Faecal volatile organic compounds analysis using field asymmetric ion mobility spectrometry : non-invasive diagnostics in paediatric inflammatory bowel disease

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), remains challenging to diagnose. Diagnostic work up carries a high burden, especially in paediatric patients, due to invasive endoscopic procedures. IBD is associated with alterations in intestinal microbiota composition. Faecal volatile organic compounds (VOCs) reflect gut microbiota composition. Aim of this study was to assess the diagnostic accuracy of faecal VOC profiling as non-invasive diagnostic biomarker for paediatric IBD

Optimized sampling conditions for fecal volatile organic compounds analysis by means of field asymmetric ion mobility spectrometry

Background Fecal volatile organic compounds (VOCs) are increasingly considered as potential non-invasive, diagnostic biomarkers for various gastrointestinal diseases. Knowledge of influence of sampling conditions on VOC outcomes is limited. We aimed to evaluate effects of sampling conditions on fecal VOC profiles and to assess under which conditions an optimal diagnostic accuracy in the discrimination between pediatric inflammatory bowel disease (IBD) and controls could be obtained. Methods Fecal samples from de novo treatment-naïve pediatric IBD patients and healthy controls (HC) were used to assess effects of sampling conditions compared to the standard operating procedure (reference standard), defined as 500mg of sample mass, diluted with 10mL tap water, using field asymmetric ion mobility spectrometry (FAIMS). Results A total of 17 IBD (15CD and 2 UC) and 25 HC were included. IBD and HC could be discriminated with high accuracy (accuracy=0.93, AUC=0.99, p<0.0001). Smaller fecal sample mass resulted in a decreased diagnostic accuracy (300mg accuracy=0.77; AUC=0.69, p=0.02; 100mg accuracy=0.70, AUC=0.74, p=0.003). A loss of diagnostic accuracy was seen towards increased numbers of thaw-freeze cycles (one cycle: accuracy=0.61, AUC=0.80, p=0.0004, two cycles: accuracy=0.64, AUC=0.56, p=0.753, three cycles: accuracy=0.57, AUC=0.50, p=0.5101) and when samples were kept at room temperature for 180 minutes prior to analysis (accuracy=0.60, AUC=0.51, p=0.46). Diagnostic accuracy of VOC profiles was not significantly influenced by storage duration differences of 20 months. Conclusion Application of 500mg sample mass analyzed after one thaw-freeze cycle, showed best discriminative accuracy for differentiation of IBD and HC. VOC profiles and diagnostic accuracy were significantly affected by sampling conditions, underlining the need for implementation of standardized protocols in fecal VOC analysis

Preclinical detection of non-catheter related late-onset sepsis in preterm infants by fecal volatile compounds analysis : a prospective, multi-center cohort study

Background: Late onset sepsis (LOS) in preterm infants is preceded by fecal volatile organic compound (VOC) alterations, suggesting an etiological role of gut microbiota in LOS rather than being primarily caused by central venous catheters (CVC). To increase our knowledge about the involvement of the gut microbiota in LOS, we analyzed fecal samples from septic infants without a CVC. Methods: In this prospective multicenter study, fecal samples were collected daily from all infants born at ≤30 weeks gestation. Fecal VOC profiles up to 3 days prior to sepsis onset from infants with non-catheter–related LOS were compared with profiles from non-septic controls by means of High-Field Asymmetric Waveform Ion Mobility Spectrometry. Results: In total, 104 fecal samples were analyzed. Fecal VOC profiles allowed for discrimination between non-catheter–related LOS cases (n = 24) and matched controls (n = 25). Discriminative accuracy increased after focusing on center of origin (area under the curve, sensitivity, specificity; 0.95, 100%, 83%) and after focusing on LOS cases caused by Staphylococcus epidermidis (0.95, 100%, 78%), the most cultured pathogen (n = 11). Conclusions: Fecal VOC profiles of preterm LOS infants without a CVC differed from matched controls underlining the increasing notion that aberrations in gut microbiota composition and activity may play a role in LOS etiology

Een vrouw met tropische ulcera.

A 67-year-old woman had multiple ulcers due to cutaneous diphtheria, following a trip to the Philippines

Why not to pick your nose:Association between nose picking and SARS-CoV-2 incidence, a cohort study in hospital health care workers

BACKGROUND: Hospital health care workers (HCW) are at increased risk of contracting SARS-CoV-2. We investigated whether certain behavioral and physical features, e.g. nose picking and wearing glasses, are associated with infection risk. AIM: To assess the association between nose picking and related behavioral or physical features (nail biting, wearing glasses, and having a beard) and the incidence of SARS-CoV-2-infection. METHODS: In a cohort study among 404 HCW in two university medical centers in the Netherlands, SARS-CoV-2-specific antibodies were prospectively measured during the first phase of the pandemic. For this study HCW received an additional retrospective survey regarding behavioral (e.g. nose picking) and physical features. RESULTS: In total 219 HCW completed the survey (response rate 52%), and 34/219 (15.5%) became SARS-CoV-2 seropositive during follow-up from March 2020 till October 2020. The majority of HCW (185/219, 84.5%) reported picking their nose at least incidentally, with frequency varying between monthly, weekly and daily. SARS-CoV-2 incidence was higher in nose picking HCW compared to participants who refrained from nose picking (32/185: 17.3% vs. 2/34: 5.9%, OR 3.80, 95% CI 1.05 to 24.52), adjusted for exposure to COVID-19. No association was observed between nail biting, wearing glasses, or having a beard, and the incidence of SARS-CoV-2 infection. CONCLUSION: Nose picking among HCW is associated with an increased risk of contracting a SARS-CoV-2 infection. We therefore recommend health care facilities to create more awareness, e.g. by educational sessions or implementing recommendations against nose picking in infection prevention guidelines.</p

Case report: chronic relapsing cryptococcal meningitis in a patient with low mannose-binding lectin and a low naïve CD4 cell count

BACKGROUND: Cryptococcal meningitis is most commonly found in HIV-infected patients. In HIV-negative patients, its low incidence can lead to prolonged time to diagnosis. Detailed case reports of chronic cryptococcal meningitis are scarce, but could provide clues for earlier diagnosis in this patient category. CASE PRESENTATION: A 60-year old man presented June 2015 with intermittent headaches for several months without any fever. Initial work-up showed a leukocytosis, raised CSF opening pressure and raised leukocytes and protein in the CSF. An MRI revealed leptomeningeal contrast enhancement and cerebellar oedema. While malignancy and various infectious causes were excluded, the patient had a spontaneous clinical and radiological recovery. One year later, the patient returned with complaints of headaches. Also, cerebellar oedema and leptomeningeal contrast enhancement had recurred. Eventually in March 2017, the novel cryptococcal antigen lateral flow assay (CrAg LFA) was positive on CSF, and one colony of Cryptococcus neoformans was cultured from CSF. The patient was treated with the standard antifungal regimen which resulted in resolution of his headaches. In retrospect, the cryptococcal antigen test was already positive on a serum sample from June 2015. Interestingly, post-treatment immunological analysis revealed both a low mannose-binding lectin (MBL) concentration and low naïve CD4 counts. CONCLUSIONS: We present a patient with cryptococcal meningitis in an HIV-negative patient with low MBL and low naïve CD4 count suffering a chronic relapsing meningo-encephalitis with relatively mild symptoms for around 2 years. In patients with an unexplained meningo-encephalitis such as this case, early performance of CrAg LFA on serum and/or CSF is an inexpensive and rapid method to reduce time-to diagnosis

Animal olfactory detection of disease : promises and pitfalls

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