PI3K/Akt signaling in urological cancers: Tumorigenesis function, therapeutic potential, and therapy response regulation.

In addition to environmental conditions, lifestyle factors, and chemical exposure, aberrant gene expression and mutations involve in the beginning and development of urological tumors. Even in Western nations, urological malignancies are among the top causes of patient death, and their prevalence appears to be gender dependent. The prognosis for individuals with urological malignancies remains dismal and unfavorable due to the ineffectiveness of conventional treatment methods. PI3K/Akt is a popular biochemical mechanism that is activated in tumor cells as a result of PTEN loss. PI3K/Akt escalates growth and metastasis. Moreover, due to the increase in tumor cell viability caused by PI3K/Akt activation, cancer cells may acquire resistance to treatment. This review article examines the function of PI3K/Akt in major urological tumors including bladder, prostate, and renal tumors. In prostate, bladder, and kidney tumors, the level of PI3K and Akt are notably elevated. In addition, the activation of PI3K/Akt enhances the levels of Bcl-2 and XIAP, hence increasing the tumor cell survival rate. PI3K/Akt ] upregulates EMT pathways and matrix metalloproteinase expression to increase urological cancer metastasis. Furthermore, stimulation of PI3K/Akt results in drug- and radio-resistant cancers, but its suppression by anti-tumor drugs impedes the tumorigenesis.

Disparities in Emergency Department Waiting Times for Acute Gastrointestinal Bleeding: Results From the National Hospital Ambulatory Medical Care Survey, 2009-2018.

OBJECTIVE: The primary aim of this study was to assess waiting time (WT) across different racial groups to determine whether racial disparities exist in patients presenting with gastrointestinal bleeding (GIB) to the United States emergency departments (EDs). METHODS: Using the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2009 to 2018, we compared WT of patients with GIB across different racial/ethnic groups, including nonhispanic white (NHW), African American (AA), Hispanic White (HW), and Nonhispanic other. Multinomial logistic regression was applied to adjust the outcomes for possible confounders. We also assessed the trend of the WT over the study interval and compared the WT between the first (2009) and last year (2018) of the study interval. RESULTS: There were an estimated 7.8 million ED visits for GIB between 2009 and 2018. Mean WT ranged from 48 minutes in NHW to 68 minutes in AA. After adjusting for gender, age, geographic regions, payment type, type of GI bleeding, and triage status, multinomial logistic regression showed significantly higher waiting time for AA patients than NHW (OR 1.01, P =0.03). The overall trend showed a significant decrease in the mean WT ( P value<0.001). In 2009, AA waited 69 minutes longer than NHW ( P value<0.001), while in 2018, this gap was erased with no statistically significant difference ( P value=0.26). CONCLUSION: Racial disparities among patients presenting with GIB are present in the United States EDs. African Americans waited longer for their first visits. Over time, ED wait time has decreased, leading to a decline in the observed racial disparity.

Exploring the Association Between Paralytic Ileus and Endoscopic Retrograde Cholangiopancreatography Complications Using the National Inpatient Sample Database.

Introduction Paralytic ileus (PI) is often seen in critically ill hospitalized patients. Those with pancreaticobiliary diseases will require endoscopic retrograde cholangiopancreatography (ERCP) for management. Here, we will explore the association between patients with paralytic ileus who underwent ERCP and post-procedural complications, which has not been done before. Methods Patients who underwent ERCP between 2007 and 2017 in the National Inpatient Sample database were selected. Cases were matched 1:1 by age, gender, race, and the Elixhauser comorbidity index for patients with and without pre-procedural paralytic ileus. Primary outcomes were associations between paralytic ileus and length of stay, payor status, and average total charges. Secondary outcomes were associations between paralytic ileus and post-ERCP complications (infection, pancreatitis, cholangitis, cholecystitis, perforation, hemorrhage), and overall mortality. The Chi-squared analysis was used to compare categorical data, and the independent t-test was used for continuous data. Regression analysis was used to assess primary and secondary outcomes. Results Of 2,008,217 hospitalized patients from 2007 to 2017, 43,643 patients had paralytic ileus and 43,859 patients did not, before undergoing ERCP. There were no differences in age, gender, race, or the Elixhauser comorbidity index. The differences in the length of stay, payor status, and total charges were significant (p<0.001). Patients with paralytic ileus had increased risks of post-ERCP infection, pancreatitis, cholangitis, cholecystitis, perforation, hemorrhage, and overall mortality (p<0.001). Conclusions Patients hospitalized with paralytic ileus who underwent ERCP had a longer length of stay, higher total charges, and were less compensable. They also had increased risks for post-ERCP infection, pancreatitis, cholangitis, cholecystitis, perforation, hemorrhage, and overall mortality, which can be from critical illness and the systemic inflammatory response.

Complications of Endoscopic Retrograde Cholangiopancreatography in Patients With Previous Bariatric Surgery: A National Inpatient Sample Analysis, 2007-2013.

BACKGROUND: Bariatric surgery (BS) has been proven to be effective in the treatment of obesity and weight-related diseases, but the anatomic changes after BS make endoscopic retrograde cholangiopancreatography (ERCP) technically challenging. This study aims to assess the safety and clinical outcomes of ERCP in patients with previous BS. MATERIALS AND METHODS: The National Inpatient Sample from 2007 to 2013 was queried for hospitalizations of adults over 18 years of age with procedure diagnoses of ERCP. Those with prior BS were selected as cases and those without BS as controls. Case-control matching at a ratio of 1 case to 2 controls was performed based on sex, age, race, comorbidities, and obesity. The primary outcomes were inpatient mortality and ERCP-related complications. Multivariate regression analysis was used to identify independent risk factors associated to the primary outcomes. RESULTS: A total of 1,068,862 weighted hospitalizations with ERCP procedure codes were identified. Of these, 6689 with BS were selected as cases, and 13,246 were matched as controls. The reason for hospital admission was most often biliary stone disease (60.7% vs. 55.5%), followed by malignancy (3.5% vs. 12.1%) and cholangitis (7.7% vs. 4.5%) with and without BS, P<0.05. The BS group had lower rates of post-ERCP pancreatitis (0.1% vs. 1.3%), cholecystitis (0.1% vs. 0.3%), bleeding (1.0% vs. 1.4%), and inpatient mortality (0.2% vs. 0.5%), but had higher rates of cholangitis (5.0% vs. 3.7%) and systemic infections (6.2% vs. 4.8%), all P<0.05. CONCLUSIONS: BS group had lower post-ERCP pancreatitis, cholecystitis and bleeding while had more cholangitis, and systemic infection compared with those without BS. Also, BS was independently associated with reduced inpatient mortality after adjusted for age, race, and comorbidity.

In-Hospital Outcomes of Patients With Non-Alcoholic Fatty Liver Disease Who Underwent Percutaneous Coronary Intervention: A Nationwide Inpatient Sample Analysis.

Background Non-alcoholic fatty liver disease (NAFLD) is prevalent in almost 25% of the Western population and is predicted to become one of the leading causes of end-stage liver disease. There is increasing evidence that NAFLD is a risk factor for cardiovascular disease, specifically for coronary artery disease, via disruption of the metabolism of glucose and lipids in the body, leading to a state of systemic inflammation that promotes atherosclerosis. This study aims to explore outcomes in patients who underwent percutaneous coronary intervention (PCI) with or without placement of drug-eluting stents (DES) to determine whether the concurrent diagnosis of NAFLD led to worse in-hospital outcomes. Methods We used the National Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality 2016 to conduct a cross-sectional study that included all adult patients who underwent PCI with or without placement of DES during hospital admission. Patients with NAFLD were identified and compared to patients without NAFLD. Patients were selected by using ICD-10-CM and ICD-10-PCS codes. Outcomes included mortality, length of stay and total hospital charges, and major adverse cardiac events (MACE). Data on patient demographics, inpatient statistics, and comorbidities were obtained and analyzed using cross-tabulation, Pearson χ2 test, and independent samples t-test. Data were adjusted for confounders using logistic and linear regression. Results Among 429,855 patients who underwent PCI with or without placement of DES, 2,560 patients (0.6%) had a diagnosis of NAFLD. There was no significant difference with regard to mortality and MACE. The NAFLD group had a higher proportion of females, a longer average length of hospital stay, and patients presented at a younger average age. Regarding comorbidities, more patients in the NAFLD group had diabetes mellitus type II, obesity, obstructive sleep apnea (OSA), chronic kidney disease (CKD), and peripheral vascular disease (PVD). Conclusion NAFLD is emerging as a risk factor for cardiovascular disease. Increasing evidence suggests that the disease contributes to systemic atherosclerosis and thus coronary artery disease. We found that among patients who underwent PCI in 2016, those with NAFLD had a longer length of stay, were admitted at a younger age, and had significantly more cardiovascular comorbidities than those without NAFLD. Increasing evidence has shown that advanced liver disease due to NAFLD will continue to place a significant burden on the healthcare system and is, therefore, an area that the medical community should continue to focus on, especially, regarding preventative and therapeutic efforts.

The impact of bariatric surgery on in-patient clinical outcomes among patients with autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a form of liver inflammation in which immune cells target hepatocytes, inducing chronic inflammatory states. Bariatric surgery (BS) was shown to reduce inflammation in severely obese patients. We hypothesize that obese patients with AIH and BS have lower prevalence of liver-related complications and in-patient mortality compared to those without BS.The National Inpatient Sample from 2007 to 2013 was queried for hospitalizations of adults over 18 years of age with a diagnosis of AIH. Of those, hospitalizations with BS were selected as cases and those with morbid obesity as controls. Case-control 1:2 matching was done based on sex, age, race, and comorbidities. Primary outcomes were prevalence of liver-related complications and in-patient mortality. Independent risk factors of in-patient clinical outcomes were identified using multivariate regression analysis.From 137,834 hospitalizations with a diagnosis of AIH, 688 with BS were selected as cases, and 1295 were matched as controls. The prevalence of ascites was higher in the BS group compared to the control (odds ratio 1.73, 95% confidence interval (CI) 1.27-2.36). The prevalence of cirrhosis (36.8% vs 33.2%), portal hypertension (7.4% vs 10.0%), hepatic encephalopathy (10.6% vs 8.7%), and varices and variceal bleeding (3.9% vs 5.5%) was not statistically different from case controls, (P > .05).BS was an independent risk factor for ascites (adjusted odds ratio (aOR) 1.87; 95% CI 1.36-2.56) and hepatic encephalopathy (aOR 1.42; 95% CI 1.03-1.97) but was an independent protective factor against in-patient mortality (aOR 0.21, 95% CI 0.08-0.55) once adjusted for age, sex, race, and comorbidities.

The New Jersey Bowel Preparation Scale: A More Objective and Detailed Scoring System for Screening Colonoscopies.

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.

Insights into organogelation and its kinetics from Hansen solubility parameters. Toward a priori predictions of molecular gelation.

Many small molecules can self-assemble by non-covalent interactions into fibrous networks and thereby induce gelation of organic liquids. However, no capability currently exists to predict whether a molecule in a given solvent will form a gel, a low-viscosity solution (sol), or an insoluble precipitate. Gelation has been recognized as a phenomenon that reflects a balance between solubility and insolubility; however, the distinction between these regimes has not been quantified in a systematic fashion. In this work, we focus on a well-known gelator, 1,3:2,4-dibenzylidene sorbitol (DBS), and study its self-assembly in various solvents. From these data, we build a framework for DBS gelation based on Hansen solubility parameters (HSPs). While the HSPs for DBS are not known a priori, the HSPs are available for each solvent and they quantify the solvent's ability to interact via dispersion, dipole-dipole, and hydrogen bonding interactions. Using the three HSPs, we construct three-dimensional plots showing regions of solubility (S), slow gelation (SG), instant gelation (IG), and insolubility (I) for DBS in the different solvents at a given temperature and concentration. Our principal finding is that the above regions radiate out as concentric shells: i.e., a central solubility (S) sphere, followed in order by spheres corresponding to SG, IG, and I regions. The distance (R0) from the origin of the central sphere quantifies the incompatibility between DBS and a solvent-the larger this distance, the more incompatible the pair. The elastic modulus of the final gel increases with R0, while the time required for a super-saturated sol to form a gel decreases with R0. Importantly, if R0 is too small, the gels are weak, but if R0 is too large, insolubility occurs-thus, strong gels fall within an optimal window of incompatibility between the gelator and the solvent. Our approach can be used to design organogels of desired strength and gelation time by judicious choice of a particular solvent or a blend of solvents. The above framework can be readily extended to many other gelators, including those with molecular structures very different from that of DBS. We have developed a MATLAB program that will be freely available (upon request) to the scientific community to replicate and extend this approach to other gelators of interest.