Metal oxide-based gas sensor array for VOCs determination in complex mixtures using machine learning.

Detection of volatile organic compounds (VOCs) from the breath is becoming a viable route for the early detection of diseases non-invasively. This paper presents a sensor array of 3 component metal oxides that give maximal cross-sensitivity and can successfully use machine learning methods to identify four distinct VOCs in a mixture. The metal oxide sensor array comprises NiO-Au (ohmic), CuO-Au (Schottky), and ZnO-Au (Schottky) sensors made by the DC reactive sputtering method and having a film thickness of 80-100 nm. The NiO and CuO films have ultrafine particle sizes of < 50 nm and rough surface texture, while ZnO films consist of nanoscale platelets. This array was subjected to various VOC concentrations, including ethanol, acetone, toluene, and chloroform, one by one and in a pair/mix of gases. Thus, the response values show severe interference and departure from commonly observed power law behavior. The dataset obtained from individual gases and their mixtures were analyzed using multiple machine learning algorithms, such as Random Forest (RF), K-Nearest Neighbor (KNN), Decision Tree, Linear Regression, Logistic Regression, Naive Bayes, Linear Discriminant Analysis, Artificial Neural Network, and Support Vector Machine. KNN and RF have shown more than 99% accuracy in classifying different varying chemicals in the gas mixtures. In regression analysis, KNN has delivered the best results with an R2 value of more than 0.99 and LOD of 0.012 ppm, 0.015 ppm, 0.014 ppm, and 0.025 ppm for predicting the concentrations of acetone, toluene, ethanol, and chloroform, respectively, in complex mixtures. Therefore, it is demonstrated that the array utilizing the provided algorithms can classify and predict the concentrations of the four gases simultaneously for disease diagnosis and treatment monitoring.

Immunomodulator use does not prevent first loss of response to anti-tumour necrosis factor alpha therapy in inflammatory bowel disease: long-term outcomes in a real-world cohort.

BACKGROUND: Recent prospective studies suggest combination therapy with immunomodulators improves efficacy, but long-term data is limited. AIM: To assess whether anti-tumour necrosis factor alpha (anti-TNF) monotherapy was associated with earlier loss of response (LOR) than combination therapy in a real-world cohort with long-term follow up. METHODS: A retrospective audit was conducted of inflammatory bowel disease patients receiving anti-TNF therapy in a tertiary centre and specialist private practices. All patients with accurate data for anti-TNF commencement and adequate correspondence to determine end-points were included. Outcomes measured included time to first LOR, causes and biochemical parameters. RESULTS: Two hundred and twenty-four patients were identified; 139 (62.1%) on combination therapy and 85 (37.9%) on monotherapy. Forty-five percent of patients had LOR during follow up until a maximum of 8.5 years; 59.4% on combination therapy and 40.6% on monotherapy (P = 0.533). The median time to LOR was not different between groups; 1069 days for combination therapy and 1489 days for monotherapy (P = 0.533). There was no difference in time to LOR between patients treated with different combination regimens or different anti-TNF agents. CONCLUSION: In this large cohort of patients in a real-world setting, patients treated with anti-TNF monotherapy had similar rates of LOR as patients on anti-TNF combination therapy, at both short- and long-term follow up.

Rituximab-induced Crohn's disease.

The use of rituximab has significantly improved outcomes in patients with haematological malignancies and autoimmune disease. There are reports of rituximab-associated ulcerative colitis; however, we report for the first time, two cases of rituximab-induced Crohn's disease in elderly patients treated for lymphoma. Both patients had evidence of inflammation, ulceration, and granulomas consistent with Crohn's disease, and responded well to immunosuppression. The association of rituximab and ileocolitis suggests a protective effect of CD20 + lymphocytes in the gut, and implicates their depletion to the development and exacerbation of inflammatory bowel disease.

Sorafenib in the treatment of hepatocellular carcinoma: a multi-centre real-world study.

OBJECTIVE: Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes. MATERIAL AND METHODS: Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients. RESULTS: Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2-3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2-3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015). CONCLUSIONS: Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.

Trend of severe abdominal injuries from bicycle accidents in children: a preventable condition.

AIM: Bicycle riding is a common recreational and sport activity enjoyed by many children. Bicycle accidents are a common cause of abdominal injuries. We aim to establish the trend and the associated risk factor(s) of bicycle-related abdominal injuries. METHODS: A retrospective review of all children admitted following bicycle accidents to a single tertiary referral centre was carried out over an approximately 5-year period. The data were tabulated and regression analyses were carried out. RESULTS: Over the study period, 196 children were admitted into the Emergency Department. Abdominal injuries (16%) were the third largest group after orthopaedic and head injuries. There were 19 major visceral injuries, seven of whom underwent major surgeries. Forty-two percent (8/19) of these major injuries were related to stunts. Over the same period, no child with head injury required any surgical intervention. In addition, there was a definite trend that abdominal injuries were accounting for greater percentage of bicycle-related injuries in children. CONCLUSIONS: Severe intra-abdominal trauma following bicycle injuries appears to be seen more often in adolescent males, especially when related to BMX stunts. These injuries have surpassed head injuries as the prime cause of morbidity from bicycle accidents. These injuries are largely preventable.

An unusual case of multiple gastrointestinal stromal tumors in the small bowel presenting as occult and overt gastrointestinal bleeding.

We present a case report of a 59-year-old woman with multiple gastrointestinal stromal tumors as a cause of gastrointestinal bleeding. She initially presented with recurrent iron deficiency anemia and subsequent gastrointestinal bleeding over 10 years. An initial angiodysplastic lesion was identified, treated, and spot tattooed. Recurrent symptoms occurred leading to repeat investigations with a further subepithelial lesion with ulceration being identified. Computerized tomography enterography subsequently revealed an ileal intraluminal enhancing lesion, and she was referred to surgery. Surgical resection was ultimately performed, and multiple lesions were found to be present with histology revealing multiple gastrointestinal stromal tumors.

Does ERCP position matter? A randomized controlled trial comparing efficacy and complications of left lateral versus prone position (POSITION study).

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) is traditionally performed with patients in the prone position (PP). However, this poses a potentially increased risk of anesthetic complications. An alternative is the left lateral (LL) decubitus position, which is commonly used for endoscopic procedures. Our aim was to compare cannulation rate, time, and outcomes in ERCP performed in LL versus PP. Patients and methods We conducted a non-inferiority, prospective, randomized control trial with 1:1 randomization to either LL or PP position. Patients > 18 years of age with native papillae requiring a therapeutic ERCP were recruited between March 2017 and November 2018 in a single tertiary center. Results A total of 253 patients were randomized; 132 to LL (52.2 %) and 121 to PP (47.8 %). Cannulation rates were 97.0 % in LL vs 99.2 % in PP (difference -2.2 % (one-sided 95 % CI: -5 % to 0.6 %). Median time to biliary cannulation was 03:50 minutes in LL vs 02:57 minutes in PP ( P  = 0.62). Pancreatitis rates were 2.3 % in LL vs 5.8 % in PP ( P  = 0.20). There were significantly lower radiation doses used in PP (0.23 mGy/m 2 in LL vs 0.16 mGy/m 2 in PP, P  = 0.008) without a difference in fluoroscopy times. Conclusions Our analysis comparing LL to PP during ERCP shows comparable procedural and anesthetic outcomes, with significantly lower radiation exposure when performed in PP. We conclude that ERCP undertaken in the LL position is not inferior to PP, except for higher radiation exposure, and should be considered as a safe alternate position for patients undergoing ERCP.

Narrow band imaging versus white light for detecting sessile serrated lesion: A prospective randomized multicenter study.

Objectives: Colonoscopy is the gold standard diagnostic test used to detect early colorectal lesions and prevent colorectal carcinoma. Narrow band imaging (NBI) is an imaging technique that provides improved image resolution of the mucosa during endoscopy. Whether NBI improves the detection of sessile serrated lesion (SSL) is controversial-our aim was to assess this during routine colonoscopy. Methods: We conducted a multicenter, prospective, randomized, controlled trial. Patients underwent colonoscopy for screening, surveillance, or symptoms. They were randomized to either high-definition white light (HD-WL) or NBI in a 1:1 ratio. The primary outcome was SSL detection rate. Secondary outcomes were adenoma detection rate (ADR) and polyp detection rate (PDR). Results: A total of 400 patients were randomized to NBI (N = 200) or HD-WL (N = 200). The total colonoscopy time was slightly longer in the NBI group compared to HD-WL (median time 14 vs. 12 min, p = 0.033). There were no statistically significant differences in SSL detection rate (7.5% NBI vs. 8.0% HD-WL; p = 0.852), ADR (41.0% NBI vs. 37.5% HD-WL; p = 0.531), or PDR (61.0% NBI vs. 54.0% HD-WL; p = 0.157) between the two groups. No significant predictors of SSL detection were found on univariable or multivariable analysis. Increasing age and increased withdrawal time were an independent predictors of polyp detection and increasing age was also an independent predictor of adenoma detection on multivariable analysis. Conclusion: In the hands of experienced colonoscopists, NBI does not improve SSL detection compared to HD-WL. Withdrawal time and patient age remain important factors for polyp and adenoma detection.

The EUS molecular evaluation of pancreatic cancer: A prospective multicenter cohort trial.

BACKGROUND AND OBJECTIVES: Patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (A-PDAC) are not candidates for surgical resection and are often offered palliative chemotherapy. The ready availability of a safe and effective tumor sampling technique to provide material for both diagnosis and comprehensive genetic profiling is critical for informing precision medicine in A-PDAC, thus potentially increasing survival. The aim of this study is to examine the feasibility and benefits of routine comprehensive genomic profiling (CGP) of A-PDAC using EUS-FNA material. METHODS: This is a prospective cohort study to test the clinical utility of fresh frozen or archival EUS-FNA samples in providing genetic material for CGP. The results of the CGP will be reviewed at a molecular tumor board. The proportion of participants that have a change in their treatment recommendations based on their individual genomic profiling will be assessed. Correlations between CGP and stage, prognosis, response to treatment and overall survival will also be investigated. This study will open to recruitment in 2020, with a target accrual of 150 A-PDAC patients within 36 months, with a 2-year follow-up. It is expected that the majority of participants will be those who have already consented for their tissue to be biobanked in the Victorian Pancreatic Cancer Biobank at the time of diagnostic EUS-FNA. Patients without archival or biobanked material that is suitable for CGP may be offered a EUS-FNA procedure for the purposes of obtaining fresh frozen material. DISCUSSION: This trial is expected to provide crucial data regarding the feasibility of routine CGP of A-PDAC using EUS-FNA material. It will also provide important information about the impact of this methodology on patients' survival.