Baseline Ultrasound and Clinical Correlates in Children with Cystic Fibrosis.
ABSTRACT: OBJECTIVE:To investigate the relationship between abdominal ultrasound findings and demographic, historical, and clinical features in children with cystic fibrosis (CF). STUDY DESIGN:Children age 3-12 years with CF without known cirrhosis, were enrolled in a prospective, multicenter study of ultrasound to predict hepatic fibrosis. Consensus ultrasound patterns were assigned by 3 radiologists as normal, heterogeneous, homogeneous, or cirrhosis. Data were derived from direct collection and US or Toronto CF registries. χ(2) or ANOVA were used to compare variables among ultrasound groups and between normal and abnormal. Logistic regression was used to study risk factors for having abnormal ultrasound. RESULTS:Findings in 719 subjects were normal (n = 590, 82.1%), heterogeneous (64, 8.9%), homogeneous (41, 5.7%), and cirrhosis (24, 3.3%). Cirrhosis (P = .0004), homogeneous (P < .0001), and heterogeneous (P = .03) were older than normal. More males were heterogeneous (P = .001). More heterogeneous (15.0%, P = .009) and cirrhosis (25.0%, P = .005) had CF-related diabetes or impaired glucose tolerance vs normal (5.4%). Early infection with Pseudomonas aeruginosa (<2 years old) was associated with a lower risk (OR 0.42, P = .0007) of abnormal. Ursodeoxycholic acid use (OR 3.69, P < .0001) and CF-related diabetes (OR 2.21, P = .019) were associated with increased risk of abnormal. CONCLUSIONS:Unsuspected cirrhosis is seen in 3.3% of young patients with CF, heterogeneous in 8.9%. Abnormal ultrasound is associated with CF-related diabetes, and early P aeruginosa is associated with normal ultrasound. Prospective assessment of these risk factors may identify potential interventional targets. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01144507.
Project description:Liver disease is the third leading cause of death in patients with cystic fibrosis (CF), but features of patients with CF, severe liver disease, and portal hypertension have not been characterized fully.We performed a retrospective analysis of data from 561 patients with CF (63% male, 99% with pancreatic insufficiency), liver disease (hepatic parenchymal abnormalities consistent with cirrhosis, confirmed by imaging), and portal hypertension (esophageal varices, portosystemic collaterals, or splenomegaly), with no alternate causes of liver disease. All patients were enrolled in the Genetic Modifier Study of Severe CF Liver Disease at 76 international centers, from January 1999 through July 2013.Male patients were diagnosed with liver disease at a younger age than female patients (10 vs 11 y; P = .01). Splenomegaly was observed in 99% of patients and varices in 71%. Levels of liver enzymes were near normal in most patients. Thrombocytopenia affected 70% of patients and was more severe in patients with varices (88 × 10(9)/L vs 145 × 10(9)/L; P < .0001). Ninety-one patients received liver transplants (16%), at a median age of 13.9 years. Compared with patients who did not receive liver transplants, patients who received liver transplants had lower platelet counts (78 × 10(9)/L vs 113 × 10(9)/L; P < .0001), higher international normalized ratios (P < .0001), and lower levels of albumin (P = .0002). The aminotransferase to platelet ratio index (APRi) and fibrosis index based on 4 factor (FIB-4) values were higher than the diagnostic thresholds for CF liver disease in 96% and in 90% of patients, respectively. Patients who received liver transplants or who had varices had higher APRi and FIB-4 values than patients who did not.In patients with CF, severe liver disease develops early in childhood (approximately 10 years of age), and is more common in boys than in girls. Patients with varices and those who receive liver transplants have more abnormal platelet counts and APRi and FIB-4 scores.
Project description:OBJECTIVES:Early identification of children with cystic fibrosis (CF) at risk for severe liver disease (CFLD) would enable targeted study of preventative therapies. There is no gold standard test for CFLD. Ultrasonography (US) is used to identify CFLD, but with concerns for its diagnostic accuracy. We aim to determine if differences in standard blood tests, imaging variables and noninvasive liver fibrosis indices correlate with liver US patterns, and thus provide supportive evidence that a heterogeneous US liver pattern reflects clinically relevant liver disease. METHODS:We studied baseline research abdominal US and bloodwork from 244 children with pancreatic insufficient CF, ages 3 to 12 years, enrolled in a prospective study of the ability of US to predict CF cirrhosis (PUSH study). Children with a heterogeneous (HTG) liver pattern on US (n?=?62) were matched 1?:?2 in design with children with normal US (NL, n?=?122). Analyses included children with nodular (NOD, n?=?22) and homogeneous hyperechoic (HMG, n?=?38) livers. RESULTS:Univariate analysis showed significant differences between US groups for standard blood tests, spleen size, and noninvasive liver fibrosis indices. Multivariable models discriminated NOD versus NL with excellent accuracy (AUROC 0.96). Models also distinguish HTG versus NL (AUROC 0.76), NOD versus HTG (0.78), and HMG versus NL (0.79). CONCLUSIONS:Liver US patterns in children with CF correlate with platelet count, spleen size and indices of liver fibrosis. Multivariable models of these biomarkers have excellent discriminating ability for NL versus NOD, and good ability to distinguish other US patterns, suggesting that US patterns correlate with clinically relevant liver disease.
Project description:OBJECTIVE:Cystic fibrosis associated liver disease (CFLD) is the third largest cause of mortality in CF. Our aim was to define the burden of CFLD in the UK using national registry data and identify risk factors for progressive disease. METHODS:A longitudinal population-based cohort study was conducted. Cases were defined as all patients with CFLD identified from the UK CF Registry, 2008-2013 (n = 3417). Denominator data were derived from the entire UK CF Registry. The burden of CFLD was characterised. Regression analysis was undertaken to identify risk factors for cirrhosis and progression. RESULTS:Prevalence of CFLD increased from 203.4 to 228.3 per 1000 patients during 2008-2013. Mortality in CF patients with CFLD was more than double those without; cirrhotic patients had higher all-cause mortality (HR 1.54, 95% CI 1.09 to 2.18, p = 0.015). Median recorded age of cirrhosis diagnosis was 19 (range 5-53) years. Male sex, Pseudomonas airway infection and CF related diabetes were independent risk factors for cirrhosis. Ursodeoxycholic acid use was associated with prolonged survival in patients without cirrhosis. CONCLUSIONS:This study highlights an important changing disease burden of CFLD. The prevalence is slowly increasing and, importantly, the disease is not just being diagnosed in childhood. Although the role of ursodeoxycholic acid remains controversial, this study identified a positive association with survival.
Project description:OBJECTIVES:Cirrhosis occurs in 5% to 10% of cystic fibrosis (CF) patients, often accompanied by portal hypertension. We analyzed 3 adverse liver outcomes, variceal bleeding (VB), liver transplant (LT), and liver-related death (LD), and risk factors for these in CF Foundation Patient Registry subjects with reported cirrhosis. METHODS:We determined 10-year incidence rates for VB, LT, LD, and all-cause mortality (ACM), and examined risk factors using competing risk models and Cox-proportional hazard regression. RESULTS:From 2003 to 2012, 943 participants (41% females, mean age 18.1 years) had newly reported cirrhosis; 24.7% required insulin, 85% had previous pseudomonas. Seventy-three subjects had reported VB: 38 with first VB and new cirrhosis reported simultaneously and 35 with VB after cirrhosis report. Ten-year cumulative VB, LT, and LD rates were 6.6% (95% confidence interval [CI]: 4.0, 9.1%), 9.9% (95% CI: 6.6%, 13.2%), and 6.9% (95% CI: 4.0%, 9.8%), respectively, with an ACM of 39.2% (95% CI: 30.8, 36.6%). ACM was not increased in subjects with VB compared to those without (hazard ratio [HR] 1.10, 95% CI: 0.59, 2.08). CF-related diabetes (HR: 3.141, 95% CI:1.56, 6.34) and VB (HR: 4.837, 95% CI: 2.33, 10.0) were associated with higher LT risk, whereas only worse lung function was associated with increased LD in multivariate analysis. Death rate among subjects with VB was 24% with LT and 20.4% with native liver. CONCLUSIONS:VB is an uncommon complication of CF cirrhosis and can herald the diagnosis, but does not affect ACM. Adverse liver outcomes and ACM are frequent by 10 years after cirrhosis report.
Project description:Idiopathic portal hypertension (IPH) mimics liver cirrhosis in many aspects, and no efficient imaging method to differentiate the two diseases has been reported to date. In this study, the imaging and pathological characteristics were analysed for both IPH and cirrhosis. From January 2015 to March 2019, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) images and pathological results from 16 IPH and 16 liver cirrhosis patients, as well as imaging results of 16 normal patients as a control group, were retrospectively reviewed. The age of the patients was 39?±?20 years. There was a significant difference in the mean lumen diameter, wall thickness and ratio of thickness to diameter between the IPH and liver cirrhosis patients in the main and sagittal portal veins (P?<?0.05), as well as in the lumen diameter and ratio of thickness to diameter between the IPH and liver cirrhosis patients in the Segment 3 (S3) portal vein (P?<?0.05). In IPH patients, the main imaging changes were portal vein wall thickening, stenosis or occlusion, a low enhancement area along the portal vein in the delay phase in contrast-enhanced imaging, and a non-homogeneous change in T1WI. The corresponding pathological changes included interlobular vein thickening, stenosis, occlusion, portal area fibrosis, and atrophy or apoptosis of hepatocytes. The main imaging characteristic of liver cirrhosis was a nodular change in T1WI, and the related pathological change was pseudolobule formation. The imaging characteristics of IPH include thickening of the portal vein vascular wall, stenosis of the portal vein lumen and the absence of diffuse cirrhosis-like nodules. These imaging features have a definite pathological basis and could help make differential diagnoses between IPH and cirrhosis.
Project description:Xerostomia (dry mouth), secondary to irradiation of the parotid glands, is one of the most common side effects of head-and-neck cancer radiotherapy. Diagnostic tools able to accurately and efficiently measure parotid gland injury have yet to be introduced into the clinic. This study's purpose is to investigate sonographic textural features as potential imaging signatures for quantitative assessment of parotid-gland injury after head-and-neck radiotherapy.The authors have investigated a series of sonographic features obtained from the gray level co-occurrence matrix (GLCM) - a second order statistical method of texture analysis. These GLCM textural features were selected based on empirical observations that the normal parotid gland exhibits homogeneous echotexture, whereas the postradiotherapy parotid gland often exhibits heterogeneous echotexture. We employed eight sonographic features: (1) angular second moment (ASM), (2) inverse differential moment (IDM), (3) contrast, (4) variance, (5) correlation, (6) entropy, (7) cluster shade, and (8) cluster prominence. Altogether, sonographic properties of the parotid glands were quantified by their degrees of homogeneity (ASM and IDM), heterogeneity (contrast and variance), smoothness (correlation), randomness (entropy), and symmetry (cluster shade and prominence). The sonographic features were tested in a pilot study of 12 postradiotherapy patients and 7 healthy volunteers. The mean follow-up time for the postradiotherapy patients was 17.2 months (range: 12.1-23.9 months) and the mean radiation dose to the parotid glands was 32.3 Gy (range: 11.0-63.4 Gy). Each participant underwent one ultrasound study in which longitudinal (vertical) ultrasound scans were performed on the bilateral parotids - a total of 24 postirradiation and 14 normal parotid glands were examined. The 14 normal parotid glands served as the control group. A radiologist contoured the parotid glands on the B-mode images and the sonographic features were computed from the contoured region-of-interest.The authors observed significant differences (p < 0.05) in all sonographic features between the normal and postradiotherapy parotid glands. The sonographic findings were consistent with the clinical observations of the ultrasound images: normal parotid glands exhibited homogeneous texture, while the postradiotherapy parotid glands exhibited heterogeneous echotexture (e.g., hyperechoic lines and spots), which likely represents fibrosis.The authors have demonstrated the feasibility of ultrasonic texture evaluation of parotid glands; and the sonographic features may serve as imaging signatures to assess radiation-induced parotid injury.
Project description:As decreased bone mineral density (BMD) is a common problem in cystic fibrosis (CF) and milk products may have pivotal dietary role affecting BMD, we aimed to assess the potential influence of adult-type hypolactasia (ATH) and lactose malabsorption (LM) on BMD in adolescent and young adult patients. In 95 CF pancreatic-insufficient patients aged 10-25 years (without liver cirrhosis, steatosis and cholestasis, diabetes mellitus, systemic glucocorticoid therapy), lumbar BMD, the nutritional status, pulmonary function, vitamin D3 concentration, calcium intake and single-nucleotide polymorphism upstream of the lactase gene were assessed. In subjects with the -13910 C/C genotype predisposing to ATH, the presence of LM was determined with the use of a hydrogen-methane breath test (BT). BMD and calcium intake were significantly lower in patients with the C/C genotype (P<0.028 and P<0.043, respectively). The abnormal BMD was stated more frequently in patients with the C/C genotype (P<0.042) and with LM (P<0.007). BMD, daily calcium intake and serum vitamin D concentration were significantly lower in LM subjects than in the other patients (P<0.037, P<0.000004 and P<0.0038, respectively). In logistic regression analysis, the relationship between examined parameters and BMD, was found to be statistically significant (P<0.001). However, only standardized body weight and LM were documented to influence BMD (P<0.025 and P<0.044, respectively). In conclusion, LM seems to be an independent risk factor for decreased BMD in CF patients.
Project description:Diabetes in whites of European descent with hemochromatosis was first attributed to pancreatic siderosis. Later observations revealed that the pathogenesis of diabetes in HFE hemochromatosis is multifactorial and its clinical manifestations are heterogeneous. Increased type 2 diabetes risk in HFE hemochromatosis is associated with one or more factors, including abnormal iron homeostasis and iron overload, decreased insulin secretion, cirrhosis, diabetes in first-degree relatives, increased body mass index, insulin resistance, and metabolic syndrome. In p.C282Y homozygotes, serum ferritin, usually elevated at hemochromatosis diagnosis, largely reflects body iron stores but not diabetes risk. In persons with diabetes type 2 without hemochromatosis diagnoses, serum ferritin levels are higher than those of persons without diabetes, but most values are within the reference range. Phlebotomy therapy to achieve iron depletion does not improve diabetes control in all persons with HFE hemochromatosis. The prevalence of type 2 diabetes diagnosed today in whites of European descent with and without HFE hemochromatosis is similar. Routine iron phenotyping or HFE genotyping of patients with type 2 diabetes is not recommended. Herein, we review diabetes in HFE hemochromatosis and the role of iron in diabetes pathogenesis in whites of European descent with and without HFE hemochromatosis.
Project description:OBJECTIVES:As most hepatocellular carcinoma (HCC) patients have cirrhosis, the association between diabetes and HCC may be confounded by the fact that diabetes is common in patients with cirrhosis. The aim of this study is to investigate whether diabetes increases the risk of HCC in patients with cirrhosis and whether the etiology of liver disease modifies the association between diabetes and HCC. METHODS:All liver cirrhosis patients who had repeated radiographic evaluation of the liver (that is, ultrasound, computed tomography, or magnetic resonance image) at Mayo Clinic Rochester between January 2006 and December 2011 were included. The Cox proportional hazard regression analysis was used to investigate the effect of diabetes on the risk of HCC. RESULTS:A total of 739 patients met the eligibility criteria, of whom 253 (34%) had diabetes. After a median follow-up of 38 months, 69 (9%) patients developed HCC. In patients without hepatitis C virus (HCV) infection, diabetes was significantly associated with the risk of developing HCC (hazard ratio (HR)=2.1, 95% confidence interval (CI)=1.1-4.1), whereas in patients with HCV, there was no association (HR=0.8, 95% CI=0.4-1.8). When adjusted for covariates, the interaction between HCV and diabetes remained significant (HR for non-HCV=1.9, 95% CI=0.9-3.7; HR for HCV=0.6, 95% CI=0.2-1.3). Lack of association between diabetes and HCC was externally validated in 410 patients with HCV cirrhosis enrolled in the HALT-C trial. CONCLUSIONS:Diabetes increases the risk of HCC in patients with non-HCV cirrhosis. In HCV cirrhosis patients who already have very high risk, diabetes may not increase the risk any further.
Project description:The AAP (American Academy of Pediatrics) no longer recommends voiding cystourethrogram in children 2 to 24 months old who present with a first urinary tract infection if renal-bladder ultrasound is normal. We identified factors associated with abnormal imaging and recurrent pyelonephritis in this population.We retrospectively evaluated children diagnosed with a first episode of pyelonephritis at age 2 to 24 months using de-identified electronic medical record data from an institutional database. Data included age at first urinary tract infection, gender, race/ethnicity, need for hospitalization, intravenous antibiotic use, history of abnormal prenatal ultrasound, renal-bladder ultrasound and voiding cystourethrogram results, urinary tract infection recurrence and surgical intervention. Risk factors for abnormal imaging and urinary tract infection recurrence were analyzed by univariate logistic regression, the chi-square test and survival analysis.We identified 174 patients. Of the 154 renal-bladder ultrasounds performed 59 (38%) were abnormal. Abnormal prenatal ultrasound (p = 0.01) and the need for hospitalization (p = 0.02) predicted abnormal renal-bladder ultrasound. Of the 95 patients with normal renal-bladder ultrasound 84 underwent voiding cystourethrogram. Vesicoureteral reflux was more likely in patients who were white (p = 0.003), female (p = 0.02) and older (p = 0.04). Despite normal renal-bladder ultrasound, 23 of 84 patients (24%) had dilating vesicoureteral reflux. Of the 95 patients with normal renal-bladder ultrasound 14 (15%) had recurrent pyelonephritis and 7 (7%) went on to surgical intervention.Despite normal renal-bladder ultrasound after a first pyelonephritis episode, a child may still have vesicoureteral reflux, recurrent pyelonephritis and the need for surgical intervention. If voiding cystourethrogram is deferred, parents should be counseled on these risks.