Can bacterial virulence factors predict antibiotic resistant Helicobacter pylori infection?

AIM To evaluate the association between virulence factor status and antibiotic resistance in Helicobacter pylori(H. pylori)-infected patients in Ireland. METHODS DNA was extracted from antral and corpus biopsies obtained from 165 H. pylori-infected patients. Genotyping for clarithromycin and fluoroquinolone-mediating mutations was performed using the Genotype Helico DR assay. cag A and vac A genotypes were investigated using PCR. RESULTS Primary, secondary and overall resistance rates for clarithromycin were 50.5%(n = 53/105), 78.3%(n = 47/60) and 60.6%(n = 100/165), respectively. Primary, secondary and overall resistance rates for fluoroquinolones were 15.2%(n = 16/105) and 28.3%(n = 17/60) and 20%(n = 33/165), respectively. Resistance to both antibiotics was 12.4%(n = 13/105) in treatment-na?ve patients, 25%(n = 15/60) in those previously treated and 17%(n = 28/165) overall. A cag A-positive genotype was detected in 22.4%(n = 37/165) of patient samples. The dominant vac A genotype was S1/M2 at 44.8%(n = 74/165), followed by S2/M2 at 26.7%(n = 44/165), S1/M1 at 23.6%(n = 39/165) and S2/M1 at 4.8%(n = 8/165). Primary clarithromycin resistance was significantly lower in cag A-positive strains than in cag A-negative strains [32%(n = 8/25) vs 56.3%(n = 45/80); P = 0.03]. Similarly, in patients infected with more virulent H. pylori strains bearing the vac A s1 genotype, primary clarithromycin resistance was significantly lower than in those infected with less virulent strains bearing the vac A s2 genotype, [41%(n = 32/78) vs 77.8%(n = 21/27); P = 0.0001]. No statistically significant association was found between primary fluoroquinolone resistance and virulence factor status.CONCLUSION Genotypic H. pylori clarithromycin resistance is high and cag A-negative strains are dominant in our population. Less virulent(cag A-negative and vac A S2-containing) strains of H. pylori are associated with primary clarithromycin resistance.     

The Management and Outcomes of Patients with Extra-Pulmonary Neuroendocrine Neoplasms and Brain Metastases

Background: Brain metastases (BMs) in patients with extra-pulmonary neuroendocrine neoplasms (EP–NENs) are rare, and limited clinical information is available. The aim of this study was to detail the clinicopathological features, management and outcomes in patients with EP–NENs who developed BMs. Methods: A retrospective single-centre analysis of consecutive patients with EP–NENs (August 2004–February 2020) was conducted. Median overall survival (OS)/survival from BMs diagnosis was estimated (Kaplan–Meier). Results: Of 730 patients, 17 (1.9%) had BMs, median age 61 years (range 15–77); 8 (53%) male, unknown primary NEN site: 40%. Patients with BMs had grade 3 (G3) EP–NENs 11 (73%), G2: 3 (20%), G1: 1 (7%). Eight (53%) had poorly differentiated NENs, 6 were well-differentiated and 1 was not recorded. Additionally, 2 (13%) patients had synchronous BMs at diagnosis, whilst 13 (87%) developed BMs metachronously. The relative risk of developing BMs was 7.48 in patients with G3 disease vs. G1 + G2 disease (p = 0.0001). Median time to the development of BMs after NEN diagnosis: 15.9 months (range 2.5–139.5). Five patients had a solitary BM, 12 had multiple BMs. Treatment of BMs were surgery (n = 3); radiotherapy (n = 5); 4: whole brain radiotherapy, 1: conformal radiotherapy (orbit). Nine (53%) had best supportive care. Median OS from NEN diagnosis was 23.6 months [95% CI 15.2–31.3]; median time to death from BMs diagnosis was 3.0 months [95% CI 0.0–8.3]. Conclusion: BMs in patients with EP–NENs are rare and of increased risk in G3 vs. G1 + G2 EP–NENs. Survival outcomes are poor, and a greater understanding is needed to improve therapeutic outcomes.     

Development and Validation of Empirical Models to Predict Metal Additively Manufactured Part Density and Surface Roughness from Powder Characteristics

Metal additive manufacturing (AM) processes, viz laser powder bed fusion (L-PBF), are becoming an increasingly popular manufacturing tool for a range of industries. The powder material used in L-PBF is costly, and it is rare for a single batch of powder to be used in a single L-PBF build. The un-melted powder material can be sieved and recycled for further builds, significantly increasing its utilisation. Previous studies conducted by the authors have tracked the effect of both powder recycling and powder rejuvenation processes on the powder characteristics and L-PBF part properties. This paper investigates the use of multiple linear regression to build empirical models to predict the part density and surface roughness of 316L stainless steel parts manufactured using recycled and rejuvenated powder based on the powder characteristics. The developed models built on the understanding of the effect of powder characteristics on the part properties. The developed models were found to be capable of predicting the part density and surface roughness to within ±0.02% and ±0.5 Ra, respectively. The models developed enable L-PBF operators to input powder characteristics and predict the expected part density and surface roughness.     

TOPORS as a novel causal gene for Joubert syndrome

Joubert syndrome (JBTS) is a Mendelian disorder of the primary cilium defined by the clinical triad of hypotonia, developmental delay, and a distinct cerebellar malformation called the molar tooth sign. JBTS is inherited in an autosomal recessive, autosomal dominant, or X-linked recessive manner. Though over 40 genes have been identified as causal for JBTS, molecular diagnosis is not made in 30%–40% of individuals who meet clinical criteria. TOPORS encodes topoisomerase I-binding arginine/serine-rich protein, and homozygosity for a TOPORS missense variant (c.29C > A; p.(Pro10Gln)) was identified in individuals with the ciliopathy oral-facial-digital syndrome in two families of Dominican descent. Here, we report an additional proband of Dominican ancestry with JBTS found by exome sequencing to be homozygous for the identical p.(Pro10Gln) TOPORS missense variant. Query of the Mount Sinai BioMe biobank, which includes 1880 individuals of Dominican ancestry, supports a high carrier frequency of the TOPORS p.(Pro10Gln) variant in individuals of Dominican descent. Our data nominates TOPORS as a novel causal gene for JBTS and suggests that TOPORS variants should be considered in the differential of ciliopathy-spectrum disease in individuals of Dominican ancestry.