 8% (47/578); and high FGFR2 mRNA expression of score 4 (>10 dots/cell and >10% of positive cells with dot clusters under a 20× objective) was seen in 4% (29/718). For 468 samples, both mRNA and DISH data were available. FGFR2 mRNA expression levels were associated with gene amplification; FGFR2 mRNA levels were highest in the highly amplified samples (
n
= 12). All highly amplified samples showed very strong FGFR2 mRNA expression (dense clusters of the signal visible under a 1× objective). Patients with very strong FGFR2 mRNA expression showed more homogeneous FGFR2 mRNA expression compared to patients with lower FGFGR2 mRNA expression. Gastric cancer patients with tumors that had an FGFR2 mRNA expression score of 4 had shorter RFS compared with score 0–3 patients.
Conclusion
RNAscope and DISH are suitable methods to evaluate FGFR2 status in gastric cancer. Formalin-fixed paraffin-embedded (FFPE) tissue slides allowed evaluation of the intratumor heterogeneity of these FGFR2 biomarkers.
IntroductionTo evaluate awareness and knowledge of diabetic ketoacidosis (DKA), a common and potentially life-threatening complication in people living with type 1 diabetes (T1D).Research design and ...methodsA survey was developed to assess individuals’ current knowledge, management, and unmet needs regarding DKA. The study was conducted in six Swiss and three German endocrine outpatient clinics specialized in the treatment of diabetes.ResultsA total of 333 participants completed the questionnaire (45.7% female, mean age of 47 years, average duration of T1D at 22 years). Surprisingly, 32% of individuals were not familiar with the term ‘diabetic ketoacidosis’. Participants rated their own knowledge of DKA significantly lower than their physicians (p<0.0001). 46% of participants were unable to name a symptom of DKA, and 45% were unaware of its potential causes. 64% of participants did not test for ketones at all. A significant majority (67%) of individuals expressed the need for more information about DKA.ConclusionsIn patients treated in specialized centers, knowledge of DKA was found to be inadequate, with a lack of understanding regarding symptoms and causes. Healthcare professionals tended to overestimate individuals’ knowledge. Future efforts should focus on addressing these knowledge gaps and incorporating protective factors into the treatment of T1D.
Clonal clusters and gene repertoires of Staphylococcus aureus are essential to understand disease and are well characterized in industrialized countries but poorly analysed in developing regions. The ...objective of this study was to compare the molecular-epidemiologic profiles of S. aureus isolates from Sub-Saharan Africa and Germany. S. aureus isolates from 600 staphylococcal carriers and 600 patients with community-associated staphylococcal disease were characterized by DNA hybridization, clonal complex (CC) attribution, and principal component (PCA)-based gene repertoire analysis. 73% of all CCs identified representing 77% of the isolates contained in these CCs were predominant in either African or German region. Significant differences between African versus German isolates were found for alleles encoding the accessory gene regulator type, enterotoxins, the Panton-Valentine leukocidin, immune evasion gene cluster, and adhesins. PCA in conjunction with silhouette analysis distinguished nine separable PCA clusters, with five clusters primarily comprising of African and two clusters of German isolates. Significant differences between S. aureus lineages in Africa and Germany may be a clue to explain the apparent difference in disease between tropical/(so-called) developing and temperate/industrialized regions. In low-resource countries further clinical-epidemiologic research is warranted not only for neglected tropical diseases but also for major bacterial infections.
Antimicrobial peptides and proteins (AMP) are highly active molecules with a broad‐spectrum of microbicidal activity. Human beta‐defensins (hBD)‐2 and hBD‐3 were initially isolated from ...psoriatic‐scale extracts, and other AMP have been identified in high concentrations in psoriatic skin explaining the uncommonness of skin infections in these patients. When a 71‐year‐old male patient suffering from a mild form of psoriasis (Psoriasis Area Severity Index PASI 4.4) presented a soft tissue infection (erysipelas) surrounding a psoriatic plaque of the elbow, we asked whether a local deficiency of AMP could be the reason for this infection. A detailed analysis of the expression and secretion levels of different classes of AMP was conducted. Induction of AMP was clearly shown by immunohistochemistry as well as by ELISA performed using skin‐washing fluids. Therefore, other factors, for example deep penetrating injuries bypassing the keratinocyte innate defense system, must have caused the soft tissue infection.
Background. In May–July 2011, Germany experienced a large food-borne outbreak of Shiga toxin 2—producing Escherichia coli (STEC O104:H4) with 3842 cases, including 855 cases with hemolytic uremic ...syndrome (HUS) and 53 deaths. Methods. A multicenter study was initiated in 5 university hospitals to determine pathogen shedding duration. Diagnostics comprised culture on selective media, toxin enzyme-linked immunosorbent assay, and polymerase chain reaction. Results were correlated with clinical and epidemiologic findings. Testing for pathogen excretion was continued after discharge of the patient. Results. A total of 321 patients (104 male, 217 female) were included (median age, 40 years range, 1–89 days). Median delay from onset of symptoms to hospitalization was 4 days (range, 0–17 days). Two hundred nine patients presented with HUS. The estimate for the median duration of shedding was 17–18 days. Some patients remained STEC O104:H4 positive until the end of the observation time (maximum observed shedding duration: 157 days). There was no significant influence of sex on shedding duration. Patients presenting with HUS had a significantly shortened shedding duration (median, 13–14 days) compared to non-HUS patients (median, 33–34 days). Antimicrobial treatment was also significantly associated with reduced shedding duration. Children (age ≤15 years) had longer shedding durations than adults (median, 35–41 vs 14–15 days). Conclusions. STEC O104:H4 is usually eliminated from the human gut after 1 month, but may sometimes be excreted for several months. Proper follow-up of infected patients is important to avoid further pathogen spread.
The name 'Mycobacterium alsiense', although reported in 2007, has not been validly published. Polyphasic characterization of three available strains of this species led us to the conclusion that they ...represent a distinct species within the genus Mycobacterium. The proposed novel species grows slowly and presents pale yellow-pigmented colonies. Differentiation from other mycobacteria is not feasible on the basis of biochemical and cultural features alone while genetic analysis, extended to eight housekeeping genes and one spacer region, reveals its clear distinction from all other mycobacteria. Mycobacterium asiaticum is the most closely related species on the basis of 16S rRNA gene sequences (similarity 99.3 %); the average nucleotide identity between the genomes of the two species is 80.72 %, clearly below the suggested cut-off (95-96 %). The name Mycobacterium alsense sp. nov. is proposed here for the novel species and replaces the name 'M. alsiense', ex Richter et al. 2007, given at the time of isolation of the first strain. The type strain is TB 1906T ( = DSM 45230T = CCUG 56586T).
Multidrug-resistant bacteria represent a substantial global burden for human health, potentially fuelled by migration waves: in 2015, 476,649 refugees applied for asylum in Germany mostly as a result ...of the Syrian crisis. In Arabic countries, multiresistant bacteria cause significant problems for healthcare systems. Currently, no data exist describing antibiotic resistances in healthy refugees. Here, we assess the microbial landscape and presence of antibiotic resistance genes (ARGs) in refugees and German controls. To achieve this, a systematic study was conducted in 500 consecutive refugees, mainly from Syria, Iraq, and Afghanistan and 100 German controls. Stool samples were subjected to PCR-based quantification of 42 most relevant ARGs, 16S ribosomal RNA gene sequencing-based microbiota analysis, and culture-based validation of multidrug-resistant microorganisms.
The fecal microbiota of refugees is substantially different from that of resident Germans. Three categories of resistance profiles were found: (i) ARGs independent of geographic origin of individuals comprising BIL/LAT/CMA, ErmB, and mefE; (ii) vanB with a high prevalence in Germany; and (iii) ARGs showing substantially increased prevalences in refugees comprising CTX-M group 1, SHV, vanC1, OXA-1, and QnrB. The majority of refugees carried five or more ARGs while the majority of German controls carried three or less ARGs, although the observed ARGs occurred independent of signatures of potential pathogens.
Our results, for the first time, assess antibiotic resistance genes in refugees and demonstrate a substantially increased prevalence for most resistances compared to German controls. The antibiotic resistome in refugees may thus require particular attention in the healthcare system of host countries.
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