United States

Introduction: Gallbladder cancer is the most common biliary tract cancer and is a fatal malignancy with a 5-year survival rate of only 18%. The Incidence of gallbladder cancer is 0.26% for women and 0.25% for men globally. It is unclear how the burden of this disease differs between nations. Using the Global Burden of Disease (GBD) Study database, we studied the trends in mortality, Incidence, and disability-adjusted life years (DALYs) from gallbladder cancer between 1990-2019 in European Union (EU) 15+ nations, which constitutes a comparable group of countries for observation analyses.

Methods: We extracted data from the GBD Study database between 1990 - 2019 based on the International Classification of Disease, including Age-Standardized Incidence Rates (ASIR), Mortality (ASMR), Mortality-to-Incidence (MIR) ratios, as well as DALYs for gallbladder cancer. Joinpoint regression analysis was carried out for the evaluation of trends. EU15+ countries is a readily comparable group of 19 countries with similar healthcare infrastructure. We also computed the male-to-female ratio to evaluate the difference in burden between the two genders.
Results: ASIR decreased globally (-2.54% males, -20.93% females) as well as for EU15+ countries except for males in Norway +6.1%, Greece+18.1% and Denmark +27.4%. At the same time, Incidence decreased by approximately 8 times in females than in males. ASMRs also decreased globally (-5.42% males, -22.47% females) by approximately 4 times higher in females. Similarly, ASMR decreased for all EU15+ countries except Greece (+14.5%) for males. Along with Incidence and mortality, MIR also decreased globally (-2.96% males, -1.95% females) and for EU15+ countries except for Sweden (+9.7% males, +28.9% females). We also observed a decreasing trend in DALYs globally for both genders (males -9.3%, females -24.2%). Amongst EU15+ countries, DALYS decreased for all countries except for males in Greece (+13.3%). 
Conclusion: Overall, Incidence, mortality, and DALYs due to gallbladder cancer have decreased globally and in most EU15+ countries. However, countries like Greece have shown discordant trends. Interestingly, the burden of gallbladder cancer has significantly decreased for females with a disproportionate decrease for males. Further studies will help evaluate these discordant trends in detail.

AMA Research Challenge 2022

A comparison of the burden of gallbladder cancer between the European Union 15+ countries, 1990-2019: estimates from the Global Burden of Disease Study

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Background: Liver failure (LF) is associated with a high mortality rate, requiring a liver transplant as the definitive treatment. The Molecular Adsorbent Recirculating System (MARS) is a non-biologic system that removes toxic metabolites from the bloodstream by providing extracorporeal support while waiting for a liver transplant. Conflicting pieces of evidence from multiple studies are present regarding the outcome of MARS therapy. We evaluated the effect of MARS therapy on patients with liver failure by measuring the changes in their laboratory parameters. 

Methods: In this retrospective cohort analysis, we evaluated 44 patients, by comparing relevant laboratory variables measured before and after MARS therapy. Paired t-test was used for statistical analysis. The primary outcome was an improvement in laboratory parameters following MARS therapy. 

Results: Most of our study cohort were females (63.64%) and white (72.72%). The predominant causes of liver failure were NASH (non-alcoholic steatohepatitis) (22.73%) and alcoholism (22.73%). At admission, the mean Child-Pugh score was 11.45 (SD: 1.97), and the mean SOFA (sequential organ failure assessment) score was 10.95 (SD: 3.65). The mean number of MARS sessions was 4.32 (SD: 2.28) and the mean duration for patients on MARS therapy was 4.64 days (SD: 2.44).
Our analysis demonstrates a statistically significant improvement in mean serum bilirubin, ammonia, urea, creatinine, ALT, and AST levels following MARS therapy. The mean model for end-stage liver disease (MELD-Na) scores also significantly improved. 59.09% of our total patient population survived the hospital stay and 40.91% died in hospital, with 73.07% of the survivors eventually receiving a liver transplant. 94.74% of the patients with whom we were able to bridge MARS therapy until liver transplant, had survived through the follow-up period.

Conclusion: Our study findings suggest that MARS improves the liver-failure-associated laboratory parameters and may be effective therapy as a bridge to liver transplant.


A Retrospective Study on the Effect of Molecular Adsorbent Recirculating System in Patients with Liver Failure

Acute Pancreatitis related to COVID-19 Infection. A Systematic Review and Analysis of Data.

Association of Statins with the Onset and Progression of Non-Alcoholic
Fatty Liver Disease in Veterans with Diabetes: A Retrospective Propensity
Score-Matched Cohort Study

Association of Statins with the Onset and Progression of Non-Alcoholic Fatty Liver Disease in Veterans with Diabetes: A Retrospective Propensity Score-Matched Cohort Study

With a 5-year survival rate of just 20%, esophageal cancer is a disease that must have improved early diagnostics and characterization, obtainable at a moderate cost within an endoscopy suite setting.
In an effort to address this need, including enhanced evaluation of diseases of the esophagus and pharynx, we developed and demonstrated on cadavers a new AI-based experimental 3D endoscope, E3D (Esophagoscope-3D), a slender (~1 cm diameter) endoscope capable of obtaining 3D images inside the mouth and esophagus.
Team members from Pensievision, Inc. built the endoscope hardware and wrote the AI-based image processing software, while MUSC team members guided the device’s development to meet clinical requirements and conducted cadaver tests to evaluate feasibility and demonstrate 3D sensitivities. During cadaver testing, E3D successfully accessed the esophagus via the cadaver’s contracted 1 cm diameter esophagus entrance. We were then able to generate the first macroscopic (~2cm field-of-view) 3D image ever to be collected of the esophagus using an imaging endoscope.

Demonstration of AI-Based, 3D-Imaging of the Esophagus Using a Novel Imaging Endoscope

Inflammatory Bowel Disease and its Association with Melanoma and Non-Melanoma Skin Cancers

Background
Inflammatory bowel disease (IBD) is complex, easily misdiagnosed and mismanaged. Multidisciplinary care improves patient outcomes. Yet, few hospitals have a multidisciplinary team approach to IBD care that consistently includes a gastrointestinal expert pathologist. This study aims to quantify the impact an expert pathologist has on a multidisciplinary team in the care of difficult IBD patients.

Methods
A retrospective chart analysis was performed on patients (N=283) discussed at the semi-monthly multidisciplinary IBD conference at Carilion Clinic, from June 1, 2013 through December 31, 2019. Each patient was presented between one and six times at the conference. Data collected: demographics, baseline clinical characteristics, diagnosis before and after conference, reason for diagnostic change, endoscopy findings, medications, surgeries, and if clinical remission was achieved within 6 months after conference.

Results
After the first conference, 42% of patients presented had a diagnostic change: 84% due to expert pathologist interpretation, 12% due to radiology, and 4% due to other reasons. Majority of diagnostic changes after the second (73%), third (67%), and fourth (100%) conferences were also attributed to pathology. Crohn disease was the most common new diagnosis after conference, and indeterminate colitis was the most commonly changed diagnosis. For patients newly diagnosed with ulcerative colitis after conference, most had moderate active colitis (54%), whereas for those newly diagnosed with Crohn disease, colitis severity was distributed similarly between none (22%), mild (26%), moderate (28%), and severe (24%). Approximately 24% to 35% of patients presented had a change in IBD medication, among which ~34% to 40% had a diagnostic change. Following the conference, ~17% to 20% of patients underwent surgical intervention, among which ~12% to 27% had a diagnostic change. A majority of these patients achieved clinical remission within 6 months of the conference.

Conclusion
The majority of diagnostic changes made at the multidisciplinary IBD conference were due to histopathologic re-interpretation. A change in diagnosis at times led to significant modifications in disease management through surgery or medication changes. Multidisciplinary care teams are essential to the best management of complex IBD patients. An expert gastrointestinal pathologist is a critical team member to the discussion of nuances of each patient’s case.



Multidisciplinary Inflammatory Bowel Disease Conference: The Contribution and Impact of Pathology on Patient Care 

Background
Ogilvie syndrome, also known as acute colonic pseudo-obstruction (ACPO), is a rare form of idiopathic colonic dilation without mechanical obstruction. It typically occurs in elderly patients who have recently been hospitalized or undergone surgery with an incidence rate of about 100 cases per 100,000 hospitalizations every year. Despite neostigmine being the treatment of choice, we highlight the importance of early management and diagnosis. 

Case Presentation
A 76-year-old male with a history of class III obesity, diabetes mellitus, systolic heart failure, and ulcerative colitis well-controlled with sulfasalazine was admitted due to acute lower back pain with radiculopathy to lower extremities after lifting heavy boxes. The hospital course was complicated by developing acute kidney injury. In addition, a gradually enlarging but painless abdominal distension was noted, along with severe constipation. Serum measurements reflected persistent hypokalemia, leukocytosis, and elevated creatinine. Abdominal imaging revealed a markedly dilated colon with a cecal diameter of 12.8 cm but without signs of inflammation or perforation. Although neostigmine, correction of electrolytes, and rectal tube placement initially alleviated his condition, the abdominal distention continued to worsen. On day 16 of his stay, a repeat abdominal computed tomography showed pneumoperitoneum and the patient required emergent surgery. A 4cm perforation was appreciated in the transverse colon resulting in a total colectomy with end ileostomy. The patient recovered without complications after the surgery. 

Discussion
Although the etiology remains unclear, our patient’s advanced age and renal and cardiac comorbidities potentially precipitated the onset of Ogilvie syndrome, causing a perforated colon. The risk of perforation is increased when the cecal diameter is larger than 12cm, and the colonic distension lasts greater than 6 days, both of which were observed in our patient. Management of Ogilvie syndrome is primarily focused on urgent bowel decompression and correction of electrolyte abnormalities. Although neostigmine has been shown to rapidly alleviate Ogilvie syndrome, our patient did not respond accordingly. The mortality rate in Ogilvie syndrome increases with surgical management, regardless of the presence of perforation, and can reach up to 40% following a perforated colon. Therefore, early diagnosis and conservative management of Ogilvie syndrome are important to prevent serious complications.

Perforated Colon Caused by Neostigmine Refractory Ogilvie Syndrome

Background: Children with inflammatory bowel disease (IBD) are at risk of venous thromboembolic events (VTE). The efficacy of low molecular-weight heparin (LMWH) in preventing VTE in pediatrics is undetermined, but it is used for VTE prophylaxis. We offered prophylaxis to high-risk inpatients based on risk-stratification. We aimed to assess the efficacy of prophylactic LMWH in preventing VTE in high-risk pediatric IBD inpatients.

Methods: We performed a retrospective chart review at Seattle Children’s Hospital from 2012–2021. We included IBD patients aged 0-18 hospitalized with colitis flares. Patients admitted for surgery, perianal abscess, or non-IBD colitis were excluded. VTE risk factors were personal or family history of VTE, thrombophilia, thrombogenic medication use, smoking, obesity, or central venous line (CVL). Serious events were pulmonary embolus, stroke, or cerebral sinus venous thrombosis. The index case, first admission during the study period or with VTE, was used for analysis.

Results: 415 patients were included. Mean age was 13 ± 4, with 52.8% male. 239 (57.6%) had Crohn’s disease and 170 (41.0%) ulcerative colitis. Common risk factors were CVL (45, 10.8%) and obesity (19, 4.6%). 25 patients received prophylaxis (6.0%). There were 10 VTE events (2.4%), 3/25 (12.0%) in patients on LMWH and 7/383 (1.8%) without. There was one serious event of left middle cerebral artery thrombus and stroke in a patient not on LMWH with no risk factors. There were no serious events in patients on LMWH. The incidence of VTE was significantly higher in patients on LWMH (p=0.001, 95% CI 0.039-0.165) with RR 6.7 (p=0.0039, 95% CI 1.84-24.3). Of the 7 VTE in patients not on prophylaxis, 3 occurred in patients with no risk factors, 2 in patients with 1 risk factor, and 2 in patients with 2 risk factors.

Conclusion: Prophylactic LMWH did not prevent VTE in high-risk pediatric IBD patients. However, our population at a tertiary hospital may be sicker than the baseline. An alternative prophylaxis regimen may be needed for high-risk patients. Further data is required to identify other risk factors for VTE, and randomized control trials are needed to establish the true efficacy of LMWH in this population.

Prophylactic enoxaparin fails to prevent thrombosis in high-risk pediatric inflammatory bowel disease

Background: COVID-19 has been accompanied by a 34% increase in revenue from the sale of alcohol largely attributed to young adults, households with children, and minority groups. From 2007-2014 hospitalizations due to alcoholic hepatitis and cirrhosis increased. As alcoholic liver disease is the leading cause for liver transplant in the U.S. and nearly 50% of liver related deaths, it is vital to better understand the pathophysiology of alcoholic cirrhosis and to identify biomarkers that predict which patients will progress to fibrosis.

Methods: Subjects were recruited with alcoholic cirrhosis at stage F4 of fibrosis (n = 11) and heavy drinkers without cirrhosis at stages F0-F3 of fibrosis (n = 11). Fibrosis was assessed by elastography, and alcohol consumption with the Alcoholic Use Disorders Identification Test-Concise (AUDIT-C) questionnaire. Untargeted LC-MS was performed on serum by Metabolon. Significance was assessed by Welch’s two sample t-test.

Results: There were no differences in age, gender, BMI, or AUDIT-C scores. Overall, 122 metabolites were upregulated and 127 downregulated in subjects with scores of F4 versus F0-F3. Pathway analysis revealed diacylgycerols, androgenic steroids, dihydroceramides, and glutathione metabolites were increased in non-cirrhotic subjects, while cirrhotic subjects showed increases in sterol metabolism, hemoglobin and porphyrin metabolism, and bile acid (primary and secondary) metabolism. Additionally, thymine and uracil pyrimidine metabolism were upregulated in cirrhotic subjects (F4), uncovering novel pathways for future biomarker studies. Specifically, cirrhotic subjects demonstrated increases in abundance of 5,6-dihydrothymine, 2’-O-methyluridine, 3-ureidopropionate, 5,6-dihydrouracil, and uracil. With respect to tryptophan metabolites, our analysis showed significant upregulation in circulating levels of kynurenine, oxindolylalanine, tryptophan, as well as significant decreases in 3-indoxyl sulfate, serotonin, and xanthurenate in F4 subjects compared to F0-F3. The suggests an increase in IDO-1 activity during cirrhosis, shunting tryptophan away from serotonin synthesis towards kynurenine. We also identified metabolites with significant associations with fibrosis score such as 5,6-dihydrothymine (r = 0.88), taurochenodeoxycholic acid 3-sulfate (r = 0.84), leucine (r = -0.8), and retinol (r = -0.8)

Conclusion: Our findings elucidate metabolic alterations in alcoholic liver fibrosis with the identification of several pyrimidine and tryptophan metabolites that may be used for the assessment of alcoholic liver disease.

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A Retrospective Study on the Effect of Molecular Adsorbent Recirculating System in Patients with Liver Failure

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