Features associated with high-risk sessile serrated polyps at index and follow-up colonoscopy.

BACKGROUND AND AIM: Clinically significant serrated polyps are precursors of colorectal cancers, with features considered high risk including size ≥10 mm, dysplasia, and presence of synchronous conventional adenoma. While these features have been described in cohorts undergoing screening colonoscopy, there is little information regarding the prevalence and patient characteristics associated with high-risk sessile serrated polyps (SSPs) in those undergoing surveillance colonoscopy. METHODS: Polyp pathology at the index and first follow-up colonoscopy performed between 2004 and 2019 were examined in patients enrolled in a surveillance program because of an index finding of adenoma and/or SSP. Demographics and pathology features for SSP were compared between the colonoscopies. RESULTS: Of 6297 patients undergoing index colonoscopy, 2035 underwent follow-up colonoscopy after 3.3 years (interquartile range 2.1-4.8 years). The proportion with SSP decreased from 7.6% at index to 5.0% at follow-up (P < 0.001); however, the proportion of SSPs that were considered high risk was not different between the colonoscopies (62.8% vs 62.4%). Female gender was associated with the presence of high-risk SSP at index colonoscopy (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.28-2.06), while age ≥75 years (OR 3.38, 95% CI 1.67-6.81) and previous high-risk SSP (OR 9.40, 95% CI 4.23-20.88) were independently associated with high-risk SSP at follow-up. CONCLUSIONS: The prevalence of SSP falls by one-third at first follow-up colonoscopy although the proportion of SSP with high-risk features remains the same. While females were more likely to have a high-risk SSP at the index colonoscopy, those at greatest risk for high-risk SSP at follow-up colonoscopy were age >75 years and an index high-risk SSP.

High rates of indeterminate interferon-gamma release assays for the diagnosis of latent tuberculosis infection in liver transplantation candidates.

BACKGROUND AND AIMS: Screening for latent tuberculosis infection (LTBI) is recommended prior to solid organ transplantation. Interferon-gamma release assays (IGRAs) are the most widely used test for LTBI screening; however, assessment of IGRA performance in patients with end-stage liver disease is limited. The purpose of this study was to evaluate the prevalence and predictors of indeterminate (INDT) IGRA results in liver transplantation candidates. METHODS: Between March 2011 and May 2018, we retrospectively analyzed 155 patients undergoing liver transplantation assessment, who underwent IGRA testing (Quantiferon-TB Gold, QFT-G) to exclude LTBI. Characteristics of patients, including age, gender, etiology of liver disease, MELD score, and absolute lymphocyte counts, were compared by QFT-G result (determinate vs INDT). RESULTS: Of the 155 patients screened, the rate of positive, negative, and INDT results were 5.2%, 69.8%, and 25%, respectively. The only variable independently associated with an indeterminate test on multivariate analysis was MELD score (odds ratio = 1.07, 95% CI = 1.01-1.14 per unit increase; P = 0.014). In 95% of INDT tests, both TB antigen tube and the positive control tube were negative and repeat testing gave the same indeterminate result, suggestive of anergy rather than laboratory error. CONCLUSIONS: Our study suggests a high rate of INDT IGRA results during screening of liver transplant candidates for LTBI, associated with severity of liver disease and anergy. Because of the high rate of INDT QFT-G testing in this setting, individualized risk assessment is required including a thorough assessment of clinical risk factors and knowledge of local TB prevalence.

Low Sensitivity of Fecal Immunochemical Tests and Blood-Based Markers of DNA Hypermethylation for Detection of Sessile Serrated Adenomas/Polyps.

BACKGROUND: Early detection and removal of precursor lesions reduce colorectal cancer morbidity and mortality. Sessile serrated adenomas/polyps (SSP) are a recognized precursor of cancer, but there are limited studies on whether current screening techniques detect this pathology. AIMS: To investigate the sensitivity of fecal immunochemical tests (FIT) and epigenetic biomarkers in blood for detection of SSP. METHODS: A prospective study offered FIT and a blood test (Colvera for methylated BCAT1 and IKZF1) to adults referred for colonoscopy. Sensitivity of FIT and the blood test were determined for four types of pathology: low-risk conventional adenoma, high-risk adenoma, SSP, and absence of neoplasia. Comparisons were made for FIT positivity at 10 and 20 µg hemoglobin (Hb)/g feces. RESULTS: One thousand eight hundred and eighty-two subjects completed FIT and underwent colonoscopy. One thousand four hundred and three were also tested for methylated BCAT1/IKZF1. The sensitivity of FIT (20 µg Hb/g feces) for SSP was 16.3%. This was lower than the sensitivity for high-risk adenomas (28.7%, p < 0.05), but no different to that for low-risk adenomas (13.1%) or no neoplasia (8.4%). A positive FIT result for SSP was not associated with demographics, morphology, concurrent pathology or intake of medications that increase bleeding risk. FIT sensitivity for SSP did not significantly increase through lowering the positivity threshold to 10 µg Hb/g feces (20.4%, p > 0.05). Sensitivity of the blood test for SSP was 8.8%, and 26.5% when combined with FIT. CONCLUSIONS: Both FIT and blood-based markers of DNA hypermethylation have low sensitivity for detection of SSP. Further development of sensitive screening tests is warranted.

Sessile Serrated Polyps with Synchronous Conventional Adenomas Increase Risk of Future Advanced Neoplasia.

BACKGROUND: Surveillance colonoscopy guidelines following adenomas or sessile serrated adenomas/polyps (SSPs) are based on pathology features known to be associated with risk of future colorectal cancer. A synchronous conventional adenoma may increase the malignant potential of SSP, but current guidelines do not address this combination of pathologies. AIMS: The aim was to assess the risk of advanced neoplasia after SSP with or without synchronous adenoma compared to that following a conventional adenoma. METHODS: An audit was conducted on colonoscopies performed between 2000 and 2014 as part of a surveillance program. Index colonoscopy findings were classified as: low-risk SSP and high-risk SSP (size ≥ 10 mm or with cytological dysplasia) with and without synchronous adenoma; high-risk adenoma and low-risk adenoma. Risk of advanced neoplasia was determined at subsequent surveillance colonoscopies. RESULTS: In total, 2157 patients had adenoma or SSP found at index colonoscopy-low-risk adenoma (40%), high-risk adenoma (54%) and SSP (4%). Synchronous adenomas were seen with 47% of SSP. The median follow-up was 50.3 months (interquartile range 28.1-79.3). Compared to an index finding of low-risk adenoma, index findings of high-risk adenoma, as well as SSP with synchronous adenoma, were independent predictors of future advanced neoplasia (high-risk adenoma: hazard ratio (HR) = 2.04 (95% CI 1.70-2.45); high-risk SSP + adenoma HR = 3.20 (95% CI 1.31-7.82); low-risk SSP + adenoma: HR = 2.20 (95% CI 1.03-4.68)). CONCLUSIONS: Synchronous adenoma increases the risk of advanced neoplasia for SSP equivalent to that seen following high-risk adenoma. Guidelines for surveillance should take into account concurrent pathologies with SSP.

Thermal Management of Microelectronic Devices Using Nanofluid with Metal foam Heat Sink.

Microelectronic components are used in a variety of applications that range from processing units to smart devices. These components are prone to malfunctions at high temperatures exceeding 373 K in the form of heat dissipation. To resolve this issue, in microelectronic components, a cooling system is required. This issue can be better dealt with by using a combination of metal foam, heat sinks, and nanofluids. This study investigates the effect of using a rectangular-finned heat sink integrated with metal foam between the fins, and different water-based nanofluids as the working fluid for cooling purposes. A 3D numerical model of the metal foam with a BCC-unit cell structure is used. Various parameters are analyzed: temperature, pressure drop, overall heat transfer coefficient, Nusselt number, and flow rate. Fluid flows through the metal foam in a turbulent flow with a Reynold's number ranging from 2100 to 6500. The optimum fin height, thickness, spacing, and base thickness for the heat sink are analyzed, and for the metal foam, the material, porosity, and pore density are investigated. In addition, the volume fraction, nanoparticle material, and flow rate for the nanofluid is obtained. The results showed that the use of metal foam enhanced the thermal performance of the heat sink, and nanofluids provided better thermal management than pure water. For both cases, a higher Nusselt number, overall heat transfer coefficient, and better temperature reduction is achieved. CuO nanofluid and high-porosity low-pore-density metal foam provided the optimum results, namely a base temperature of 314 K, compared to 341 K, with a pressure drop of 130 Pa. A trade-off was achieved between the temperature reduction and pumping power, as higher concentrations of nanofluid provided better thermal management and resulted in a large pressure drop.

Split-dose 1 L polyethylene glycol (PEG) with ascorbate is non-inferior to split-dose PEG with sodium picosulfate and magnesium citrate with similar tolerability: a randomized study.

BACKGROUND AND AIM: Post-marketing studies comparing low-volume polyethylene glycol (PEG)-based regimens are limited. This randomized study aimed to compare the efficacy and tolerability of a novel 1-L low-volume PEG-based preparation: 1 L PEG+Asc (PEG3350, sodium ascorbate, sodium sulfate, ascorbic acid, sodium chloride, and potassium chloride) with PEG+SPMC (PEG3350, sodium chloride, potassium chloride and sodium sulfate, sodium picosulfate, magnesium oxide, citric acid, and aspartame), prior to routine colonoscopy at an Australian tertiary referral center. METHODS: Outpatients undergoing colonoscopy were randomized to receive either split-dose 1 L PEG+Asc or split-dose PEG+SPMC. Bowel preparation quality using the Boston Bowel Preparation Scale (BPPS), modified Aronchick scores, procedure time, cecal intubation, and adenoma detection rates were recorded. Patient compliance and tolerability were captured using a standardized questionnaire. RESULTS: A total of 173 patients were randomized, of whom 164 completed the study and were allocated to 1 L PEG+Asc (n = 82) or PEG+SPMC (n = 82). Non-inferiority of 1 L PEG+Asc was demonstrated with 89% achieving successful preparation (total BPPS ≥6 and each sub-score ≥2) compared with 85.4% in the PEG+SPMC group, resulting in an estimated difference of 3.7% (95% CI -6.6% to 13.9%). The median BBPS was non-inferior in all colonic segments with 1 L PEG+Asc (BBPS 3 [interquartile range 2-3]) vs PEG+SPMC (BBPS 2 [interquartile range 2-3]). More 1 L PEG+Asc patients reported moderate to severe nausea (P = 0.028), but overall tolerability was similar. CONCLUSIONS: The quality of bowel preparation achieved with 1 L PEG+Asc is non-inferior to that with PEG+SPMC, with similar tolerability outcomes. Further studies are required in patients at risk of suboptimal bowel preparation.