Effects of empagliflozin on liver fat in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus: A randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: We investigated whether empagliflozin reduces hepatic steatosis in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus. APPROACH AND RESULTS: This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without diabetes mellitus (fasting plasma glucose < 7 mmol/L and HbA1c < 6.5%) who had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. The primary outcome was the difference in change of MRI-PDFF between the 2 groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF < 5%), alanine aminotransferase drop ≥ 17 U/L, MRI-PDFF decline ≥ 30%, a combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age: 55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. The Empagliflozin group had a greater reduction in median MRI-PDFF compared to the placebo group (-2.49% vs. -1.43%; p = 0.025), with a nonsignificant trend of resolution of hepatic steatosis (44.9% vs. 28.6%; p = 0.094). There was no significant difference in alanine aminotransferase drop ≥ 17 U/L (16.3% vs. 12.2%; p = 0.564), MRI-PDFF drop ≥ 30% (49.0% vs. 40.8%; p = 0.417), and composite outcome (8.2% vs. 8.2%; p = 1.000). Empagliflozin group had a greater drop in body weight (-2.7 vs. -0.2 kg), waist circumference (-2.0 vs. 0 cm), fasting glucose (-0.3 vs. 0 mmol/L), and ferritin (-126 vs. -22 pmol/L) (all p < 0.05). CONCLUSIONS: Empagliflozin for 52 weeks reduces hepatic fat content in subjects with nondiabetic metabolic dysfunction-associated steatotic liver disease. (ClinicalTrials.gov Identifier: NCT04642261).

Predicting the level of difficulty of the double-stapling technique in laparoscopic total mesorectal excision.

BACKGROUND: The transection of rectum and fashioning of anastomosis is a crucial step in laparoscopic total mesorectal excision (TME) and the double-stapling technique (DST) is often employed. This study aimed to evaluate the factors that were associated with difficult DST. METHOD: Cases of laparoscopic TME were retrospectively reviewed. The clinico-anatomical parameters were retrieved from a prospectively maintained database. In addition, pelvic dimensions were taken by reviewing the magnetic resonance imaging scan. The number of stapler cartridges used for intracorporeal transection of rectum was used as a surrogate for the level of difficulty of DST and its relationship with various parameters were evaluated. RESULTS: There were a total of 121 consecutive cases analyzed. The mean number of stapler cartridges used was 2.1 ± 0.7. Pelvic inlet (p = 0.002) and tumor height (p = 0.015) were predictors of the number of cartridges used, R2 = 0.366. A model was developed to predict the likelihood of transecting the rectum with two or less stapler cartridges, which included the following parameters: gender, pelvic inlet, interspinous distance, intertuberous distance, and tumor height. The predicted probability also correlated with overall operation time (p = 0.009) and anastomotic leakage (p = 0.023). CONCLUSION: The difficulty of DST was associated with patient's clinico-anatomical factors. Surgeons can consider other feasible alternatives, like transanal anastomosis, when a technically challenging DST is anticipated.

Development and validation of an imaging and clinical scoring system to predict early mortality in spontaneous ruptured hepatocellular carcinoma treated with transarterial embolization.

PURPOSE: To develop and validate a scoring system using a combination of imaging and clinical parameters to predict 30-day mortality in ruptured HCC (rHCC) patients after transarterial embolization (TAE). METHODS: 98 consecutive patients with rHCC who underwent abdominal CT and subsequent TAE between January 2007 and December 2016 were retrospectively reviewed. The CT scans were reviewed by two radiologists blinded to the patient outcome. Clinical parameters including serum bilirubin, albumin, INR, creatinine, and hemoglobin were recorded. Independent risk factors for 30-day mortality after TAE were identified using multivariate binary logistic regression, for development of a scoring system. The scoring system was then validated in 20 patients between January 2017 and May 2018. RESULTS: In the development cohort, bilobar tumor distribution (OR = 29.6), clinical parameters of bilirubin > 2.5 mg/dL (OR = 5.9), and albumin < 30 g/L (OR = 4.1) were independent predictors for 30-day mortality. A 6-point score was derived and yielded area-under-the-receiver-operating-characteristic-curve (AUC) of 0.904. A score ≥ 4 resulted in sensitivity of 80.5% and specificity of 91.2% for 30-day mortality. In the validation cohort, AUC for 30-day mortality was 0.939. A score ≥ 4 resulted in sensitivity of 81.2% and specificity of 88.9%. In both development and validation cohorts, the proposed scoring system was better than biochemical components of Child-Pugh score and serum bilirubin to predict 30-day mortality. CONCLUSION: Imaging and clinical parameters can be combined into a scoring system to accurately predict 30-day mortality after TAE in rHCC patients. The score may help identify and counsel high-risk patients.

Left ventricular torsional mechanics and myocardial iron load in beta-thalassaemia major: a potential role of titin degradation.

BACKGROUND: Iron may damage sarcomeric proteins through oxidative stress. We explored the left ventricular (LV) torsional mechanics in patients with beta-thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell and B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin. METHODS AND RESULTS: In 44 thalassaemia patients aged 25 ± 7 years and 38 healthy subjects, LV torsion and twisting velocities were determined at rest using speckle tracking echocardiography. Changes in LV torsional parameters during submaximal exercise testing were further assessed in 32 patients and 17 controls. Compared with controls, patients had significantly reduced LV apical rotation, torsion, systolic twisting velocity, and diastolic untwisting velocity. T2* cardiac magnetic resonance findings correlated with resting diastolic untwisting velocity. The increments from baseline and resultant LV torsion and systolic and diastolic untwisting velocities during exercise were significantly lower in patients than controls. Significant correlations existed between LV systolic torsion and diastolic untwisting velocities in patients and controls, both at rest and during exercise. In HL-1 cells and ventricular myocardium of B6D2F1 mice overloaded with iron, the titin-stained pattern of sarcomeric structure became disrupted. Gel electrophoresis of iron-overloaded mouse myocardial tissue further showed significant decrease in the amount of titin isoforms and increase in titin degradation products. CONCLUSIONS: Resting and dynamic LV torsional mechanics is impaired in patients with beta-thalassaemia major. Cell and animal models suggest a potential role of titin degradation in iron overload-induced alteration of LV torsional mechanics.

Depiction of celiac ganglia on positron emission tomography and computed tomography in patients with lung cancer.

OBJECTIVE: To differentiate imaging characteristics of celiac ganglia from metastatic lesion on positron emission tomography-computed tomography (PET-CT) in patients with lung cancer and correlate these findings to postmortem multidetector row computed tomography (MDCT). METHODS: One hundred twenty-nine patients were included. Imaging characteristics and fluorodeoxyglucose (FDG) avidity of the celiac ganglia were recorded. Postmortem MDCT of 20 subjects were reviewed. RESULTS: Celiac ganglia were identified unilaterally in 127 and bilaterally in 108 patients without abnormal FDG uptake. Postmortem images showed celiac ganglia in all cases with no significant difference compared to our patients. CONCLUSIONS: Familiarity with CT characteristics and FDG-avidity of celiac ganglia enable us to distinguish them from metastatic lesions in their vicinity.

Total colorectal and terminal ileal duplication presenting as intussusception and intestinal obstruction.

Colonic intussusception and gastrointestinal duplication are diseases that arise in young children. The clinical presentation of adult cases of intussusception and enteric duplication is non-specific and thus poses a diagnostic challenge. A computed tomography (CT) scan is recommended in adult cases as the most sensitive diagnostic tool and the pathognomonic finding of outer intussuscepiens and central intussusceptum is diagnostic. A septum of a duplicated colon in a non-intussuscepted segment has been rarely reported in the literature. With advancements in radiological imaging technology and the increased availability of CT scanners, the capacity for a correct pre-operative diagnosis has been significantly enhanced. Our current case report illustrates the importance of considering an uncommon etiology for enteric intussusception and duplication as a differential diagnosis of acute abdomen in an adult patient. Our analyses of this patient also highlight the successful use of CT scanning to make this diagnosis.

Dynamic dyssynchrony and impaired contractile reserve of the left ventricle in beta-thalassaemia major: an exercise echocardiographic study.

BACKGROUND: Performance of the left ventricle during exercise stress in thalassaemia patients is uncertain. We aimed to explore the phenomenon of dynamic dyssynchrony and assess contractile reserve in patients with beta-thalassaemia major and determine their relationships with myocardial iron load. METHODS AND RESULTS: Thirty-two thalassaemia patients (16 males), aged 26.8 ± 6.9 years, without heart failure and 17 healthy controls were studied. Their left ventricular (LV) volumes, ejection fraction, systolic dyssynchrony index (SDI), and myocardial acceleration during isovolumic LV contraction (IVA) were determined at rest and during submaximal bicycle exercise testing using 3-dimensional and tissue Doppler echocardiography. Myocardial iron load as assessed by T2* cardiac magnetic resonance in patients were further related to indices of LV dyssynchrony and contractile reserve. At rest, patients had significantly greater LV SDI (p<0.001) but similar IVA (p = 0.22) compared with controls. With exercise stress, the prevalence of mechanical dyssynchrony (SDI>4.6%, control+2SD) increased from baseline 25% to 84% in patients. Δ SDI(exercise-baseline) correlated with exercise-baseline differences in LV ejection fraction (p<0.001) and stroke volume (p = 0.006). Compared with controls, patients had significantly less exercise-induced increase in LV ejection fraction, cardiac index, and IVA (interaction, all p<0.05) and had impaired contractile reserve as reflected by the gentler IVA-heart rate slope (p = 0.018). Cardiac T2* in patients correlated with baseline LV SDI (r = -0.44, p = 0.011) and IVA-heart rate slope (r = 0.36, p = 0.044). CONCLUSIONS: Resting LV dyssynchrony is associated with myocardial iron load. Exercise stress further unveils LV dynamic dyssynchrony and impaired contractile reserve in patients with beta-thalassaemia major.

"Venous cut-off sign" as an adjunct to the "whirl sign" in recognizing acute small bowel volvulus via CT scan.

INTRODUCTION: A young adult patient was admitted for signs and symptoms of acute abdomen. MATERIALS AND METHODS: Urgent CT scan was performed and small bowel volvulus was confirmed. The "whirl sign" diagnostic of small bowel volvulus was present. RESULTS: Furthermore, the accompanying superior mesenteric vein was noted to be truncated at the point of torsion. CONCLUSION: The "venous cut-off sign" can be a useful adjunct sign to the diagnosis.

Case report: Completely unroofed coronary sinus with a left superior vena cava draining into the left atrium studied by cardiovascular magnetic resonance.

A persistent left superior vena cava (LSVC) draining through a dilated coronary sinus into the right atrium is a relatively common congenital cardiovascular anomaly. It is readily identified by cardiovascular magnetic resonance (CMR). However, a LSVC draining into the left atrium (LA) and associated with unroofing of the coronary sinus, with resulting interatrial communication, is rare and may have important clinical consequences. As with any large atrial septal defect, it can be associated with a higher than expected incidence of pulmonary arterial hypertension, systemic embolization, and brain abscesses. In this report, we present a case of a completely unroofed coronary sinus with a persistent LSVC draining directly into the LA and illustrate the role of CMR in the diagnosis and evaluation of such anomalies.