Magnetic Resonance Imaging: A Personalized Approach to Understanding Fatty Liver Disease.

OBJECTIVES: To assess information retention by parents/caretakers regarding nonalcoholic fatty liver disease (NAFLD) utilizing the actual image of their child's affected liver. METHODS: In this pilot study, parents/caretakers of children with newly diagnosed NAFLD were presented with an magnetic resonance (MR) image of their child's fatty liver. An adjacent image of a normal-appearing liver was used to highlight the degree of fat accumulation present in their child's liver. The appearance of the fatty liver was used as an adjunct to patient education as provided by a nurse clinician. The efficacy of this approach was determined by a set of image- and disease-specific queries. Health literacy was assessed concurrently by the Newest Vital Sign (NVS) instrument. The image- and disease-specific queries were then repeated by telephone follow-up 2 to 4 weeks after initial clinic visit. RESULTS: Parents/caretakers initially gave 100% correct responses regarding the variation of appearance of normal liver (pink) and their child's fatty liver (yellow). They also all correctly stated the fat content initially. At follow-up, their recall was 95% for the appearance of normal liver and 81% for fatty liver; recall was only 52% for fat content at follow-up. Nonvisualized elements of nonalcoholic steatohepatitis (NASH) and cirrhosis were not identified or recalled as well. Results may have been influenced by parent/caretaker health literacy competence. CONCLUSIONS: Personalized images of fatty liver were effective visualization tools for parents/caretakers to comprehend NAFLD and comprehension was not compromised by health literacy. Clear visual instruments may improve parent/caretaker comprehension of these conditions and may help to address deficiencies in health literacy.

Metabolic profile of children with extrahepatic portal vein obstruction undergoing meso-Rex bypass.

BACKGROUND: Extrahepatic portal vein obstruction (EHPVO) in children is often associated with growth restriction, which improves after the restoration of portal venous flow with a meso-Rex bypass, but the physiologic mechanism is unknown. The purpose of this study was to investigate the mechanism of growth delay in children with EHPVO by detailing the metabolic and nutritional profile before and after meso-Rex bypass. METHODS: Twenty consecutive children with EHPVO were prospectively studied before and 1 year after meso-Rex bypass. Caloric balance was determined by investigating caloric intake via a calorie count, total energy expenditure via a doubly labeled water isotope assay and stool caloric loss by bomb calorimetry. Laboratory markers of nutrition and growth hormone resistance were tested. RESULTS: Fifteen of the 20 children underwent successful meso-Rex bypass at a median age of 4.3 years. Prealbumin level was abnormally low (14.6 ± 3.0 mg/dL) at surgery but improved (17.0 ± 4.3 mg/dL) 1 year later (P = 0.026). Mean insulin-like growth factor 1 (IGF-1) level at baseline was 1.57 standard deviations below normal. IGF-1 levels increased from 88.3 ± 38.9 to 117.3 ± 54.5 ng/mL in the year after surgery (P = 0.047). Caloric intake divided by basal metabolic rate (1.90 ± 0.61), total energy expenditure (97.2 ± 15.0% of expected), and stool caloric losses (3.7 ± 1.8% of caloric intake) were all normal at baseline. CONCLUSIONS: Children with EHPVO suffer from malnutrition and growth hormone resistance, which may explain their well-established finding of growth restriction. Prealbumin and IGF-1 levels improve after a successful meso-Rex bypass.

Serum Phosphorus, Serum Bicarbonate, and Renal Function in Relation to Liver CYP1A2 Activity.

The liver plays an important role in normal metabolism and physiological functions such as acid-base balance; however, limited epidemiologic studies have investigated how the liver contributes toward acid-base balance using non-invasive biomarkers. We determined associations between serum biomarkers related to acid-base balance and renal function with liver CYP1A2 activity. We used data from 1381 participants of the 2009-2010 National Health and Nutrition Examination Survey (NHANES) with measurements of serum phosphorus, serum bicarbonate, caffeine intake, caffeine metabolites, and estimated glomerular filtration rate (eGFR). Liver CYP1A2 activity was estimated using urine caffeine metabolite indices, which were calculated as the ratio of one of the urine caffeine metabolites (i.e., paraxanthine and 1-methyluric acid) to caffeine intake. We analyzed associations in the whole data set and in different strata of hepatic steatosis index (HSI) based on different cut-points. We found that serum bicarbonate was positively associated with CYP1A2 activity in the whole data set when comparing persons with bicarbonate at Q4 to Q1 (ß = 0.18, p = 0.10 for paraxanthine; ß = 0.20, p = 0.02 for 1-methyluric acid). Furthermore, serum phosphorus was positively associated with CYP1A2 activity only in the stratum of 30 ≤ HSI < 36. Lastly, low eGFR was significantly associated with lower CYP1A2 activity measured with paraxanthine in the whole dataset and in all the strata with HSI < 42; when comparing eGFR < 60 to eGFR > 90, ß estimates ranged from -0.41 to -1.38, p-values ranged from 0.0018 to 0.004. We observed an opposite trend in the highest stratum (HSI ≥ 42). Non-invasive measurements of serum bicarbonate, serum phosphorus, and eGFR have dynamic associations with CYP1A2 activity. These associations depend on the extent of liver damage and the caffeine metabolite used to assess CYP1A2 activity.

Cold Exposures in Relation to Dysmenorrhea among Asian and White Women.

Dysmenorrhea is highly prevalent, ranging from 16% to 91% among women, and it can lead to multiple reproductive disorders. However, risk factors associated with dysmenorrhea remain unexamined. Cold exposures can significantly disturb blood circulation and prostaglandin production in the uterus, leading to dysmenorrhea. This study investigated the relationship between cold exposures and dysmenorrhea, as well as potential disparities between Asians and Whites and the potential cultural influences on these associations. This was a cross-sectional survey among 197 Asian and 222 non-Asian women recruited from the U.S., with more than 40% from California. We assessed cold exposures, such as the frequency of consumption of cold water/drinks and ice cream, as well as room temperatures at home and public places, for both summer and winter over the past 12 months. The type of cold exposure associated with dysmenorrhea differs between Asian and White women. We found that among Asian women, a higher frequency of ice cream consumption in winter (beta = 1.19, p = 0.0002 when comparing high to low categories) was associated with dysmenorrhea; however, among White women, increased consumption of cold water/drinks in winter (beta = 0.49, p = 0.04 when comparing high to low categories) was also associated with dysmenorrhea. Higher home room temperatures in winter were associated with reduced severity of dysmenorrhea among White women but not among Asian women. All these associations supported our hypothesis and were stronger among women who lived in states with colder winters. However, there are a few exceptions. For instance, women who drank cold water/drinks less frequently during their menstrual period were more likely to experience more severe dysmenorrhea. In conclusion, this study provides crucial evidence to support the link between cold exposures and dysmenorrhea among Asians and Whites. The associations contradictory to our hypothesis are likely due to reserved causation influenced by Asian cultural practice. This paper sheds light on an understudied area that profoundly affects women's quality of life.

CD4 and IL-2 mediated NK cell responses after COVID-19 infection and mRNA vaccination in adults.

A detailed understanding of protective immunity against SARS-CoV-2 is incredibly important in fighting the pandemic. Central to protective immunity is the ability of the immune system to recall previous exposures. Although antibody and T cell immunity have gained considerable attention, the contribution of the NK cell compartment to immune recall and protection from SARS-CoV-2 has not been explored. In this study, we investigate the NK cell responses to stimulation with SARS-CoV-2 in previously exposed and non-exposed individuals. We show that NK cells demonstrate an enhanced CD4+ T cell dependent response when re-exposed to SARS-CoV-2 antigen. The enhanced response is dependent on T cells and correlates with the number of SARS-CoV-2 specific CD4 T cells. We find that IL-2 is a critical mediator of NK cell function. These findings suggest that NK cells contribute to the protective responses against SARS-CoV-2 through a cooperation with antigen-specific CD4 T cells and have significant implications on our understanding of protective immunity in SARS-CoV-2.

Exome sequencing of an adolescent with nonalcoholic fatty liver disease identifies a clinically actionable case of Wilson disease.

Diagnostic whole-exome sequencing has proven highly successful in a range of rare diseases, particularly early-onset genetic conditions. In more common conditions, however, exome sequencing for diagnostic purposes remains the exception. Here we describe a patient initially diagnosed with a common, complex liver disease, nonalcoholic fatty liver disease (NAFLD), who was determined to have Wilson disease (WD) upon research-related exome sequencing. The patient presented as a 14.5-yr-old adolescent with chronically elevated aminotransferases, normal ceruloplasmin, and histologic examination consistent with NAFLD with advanced fibrosis. He was enrolled in a large longitudinal study of patients with NAFLD and was found to have WD by exome sequencing performed 4 yr later. This new diagnosis, confirmed clinically by 24 h urine copper quantification, led to a change in the therapy from lifestyle counseling to directed treatment with d-penicillamine, a copper chelating agent. In this case, the likelihood of making the correct diagnosis and thereby choosing the appropriate treatment was increased by exome sequencing and careful interpretation. This example illustrates the utility of exome sequencing diagnostically in more common conditions not currently considered as targets for genome-wide evaluation and adds to a growing body of evidence that patients diagnosed with more common conditions often in fact have rarer genetically determined syndromes that have escaped clinical detection.

Advantages of the meso-Rex bypass compared with portosystemic shunts in the management of extrahepatic portal vein obstruction in children.

BACKGROUND: Consequences of extrahepatic portal vein obstruction (EHPVO) include variceal bleeding and hypersplenism due to portal hypertension, as well as metabolic abnormalities secondary to impaired portal venous circulation. The purpose of this study was to compare the effectiveness of meso-Rex bypass and portosystemic shunt (PSS) for reversing these symptoms in children with EHPVO. STUDY DESIGN: All children with idiopathic EHPVO evaluated for potential meso-Rex bypass at a single institution between 1997 and 2010 were reviewed. Portosystemic shunt was performed in patients with refractory portal hypertension when meso-Rex bypass was not technically feasible. Outcomes of meso-Rex bypass and PSS were compared, including resolution of portal hypertensive bleeding and hypersplenism, as well as changes in liver synthetic function, ammonia levels, and somatic growth. RESULTS: Sixty-five children with EHPVO underwent successful meso-Rex bypass, while 16 required PSS. Nearly all patients experienced complete relief of variceal bleeding after meso-Rex (96%) bypass and PSS (100%). The improvements in platelet count (+82.1 ± 60.0 vs +32.4 ± 56.3 thousand/µL; p=0.004), internal normalized ratio (-0.22 ± 0.27 vs 0.01 ± 0.14; p=0.022), and serum ammonia level (-26.8 ± 36.8 vs +19.4 ± 33.1 µM/L; p=0.002) were greater after meso-Rex bypass than PSS. Among patients with below average (standard deviation z-score<0) preoperative weight for age, the improvement in weight-for-age z-score was greater after meso-Rex bypass (+0.84 ± 0.98) than PSS (+0.17 ± 0.79, p=0.044). Median duration of follow-up was 4.45 years after meso-Rex bypass and 1.8 years after PSS. CONCLUSIONS: Both meso-Rex bypass and PSS effectively relieve symptoms of portal hypertensive bleeding in children with EHPVO, although the meso-Rex better relieves hypersplenism. By restoring normal portal venous circulation, the meso-Rex bypass has additional metabolic benefits.

Tethered cord release: a long-term study in 114 patients.

OBJECT: All children born with a myelomeningocele at the authors' institution undergo aggressive treatment to maintain or improve functional outcome. Consequently, when any neurological, orthopedic, and/or urological changes are noted, a search for the cause is initiated. The most common cause of decline in a child born with a myelomeningocele is shunt malfunction. The second most common cause is tethering of the distal spinal cord at the site of the original back closure. In this report, the authors review the indicators of symptomatic spinal cord tethering and discuss the surgical interventions and outcomes in the children with myelomeningocele who underwent treatment at Children's Memorial Hospital from 1975 to 2008. METHODS: Among the 502 children who underwent original closure at Children's Memorial Hospital, a symptomatic tethered spinal cord developed in 114 (23%). Eighty-one patients (71%) have undergone 1 untethering procedure, and 33 patients (29%) have undergone multiple untetherings, for a total of 163 total surgeries. The indicators of symptomatic spinal cord tethering include scoliosis, decline in lower-extremity (LE) motor strength, LE contractures, LE spasticity, gait change, urinary changes, and pain. RESULTS: Pain has shown the best response to surgical untethering, with 100% of children experiencing postoperative improvement. The results of long-term follow-up (average 12 years, range 1 month-23.3 years) in this cohort demonstrated scoliosis progression after surgical untethering in 52% of patients, with 28% requiring spinal fusion. On the 3-month postoperative manual muscle test, 70% of patients showed improved LE muscle strength compared to preoperatively. Gait was also similarly improved after untethering as evaluated by an orthopedic surgeon. Spasticity improved in two-thirds of the cohort, and as expected, LE contractures were stable (78%) postoperatively, as assessed by orthopedic and rehabilitation medicine specialists. Urologically, 64% of patients showed improvements on postoperative bladder evaluation. CONCLUSIONS: Although this is a clinical outcome study with no control group, the authors' experience has been that tethered cord release is beneficial in maintaining neurological, urological, and orthopedic functioning in children born with a myelomeningocele.