Dynamics and phase behavior of metallo-dielectric rod-shaped microswimmers driven by alternating current electric field.

The ability to move and self-organize in response to external stimuli is a fascinating feature of living active matter. Here, the metallo-dielectric rod-shaped microswimmers are shown to have a similar behavior in the presence of an AC electric field. The silica-copper Janus microrods were fabricated using the physical vapor deposition-based glancing angle deposition technique (GLAD). When the aqueous solution of the microrods was under the influence of an external AC electric field, they were found to exhibit different phases such as clustering, swimming, and vertical standing in response to variation of the applied frequency. The swimming behavior (5-90 kHz) of the rods is attributed to the induced-charge electrophoresis (ICEP) phenomenon, whereas the dynamic clustering (<5 kHz) could be explained in terms of the electrohydrodynamic (EHD) interaction. Interestingly, the rods flip to attain the vertically standing position when responding to the applied electric field above 90 kHz. The reorientation and switching of the major axis of the rod along the field direction is attributed to the electro-orientation phenomenon. This is basically due to the dominance of the electric torque above the upper limit of the characteristic frequency, where the strength of slip flows around the microrods is predicted to be poor. The present study not only offers insight into the fundamental aspects of the dynamics and the phase behavior of rod-shaped microswimmers, but also opens an avenue to design reconfigurable active matter systems with features inspired by biological systems.

Light-driven micromotors for on-demand and local pH sensing applications.

In recent years, self-propelled light-driven micromotors have gained significant attention due to their capabilities for a wide range of applications, including cargo delivery, chemical sensing, environmental monitoring, etc. Here, we demonstrate the design of light-driven micromotors for local pH sensing applications. The micromotors are spherical Janus particles with multiple functional coatings that provide them with interesting features, like a dual optical response, i.e., controlled swimming under UV light (320-400 nm) and pH-dependent fluorescence signal emission when excited with blue light (450 nm), and moving path guidance using a weak external uniform magnetic field (50 G). All of these features allow the micromotors to sense the pH of the medium on-demand and locally or of a target location by guiding them to swim to the target location. The pH-dependent change in the fluorescence signal intensity is used for the measurement of the local pH of the medium. It is observed that the careful measurement of small pH changes requires a spectrometer that precisely measures the intensity change. However, the fluorescence signal of the micromotors was good enough to provide a clear visual demarcation for large pH changes. Systematic experimental studies supported by controlled experiments are performed to optimize the system as well as to calibrate the micromotors for local pH sensing applications. The characteristics like easy-to-design structure, light activation, directional swimming, and ability to measure the pH on-demand and locally prove that micromotors have the potential to revolutionize pH monitoring in various domains, including lab-on-a-chip devices, biomedical research, environmental monitoring, quality control in industrial processes, etc.

pH-Responsive swimming behavior of light-powered rod-shaped micromotors.

Micromotors have emerged as promising devices for a wide range of applications e.g., microfluidics, lab-on-a-chip devices, active matter, environmental monitoring, etc. The control over the activity of micromotors with the ability to exhibit multimode swimming is one of the most desirable features for many of the applications. Here, we demonstrate a rod-shaped light-driven micromotor whose activity and swimming behavior can easily be controlled. The rod-shaped micromotors are fabricated through the dynamic shadowing growth (DSG) technique, where a 2 µm long arm of titanium dioxide (TiO2) is grown over spherical silica (SiO2) particles (1 µm diameter). Under low-intensity UV light exposure, the micromotors exhibit self-propulsion in an aqueous peroxide medium. When activated, the swimming behavior of micromotors greatly depends on the pH of the medium. The swimming direction, i.e., forward or backward movement, as well as swimming modes like translational or rotational motion, can be controlled by changing the pH values. The observed dynamics has been rationalized using a theoretical model incorporating chemical activity, hydrodynamic flow, and the effect of gravity for a rod-shaped active particle near a planar wall. The pH-dependent translational and rotational dynamics of micromotors provide a versatile platform for achieving controlled and responsive behaviors. Continued research and development in this area hold great promise for advancing micromotors and enabling novel applications in microfluidics, micromachining, environmental sciences, and biomedicine.

COVID-19 Related Predisposition to Diabetic Ketoacidosis.

Background and aims Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can exacerbate hyperglycemia and can cause life-threatening diabetic ketoacidosis (DKA) in patients with diabetes mellitus (DM). The objective of this study is to compare the characteristics of diabetic COVID-19 patients with and without DKA and to determine the predictors of mortality in the setting of COVID-19 and DKA. Methods This is a retrospective single-center cohort study including patients admitted to our hospital with COVID-19 and DM from March 2020 to June 2020. Patients with DKA were filtered as per the diagnostic criteria set by the American Diabetes Association (ADA). Patients with hyperosmolar hyperglycemic state (HHS) were excluded. A retrospective analysis was performed, which included those who developed DKA and those with neither DKA nor HHS. The primary outcome measurement was mortality rate and predictors of mortality for DKA. Results Out of 301 patients with COVID-19 and DM, 30 (10%) had DKA and five (1.7%) had HHS. Mortality was significantly higher in the DKA group compared to the non-DKA/HHS group (36.6% vs 19.5%; OR: 2.38; p=0.03). After adjusting for parameters used for multivariate logistic model for mortality, DKA was no longer associated with mortality (OR: 2.08, p=0.35). The independent predictors for mortality were age, platelet count, serum creatinine, C-reactive protein, hypoxic respiratory failure, need for intubation, and need for vasopressors. Conclusion Our study demonstrates higher mortality rate in diabetic COVID-19 patients with DKA. Though direct and independent statistical association of mortality with DKA could not be proven in our multivariate logistic model, physicians must be vigilant in risk-stratifying and managing these patients in a timely manner.

Effectiveness and Safety of EUS Rendezvous After Failed Biliary Cannulation With ERCP: A Systematic Review and Proportion Meta-analysis.

BACKGROUND: Endoscopic ultrasound-guided rendezvous (EUS-RV) endoscopic retrograde cholangiopancreatography (ERCP) is an alternative to interventional radiology-guided rendezvous ERCP in patients who failed biliary cannulation with conventional ERCP. However, there is significant variation in reported rates of success and adverse events associated with EUS-RV-assisted ERCP. We performed a systematic review and a proportion meta-analysis to reliably assess the effectiveness and safety of the EUS-RV-assisted ERCP. MATERIALS AND METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through August 2020) to identify studies reporting EUS-RV-assisted ERCP in patients who failed biliary cannulation with conventional ERCP techniques. Using the random-effects model described by DerSimonian and Laird, we calculated the pooled rates of technical success, clinical success, and adverse events of EUS-RV-assisted ERCP. RESULTS: Twelve studies reporting a total of 342 patients were included in the meta-analysis. The pooled rate of technical success (12 studies reporting a total of 342 patients) was 86.1% [95% confidence interval (CI): 78.4-91.3]. The pooled rate of clinical success (4 studies reporting a total of 94 patients) was 80.8% (95% CI: 64.1-90.8). The pooled rate of overall adverse events (12 studies; 42 events in 342 patients) was 14% (95% CI: 10.5-18.4). Low to moderate heterogeneity was noted in the analyses. CONCLUSIONS: EUS-RV-assisted ERCP appears to be effective and safe in patients who failed biliary cannulation with conventional ERCP. Given the risk of adverse events, it should be performed in centers with expertise in therapeutic endoscopic ultrasound.

Light-driven microrobots: capture and transport of bacteria and microparticles in a fluid medium.

The design of simple microrobotic systems with capabilities to address various applications like cargo transportation, as well as biological sample capture and manipulation in an individual unit, provides a novel route for designing advanced multifunctional microscale systems. Here, we demonstrate a facile approach to fabricate such multifunctional and fully controlled light-driven microrobots. The microrobots are titanium dioxide-silica Janus particles that are propelled in aqueous hydroquinone/benzoquinone fuel when illuminated by low-intensity UV light. The application of light provides control over the speed as well as activity of the microrobots. When modified with additional thin film coatings of nickel and gold, the microrobots exhibit the capturing and transportation of silica microparticles and E. coli bacteria. While transporting, they also show guided swimming under an external uniform magnetic field, which is interesting for deciding their moving path or the start/end positions. The fluorescent dye-based live/dead tests confirm that in the microrobot system almost no bacteria were harmed during the capturing or transportation. The simplistic design and steerable swimming with the ability to capture and transport are the important features of the microrobots. These features make them an ideal candidate for in vitro or lab-on-a-chip based studies, e.g., drug delivery, bacterial sensing, cell treatment, etc., where the capturing and transport of microscopic entities play a crucial role.

Biliary Sphincterotomy Alone versus Biliary Stent with or without Biliary Sphincterotomy for the Management of Post-Cholecystectomy Bile Leak: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic therapy with endoscopic retrograde cholangiopancreatography is considered the first-line treatment in the management of post-cholecystectomy bile leak (PCBL). Currently, there is no consensus on the most effective endoscopic intervention for PCBL. Hence, we performed a systematic review and meta-analysis to compare the effectiveness and safety of the two interventional groups (biliary sphincterotomy [BS] alone vs. biliary stent ± BS) in management of PCBL. METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings (from inception through January 2021). The primary outcome was to compare the pooled rate of clinical success between the 2 groups. The secondary outcome was to estimate the pooled rate of adverse events. RESULTS: The pooled rate of clinical success with BS alone (5 studies, 299 patients) was 88% (95% confidence interval (CI): 84-92%, I2: 0%) and for biliary stent ± BS (5 studies, 864 patients) was 97% (CI: 93-100%, I2: 79%). The rate of clinical success in biliary stent ± BS group was significantly higher than BS alone group (OR: 3.91 95% CI: 2.29-6.69, p < 0.001, I2: 13%). The rate of adverse events was numerically lower in biliary stent ± BS group compared to BS alone (3 studies; OR: 0.65 95% CI: 0.41-1.03, p = 0.07) without statistical significance. Low heterogeneity was noted in the analysis. CONCLUSIONS: Biliary stent ± BS is more effective in endoscopic management of PCBL compared to BS alone. This may be related to inter-endoscopist variation in completeness of sphincterotomy and post-sphincterotomy edema, which can influence the preferential trans-papillary flow of bile.

Combined Use of Wells Scores and D-dimer Levels for the Diagnosis of Deep Vein Thrombosis and Pulmonary Embolism in COVID-19: A Retrospective Cohort Study.

Introduction Deep vein thrombosis (DVT) and pulmonary embolism (PE) are key complications of coronavirus disease 2019 (COVID-19). The study's primary outcome was assessing the utility of Wells DVT, Wells PE scores, and D-dimers in diagnosing DVT and PE. Secondary outcomes were the risk factors for the development of PE and DVT in COVID-19 patients. Materials and methods We compared COVID-19 patients with a positive and negative lower extremity (LE) duplex. A similar approach was made for patients who underwent imaging for PE. Results The prevalence of PE was 23.8% (26 out of 109 patients), and the prevalence of DVT was 33% (35 out of 106). A D-dimer of 500 ng/mL had a sensitivity of 95.6% and 93.7% for the diagnosis of PE and DVT, respectively. A Wells DVT score of 3 points had a specificity of 92.9% and sensitivity of 8.8% for DVT diagnosis in COVID-19. A Wells PE score of 4 had a specificity of 100% and a sensitivity of 20% for the diagnosis of PE. The combined approach of using a Wells DVT score of 3 in suspected DVT and a Wells PE score of 4 in suspected PE and D-dimers of 500 ng/ml has a sensitivity of 94.2% and 96.1%, respectively. In the suspected DVT group, male gender (OR 3.88, 95% CI 1.55-9.7, P=0.004), lower body mass index (BMI) (OR 0.92, 95% CI 0.86-0.99, P=0.037), antiplatelet use (OR 0.19, 95% CI 0.04-0.88, P=0.035), systolic blood pressure ≤100 mmhg (OR 4.96, 95% CI 1.37-17.86, P=0.014), absolute lymphocytes ≤1 (OR 2.57, 95% CI 1.07-6.12, P=0.033), D-dimer ≥500 ng/ml (OR 6.42, 95% CI 1.40-29.38, P=0.016), blood urea nitrogen (BUN) ≥20 mg/dl (OR 2.33, 95% CI 1.00-5.41, P=0.048), and intubation (OR 3.32, 95% CI 1.26-8.78, P=0.015) were found to be statistically significant for DVT. In the suspected PE group, history of cancer (OR 10.69, 95% CI 1.06-107.74, P=0.044), total WBC count (OR 1.07, 95% CI 0.95-1.21, P=0.032), platelets ≥ 400,000 (OR 5.13, 95% CI 1.79-14.68, P=0.002), D-dimer levels ≥ 500 ng/ml (OR 25.47, 95% CI 3.27-197.97, P=0.002), Wells PE score (OR 2.46, 95% CI 1.50-4.06, P<0.001), pulmonary embolism rule-out criteria (PERC) score (OR 1.79, 95% CI 1.05-3.05, P=0.054), and Sequential Organ Failure Assessment (SOFA) score (OR 1.91, 95% CI 1.16-3.12, P=0.002) were statistically significant. Conclusions The combined approach of using a Wells DVT score of 3 in suspected DVT and Wells PE score of 4 in suspected PE and D-dimers of 500 ng/ml may be used to diagnose PE and DVT in COVID-19. Venous thromboembolism (VTE) occurrence in COVID-19 is associated with non-traditional risk factors such as intubation and higher severity of systemic inflammation, and these patients may benefit from more aggressive testing for VTE.

Determining age and sex-specific distribution of pancreatic whole-gland CT attenuation using artificial intelligence aided image segmentation: Associations with body composition and pancreatic cancer risk.

BACKGROUND & AIMS: Increased intrapancreatic fat is associated with pancreatic diseases; however, there are no established objective diagnostic criteria for fatty pancreas. On non-contrast computed tomography (CT), adipose tissue shows negative Hounsfield Unit (HU) attenuations (-150 to -30 HU). Using whole organ segmentation on non-contrast CT, we aimed to describe whole gland pancreatic attenuation and establish 5th and 10th percentile thresholds across a spectrum of age and sex. Subsequently, we aimed to evaluate the association between low pancreatic HU and risk of pancreatic ductal adenocarcinoma (PDAC). METHODS: The whole pancreas was segmented in 19,456 images from 469 non-contrast CT scans. A convolutional neural network was trained to assist pancreas segmentation. Mean pancreatic HU, volume, and body composition metrics were calculated. The lower 5th and 10th percentile for mean pancreatic HU were identified, examining the association with age and sex. Pre-diagnostic CT scans from patients who later developed PDAC were compared to cancer-free controls. RESULTS: Less than 5th percentile mean pancreatic HU was significantly associated with increase in BMI (OR 1.07; 1.03-1.11), visceral fat (OR 1.37; 1.15-1.64), total abdominal fat (OR 1.12; 1.03-1.22), and diabetes mellitus type 1 (OR 6.76; 1.68-27.28). Compared to controls, pre-diagnostic scans in PDAC cases had lower mean whole gland pancreatic HU (-0.2 vs 7.8, p = 0.026). CONCLUSION: In this study, we report age and sex-specific distribution of pancreatic whole-gland CT attenuation. Compared to controls, mean whole gland pancreatic HU is significantly lower in the pre-diagnostic phase of PDAC.

Impact of real-time use of artificial intelligence in improving adenoma detection during colonoscopy: A systematic review and meta-analysis.

Background and study aims With the advent of deep neural networks (DNN) learning, the field of artificial intelligence (AI) is rapidly evolving. Recent randomized controlled trials (RCT) have investigated the influence of integrating AI in colonoscopy and its impact on adenoma detection rates (ADRs) and polyp detection rates (PDRs). We performed a systematic review and meta-analysis to reliably assess if the impact is statistically significant enough to warrant the adoption of AI -assisted colonoscopy (AIAC) in clinical practice. Methods We conducted a comprehensive search of multiple electronic databases and conference proceedings to identify RCTs that compared outcomes between AIAC and conventional colonoscopy (CC). The primary outcome was ADR. The secondary outcomes were PDR and total withdrawal time (WT). Results Six RCTs (comparing AIAC vs CC) with 5058 individuals undergoing average-risk screening colonoscopy were included in the meta-analysis. ADR was significantly higher with AIAC compared to CC (33.7 % versus 22.9 %; odds ratio (OR) 1.76, 95 % confidence interval (CI) 1.55-2.00; I 2  = 28 %). Similarly, PDR was significantly higher with AIAC (45.6 % versus 30.6 %; OR 1.90, 95 %CI, 1.68-2.15, I 2  = 0 %). The overall WT was higher for AIAC compared to CC (mean difference [MD] 0.46 (0.00-0.92) minutes, I 2  = 94 %). Conclusions There is an increase in adenoma and polyp detection with the utilization of AIAC.

Two-stage deep learning model for fully automated pancreas segmentation on computed tomography: Comparison with intra-reader and inter-reader reliability at full and reduced radiation dose on an external dataset.

PURPOSE: To develop a two-stage three-dimensional (3D) convolutional neural networks (CNNs) for fully automated volumetric segmentation of pancreas on computed tomography (CT) and to further evaluate its performance in the context of intra-reader and inter-reader reliability at full dose and reduced radiation dose CTs on a public dataset. METHODS: A dataset of 1994 abdomen CT scans (portal venous phase, slice thickness ≤ 3.75-mm, multiple CT vendors) was curated by two radiologists (R1 and R2) to exclude cases with pancreatic pathology, suboptimal image quality, and image artifacts (n = 77). Remaining 1917 CTs were equally allocated between R1 and R2 for volumetric pancreas segmentation [ground truth (GT)]. This internal dataset was randomly divided into training (n = 1380), validation (n = 248), and test (n = 289) sets for the development of a two-stage 3D CNN model based on a modified U-net architecture for automated volumetric pancreas segmentation. Model's performance for pancreas segmentation and the differences in model-predicted pancreatic volumes vs GT volumes were compared on the test set. Subsequently, an external dataset from The Cancer Imaging Archive (TCIA) that had CT scans acquired at standard radiation dose and same scans reconstructed at a simulated 25% radiation dose was curated (n = 41). Volumetric pancreas segmentation was done on this TCIA dataset by R1 and R2 independently on the full dose and then at the reduced radiation dose CT images. Intra-reader and inter-reader reliability, model's segmentation performance, and reliability between model-predicted pancreatic volumes at full vs reduced dose were measured. Finally, model's performance was tested on the benchmarking National Institute of Health (NIH)-Pancreas CT (PCT) dataset. RESULTS: Three-dimensional CNN had mean (SD) Dice similarity coefficient (DSC): 0.91 (0.03) and average Hausdorff distance of 0.15 (0.09) mm on the test set. Model's performance was equivalent between males and females (P = 0.08) and across different CT slice thicknesses (P > 0.05) based on noninferiority statistical testing. There was no difference in model-predicted and GT pancreatic volumes [mean predicted volume 99 cc (31cc); GT volume 101 cc (33 cc), P = 0.33]. Mean pancreatic volume difference was -2.7 cc (percent difference: -2.4% of GT volume) with excellent correlation between model-predicted and GT volumes [concordance correlation coefficient (CCC)=0.97]. In the external TCIA dataset, the model had higher reliability than R1 and R2 on full vs reduced dose CT scans [model mean (SD) DSC: 0.96 (0.02), CCC = 0.995 vs R1 DSC: 0.83 (0.07), CCC = 0.89, and R2 DSC:0.87 (0.04), CCC = 0.97]. The DSC and volume concordance correlations for R1 vs R2 (inter-reader reliability) were 0.85 (0.07), CCC = 0.90 at full dose and 0.83 (0.07), CCC = 0.96 at reduced dose datasets. There was good reliability between model and R1 at both full and reduced dose CT [full dose: DSC: 0.81 (0.07), CCC = 0.83 and reduced dose DSC:0.81 (0.08), CCC = 0.87]. Likewise, there was good reliability between model and R2 at both full and reduced dose CT [full dose: DSC: 0.84 (0.05), CCC = 0.89 and reduced dose DSC:0.83(0.06), CCC = 0.89]. There was no difference in model-predicted and GT pancreatic volume in TCIA dataset (mean predicted volume 96 cc (33); GT pancreatic volume 89 cc (30), p = 0.31). Model had mean (SD) DSC: 0.89 (0.04) (minimum-maximum DSC: 0.79 -0.96) on the NIH-PCT dataset. CONCLUSION: A 3D CNN developed on the largest dataset of CTs is accurate for fully automated volumetric pancreas segmentation and is generalizable across a wide range of CT slice thicknesses, radiation dose, and patient gender. This 3D CNN offers a scalable tool to leverage biomarkers from pancreas morphometrics and radiomics for pancreatic diseases including for early pancreatic cancer detection.

Outcomes of Radiofrequency Ablation versus Endoscopic Surveillance for Barrett's Esophagus with Low-Grade Dysplasia: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic therapy using radiofrequency ablation (RFA) is a recommended treatment for Barrett's esophagus with high-grade dysplasia (BE-HGD) without a visible lesion which is managed by resection. However, currently, there is no consensus on the management of BE with low-grade dysplasia (BE-LGD) - RFA versus endoscopic surveillance. Hence, we performed a systematic review and meta-analysis of these comparative studies to compare the risk of progression to HGD or esophageal adenocarcinoma (EAC) among patients with BE-LGD treated with RFA versus endoscopic surveillance. METHODS: The primary outcome was to compare the risk of progression to HGD or EAC among patients with BE-LGD treated with RFA versus endoscopic surveillance. RESULTS: Four comparative studies reporting a total of 543 patients with BE-LGD were included in the meta-analysis (234 in RFA and 309 in endoscopic surveillance). The progression of BE-LGD to either HGD or EAC was significantly lower in patients treated with RFA compared to endoscopic surveillance (OR: 0.17, 95% confidence interval [CI]: 0.04-0.65, p = 0.01). The progression to HGD alone was significantly lower in patients treated with RFA versus endoscopic surveillance (OR: 0.23, 95% CI: 0.08-0.61, p = 0.003). The progression to EAC alone was numerically lower in RFA than endoscopic surveillance without statistical significance (OR: 0.44, 95% CI: 0.17-1.16, p = 0.09). Moderate heterogeneity was noted in the analysis. CONCLUSIONS: Based on our meta-analysis, there was a significant reduction in the risk of progression to HGD or EAC among patients with BE-LGD treated with RFA compared with those undergoing endoscopic surveillance. Endoscopic eradication therapy with RFA should be the preferred management approach for BE-LGD.

Accuracy of Smoking Status Reporting: Proxy Information in a Rapidly Fatal Cancer Setting.

OBJECTIVE: To assess whether patients and relatives can serve as reliable proxy reporters of other family members' cigarette-smoking history. PATIENTS AND METHODS: Two samples (325 patients, 707 relatives) were identified from the Mayo Clinic Biospecimen Resource for Pancreas Research, enrolled from November, 6, 2000, to March 15, 2018. Smoking-history data, including categorical (ever/never) and quantitative (packs per day and years smoked) smoking measures, were obtained from self-completed questionnaires by patients and relatives. Relative reports were compared with patient reports on self; patient reports were compared with relative reports on self. RESULTS: Overall, spouses and first-degree relatives (FDRs) were accurate (94.5%) when reporting patient ever smoking; spouse reports were 98.6% sensitive and 97.7% accurate. Accuracy of patient reports was 97.8% for spouse smoking and 85.5% for FDR smoking; accuracy varied by relationship of FDR. When not concordant, patients generally over-reported daily packs smoked by relatives and under-reported years smoked. Within a 25% agreement range, spouse reports about patients' daily packs smoked was 46.7%, and years smoked was 69.6%, whereas FDRs were 50% and 64.6%, respectively. When not concordant, relatives generally over-reported daily packs smoked by patients, but no consistent pattern was observed of over- or under-reporting years smoked by patients. CONCLUSIONS: Patients and relatives can be reliable proxies for smoking history (ever/never) in their family members, especially spouses. An accurate reporting of smoking status will help physicians to better gauge performance status and family smoking exposures to inform disease management.

Computerized tomography scan in pre-diagnostic pancreatic ductal adenocarcinoma: Stages of progression and potential benefits of early intervention: A retrospective study.

BACKGROUND: The frequency, nature and timeline of changes on thin-slice (≤3 mm) multi-detector computerized tomography (CT) scans in the pre-diagnostic phase of pancreatic ductal adenocarcinoma (PDAC) are unknown. It is unclear if identifying imaging changes in this phase will improve PDAC survival beyond lead time. METHODS: From a cohort of 128 subjects (Cohort A) with CT scans done 3-36 months before diagnosis of PDAC we developed a CTgram defining CT Stages (CTS) I through IV in the radiological progression of pre-diagnostic PDAC. We constructed Cohort B of PDAC resected at CTS I and II and compared survival in CTS I and II in Cohort A (n = 22 each; control natural history cohort) vs Cohort B (n = 33 and 72, respectively; early interception cohort). RESULTS: CTs were abnormal in 16% and 85% at 24-36 and 3-6 months respectively, before PDAC diagnosis. The PDAC CTgram stages, findings and median lead times (months) to clinical diagnosis were: CTS I: Abrupt duct cut-off/duct dilatation (-12.8); CTS II: Low density mass confined to pancreas (-9.5), CTS III: Peri-pancreatic infiltration (-5.8), CTS IV: Distant metastases (only at diagnosis). PDAC survival was better in cohort B than in cohort A despite inclusion of lead time in Cohort A: CTS I (36 vs 17.2 months, p = 0.03), CTS II (35.2 vs 15.3 months, p = 0.04). CONCLUSION: Starting 12-18 months before PDAC diagnosis, progressive and increasingly frequent changes occur on CT scans. Resection of PDAC at the time of pre-diagnostic CT changes is likely to provide survival benefit beyond lead time.

Microchannels with Self-Pumping Walls.

When asymmetric Janus micromotors are immobilized on a surface, they act as chemically powered micropumps, turning chemical energy from the fluid into a bulk flow. However, such pumps have previously produced only localized recirculating flows, which cannot be used to pump fluid in one direction. Here, we demonstrate that an array of three-dimensional, photochemically active Au/TiO2 Janus pillars can pump water. Upon UV illumination, a water-splitting reaction rapidly creates a directional bulk flow above the active surface. By lining a 2D microchannel with such active surfaces, various flow profiles are created within the channels. Analytical and numerical models of a channel with active surfaces predict flow profiles that agree very well with the experimental results. The light-driven active surfaces provide a way to wirelessly pump fluids at small scales and could be used for real-time, localized flow control in complex microfluidic networks.

ERCP with overtube-assisted enteroscopy in patients with Roux-en-Y gastric bypass anatomy: a systematic review and meta-analysis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y gastric bypass (RYGB) anatomy is challenging. Overtube-assisted enteroscopy (OAE) is usually needed to perform ERCP in these patients. There is significant variation in the reported rates of success and adverse events across published studies. We performed a systematic review and meta-analysis to reliably estimate the pooled rates of success and adverse events. METHODS: We performed a systematic search of multiple electronic databases through February 2020 to identify studies reporting outcomes of OAE-ERCP in post-RYGB patients. The pooled rates of enteroscopy success, technical success, and adverse events were estimated for OAE-ERCP. The pooled rates of success and adverse events were also estimated for ERCP using double-balloon enteroscopes (DBE) alone. RESULTS: 10 studies reporting a total of 398 procedures were included in the meta-analysis. The pooled rates of enteroscopy and technical success of OAE-ERCP were 75.3 % (95 % confidence interval [CI] 64.5 - 83.6) and 64.8 % (95 %CI 53.1 - 74.9) respectively. The pooled rate of adverse events was 8.0 % (95 %CI 5.2 - 12.2). The pooled rates of enteroscopy and technical success of DBE-ERCP (four studies) were 83.5 % (95 %CI 68.3 - 92.2) and 72.5 % (95 %CI 52.3 - 86.4), respectively. The pooled rate of adverse events with DBE-ERCP was 9.0 % (95 %CI 5.4 - 14.5). Substantial heterogeneity was noted. CONCLUSIONS: OAE-ERCP appears to be effective and safe in post-RYGB patients. Among the currently available techniques, OAE-ERCP is the least invasive approach in this challenging group of patients. Future studies comparing the effectiveness and safety of alternative novel techniques, such as endosonography-directed transgastric ERCP, with OAE-ERCP are needed.

EUS-guided versus endoscopic transpapillary gallbladder drainage in high-risk surgical patients with acute cholecystitis: a systematic review and meta-analysis.

BACKGROUND: In patients with acute cholecystitis who are deemed high risk for cholecystectomy, percutaneous cholecystostomy (PC) was historically performed for gallbladder drainage (GBD). There are several limitations associated with PC. Endoscopic GBD [Endoscopic transpapillary GBD (ET-GBD) and EUS-guided GBD (EUS-GBD)] is an alternative to PC. We performed a systematic review and meta-analysis to compare the effectiveness and safety of EUS-GBD versus ET-GBD. METHODS: We performed a systematic search of multiple databases through May 2019 to identify studies that compared outcomes of EUS-GBD versus ET-GBD in the management of acute cholecystitis in high-risk surgical patients. Pooled odds ratios (OR) of technical success, clinical success and adverse events between EUS-GBD and ET-GBD groups were calculated. RESULTS: Five studies with a total of 857 patients (EUS-GBD vs ET-GBD: 259 vs 598 patients) were included in the analysis. EUS-GBD was associated with higher technical [pooled OR 5.22 (95% CI 2.03-13.44; p = 0.0006; I2 = 20%)] and clinical success [pooled OR 4.16 (95% CI 2.00-8.66; p = 0.0001; I2 = 19%)] compared to ET-GBD. There was no statistically significant difference in the rate of overall adverse events [pooled OR 1.30 (95% CI 0.77-2.22; p = 0.33, I2 = 0%)]. EUS-GBD was associated with lower rate of recurrent cholecystitis [pooled OR 0.33 (95% CI 0.14-0.79; p = 0.01; I2 = 0%)]. There was low heterogeneity in the analyses. CONCLUSION: EUS-GBD has higher rate of technical and clinical success compared to ET-GBD. While the rates of overall adverse events are statistically similar, EUS-GBD has lower rate of recurrent cholecystitis. Hence, EUS-GBD is preferable to ET-GBD for endoscopic management of acute cholecystitis in select high-risk surgical patients.

Significance of peripheral eosinophilia for diagnosis of IgG4-related disease in subjects with elevated serum IgG4 levels.

OBJECTIVES: In this study, we aim to assess the diagnostic utility of elevated serum IgG4 (sIgG4) concentration alone and in combination with peripheral eosinophilia (PE) for IgG4-related disease (IgG4-RD). METHODS: From the Mayo Clinic, Rochester electronic medical record database we identified 409 patients with above normal levels of sIgG4 (reference range 121-140 mg/dL) who had sIgG4 measured to differentiate IgG4-RD from another disease. RESULTS: Among 409 patients with any elevation in sIgG4 levels, 129 (31.5%) had a definite diagnosis of IgG4-RD. The prevalence of PE increased with increasing sIgG4 levels and was more likely to be seen in subjects with IgG4-RD vs. non-IgG4-RD at ≥1X (n = 35/120, 29.2% vs. n = 23/258, 8.9%; p < 0.001), ≥2X (n = 23/64, 35.9% vs. n = 5/54,9.3%; p = 0.001) and ≥3X (n = 18/42, 42.9% vs. n = 0/9, 0%; p = 0.015) of sIgG4 upper limit of normal (ULN), respectively. After adjusting for gender and age, sIgG4 levels ≥ 2X ULN with PE as a predictor, had a higher positive predictive value in predicting IgG4-RD (72.2% vs. 65.9%) with an Area Under the Receiver Operatic Characteristic Curve (AUC) of 0.776, compared to sIgG4 ≥ 2X ULN without PE predictor (AUC = 0.74), p = 0.016. PE, sIgG4≥2X ULN, male gender, and age independently predicted the disease with odds ratio of 4.89 (95% CI:2.51-9.54), 3.78 (95% CI:2.27-6.28), 2.78 (95% CI:1.55-4.97), and 1.03 (95% CI:1.02-1.05), respectively. CONCLUSION: Even in subjects in whom IgG4-RD is suspected, only a minority (∼30%) with elevated sIgG4 levels have IgG4-RD. sIgG4 by itself is more specific at higher levels, though never diagnostic. PE increases with increasing sIgG4 and adds diagnostic value at higher sIgG4 levels.

Uremic serum-induced calcification of human aortic smooth muscle cells is a regulated process involving Klotho and RUNX2.

Vascular calcification (VC) is common in subjects with chronic kidney disease (CKD) and is associated with increased cardiovascular risk. It is an active process involving transdifferentiation of arterial smooth muscle cells (SMCs) into osteogenic phenotype. We investigated the ability of serum from CKD subjects to induce calcification in human SMCs in vitro (calcific potential of sera: CP), and associated changes in expression of Runt-related transcription factor 2 (RUNX2), SM22α, and Klotho. Sera from subjects with CKD (18 stage 3, 17 stage 4/5, and 29 stage 5D) and 20 controls were added to human cultured SMCs and CP quantified. The CP of CKD sera was greater (P<0.01) than that of controls, though not influenced by CKD stage. Modification of diet in renal disease estimated glomerular filtration rate (MDRD-4 eGFR) (P<0.001), serum phosphate (P=0.042), receptor activator of nuclear factor κappa-B ligand (RANKL) (P=0.001), parathyroid hormone (PTH) (P=0.014), and high-density lipoprotein (HDL)/cholesterol ratio (P=0.026) were independent predictors of CP accounting for 45% of variation. Adding calcification buffer (CB: calcium chloride [7 mM] and ß-glycerophosphate [7 mM]) increased the CP of control sera to approximate that of CKD sera. CP of CKD sera was unchanged. CKD sera increased RUNX2 expression (P<0.01) in human SMCs and decreased SM22α expression (P<0.05). Co-incubating control but not CKD serum with CB further increased RUNX2 expression (P<0.01). Both SM22α and Klotho expression decreased significantly (P<0.01) in the presence of CKD serum, and were virtually abolished with stage 5D sera. These findings support active regulation by CKD serum of in vitro VC by induction of RUNX2 and suppression of SM22α and Klotho.

Chemical Nanomotors at the Gram Scale Form a Dense Active Optorheological Medium.

The rheological properties of a colloidal suspension are a function of the concentration of the colloids and their interactions. While suspensions of passive colloids are well studied and have been shown to form crystals, gels, and glasses, examples of energy-consuming "active" colloidal suspensions are still largely unexplored. Active suspensions of biological matter, such as motile bacteria or dense mixtures of active actin-motor-protein mixtures have, respectively, reveals superfluid-like and gel-like states. Attractive inanimate systems for active matter are chemically self-propelled particles. It has so far been challenging to use these swimming particles at high enough densities to affect the bulk material properties of the suspension. Here, it is shown that light-triggered asymmetric titanium dioxide that self-propel, can be obtained in large quantities, and self-organize to make a gram-scale active medium. The suspension shows an activity-dependent tenfold reversible change in its bulk viscosity.