bluuebunny/crossref_metadata_2025_split huggingface dataset:
A217 NONINVASIVE ASSESSMENTS TO IDENTIFY PATIENTS WITH ADVANCED FIBROSIS DUE TO NASH: SCREENED POPULATION FROM THE REGENERATE TRIAL
Authors: Montano-Loza A J , Boursier J , Sanyal A J , Ratziu V , Rinella M , Loomba R , Dufour J , Mozaffari E , Shringarpure R , MacConell L , Granston T , Zhou H , Trylesinski A , Harrison S A , Bedossa P , Goodman Z , Younossi Z , Noureddin M , Bugianesi E , Anstee Q M 
Published: March 2021

Abstract

Aims
We explored the ability of noninvasive tests (NITs) to identify patients (pts) with advanced fibrosis due to NASH.

Methods
All screened pts from the ongoing phase 3 REGENERATE with available histology data were included. Five NITs were evaluated using established literature cutoffs to identify or exclude advanced fibrosis (values between upper and lower thresholds were considered indeterminate): Aspartate Transaminase-to-Platelet Ratio Index (APRI; ≥0.57, ≤0.84), Enhanced Liver Fibrosis (ELF; ≥7.7, &lt;9.8), Fibrosis-4 (FIB-4; ≥1.30, &lt;2.67), NAFLD fibrosis score (NFS; ≥−1.455, &lt;0.676), and Transient Elastography (TE; ≥7.9 kPa, &lt;9.6 kPa). Three testing methods applied were single NIT, 2 simultaneous NITs weighted equally (NFS+ELF, FIB-4+ELF, NFS+TE, FIB-4+TE), and 2 sequential NITs with the second test performed only if the first test was indeterminate (NFS→ELF, FIB-4→ELF, NFS→TE, FIB-4→TE).

Results
4133 pts in the REGENERATE screened population had an available biopsy (baseline liver biopsy: F0, 15.5%; F1, 27.2%; F2, 21.2%; F3, 29.6%; F4, 6.5%). Of these, 96% had FIB-4, NFS, and APRI, 41% had TE, and 28% had ELF. Single NITs with upper thresholds demonstrating strong specificity for identification of advanced fibrosis were FIB-4 (97%), NFS (94%), and APRI (86%); NITs with lower thresholds demonstrating good sensitivity for identification of early fibrosis were ELF (100%) and TE (88%). Evaluation of 2 simultaneous NITs resulted in a greater percentage of pts in the indeterminate zone. Application of 2 sequential tests improved the accuracy of identification and reduced misclassification vs 2 simultaneous tests.

Conclusions
Sequential NIT strategies may decrease liver biopsy rates while maintaining the accuracy of noninvasive diagnosis in pts with advanced fibrosis due to NASH.

Funding Agencies
Intercept Pharmaceuticals
A218 A CASE REPORT OF PSEUDOHYPONATREMIA IN CHOLESTATIC LIVER DISEASE
Authors: Shpoliansky M , Kamath B 
Published: March 2021

Abstract

Background
True hyponatremia in the setting of cholestatic liver disease may signify cirrhosis with fluid overload, and is therefore an ominous sign of deteriorating liver function. In pediatric liver transplant candidates, it is associated with increased waitlist mortality. Pseudohyponatremia however, is a falsely low measurement of plasma sodium when measured by indirect potentiometry. Pseudohyponatremia secondary to hypercholesterolemia is a phenomenon that occurs due to a reduced aqueous fraction of the plasma when levels of cholesterol or triglycerides are greatly elevated. Severe hypercholesterolemia due to Lipoprotein X accumulation may be the cause of pseudohyponatremia in biliary obstruction or cholestasis.

Aims
To describe a case of pseudohyponatremia secondary to hypercholesterolemia in an infant with Alagille syndrome (ALGS) and cholestatic liver disease.

Methods
This 7 month-old male with ALGS (confirmed JAGGED1 mutation) and severe cholestasis, failure to thrive, and pruritus, developed new-onset progressive hyponatremia as low as 121 mmol/L at an outside institution. He was therefore transferred to our center for liver transplant assessment due to concerns of progressive liver dysfunction and for management of the hyponatremia.

Results
Upon admission, the patient was jaundiced but euvolemic, with no evidence of ascites or peripheral edema. Laboratory work drawn at our institution showed conjugated bilirubin of 180 mmol/L, ALT 300 U/L, AST 250 U/L, and GGT 1200 U/L. INR was 1.1 and albumin of 35 g/L. The cholesterol was elevated above 16.8 mmol/L, with high triglycerides 2.68 mmol/L, and the serum appeared visibly lipemic. The sodium level was 138 mmol/L as measured by direct potentiometry due to the visible lipemia. The osmolality of 288 mmol/kg was normal with a normal osmolar gap. Urine osmolality and sodium were also normal. He underwent routine evaluation and was listed for a liver transplant due to the profound cholestasis and growth failure.

Conclusions
Pseudohyponatremia is an important entity to recognize when caring for patients with cholestatic liver disease and hyponatremia. Both direct potentiometry and indirect potentiometry are currently used for sodium testing in blood in biochemistry laboratories. These measurement techniques show good agreement as long as protein and lipid concentrations in blood are normal, however, hyperlipidemia is a well-recognized cause for error in sodium estimation. It is therefore imperative to evaluate apparent hyponatremia correctly, especially when the patient appears euvolemic clinically and by normal serum osmolality. In this clinical setting, pseudohyponatremia is the likely cause and a workup should be carried out to identify possible underlying etiologies, the most probable being hypercholesterolemia. Failure to recognize this phenomenon may lead to unnecessary and potentially harmful treatments and interventions.

Funding Agencies
None
A223 FRAILTY INCREASES THE RISK OF CIRRHOSIS DISEASE PROGRESSION, DEATH, AND HOSPITALIZATION IN CIRRHOSIS
Authors: Wang S , Xu C , Whitlock R , Taneja S , Singh S , Abraldes J , Lai J , Tandon P 
Published: March 2021

Abstract

Background
In cirrhosis, frailty is associated with increased risk of morbidity and mortality, including an increased risk of hospitalization. While frailty is established as a prognostic marker in cirrhosis, its impact on the progression of cirrhosis, especially in earlier stages of disease, remains unclear.

Aims
To determine the relationship between frailty and risk of cirrhosis progression, mortality, and unplanned hospitalizations in patients with cirrhosis across the spectrum of disease.

Methods
Adult patients with cirrhosis from two centers in North America and one in India were included in this retrospective review of prospectively collected data. Frailty was measured at baseline using the Liver Frailty Index (LFI), comprising grip strength, chair stands, and balance testing. Progression of cirrhosis was defined by an increase from one ordinal stage to the next using the D’Amico classification. Factors associated with progression, mortality, and hospitalizations were evaluated using multivariate competing risk regression models, with transplant as a competing risk.

Results
In total, 822 patients with cirrhosis were included. The median MELD score was 15.5 ± 6.0. Of these patients, 201 (24.5%), 488 (59.4%), and 133 (16.2%) were classified as frail, pre-frail, and robust, respectively. Over a median follow up time of 1.2 years, 60 (7.3%) patients developed progression of cirrhosis, 187 (22.7%) died, 233 (28.3%) underwent liver transplantation, and 342 (41.6%) were alive without cirrhosis progression or transplant. Adjusting for age, sex, and MELD at baseline, being frail was associated with an increased risk of progression to the next cirrhosis stage or to death as compared to being robust (HR 2.47, 95% CI 1.63–3.76, p&lt;0.001). As a continuous variable, every increase in the LFI by 0.1 unit increased the risk of decompensation or death by 1.05-fold (95% CI 1.04–1.07, p&lt;0.001). Similarly, patients who were frail were more likely to be hospitalized as compared to patients who were robust (HR 2.88, 95% CI 2.08–3.98, p&lt;0.001).

Conclusions
Frailty was associated with an increased risk of cirrhosis progression or death, and hospitalization, independent of MELD at baseline. Future studies are needed to evaluate the possibility of slowing cirrhosis disease progression by reversing or preventing frailty.

Funding Agencies
None
A225 INFERIOR VENA CAVA STENOSIS AFTER HEPATIC LOBECTOMY: A RARE CAUSE OF PORTAL HYPERTENSION AND REFRACTORY ASCITES
Authors: Collins A W , Brahmania M , Tsoi K 
Published: March 2021

Abstract

Background
Inferior vena cava (IVC) stenosis is a rare occurrence in post-liver transplant patients, affecting less than 3% of recipients. IVC stenosis is rarely described in non-transplant patients or considered in the differential of portal hypertension and refractory ascites. Patients with IVC stenosis may experience lower extremity edema, dyspnea, ascites and other signs of portal hypertension.

Aims
We describe a case of portal hypertension and refractory ascites secondary to IVC stenosis following hepatic lobectomy.

Methods
Case report.

Results
We report a 61-year-old woman with a history of diabetes, obesity status post sleeve gastrectomy and solitary neuroendocrine tumor of the right hepatic lobe, adjacent to the porta hepatis with no evidence of metastasis. She underwent a laparoscopic right hepatectomy with wedge resection (&lt;5 cm) in segment 4 to remove the neuroendocrine tumor in 2016. Surgery also included an intraoperative cholangiogram and placement of intra-ductal stent using endoscopic retrograde cholangiopancreatography (ERCP) technology as well as significant adhesiolysis along the IVC, right hepatic vein and biliary tract. In February 2020, the patient was referred to Hepatology for evaluation of new ascites. Imaging did not demonstrate evidence of tumor recurrence or features of cirrhosis but identified a new findings of portal hypertension and moderate ascites. Common causes of chronic liver disease were excluded and hepatic synthetic function was normal. Paracentesis revealed a high serum albumin ascites gradient (SAAG; 20 g/L) and a high ascitic fluid protein (34 g/L). Although these findings were suggestive of cardiac ascites, a 2D echocardiogram was normal. A trans-jugular liver biopsy was attempted in July 2020. The right atrial pressure was 8 mmHg and inferior vena cava (IVC) pressure was 22 mmHg at the level of the liver. Loss of pulsation suggested hemodynamically significant stenosis of the hepatic IVC. The wedged hepatic venous pressure was 3 mmHg and the calculated portal systemic gradient was 4 mmHg. A trans jugular biopsy failed due to unfavourable anatomy. These findings, taken in conjunction with previous results, suggested non-cirrhotic post-hepatic portal hypertension. Subsequent computed tomography imaging confirmed stenosis of the hepatic portion of the IVC and this was felt to be the ultimate cause of the portal hypertension. She has since been referred back to interventional radiology (IR) for consideration of balloon angioplasty dilation of the IVC stenosis as well as additional testing to determine if there is any underlying hepatic fibrosis related to congestive hepatopathy.

Conclusions
IVC stenosis post hepatic lobectomy is a rare phenomenon described in the literature but warrants high suspicion in cases of refractory ascites.

Funding Agencies
None
A228 WHEN ASCITES & VARICEAL BLEEDING ARE NOT FROM CIRRHOSIS: A CASE OF MUTIPLE ARTERIOPORTAL FISTULAE CAUSING PORTAL HYPERTENSION
Authors: Leung K , Jaberi A , Kachura J , Duan K , Wong D 
Published: March 2021

Abstract

Background
Portal hypertension is usually due to increased resistance from cirrhosis. However, pressures can also be elevated due to increased flow.

Aims
To describe a peculiar case of non-cirrhotic portal hypertension.

Methods
A case report and literature review was performed.

Results
A 47-year-old previously well man presented with a 6 month history of rapidly progressive weight loss, ascites and variceal bleed. Workup ruled out common causes of primary liver disease. Initial imaging demonstrated a heterogenous liver, splenomegaly, ascites, patent hepatic/portal veins and multiple poorly defined low-density hepatic lesions with the largest measuring 2.1 cm. Transient elastography was 7.3 kPa (F1-mild fibrosis). At transjugular liver biopsy, hepatic venogram ruled out Budd-Chiari and hepatic vein pressure gradient was normal at 3–4 mmHg. Histology unfortunately showed hemangioma. A percutaneous liver biopsy suggested nodular regenerative hyperplasia, minimal fibrosis and mild cholestasis. Given worsening ascites, hyponatremia and 7 months of rapidly progressive decline, transjugular intrahepatic portosystemic shunt (TIPSS) was inserted. Intra-procedure, portal vein pressure was noted to be 51 mmHg, with a portosystemic gradient of 42 mmHg. Although numerous abdominal CT and MRI did not show AV shunting, ultrasound post-TIPSS showed hepatic pseudoaneurysms & arterioportal fistulae (APF). Direct angiogram showed numerous hepatic pseudoaneurysms and intrahepatic fistulae making embolization impossible. CT showed no evidence of pseudoaneurysms or fistulae outside of the liver. Workup for autoimmune rheumatological diseases and congenital telangiectatic syndromes were negative. Given the high pressures being directed through the new TIPSS, right heart failure is an ongoing concern.
APF are rarely encountered causes of presinusoidal portal hypertension, with communications most commonly arising from the hepatic (65%) & splenic arteries (11%) & the portal vein. Causes include traumatic (28%), iatrogenic (16%), vascular/telangiectatic malformations (15%), tumors (15%), aneurysms (14%) & congenital disease. Endovascular embolization can be used to treat single lesions. In complex cases with mulitple APF, surgery and/or liver transplantation may be required.

Conclusions
We report a rare case of non-cirrhotic portal hypertension due to increased flow rather than increased resistance secondary to APF.

Funding Agencies
None
A235 EFFECTS OF SACRAL PHOTOBIOMODULATION ON THE AUTONOMIC NERVOUS SYSTEM IN PATIENTS WITH COLONIC DYSMOTILITY
Authors: Chen J , Liu L , Ali M , Huizinga J D 
Published: March 2021

Abstract

Background
Patients with chronic refractory constipation show colon dysmotility, including impaired coordination of descending colon-sigmoid colon-rectum-anal sphincter motor functions; this may involve slow colonic transit and colo-anal dyssynergia. Impaired neuronal communication between the sacral defecation center and the distal colon may be causative. In addition, patients with lumbosacral neurological conditions (with lower back pain) may not be able to evoke an effective defecation reflex.

Aims
To evaluate if a single therapeutic session of sacral low-level laser therapy (LLLT) would affect the autonomic activity in patients with chronic constipation as revealed by changes in heart rate variability, and to report a multi-session treatment case study.

Methods
In 41 patients with chronic constipation, one session of LLLT was executed, using red LED light at a wavelength of 660 nm for 10 minutes and infrared LED light at wavelength of 840 nm for 10 minutes followed by infrared laser light with wavelength of 825 nm for 20 minutes, while measuring the electrocardiogram. One patient received this treatment 8x over 3 weeks.

Results
The lumbar-sacral light array treatment showed a significant decrease in parasympathetic activity (RSA & RMSSD) whereas pure sacral laser light treatment showed a significant increase in parasympathetic activity (RSA & RMSSD) as well as a reduction in sympathetic activity (Baevsky’s stress index: SI) (table). A single session of LLLT was also executed during HRCM in 8 patients with some but not all showing evoked colonic motility. Before COVID-19 shutdown, one patient was successfully treated. With a history of chronic constipation without ability to have spontaneous bowel movements for 5 years, symptoms improved from 13 to 8 (on a 20 scale) and quality of life improved from 1.5 to 2.5 (on a 0–4 scale) after 8 sessions. Sympathetic reactivity from supine to standing markedly reduced, from highly elevated measured as the Baevsky index from 55 to 153 s-2 it improved from 42 to 75 s-2 upon standing after 4 sessions. Parasympathetic reactivity did not change.

Conclusions
A single session of sacral LLLT markedly affected autonomic nervous activity reflected in changes in HRV. The LLLT is likely affecting the sacral defecation center through peripheral nerves entering and exiting the spinal cord including the dorsal root ganglia. LLLT treatment of a patient with inability to generate spontaneous bowel movements, resulted in ability to have complete evacuations associated with marked reduction in sympathetic reactivity during the supine-standing test, after 4 LLLT sessions.

Funding Agencies
CIHRFarncombe Family Digestive Health Research Institute
A238 ABSENCE OF AGE-RELATED MEMORY DECLINE IN GERM-FREE MICE
Authors: Kraimi N , De Palma G , Lu J , Bowdish D , Verdu E , Sibille E , Prevot T , Collins S M , Bercik P 
Published: March 2021

Abstract

Background
Age-associated deterioration of cognitive function and memory capacity occur in a variety of mammals, from humans to rodents. For example, significant memory deficits have been reported in conventionally raised (SPF) old mice compared to conventionally raised young mice submitted to a spatial memory task (Prevot et al., Mol Neuropsychiatry 2019). Microbiota to brain signaling is now well established in mice, but the extent to which this influences age-related memory decline is unknown.

Aims
Our project aims to determine whether the intestinal microbiota contributes to age-related changes in brain function. We address the hypothesis that age-related cognitive decline is attenuated in the absence of the intestinal microbiota.

Methods
We studied locomotor behavior and spatial memory performance in young germ-free (GF) mice (2–3 months of age, n=24) and senescent GF mice (13–27 months old, n=22) maintained in axenic conditions, and compared them to conventionally raised (SPF) mice. We used the Y-maze test based on a spontaneous alternations task to assess cognition, with alternation rate as a proxy of spatial working memory performance. The locomotor activity was measured using the open-field test.

Results
GF old mice traveled less distance (458.9 cm) than GF young mice (875.7 cm, p &lt; 0.001) but these differences in locomotor activity did not influence spatial memory performance. Indeed, both GF old and GF young mice had an identical alternation rate of 73.3% (p &gt; 0.05). This contrasted with the memory impairment found in old SPF mice that displayed lower alternation rate of 58.3%, compared to that found in young SPF mice (76.2%, p = 0.13).

Conclusions
We conclude that the absence of age-related memory decline in germ-free mice is consistent with a role for the microbiota in the cognitive decline associated with aging, likely through action on the immune system, well documented in SPF mice (Thevaranjan et al., Cell Host & Microbe 2017). We propose that novel microbiota-targeted therapeutic strategies may delay or prevent the cognitive decline of aging.

Funding Agencies
CIHRBalsam Family Foundation
A241 A REVIEW OF 101 CHILDREN WITH GASTRO-JEJUNAL FEEDING TUBES INCLUDING THEIR COMPLICATIONS AT BC CHILDREN’S HOSPITAL.
Authors: Avinashi V , Hoang T , Lee E , Dewan T , Heran M , Maroo S 
Published: March 2021

Abstract

Background
The use of GastroJejunal Tubes (GJTs) is an increasingly common method for providing post-pyloric enteral nutrition in pediatric patients.

Aims
To describe the patients with GJT including the indication, comorbidities including by system, as well as tube related complications.

Methods
The charts of 101 patients who had a GJT over a one-year period (2019–20) were retrospectively reviewed including demographics, medical diagnoses, information about tube placement, maintenance, and complications including malposition, balloon failure, blockages, and leakages / breaks.

Results
The top indications for GJT are aspiration and GERD. 73.3% have &gt;3 system comorbidities (ie CNS, GI, Resp). Mean age of GJT placement was 43 months. 78% remain on a PPI and 24% are on a prokinetic. 24% continue to eat some amount orally. Over this one-year period, 92% continue with a GJT (mean duration 4 years, max 15), 4% have reverted back to a G-tube, 1% had a surgical J tube placed, and 3% died (not due to the GJT). Following initial placement, these 101 patients underwent 1194 GJT related procedures, (417 urgent changes, 777 routine changes) with 98.3% technical success. Patients needed an average of one urgent repair per year (3.2/1000 GJT days) and the majority of patients required &gt;1 emergency visit. Those with routine GJT changes seem to have fewer urgent repairs (Figure 1).

Conclusions
Children with GJT represent a growing complex patient population. GJT are being used for the longer term. Routine maintenance seems supported by our data although doesn’t prevent the need for urgent repairs or other complications. Frameworks and guidelines are needed for this essential technology to improve clinical care.

Funding Agencies
None
A246 THE GLOBAL INCIDENCE OF ACUTE PANCREATITIS IS INCREASING OVER TIME: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Iannuzzi J , Leong J H , Quan J , King J A , Windsor J W , Tanyingoh D , Coward S , Forbes N , Heitman S , Buie M , Underwood F , Kaplan G G 
Published: March 2021

Abstract

Background
Acute pancreatitis is a common disease with significant associated morbidity and mortality. Historically, acute pancreatitis has been considered a disease with multiple etiologies and risk factors but is driven by alcohol and biliary disease. Multiple studies have shown that the incidence of acute pancreatitis is increasing globally among both adults and children.

Aims
The purpose of this study was to assess temporal trends in incidence of acute pancreatitis globally.

Methods
We performed a systematic literature search to identify population-based studies reporting the annual incidence of acute pancreatitis. Abstracts were independently assessed in duplicate to identify applicable papers for full-text review and data extraction. Joinpoint temporal trend analyses were performed to calculate the average annual percent change (AAPC) with 95% confidence intervals (CI). The AAPCs were pooled in a meta-analysis to capture the overall and regional trends in acute pancreatitis incidence over time. Temporal data were summarized in a static map and an interactive, web-based map to illustrate global differences.

Results
Forty-five studies reported the temporal incidence of acute pancreatitis (static map provided, online interactive map: https://kaplan-acute-pancreatitis-ucalgary.hub.arcgis.com/). The incidence of acute pancreatitis has increased from 1961 to 2016 (AAPC = 2.89%; 95% CI: 2.26, 3.52; n=41). Increasing incidence was observed in North America (AAPC = 2.71%; 95% CI: 1.93, 3.50; n=10) and Europe (AAPC = 2.79%; 95% CI: 1.95, 3.63; n=24). The incidence of acute pancreatitis was stable in Asia (AAPC = −0.28%; 95% CI: −5.03, 4.47; n=2).

Conclusions
This meta-analysis provides a comprehensive overview of the global incidence of acute pancreatitis over the last five decades and demonstrates a steadily rising incidence over time in most countries of the Western world. More studies are needed to better define the changing incidence of acute pancreatitis in Asia, Africa and Latin America.

Funding Agencies
None