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Abstract The gold standard for enrollment and endpoint assessment in metabolic dysfunction‐associated steatosis clinical trials is histologic assessment of a liver biopsy performed on glass slides. However, obtaining the evaluations from several expert pathologists on glass is challenging, as shipping the slides around the country or around the world is time‐consuming and comes with the hazards of slide breakage. This study demonstrated that pathologic assessment of disease activity in steatohepatitis, performed using digital images on the AISight whole slide image management system, yields results that are comparable to those obtained using glass slides. The accuracy of scoring for steatohepatitis (nonalcoholic fatty liver disease activity score ≥4 with ≥1 for each feature and absence of atypical features suggestive of other liver disease) performed on the system was evaluated against scoring conducted on glass slides. Both methods were assessed for overall percent agreement with a consensus “ground truth” score (defined as the median score of a panel of three pathologists’ glass slides). Each case was also read by three different pathologists, once on glass and once digitally with a minimum 2‐week washout period between the modalities. It was demonstrated that the average agreement across three pathologists of digital scoring with ground truth was noninferior to the average agreement of glass scoring with ground truth [noninferiority margin: −0.05; difference: −0.001; 95% CI: (−0.027, 0.026); and p

Background Cardiac arrest is 1 of the leading causes of morbidity and mortality, with an estimated 340 000 out‐of‐hospital and 292 000 in‐hospital cardiac arrest events per year in the United States. Survival rates are lower in certain racial and socioeconomic groups. Methods and Results We performed a county‐level cross‐sectional longitudinal study using the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research multiple causes of death data set between 2016 and 2020 among individuals of all ages whose death was attributed to cardiac arrest. The Social Vulnerability Index is a composite measure that includes socioeconomic vulnerability, household composition, disability, individuals from racial and ethnic minority groups status and language, and housing and transportation domains. We examined the impact of social determinants on cardiac arrest mortality stratified by age, race, ethnicity, and sex in the United States. All age‐adjusted mortality rate (cardiac arrest AAMRs) are reported as per 100 000. Overall cardiac arrest AAMR during the study period was 95.6. The cardiac arrest AAMR was higher for men compared with women (119.6 versus 89.9) and for the Black population compared with the White population (150.4 versus 92.3). The cardiac arrest AAMR increased from 64.8 in counties in quintile 1 of Social Vulnerability Index to 141 in quintile 5, with an average increase of 13% (95% CI, 9.8%–16.9%) in AAMR per quintile increase. Conclusions Mortality from cardiac arrest varies widely, with a >2‐fold difference between the counties with the highest and lowest social vulnerability, highlighting the differential burden of cardiac arrest deaths throughout the United States based on social determinants of health.

Background: Vitamin D has proven immunomodulatory effects. As per the literature, there is a vitamin D deficiency observed in critically ill sepsis patients. Aims and Objectives: The present study was conducted to study the association of vitamin D levels at the time of admission to the intensive care unit (ICU) with mortality and various indices of sepsis assessment like the simplified acute physiology score (SAPS II) along with the age-unadjusted Charlson Comorbidity Index (CCI) and procalcitonin. Materials and Methods: A single centric, observational-longitudinal study was conducted in the ICU with patients of sepsis (n=96). Vitamin D was measured at the time of admission to the ICU. Controls were taken from age- and gender-matched patients without sepsis and with no premorbid illnesses. The objectives of the current study were to assess SAPS II and CCI scores and their predicted mortality amongst various categories of vitamin D levels at the time of admission, to correlate various categories of vitamin D levels with hospital stay and complications or hazards and to assess the sensitivity of vitamin D for prediction of sepsis outcome. Results: The case cohort and controls had average vitamin D levels of 15.33 ng/dL and 41.11 ng/dL, respectively. Patients with vitamin D deficiency had longer hospital and ICU stays and greater rates of morbidity. Observations showed no correlation between vitamin D and serum albumin, WBC count, total cholesterol, triglycerides, LDL, or HDL. The level of vitamin D at the time of admission to the ICU was observed to be highly sensitive (90.6%) to predicting the mortality rates in the ICU due to sepsis. Conclusion: Measurement of vitamin D at the time of admission may be a possible indicator for prediction of sepsis mortality and hospital and ICU length of stay for ICU-admitted patients with sepsis.

Background: Neuroendocrine tumors (NET) are a rare group of epithelial neoplasms present in the gastrointestinal tract (GI) (67.5%) and bronchopulmonary tree (25.3–30%), and in 15% of cases, their primary sites cannot be identified. Although endoscopic screening, improvements in pathological techniques, and early detection have shown improvements in NET survival rates, the prognosis of advanced, metastatic, and poorly differentiated NET is very poor. In this study, we aimed to evaluate the effect of gastrointestinal and pancreatic (GEPs) NETs’ grade on overall survival. Method: We searched observational studies describing the overall survival or prognostic factors of primary GEP NETs from May 2011–May 2021 following the PRISMA guidelines. Studies describing the effect of primary grade 3 GEP NETs on overall survival were included. A meta-analysis was performed, and a pooled hazard ratio and their 95% confidence interval (95% CI) were obtained. Forest plots were created using random effects models and a sensitivity analysis was performed to account for the heterogeneity. Results: Seven studies with 7692 confirmed patients were included. In our meta-analysis, grade 3 GEP NETs were associated with higher odds of poor survival (pooled HR: 2.73; 95% CI: 1.36–5.47; p = 0.005), with a 92% heterogeneity between studies (p < 0.0001). To account for this heterogeneity, a sensitivity analysis was performed by removing two outlying studies (Fathi et al. and Foubert et al.) on funnel plots. The results after the sensitivity analysis did not change and still showed a significant association of grade 3 with a poor survival (pooled HR: 4.53; 95% CI: 3.54–5.78; p < 0.00001), with no heterogeneity between studies (p = 0.72; I2 = 0%). Conclusions: Our meta-analysis found that grade 3 GEP NETs are associated with poor survival and additional future studies are needed to identify other risk factors associated with poor survival in GEP NETs to improve their mortality.

Abstract Nocturnal scratch is one major factor leading to impaired quality of life in atopic dermatitis (AD) patients. Therefore, objectively quantifying nocturnal scratch events aids in assessing the disease state, treatment effect, and AD patients’ quality of life. In this paper, we describe the use of actigraphy, highly predictive topological features, and a model-ensembling approach to develop an assessment of nocturnal scratch events by measuring scratch duration and intensity. Our assessment is tested in a clinical setting against the ground truth obtained from video recordings. The new approach addresses unmet challenges in existing studies, such as the lack of generalizability to real-world applications, the failure to capture finger scratches, and the limitations in the evaluation due to imbalanced data in the current literature. Furthermore, the performance evaluation shows agreement between derived digital endpoints and the video annotation ground truth, as well as patient-reported outcomes, which demonstrated the validity of the new assessment of nocturnal scratch.

Introduction: Tobacco use is one of the most significant risk factors for stroke. Besides traditional cigarettes and combustible products, the use of e-cigarettes and electronic nicotine delivery products has been widespread among young adults in the recent era. Furthermore, the trend of vaping has increased over the last decade. However, the relationship between e-cigarettes and stroke is largely unknown. The aim of this study was to evaluate the prevalence and identify the relationship between e-cigarette smoking and stroke. Methods: A cross-sectional study was performed using the NHANES database of the US population. Adults with a history of smoking were considered in our study and divided into three groups, e-cigarette users, traditional, and dual smokers. The Chi-squared test, Wilcoxon rank-sum test, and multivariable logistic regression analysis were used to identify the prevalence and association of e-cigarette consumption and stroke. Results: Out of a total of 266,058 respondents from 2015 to 2018, we found 79,825 respondents who smoked e-cigarettes (9.72%) or traditional (29.37%) or dual smoking (60.91%). Stroke prevalence among e-cigarette smokers was 1.57%. Stroke was more prevalent among traditional smokers than among e-cigarette smokers. (6.75% vs. 1.09%; p < 0.0001) E-cigarette smokers had early onset of stroke in comparison with traditional smokers. (median age: 48 vs. 59 years; p < 0.0001). Among females with stroke, the prevalence of e-cigarette use was higher in comparison with traditional smoking (36.36% vs. 33.91%; p < 0.0001). Among the stroke population, the prevalence of e-cigarette use was higher among Mexican-Americans (21.21% vs. 6.02%) and other Hispanics (24.24% vs. 7.70%) compared with traditional smoking (p < 0.0001). The regression analysis found higher odds of stroke history among e-cigarette users than traditional smokers [aOR: 1.15; 95% CI: 1.15–1.16)]. Conclusion: Though stroke was more prevalent in traditional smokers, the incidence of stroke was early-in-onset and was strongly associated with e-cigarette use compared to traditional smokers. We have also identified vascular effects of e-cigarettes components as possible triggers for the stroke.

Background: It is vital to provide evidence-based research documentation to guide policy decision-making. There is a limited number of studies that participate in dental policy evidence-based research. Case Description: Texas is one of the states with limited dental service coverage for its Medicaid Beneficiaries. The recent senate bill 87R 1152 proposes expansion of dental preventive service to disability status Medicaid Beneficiaries. It is vital to understand how effective the extensive dental service under Medicaid coverage is through evidence-based research. True causal analysis of such public policies by utilizing observational data is only feasible through limited identification strategies. The current paper identifies that. Practical Implication: Through the identified research plan and conceptual framework, it can be established if extensive Medicaid dental service coverages effectively prevent dental disease burden in Texas.

Abstract Background Transcriptional regulation is complex, requiring multiple cis (local) and trans acting mechanisms working in concert to drive gene expression, with disruption of these processes linked to multiple diseases. Previous computational attempts to understand the influence of regulatory mechanisms on gene expression have used prediction models containing input features derived from cis regulatory factors. However, local chromatin looping and trans-acting mechanisms are known to also influence transcriptional regulation, and their inclusion may improve model accuracy and interpretation. In this study, we create a general model of transcription factor influence on gene expression by incorporating both cis and trans gene regulatory features. Results We describe a computational framework to model gene expression for GM12878 and K562 cell lines. This framework weights the impact of transcription factor-based regulatory data using multi-omics gene regulatory networks to account for both cis and trans acting mechanisms, and measures of the local chromatin context. These prediction models perform significantly better compared to models containing cis-regulatory features alone. Models that additionally integrate long distance chromatin interactions (or chromatin looping) between distal transcription factor binding regions and gene promoters also show improved accuracy. As a demonstration of their utility, effect estimates from these models were used to weight cis-regulatory rare variants for sequence kernel association test analyses of gene expression. Conclusions Our models generate refined effect estimates for the influence of individual transcription factors on gene expression, allowing characterization of their roles across the genome. This work also provides a framework for integrating multiple data types into a single model of transcriptional regulation.

Purpose: To report our intermediate-term, multi-institutional experience after robotic ureteral reconstruction for the management of long-segment proximal ureteral strictures. Materials and Methods: We retrospectively reviewed our Collaborative of Reconstructive Robotic Ureteral Surgery (CORRUS) database to identify all patients who underwent robotic ureteral reconstruction for long-segment (≥4 centimeters) proximal ureteral strictures between August 2012 and June 2019. The primary surgeon determined the specific technique to reconstruct the ureter at time of surgery based on the patient's clinical history and intraoperative findings. Our primary outcome was surgical success, which we defined as the absence of ureteral obstruction on radiographic imaging and absence of obstructive flank pain. Results: Of 20 total patients, 4 (20.0%) underwent robotic ureteroureterostomy (RUU) with downward nephropexy (DN), 2 (10.0%) underwent robotic ureterocalycostomy (RUC) with DN, and 14 (70.0%) underwent robotic ureteroplasty with buccal mucosa graft (RU-BMG). Median stricture length was 4 centimeters (interquartile range [IQR], 4–4; maximum, 5), 6 centimeters (IQR, 5–7; maximum, 8), and 5 centimeters (IQR, 4–5; maximum, 8) for patients undergoing RUU with DN, RUC with DN, and RU-BMG, respectively. At a median follow-up of 24 (IQR, 14–51) months, 17/20 (85.0%) cases were surgically successful. Two of four patients (50.0%) who underwent RUU with DN developed stricture recurrences within 3 months. Conclusions: Long-segment proximal ureteral strictures may be safely and effectively managed with RUC with DN and RU-BMG. Although RUU with DN can be utilized, this technique may be associated with a higher failure rate.

Abstract Purpose Tracking cells in vivo using imaging can provide non-invasive information to understand the pharmacology, efficacy, and safety of novel cell therapies. Zirconium-89 (t 1/2 = 78.4 h) has recently been used to synthesize [89Zr]Zr(oxinate)4 for cell tracking using positron emission tomography (PET). This work presents an in vitro approach to estimate the detection limit for in vivo PET imaging of Jurkat T cells directly labeled with [89Zr]Zr(oxinate)4 utilizing clinical PET/CT and PET/MRI. Methods Jurkat T cells were labeled with varying concentrations of [89Zr]Zr(oxinate)4 to generate different cell-specific activities (0.43–31.91 kBq/106 cells). Different concentrations of labeled cell suspensions (104, 105, and 106 cells) were seeded on 6-well plates and into a 3 × 3 cubic-well plate with 1 cm3 cubic wells as a gel matrix. Plates were imaged on clinical PET/CT and PET/MRI scanners for 30 min. The total activity in each well was determined by drawing volumes of interest over each well on PET images. The total cell-associated activity was measured using a well counter and correlated with imaging data. Simulations for non-specific signal were performed to model the effect of non-specific radioactivity on detection. Results Using this in vitro model, the lowest cell number that could be visualized on 6-well plate images was 6.8 × 104, when the specific activity was 27.8 kBq/106 cells. For the 3 × 3 cubic-well, a plate of 3.3 × 104 cells could be detected on images with a specific activity of 15.4 kBq/106 cells. Conclusion The results show the feasibility of detecting [89Zr]Zr(oxinate)4-labeled Jurkat T cells on clinical PET systems. The results provide a best-case scenario, as in vivo detection using PET/CT or PET/MRI will be affected by cell number, specific activity per cell, the density of cells within the target volume, and non-specific signal. This work has important implications for cell labeling studies in patients, particularly when using radiosensitive cells (e.g., T cells), which require detection of low cell numbers while minimizing radiation dose per cell.

Everyday use of denture cleansers to prevent microbial colonization on dentures can affect the properties of the denture base material. Limited literature is available on the effects of denture cleanser on reinforced resins. This study aimed to evaluate and compare the effect of denture cleanser on the flexural and impact strength of conventional and reinforced heat cure acrylic resins. Materials and Methods: Rectangular shaped specimens were prepared for flexural and impact strength as per ISO 1567. The denture base resins used included conventional, high impact, nylon fiber reinforced and glass fiber reinforced heat cure acrylic resins. They were further categorized into subgroups A and B depending on immersion in distilled water or denture cleanser (3.8% sodium perborate based). The flexural strength and impact strength of specimens were measured. The study design is a observational case-control study. SPSS version 25 statistical analysis software was used, and the STROBE statement checklist was followed. Results: The mean flexural strength was highest for glass fiber reinforced heat cure resin followed by conventional heat cure resin, high impact heat cure resin and nylon reinforced heat cure resin, respectively. The mean impact strength was highest for high impact heat cure resin followed by glass fiber reinforced heat cure resin, conventional heat cure resin, and nylon fiber-reinforced resin respectively.Conclusion: All the denture base resins tested exhibited a decrease in flexural and impact strength following use of a denture cleanser.

Background: Post renal transplant UTI is very common, increasing the morbidity and mortality with high chances of graft failure. Majority of centres use prophylactic antibioitcs like TMP-SMX after renal transplantation within first 6 months. Aims and Objectives: To understand the incidence of UTI and it's risk factors, to compare the effectiveness of using individual commode in decreasing incidence of post transplant UTI with historical cohort of renal transplant recipients. Materials and Methods: 25 patients were recruited from April 01, 2017, to June 01, 2017. They were encouraged to bring along a portable commode to use it during their stay as well as at home after discharge and followed for 1 month for presence of urinary tract infection. Results: 6 patients had culture proven UTI(24%) in historical cohort while no patient had UTI in study group using commode(0%). Conclusion: Individualizing personal waste disposal techniques using disposable bedside commode is an effective and economical strategy.

Abstract Purpose While the aetiology of rheumatoid arthritis (RA) remains unclear, many of the inflammatory components are well characterised. For diagnosis and therapy evaluation, in vivo insight into these processes would be valuable. Various imaging probes have shown value including dynamic contrast-enhanced (DCE) MRI and PET/CT using 18F-fluorodeoxyglucose (18F-FDG) or tracers targeting the translocator protein (TSPO). To evaluate 18F-GE-180, a novel TSPO PET tracer, for detecting and quantifying disease activity in RA, we compared 18F-GE-180 uptake with that of 18F-FDG and DCE-MRI measures of inflammation. Methods Eight RA patients with moderate-to-high, stable disease activity and active disease in at least one wrist were included in this study (NCT02350426). Participants underwent PET/CT examinations with 18F-GE-180 and 18F-FDG on separate visits, covering the shoulders and from the pelvis to the feet, including hands and wrists. DCE-MRI was performed on one affected hand. Uptake was compared visually between tracers as judged by an experienced radiologist and quantitatively using the maximum standardised uptake value (SUVmax). Uptake for both tracers was correlated with DCE-MRI parameters of inflammation, including the volume transfer coefficient K trans using Pearson correlation (r). Results PET/CT imaging with 18F-GE-180 in RA patients showed marked extra-synovial uptake around the affected joints. Overall sensitivity for detecting clinically affected joints was low (14%). 18F-GE-180 uptake did not or only weakly correlate with DCE-MRI parameters in the wrist (r = 0.09–0.31). 18F-FDG showed higher sensitivity for detecting symptomatic joints (34%), as well as strong positive correlation with DCE-MRI parameters (SUVmax vs. K trans: r = 0.92 for wrist; r = 0.68 for metacarpophalangeal joints). Conclusions The correlations between DCE-MRI parameters and 18F-FDG uptake support use of this PET tracer for quantification of inflammatory burden in RA. The TSPO tracer 18F-GE-180, however, has shown limited use for the investigation of RA due to its poor sensitivity and ability to quantify disease activity in RA.

Abstract Background Induction chemotherapy followed by chemoradiation is a treatment option for patients with locally advanced pancreatic cancer (LAPC). However, overall survival is comparable to chemotherapy alone and local progression occurs in nearly half of all patients, suggesting chemoradiation strategies should be optimised. SCALOP-2 is a randomised phase II trial testing the role of radiotherapy dose escalation and/or the addition of the radiosensitiser nelfinavir, following induction chemotherapy of gemcitabine and nab-paclitaxel (GEMABX). A safety run-in phase (stage 1) established the nelfinavir dose to administer with chemoradiation in the randomised phase (stage 2). Methods Patients with locally advanced, inoperable, non-metastatic pancreatic adenocarcinoma receive three cycles of induction GEMABX chemotherapy prior to radiological assessment. Those with stable/responding disease are eligible for further trial treatment. In Stage 1, participants received one further cycle of GEMABX followed by capecitabine-chemoradiation with escalating doses of nelfinavir in a rolling-six design. Stage 2 aims to register 262 and randomise 170 patients with responding/stable disease to one of five arms: capecitabine with high- (arms C + D) or standard-dose (arms A + B) radiotherapy with (arms A + C) or without (arms B + D) nelfinavir, or three more cycles of GEMABX (arm E). Participants allocated to the chemoradiation arms receive another cycle of GEMABX before chemoradiation begins. Co-primary outcomes are 12-month overall survival (radiotherapy dose-escalation question) and progression-free survival (nelfinavir question). Secondary outcomes include toxicity, quality of life, disease response rate, resection rate, treatment compliance, and CA19–9 response. SCALOP-2 incorporates a detailed radiotherapy quality assurance programme. Discussion SCALOP-2 aims to optimise chemoradiation in LAPC and incorporates a modern induction regimen. Trial registration Eudract No: 2013–004968-56; ClinicalTrials.gov: NCT02024009.

Background and importance: Pseudobulbar affect (PBA) is characterized by sudden, uncontrollable laughing, crying, or both in the absence of an appropriate triggering stimuli. Usually due to an underlying neurological condition, PBA has been reported less commonly in traumatic brain injury (TBI) and patients with normal pressure hydrocephalus (NPH). This case documents the successful management of a male patient with PBA and post-traumatic NPH with ventriculoperitoneal shunt placement. Clinical presentation: An 88-year-old male initially presenting with acute right subdural hematoma after a fall underwent right decompressive hemicraniectomy and cranioplasty. On 2-month follow-up, the patient was diagnosed with PBA as well as post-traumatic hydrocephalus, confirmed with Center for Neurologic Study – Liability Scale (CNS-LS) questionnaire as well as a cerebrospinal fluid tap test (CSF-TT), respectively. The patient underwent ventriculoperitoneal shunt placement with successful resolution of PBA and post-traumatic NPH. Conclusion: A select subset of patients presenting with post-traumatic NPH may demonstrate successful resolution of PBA symptoms following surgical intervention to address the underlying neurological disorder potentiating pseudobulbar affect.

Background/Aims: Systemic hyperlipidemia and intracellular lipid accumulation induced by chronic high fat diet (HFD) leads to enhanced fatty acid oxidation (FAO) and ketogenesis. The present study was aimed to determine whether activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) by surplus free fatty acids (FA) in hyperlipidemic condition, has a positive feedback regulation over FAO and ketogenic enzymes controlling lipotoxicity and cardiac apoptosis. Methods: 8 weeks old C57BL/6 wild type (WT) or PPAR-γ-/- mice were challenged with 16 weeks 60% HFD to induce obesity mediated type 2 diabetes mellitus (T2DM) and diabetic cardiomyopathy. Treatment course was followed by echocardiographic measurements, glycemic and lipid profiling, immunoblot, qPCR and immunohistochemistry (IHC) analysis of PPAR-γ and following mitochondrial metabolic enzymes 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2), mitochondrial β- hydroxy butyrate dehydrogenase (BDH1) and pyruvate dehydrogenase kinase isoform 4 (PDK4). In vivo model was translated in vitro, with neonatal rat cardiomyocytes (NRCM) treated with PPAR-γ agonist/antagonist and PPAR-γ overexpression adenovirus in presence of palmitic acid (PA). Apoptosis was determined in vivo from left ventricular heart by TUNEL assay and immunoblot analysis. Results: We found exaggerated circulating ketone bodies production and expressions of the related mitochondrial enzymes HMGCS2, BDH1 and PDK4 in HFD-induced diabetic hearts and in PA-treated NRCM. As a mechanistic approach we found HFD mediated activation of PPAR-γ is associated with the above-mentioned mitochondrial enzymes. HFD-fed PPAR-γ-/-mice display decreased hyperglycemia, hyperlipidemia associated with increased insulin responsiveness as compared to HFD-fed WT mice PPAR-γ-/–HFD mice demonstrated a more robust functional recovery after diabetes induction, as well as significantly reduced myocyte apoptosis and improved cardiac function. Conclusions: PPAR-γ has been described previously to regulate lipid metabolism and adipogenesis. The present study suggests for the first time that increased PPAR-γ expression by HFD is responsible for cardiac dysfunction via upregulation of mitochondrial enzymes HMGCS2, BDH1 and PDK4. Targeting PPAR-γ and its downstream mitochondrial enzymes will provide novel strategies in preventing metabolic and myocardial dysfunction in diabetes mellitus.

Abstract Background The ability to image vascular endothelial growth factor (VEGF) could enable prospective, non-invasive monitoring of patients receiving anti-angiogenic therapy. This study investigates the specificity and pharmacokinetics of 111In-bevacizumab binding to VEGF and its use for assessing response to anti-angiogenic therapy with rapamycin. Specificity of 111In-bevacizumab binding to VEGF was tested in vitro with unmodified radiolabelled bevacizumab in competitive inhibition assays. Uptake of 111In-bevacizumab in BALB/c nude mice bearing tumours with different amounts of VEGF expression was compared to that of isotype-matched control antibody (111In-IgG1κ) with an excess of unlabelled bevacizumab. Intratumoural VEGF was evaluated using ELISA and Western blot analysis. The effect of anti-angiogenesis therapy was tested by measuring tumour uptake of 111In-bevacizumab in comparison to 111In-IgG1κ following administration of rapamycin to mice bearing FaDu xenografts. Uptake was measured using gamma counting of ex vivo tumours and effect on vasculature by using anti-CD31 microscopy. Results Specific uptake of 111In-bevacizumab in VEGF-expressing tumours was observed. Rapamycin led to tumour growth delay associated with increased relative vessel size (8.5 to 10.3, P = 0.045) and decreased mean relative vessel density (0.27 to 0.22, P = 0.0015). Rapamycin treatment increased tumour uptake of 111In-bevacizumab (68%) but not 111In-IgGκ and corresponded with increased intratumoural VEGF165. Conclusions 111In-bevacizumab accumulates specifically in VEGF-expressing tumours, and changes after rapamycin therapy reflect changes in VEGF expression. Antagonism of mTOR may increase VEGF in vivo, and this new finding provides the basis to consider combination studies blocking both pathways and a way to monitor effects.

Goals. The goal of this study was to develop an objective and detailed scoring system to assess the quality of bowel preparation. Background. The quality of bowel preparation impacts the success of the colonoscopy. We developed and compared a new bowel preparation scoring system, the New Jersey Bowel Preparation Scale (NJBPS), with existing systems that are limited by a lack of detail and objectivity in the Boston Bowel Preparation Scale (BBPS) and the Ottawa Bowel Preparation Scale (OBPS). Methods. This was a single-center, prospective, dual-observer study performed at Rutgers New Jersey Medical School University Hospital. Patients who were at medium risk for colorectal cancer and undergoing outpatient screening colonoscopy were enrolled in the study, and their bowel preparation was assessed separately by an attending and a fellow using each of the bowel preparation scoring systems. Results. 98 patients were analyzed in the study, of which 59% were female. Most of the patient population was African American (65%) or Hispanic (25%). The average age of the patient was 60 years. Chi-squared analysis using SPSS software revealed intraclass correlation coefficient values between attending and fellow scores for each scale. The NJBPS had the highest value at 0.988, while the BBPS and OBPS had values of 0.883 and 0.894. Limitations. Single-center study. Conclusions. The NJBPS and BBPS scores demonstrated a statistically significant agreement with each other. Overall, there was good interobserver agreement for all three scoring systems when comparing attendings to fellows for the same scoring system. However, the NJBPS possessed a stronger correlation.

Waste seaweed that is collected at coastal regions of maritime provinces in Canada is creating ecological problems as it promotes an anoxic event, which produces nearly zero dissolved oxygen in water along with hydrogen sulfide emission. The work done in this study attempts to address this issue by producing a coal-like solid hydrochar and nutritious liquid slurry (processed water) by employing a rather recent thermo-chemical process called hydrothermal carbonization (HTC) on the seaweed. The HTC was carried out in a batch reactor system for three different reaction temperatures, 180 °C, 200 °C, 220 °C, and three different reaction times, 30, 60, and 120 min. Each of the produced hydrochars was characterized by different analytical methods. The effects of the process conditions on the yield and the properties of the hydrochar and process water were examined. The hydrochar produced at 220 °C and 120 min showed the highest carbon content (48.5%) and heating value (18.93 MJ/kg). The energy density and carbon to nitrogen (C/N) ratio in the hydrochar increased significantly as compared to raw seaweed. Moreover, HTC reduced the ash yield and volatile compounds of the seaweed. Thus, hydrochar can be used as a fuel for direct combustion, in soil remediation, or in carbon sequestration applications.

Category: Ankle Introduction/Purpose: Injury to the anterior inferior tibiofibular ligament (AITFL), posterior inferior tibiofibular ligament (PITFL), and interosseous membrane (IOM) of the syndesmosis is a predictive measure of residual symptoms after an ankle injury. Unstable syndesmotic injuries are typically treated surgically with constructs consisting of cortical screw and/or suture button fixation. Previous studies have shown contradicting findings regarding the effects of different surgical fixation methods on tibiofibular kinematics. Thus, the objective of this study was to quantify tibiofibular joint motion with different syndesmotic screw and suture button fixation constructs after disruption of the syndesmosis compared to the intact ankle during simulated weight bearing. Methods: Five fresh-frozen human cadaveric specimens were tested using a six degree-of-freedom robotic testing system. After subtalar joint fusion, the tibia and calcaneus were rigidly fixed to a robotic manipulator, while complete fibular length was maintained and fibular motion was unconstrained. A constant 200 N compressive load was applied to the ankle while an additional 5 Nm external rotation and 5 Nm inversion moment applied independently to the ankle at 0°, 15°, and 30° plantarflexion and 10° dorsiflexion. Fibular motion with respect to the tibia was tracked using an optical tracking system. Outcome variables included fibular medial-lateral (ML) translation, anterior-posterior (AP) translation, and external rotation (ER) in the following states: intact ankle, complete injury (AITFL, PITFL, and IOM transected), single tricortical screw fixation double tricortical screw fixation, hybrid fixation (single tricortical screw and single suture button), suture button fixation, and divergent suture button fixation. Repeated measures ANOVA was performed for statistical analysis. Results: The external rotation moment produced significant differences in fibular motion between the injury and fixation states compared to the intact state. A complete syndesmotic injury caused significantly increased fibular lateral translation, posterior translation, and external rotation in all ankle positions except 30° plantarflexion compared to the intact ankle. Single suture button and single screw fixation resulted in significantly higher fibular lateral translation at 10° dorsiflexion compared the intact ankle, while single suture button fixation also resulted in significantly higher external rotation at 10° dorsiflexion compared the intact ankle. Fibular posterior translation was significantly higher with hybrid, suture button, and divergent suture button fixation at 0° flexion and with single tricortical screw and double screw fixation at 10° dorsiflexion compared to the intact ankle (Figure 1). Conclusion: Complete injury to the syndesmosis results in significantly higher fibular lateral translation, external rotation, and posterior translation compared to the intact ankle. Hybrid or divergent suture button fixation would be recommended to restore tibiofibular motion without over-constraint. However, none of the fixation methods were able to restore AP translation in all ankle positions. Thus, it is important to evaluate syndesmotic stability in the sagittal plane at different ankle positions. Findings of this study suggest that physicians should evaluate fibular AP translation in a neutral position when using suture button fixation constructs and in dorsiflexion when using tricortical screw fixation constructs.

Atezolizumab is a monoclonal antibody that targets programmed death ligand-1. Treatments with this drug may cause immune-related adverse events by creating an exaggerated inflammatory response. The most common side effects are fatigue, rash, and gastrointestinal symptoms. Cases of central nervous system toxicity such as encephalitis and encephalopathy are uncommon. We present the case of a 53-year-old female with metastatic squamous cell carcinoma of the cervix who presented to the emergency room 13 days after receiving atezolizumab with altered mental status, headache, and meningeal signs. She was admitted to the intensive care unit. Infectious, anatomical, and neoplastic etiologies were ruled out. Auto-immune meningoencephalitis was diagnosed and treated with high-dose steroids. Within 10 days of the diagnosis, she had clinical, radiological, and laboratory improvement. Given the increasing use of novel immunotherapies and life-threatening side effects associated with them, healthcare providers in the intensive care unit should be aware of their diagnosis and management.

Clopidogrel resistance from CYP2C19 polymorphism has been associated with stent thrombosis in patients undergoing percutaneous coronary intervention with drug-eluting stents. We present a case of a 76-year-old male who received drug-eluting stents to the right coronary artery and left anterior descending artery for non-ST elevation myocardial infarction and was discharged on dual antiplatelet therapy with aspirin and clopidogrel. He subsequently presented with chest pain from anterior, anteroseptal, and inferior ST segment elevation myocardial infarction. An emergent coronary angiogram revealed acute stent thrombosis with 100% occlusion of RCA and LAD that was successfully treated with thrombus aspiration and angioplasty. Although he was compliant with his dual antiplatelet therapy, he developed stent thrombosis, which was confirmed as clopidogrel resistance from homozygous CYP2C19 polymorphism.

Introduction and objective. We examined patient waiting times, physician utilization, and exam room utilization in order to identify process improvements that may improve patient satisfaction. Methods. Time patient arrived to clinic, time patient was placed in the exam room, time the physician arrived in the exam room, and time physician discharged the patient from the exam room were prospectively recorded for 226 outpatient visits. Results. Overall, 63.2% of patients were on time for their scheduled appointment with 14.8% patient “no-shows.” On-time patients were found to have a longer wait time once in the exam room for the physician than those that were late (14.8±9.2 minutes versus 11.0±8.4 minutes, 𝑃=.005); however, those patients spent a significantly longer time with the physician (10.7±6.0 minutes versus 8.9±5.8 minutes, 𝑃=.041). Exam room utilization was lower for late patients (28.9% versus 44.7%, 𝑃=.03) with physician utilization lower in clinics with 3 or more late patients when compared to clinics with 2 or fewer (59.7% versus 68.7%, 𝑃=.004). Conclusions. Late patients had significantly less time with the physician than on-time patients. Late patients also decreased the overall efficiency of the clinic; therefore, measures to reduce late patients are vital to improve clinic efficiency.