Tuberculosis associated with Mycobacterium tuberculosis Beijing and non-Beijing genotypes: a clinical and immunological comparison

BACKGROUND: The Mycobacterium tuberculosis Beijing genotype is biologically different from other genotypes. We aimed to clinically and immunologically compare human tuberculosis caused by Beijing and non-Beijing strains. METHODS: Pulmonary tuberculosis patients were prospectively enrolled and grouped by their M. tuberculosis genotypes. The clinical features, plasma cytokine levels, and cytokine gene expression levels in peripheral blood mononuclear cells (PBMC) were compared between the patients in Beijing and non-Beijing groups. RESULTS: Patients in the Beijing group were characterized by significantly lower frequency of fever (odds ratio, 0.12, p = 0.008) and pulmonary cavitation (odds ratio, 0.2, p = 0.049). Night sweats were also significantly less frequent by univariate analysis, and the duration of cough prior to diagnosis was longer in Beijing compared to non-Beijing groups (medians, 60 versus 30 days, p = 0.048). The plasma and gene expression levels of interferon (IFN) γ and interleukin (IL)-18 were similar in the two groups. However, patients in the non-Beijing group had significantly increased IL-4 gene expression (p = 0.018) and lower IFN-γ : IL-4 cDNA copy number ratios (p = 0.01). CONCLUSION: Patients with tuberculosis caused by Beijing strains appear to be less symptomatic than those who have disease caused by other strains. Th1 immune responses are similar in patients infected with Beijing and non-Beijing strains, but non-Beijing strains activate more Th2 immune responses compared with Beijing strains, as evidenced by increased IL-4 expression

One-carbon metabolites, B vitamins and associations with systemic inflammation and angiogenesis biomarkers among colorectal cancer patients:results from the ColoCare Study

B-vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- A nd angiogenesis-related chronic diseases, such as colorectal cancer. Yet, the role of one-carbon metabolism in inflammation and angiogenesis among colorectal cancer patients remains unclear.The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed colorectal cancer patients (n=238) in the prospective ColoCare Study, Heidelberg.We cross-sectionally analyzed associations between 12 B-vitamins and one-carbon metabolites and 10 inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesized that pyridoxal-5'-phosphate (PLP) is inversely associated with inflammatory biomarkers.We observed that PLP was inversely associated with CRP (r=-0.33, plinearlinear=0.003), IL-6 (r=-0.39, plinear linear=0.02) and TNFα (r=-0.12, plinear=0.045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r=-0.14), SAA (r=-0.14) and TNFα (r=-0.15) among colorectal cancer patients. Folate catabolite apABG was positively correlated with IL-6 (r= 0.27, plinearlinear<0.0001), indicating higher folate utilization during inflammation.Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among colorectal cancer patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for colorectal cancer patients.</p

Circulating B-vitamin biomarkers and B-vitamin supplement use in relation to quality of life in patients with colorectal cancer: results from the FOCUS consortium

Background: B vitamins have been associated with the risk and progression of colorectal cancer (CRC), given their central roles in nucleotide synthesis and methylation, yet their association with quality of life in established CRC is unclear.Objectives: To investigate whether quality of life 6 months postdiagnosis is associated with: 1) circulating concentrations of B vitamins and related biomarkers 6 months postdiagnosis; 2) changes in these concentrations between diagnosis and 6 months postdiagnosis; 3) B-vitamin supplement use 6 months postdiagnosis; and 4) changes in B-vitamin supplement use between diagnosis and 6 months postdiagnosis.Methods: We included 1676 newly diagnosed stage I-III CRC patients from 3 prospective European cohorts. Circulating concentrations of 9 biomarkers related to the B vitamins folate, riboflavin, vitamin B6, and cobalamin were measured at diagnosis and 6 months postdiagnosis. Information on dietary supplement use was collected at both time points. Health-related quality of life (global quality of life, functioning scales, and fatigue) was assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 6 months postdiagnosis. Confounder-adjusted linear regression analyses were performed, adjusted for multiple testing.Results: Higher pyridoxal 5'-phosphate (PLP) was cross-sectionally associated with better physical, role, and social functioning, as well as reduced fatigue, 6 months postdiagnosis. Associations were observed for a doubling in the hydroxykynurenine ratio [3-hydroxykynurenine: (kynurenic acid + xanthurenic acid + 3-hydroxyanthranilic acid + anthranilic acid); an inverse marker of vitamin B6] and both reduced global quality of life (beta = -3.62; 95% CI: -5.88, -1.36) and worse physical functioning (beta = -5.01; 95% CI: -7.09, -2.94). Dose-response relations were observed for PLP and quality of life. No associations were observed for changes in biomarker concentrations between diagnosis and 6 months. Participants who stopped using B-vitamin supplements after diagnosis reported higher fatigue than nonusers.Conclusions: Higher vitamin B6 status was associated with better quality of life, yet limited associations were observed for the use of B-vitamin supplements. Vitamin B6 needs further study to clarify its role in relation to quality of life

Diagnostic accuracy of palpation and ultrasonography for diagnosing infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis

Objective: Although infantile hypertrophic pyloric stenosis (IHPS) is a well-known disease, there is no systematic review regarding the optimal diagnostic strategy. We conducted a systematic review and meta-analysis to obtain diagnostic accuracy of all methods to diagnose IHPS. Methods: According to the Preferred Reported Items for Systematic Reviews and Meta-Analysis guidelines, we searched MEDLINE and Embase to identify studies reporting sensitivity and specificity of all methods used to diagnose IHPS. Inclusion criteria were infants with suspicion of/or diagnosed with IHPS who underwent pyloromyotomy or had clinical follow-up. A random-effects model was used to obtain pooled estimates of sensitivity, specificity and area under the receiver oper-ating characteristic curve. Results: After screening 5364 studies, we included 43 studies with in total 6085 infants (n = 4241 IHPS; n = 1844 controls). The diagnostic sensitivity of palpation ranged from 10.0 to 93.4% and decreased over time. Different parameters for ultrasonography were found. Most used parameters were pyloric muscle thickness (PMT) ≥ 3 mm (pooled sensitivity 97.6% and specificity 98.8%), PMT ≥ 4 mm (pooled sensitivity 94.0% and specificity 98.0%) or a combination of PMT ≥ 4 mm and/or pyloric canal length ≥16 mm (pooled sensitivity 94.0% and specificity 91.7%). The AUC showed high diagnostic accuracy (0.997, 0.966 and 0.981 respectively), but large heterogeneity exists. Due to the large differences in cut-off values no meta-analysis could be conducted for pyloric canal length and pyloric diameter. Conclusion: Palpation has limited sensitivity in diagnosing IHPS. We showed that ultrasonography has highest diagnostic accuracy to diagnose IHPS and we advise to use PMT ≥ 3 mm as cut-off. Advances in knowledge: This is the first systematic review and meta-analysis on diagnosing IHPS, which summarizes the available literature and may be used as a guideline

Diagnostic accuracy of palpation and ultrasonography for diagnosing infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis

Objective: Although infantile hypertrophic pyloric stenosis (IHPS) is a well-known disease, there is no systematic review regarding the optimal diagnostic strategy. We conducted a systematic review and meta-analysis to obtain diagnostic accuracy of all methods to diagnose IHPS. Methods: According to the Preferred Reported Items for Systematic Reviews and Meta-Analysis guidelines, we searched MEDLINE and Embase to identify studies reporting sensitivity and specificity of all methods used to diagnose IHPS. Inclusion criteria were infants with suspicion of/or diagnosed with IHPS who underwent pyloromyotomy or had clinical follow-up. A random-effects model was used to obtain pooled estimates of sensitivity, specificity and area under the receiver oper-ating characteristic curve. Results: After screening 5364 studies, we included 43 studies with in total 6085 infants (n = 4241 IHPS; n = 1844 controls). The diagnostic sensitivity of palpation ranged from 10.0 to 93.4% and decreased over time. Different parameters for ultrasonography were found. Most used parameters were pyloric muscle thickness (PMT) ≥ 3 mm (pooled sensitivity 97.6% and specificity 98.8%), PMT ≥ 4 mm (pooled sensitivity 94.0% and specificity 98.0%) or a combination of PMT ≥ 4 mm and/or pyloric canal length ≥16 mm (pooled sensitivity 94.0% and specificity 91.7%). The AUC showed high diagnostic accuracy (0.997, 0.966 and 0.981 respectively), but large heterogeneity exists. Due to the large differences in cut-off values no meta-analysis could be conducted for pyloric canal length and pyloric diameter. Conclusion: Palpation has limited sensitivity in diagnosing IHPS. We showed that ultrasonography has highest diagnostic accuracy to diagnose IHPS and we advise to use PMT ≥ 3 mm as cut-off. Advances in knowledge: This is the first systematic review and meta-analysis on diagnosing IHPS, which summarizes the available literature and may be used as a guideline

Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis