Diagnosis and stabilisation of familial chylomicronemia syndrome in two infants presenting with hypertriglyceridemia-induced acute pancreatitis.

Familial chylomicronemia syndrome (FCS) is a rare disorder of triglyceride (TG) metabolism caused by loss of function variants in one of five known canonical genes involved in chylomicron lipolysis and clearance-LPL, APOC2, APOA5, LMF1, and GPIHBP1. Pathogenic variants in LPL, which encodes the hydrolytic enzyme lipoprotein lipase, account for over 80%-90% of cases. FCS may present in infancy with hypertriglyceridemia-induced acute pancreatitis and is challenging to manage both acutely and in the long-term. Here, we report our experience managing two unrelated infants consecutively diagnosed with hypertriglyceridemia-induced acute pancreatitis caused by LPL deficiency. Both had elevated TGs at presentation (205 and 30 mmol/L, respectively) and molecular genetic testing confirmed each infant carried a different homozygous pathogenic variant in the LPL gene, specifically, c.987C>A (p.Tyr329Ter) and c.632C>A (p.Thr211Lys). The more severely affected infant had cutaneous xanthomata, lipemia retinalis and lipemic plasma at presentation, and required management in an intensive care setting. Acute stabilisation was achieved using insulin and heparin infusions together with the iterative implementation of a fat-restricted diet, low in long chain triglycerides (LCT) and supplemented with medium chain triglycerides (MCT). In both cases, provision of adequate caloric intake (~110-120 kcal/kg/day) was also found to be important for a sustained TG reduction during the acute phase of management. In summary, a high index of suspicion is required to diagnose FCS in infants with hypertriglyceridemia-induced acute pancreatitis, management of which can be challenging, highlighting the need for more evidence-based recommendations.

Congenital heart surgery outcomes in patients with positive respiratory viral swabs.

OBJECTIVE: To examine whether or not viral positive patients experienced worse outcomes and assess differences in surgical outcomes between viral-positive patients with and without viral symptoms within 30 days of surgery. METHODS: This retrospective study reviewed charts of pediatric patients who underwent congenital heart surgery and routine viral testing at a single institution over a consecutive 3-year period (2017-2019). Patients with a history of heart transplants, pacemaker changes, or implants, and mediastinal washouts were excluded from the study. Surgical outcomes were compared by viral status and viral symptoms, using the Fisher exact and Wilcoxon rank sum tests. RESULTS: Among 1041 patients, 374 patients underwent routine preoperative viral testing, with 107 patients testing positive and 267 testing negative for viral swabs before surgery. There were no significant differences observed in surgical outcomes by viral status, including no differences in mortality. Among the 107 patients with positive viral swabs before surgery, comparisons between 24 patients with viral symptoms and 83 without symptoms within 30 days of surgery detected no significant differences in mortality or complication rates. However, symptomatic versus asymptomatic patients had significantly longer postoperative stay (23.4 vs 13.4 days; P = .02) and intubation time (9.8 vs 4.9 hours; P = .004). CONCLUSIONS: Patients who test positive before congenital heart surgery and are asymptomatic beyond the incubation period may proceed to surgery with no further delay. Patients who are viral positive and symptomatic have a longer postoperative stay and intubation time. A prospective study is needed to assess the importance of routine viral testing.

Temporal Quantitative Proteomic and Phosphoproteomic Profiling of SH-SY5Y and IMR-32 Neuroblastoma Cells during All-Trans-Retinoic Acid-Induced Neuronal Differentiation.

The human neuroblastoma cell lines SH-SY5Y and IMR-32 can be differentiated into neuron-like phenotypes through treatment with all-trans-retinoic acid (ATRA). After differentiation, these cell lines are extensively utilized as in vitro models to study various aspects of neuronal cell biology. However, temporal and quantitative profiling of the proteome and phosphoproteome of SH-SY5Y and IMR-32 cells throughout ATRA-induced differentiation has been limited. Here, we performed relative quantification of the proteomes and phosphoproteomes of SH-SY5Y and IMR-32 cells at multiple time points during ATRA-induced differentiation. Relative quantification of proteins and phosphopeptides with subsequent gene ontology analysis revealed that several biological processes, including cytoskeleton organization, cell division, chaperone function and protein folding, and one-carbon metabolism, were associated with ATRA-induced differentiation in both cell lines. Furthermore, kinase-substrate enrichment analysis predicted altered activities of several kinases during differentiation. Among these, CDK5 exhibited increased activity, while CDK2 displayed reduced activity. The data presented serve as a valuable resource for investigating temporal protein and phosphoprotein abundance changes in SH-SY5Y and IMR-32 cells during ATRA-induced differentiation.

Trait profiles in difficult-to-treat asthma: Clinical impact and response to systematic assessment.

BACKGROUND: Multidisciplinary systematic assessment improves outcomes in difficult-to-treat asthma, but without clear response predictors. Using a treatable-traits framework, we stratified patients by trait profile, examining clinical impact and treatment responsiveness to systematic assessment. METHODS: We performed latent class analysis using 12 traits on difficult-to-treat asthma patients undergoing systematic assessment at our institution. We examined Asthma Control Questionnaire (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ) scores, FEV1 , exacerbation frequency, and maintenance oral corticosteroid (mOCS) dose, at baseline and following systematic assessment. RESULTS: Among 241 patients, two airway-centric profiles were characterized by early-onset with allergic rhinitis (n = 46) and adult onset with eosinophilia/chronic rhinosinusitis (n = 60), respectively, with minimal comorbid or psychosocial traits; three non-airway-centric profiles exhibited either comorbid (obesity, vocal cord dysfunction, dysfunctional breathing) dominance (n = 51), psychosocial (anxiety, depression, smoking, unemployment) dominance (n = 72), or multi-domain impairment (n = 12). Compared to airway-centric profiles, non-airway-centric profiles had worse baseline ACQ-6 (2.7 vs. 2.2, p < .001) and AQLQ (3.8 vs. 4.5, p < .001) scores. Following systematic assessment, the cohort showed overall improvements across all outcomes. However, airway-centric profiles had more FEV1 improvement (5.6% vs. 2.2% predicted, p < .05) while non-airway-centric profiles trended to greater exacerbation reduction (1.7 vs. 1.0, p = .07); mOCS dose reduction was similar (3.1 mg vs. 3.5 mg, p = .782). CONCLUSION: Distinct trait profiles in difficult-to-treat asthma are associated with different clinical outcomes and treatment responsiveness to systematic assessment. These findings yield clinical and mechanistic insights into difficult-to-treat asthma, offer a conceptual framework to address disease heterogeneity, and highlight areas responsive to targeted intervention.

Retention, Fasting Patterns, and Weight Loss With an Intermittent Fasting App: Large-Scale, 52-Week Observational Study.

BACKGROUND: Intermittent fasting (IF) is an increasingly popular approach to dietary control that focuses on the timing of eating rather than the quantity and content of caloric intake. IF practitioners typically seek to improve their weight and other health factors. Millions of practitioners have turned to purpose-built mobile apps to help them track and adhere to their fasts and monitor changes in their weight and other biometrics. OBJECTIVE: This study aimed to quantify user retention, fasting patterns, and weight loss by users of 2 IF mobile apps. We also sought to describe and model starting BMI, amount of fasting, frequency of weight tracking, and other demographics as correlates of retention and weight change. METHODS: We assembled height, weight, fasting, and demographic data of adult users (ages 18-100 years) of the LIFE Fasting Tracker and LIFE Extend apps from 2018 to 2020. Retention for up to 52 weeks was quantified based on recorded fasts and correlated with user demographics. Users who provided height and at least 2 readings of weight and whose first fast and weight records were contemporaneous were included in the weight loss analysis. Fasting was quantified as extended fasting hours (EFH; hours beyond 12 in a fast) averaged per day (EFH per day). Retention was modeled using a Cox proportional hazards regression. Weight loss was analyzed using linear regression. RESULTS: A total of 792,692 users were followed for retention based on 26 million recorded fasts. Of these, 132,775 (16.7%) users were retained at 13 weeks, 54,881 (6.9%) at 26 weeks, and 16,478 (2.1%) at 52 weeks, allowing 4 consecutive weeks of inactivity. The survival analysis using Cox regression indicated that retention was positively associated with age and exercise and negatively associated with stress and smoking. Weight loss in the qualifying cohort (n=161,346) was strongly correlated with starting BMI and EFH per day, which displayed a positive interaction. Users with a BMI ≥40 kg/m2 lost 13.9% of their starting weight by 52 weeks versus a slight weight gain on average for users with starting BMI <23 kg/m2. EFH per day was an approximately linear predictor of weight loss. By week 26, users lost over 1% of their starting weight per EFH per day on average. The regression analysis using all variables was highly predictive of weight change at 26 weeks (R2=0.334) with starting BMI and EFH per day as the most significant predictors. CONCLUSIONS: IF with LIFE mobile apps appears to be a sustainable approach to weight reduction in the overweight and obese population. Healthy weight and underweight individuals do not lose much weight on average, even with extensive fasting. Users who are obese lose substantial weight over time, with more weight loss in those who fast more.

Longitudinal Natural History of Pediatric Subjects Affected with Mucopolysaccharidosis IIIB.

OBJECTIVE: To characterize the longitudinal natural history of disease progression in pediatric subjects affected with mucopolysaccharidosis (MPS) IIIB. STUDY DESIGN: Sixty-five children with a confirmed diagnosis of MPS IIIB were enrolled into 1 of 2 natural history studies and followed for up to 4 years. Cognitive and adaptive behavior functions were analyzed in all subjects, and volumetric magnetic resonance imaging analysis of liver, spleen, and brain, as well as levels of heparan sulfate (HS) and heparan sulfate nonreducing ends (HS-NRE), were measured in a subset of subjects. RESULTS: The majority of subjects with MPS IIIB achieved an apex on both cognition and adaptive behavior age equivalent scales between age 3 and 6 years. Development quotients for both cognition and adaptive behavior follow a linear trajectory by which subjects reach a nadir with a score <25 for an age equivalent of 24 months by age 8 years on average and by 13.5 years at the latest. All tested subjects (n = 22) had HS and HS-NRE levels above the normal range in cerebrospinal fluid and plasma, along with signs of hepatomegaly. Subjects lost an average of 26 mL of brain volume (-2.7%) over 48 weeks, owing entirely to a loss of cortical gray matter (32 mL; -6.5%). CONCLUSIONS: MPS IIIB exists along a continuum based on cognitive decline and cortical gray matter atrophy. Although a few individuals with MPS IIIB have an attenuated phenotype, the majority follow predicted trajectories for both cognition and adaptive behavior. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT02493998, NCT03227042, and NCT02754076.

Biallelic Variants in PYROXD2 Cause a Severe Infantile Metabolic Disorder Affecting Mitochondrial Function.

Pyridine Nucleotide-Disulfide Oxidoreductase Domain 2 (PYROXD2; previously called YueF) is a mitochondrial inner membrane/matrix-residing protein and is reported to regulate mitochondrial function. The clinical importance of PYROXD2 has been unclear, and little is known of the protein's precise biological function. In the present paper, we report biallelic variants in PYROXD2 identified by genome sequencing in a patient with suspected mitochondrial disease. The child presented with acute neurological deterioration, unresponsive episodes, and extreme metabolic acidosis, and received rapid genomic testing. He died shortly after. Magnetic resonance imaging (MRI) brain imaging showed changes resembling Leigh syndrome, one of the more common childhood mitochondrial neurological diseases. Functional studies in patient fibroblasts showed a heightened sensitivity to mitochondrial metabolic stress and increased mitochondrial superoxide levels. Quantitative proteomic analysis demonstrated decreased levels of subunits of the mitochondrial respiratory chain complex I, and both the small and large subunits of the mitochondrial ribosome, suggesting a mitoribosomal defect. Our findings support the critical role of PYROXD2 in human cells, and suggest that the biallelic PYROXD2 variants are associated with mitochondrial dysfunction, and can plausibly explain the child's clinical presentation.

Diagnostic and Therapeutic Outcomes Following Systematic Assessment of Patients with Concurrent Suspected Vocal Cord Dysfunction and Asthma.

BACKGROUND: Vocal cord dysfunction (VCD) is present in 25% to 50% of patients with asthma. When both diagnoses are suspected, accurate diagnosis and targeted management represent a clinical challenge. OBJECTIVE: To evaluate diagnostic and therapeutic outcomes following systematic assessment for patients with concurrent suspected VCD and asthma. METHODS: Patients underwent systematic evaluation by clinical assessment and validated questionnaires, followed by multidisciplinary management. VCD was confirmed by visualization of paradoxical vocal fold motion at baseline or following provocation. Asthma was confirmed by demonstrating variable airflow obstruction. Asthma medications were deescalated in those with low clinical probability of asthma and no variable airflow obstruction. Response to 2 or more sessions of speech pathology was assessed by subjective report and standardized questionnaires. RESULTS: Among 212 consecutive patients, 62 (29%) patients had both VCD and asthma, 54 (26%) had VCD alone, 51 (24%) had asthma alone, and 45 (21%) had neither. Clinician assessment and the Laryngeal Hypersensitivity Questionnaire both predicted laryngoscopy-confirmed VCD. Deescalation or discontinuation of asthma therapy was possible in 37 of 59 (63%) patients without variable airflow obstruction, and was most successful (odds ratio, 5.5) in the presence of laryngoscopy-confirmed VCD (25 of 31, or 81%) Patients with VCD responded subjectively to 2 or more sessions of speech pathology, but laryngeal questionnaire scores did not improve. CONCLUSIONS: Expert clinician assessment and the Laryngeal Hypersensitivity Questionnaire predict the presence of laryngoscopy-confirmed VCD. Systematic assessment for both VCD and asthma facilitates deescalation or discontinuation of unnecessary asthma medications. Subjective symptom improvement following speech pathology was not paralleled by laryngeal questionnaire scores in this cohort.

Financial hardship is associated with lower uptake of colorectal, breast, and cervical cancer screenings.

PURPOSE: Cancer screening uptake differs between groups in ways that cannot be explained by socioeconomic status alone. This study examined associations between material, psychosocial, and behavioral aspects of financial hardship and cancer screening behaviors. METHODS: Surveys were mailed to 7,979 people ages 18-75 who were seen in the statewide health system in Indiana. Participants reported SES, feelings about finances, and whether they had to forgo medical care due to cost. This was compared to uptake of mammogram, colonoscopy/sigmoidoscopy, and Pap testing in best-fit multivariable logistic regression analyses controlling for demographic and healthcare characteristics. RESULTS: A total of 970 surveys were returned; the majority of respondents were female (54%), non-Hispanic White (75%), and over 50 years old (76%). 15% reported forgoing medical care due to cost; this barrier was higher among Black than White participants (24% vs. 13%; p = 0.001). In a best fit regression model for colonoscopy/sigmoidoscopy, those who reported they had to forgo medical care due to cost had lower odds of screening (aOR 0.41; 95% CI 0.22-0.74). Forgoing medical care due to cost was not significantly associated with Pap testing in bivariate analyses. For mammogram, forgoing medical care due to cost was significant in bivariate analyses (OR 0.44; 95% CI 0.22-0.88), but was not significant in the multivariable model. CONCLUSION: Associations between financial hardship and cancer screening suggest the need to reduce barriers to cancer screening even among patients who have access to healthcare. Future research should explore barriers related to both healthcare and personal costs.

The role of preoperative anemia in patients undergoing colectomy for diverticular disease: does surgical urgency matter?

PURPOSE: Surgery especially in the emergent setting carries higher rates of morbidity and mortality. The aim of our study was to evaluate the impact of preoperative anemia on outcomes for patients undergoing colectomy for acute diverticulitis in both elective and emergent settings. METHODS: We performed a 4-year analysis of the ACS-NSQIP and included adult patients with acute diverticulitis who underwent colectomy. Patients were stratified into two groups based on preoperative hemoglobin levels, preop anemia and no-preop Anemia. Outcome measures were 30-day complications, anastomotic leaks, readmissions, mortality, and intra-/postoperative blood transfusion. We also performed a sub-analysis for patients who underwent emergent colectomy. RESULTS: Six thousand nine hundred sixty-three patients were included in the analysis, of which 37% (n = 2571) had preoperative anemia. Patients in the anemia group were more likely to have higher ASA class and receive blood 72-h preoperatively (5.4% vs. 0.2%, p < 0.01). Patients in the anemia group had higher rates of complications (35.4% vs. 24.7%, p < 0.01), unplanned readmission (9.2% vs 7.2%, p < 0.01), mortality (4.5% vs. 1.8%, p < 0.01), and intra/postoperative transfusion requirement (21% vs. 3.8%, p < 0.01) with no difference in rate of anastomotic leaks. On sub-analysis, 39% of the cases were completed in an emergent setting, 85% of which were due to perforation. Patients with preoperative anemia that underwent colectomy in an emergent setting had higher odds of intra/postoperative blood transfusion (OR 51.6, CI 3.87-6.87, p < 0.01) with no statistical significance in 30-day complications (p = 0.51). CONCLUSION: Preoperative anemia in patients undergoing colectomy for acute diverticular disease is associated with higher odds complications, readmissions, and intra/postoperative blood transfusions.

Dig deeper when it does not make sense: Juvenile xanthomas due to sitosterolemia.

Sitosterolemia is an extremely rare autosomal recessive disease caused by mutations in either ABCG5 or ABCG8, which encode for a sterol efflux transporter (sterolin) that pumps sterols out into the intestinal lumen or into bile. This leads to progressive accumulation of plant sterols in blood and tissues. Clinical presentation is variable and may include xanthoma, arthritis, thyroid dysfunction, premature atherosclerotic disease, splenomegaly, and hematologic manifestations. We report a child presented with multiple xanthomas at age 5.5 years, located on the elbow, knee, and toe. Juvenile xanthogranuloma was considered based on histopathologic findings. At 8 years of age, a lipid profile showed markedly elevated total cholesterol (9.4 mmol/L) and low-density lipoprotein cholesterol (LDL-C, 7.4 mmol/L). Simvastatin therapy was initiated, however, the lipid profile was persistently abnormal. At age 8.5 years, genetic testing identified two novel variants: (NM_022437.3[ABCG8]:c.1444del;p.Leu482Trpfs*40) and (NM_022437.3[ABCG8]:c.1640T>C;p.Leu547Pro) in the ABCG8 gene. Plasma sitosterol was subsequently found to be very high, confirming the diagnosis. She was started on a low plant sterol and cholesterol diet for 6 weeks with insignificant response and therefore ezetimibe (10 mg daily) was added. This resulted in significant reduction of cholesterol, LDL, sitosterol levels, and no further increase in the size of the xanthomas. This case emphasizes the diagnostic odyssey, the benefits of genomic testing and importance of a correct diagnosis in order to initiate appropriate therapy. It also illustrates the importance of considering rare conditions, such as sitosterolemia, as a differential diagnosis in patients with hypercholesterolemia and increased LDL-C.

Paradoxical Vocal Fold Motion in Difficult Asthma Is Associated with Dysfunctional Breathing and Preserved Lung Function.

BACKGROUND: Many patients with difficult asthma also have coexisting vocal cord dysfunction (VCD), evident by paradoxical vocal fold motion (PVFM) on laryngoscopy. OBJECTIVE: Among patients with difficult asthma, we sought to identify clinical features associated with laryngoscopy-diagnosed PVFM. METHODS: Consecutive patients with "difficult asthma" referred by respiratory specialists underwent systematic assessment in this observational study. Those with a high clinical suspicion for VCD were referred for laryngoscopy, either at rest or after mannitol provocation. Statistical analyses were performed to identify clinical factors associated with PVFM, and a multivariate logistic regression model was fitted to control for confounders. RESULTS: Of 169 patients with difficult asthma, 63 (37.3%) had a high clinical probability of VCD. Of 42 who underwent laryngoscopy, 32 had PVFM confirmed. Patients with PVFM more likely had preserved lung function (prebronchodilator forced expiratory ratio 74% ± 11 vs 62% ± 16, P < .001); physiotherapist-confirmed dysfunctional breathing (odds ratio [OR] = 5.52, 95% confidence interval [CI]: 2.4-12.7, P < .001), gastro-oesophageal reflux (OR = 2.6, 95% CI: 1.16-5.8, P = .02), and a lower peripheral eosinophil count (0.09 vs 0.23, P = .004). On multivariate logistic regression, independent predictors for PVFM were dysfunctional breathing (OR = 4.93, 95% CI: 2-12, P < .001) and preserved lung function (OR = 1.07, 95% CI: 1.028-1.106, P < .001). CONCLUSION: Among specialist-referred patients with difficult asthma, VCD pathogenesis may overlap with dysfunctional breathing but is not associated with severe airflow obstruction. Dysfunctional breathing and preserved lung function may serve as clinical clues for the presence of VCD.

Mepolizumab effectiveness and identification of super-responders in severe asthma.

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL-1 Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29-0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33-0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.

Safety and Efficacy of Elosulfase Alfa in Australian Patients with Morquio a Syndrome: A Phase 3b Study

Abstract The safety and efficacy of elosulfase alfa were evaluated in a multicenter, open-label, phase 3b study in Australian Morquio A patients, consisting of a 49-week initial phase and an extension phase until elosulfase alfa was government funded. Thirteen patients (1-27 years) were enrolled. No new safety concerns were identified over 138 weeks. Most drug-related adverse events were mild or moderate in severity; none led to study discontinuation. After 49 weeks of treatment, median improvements from baseline were seen in the 6-minute walk test (+41.0 m), 3-minute stair climb test (+14.0 stairs/min), forced vital capacity (+16.4%), forced expiratory volume in 1 second (+14.1%), urine keratan sulfate (-7.1 µg/mg creatinine), and pain intensity. Growth, cardiac function, sleep, and quality of life results were mixed or stable. These results provide further evidence of the acceptable safety/tolerability profile of elosulfase alfa. The improvements in endurance, pulmonary function, and pain support findings from previous studies.

Barriers to access in pediatric living-donor liver transplantation.

Children receiving a LDLT have superior post-transplant outcomes, but this procedure is only used for 10% of transplant recipients. Better understanding about barriers toward LDLT and the sociodemographic characteristics that influence these underlying mechanisms would help to inform strategies to increase its use. We conducted an online, anonymous survey of parents/caregivers for children awaiting, or have received, a liver transplant regarding their knowledge and attitudes about LDLT. The survey was completed by 217 respondents. While 97% of respondents understood an individual could donate a portion of their liver, only 72% knew the steps in evaluation, and 69% understood the donor surgery was covered by the recipient's insurance. Individuals with public insurance were less likely than those with private insurance to know the steps for LDLT evaluation (44% vs 82%; P < 0.001). Respondents with public insurance were less likely to know someone that had been a living donor (44% vs 56%; P = 0.005) as were individuals without a college degree (64% vs 85%; P = 0.007). Nearly all respondents generally trusted their healthcare team. Among respondents, 82% believed they were well-informed about LDLT but individuals with public insurance were significantly less likely to feel well-informed (67% vs 87%; P = 0.03) and to understand how donor surgery might impact donor work/time off (44% vs 81%; P = 0.001). Substantial gaps exist in parental understanding about LDLT, including its evaluation, potential benefits, and complications. Greater emphasis on addressing these barriers, especially to individuals with fewer resources, will be helpful to expand the use of LDLT.

SLC35A2-CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals.

Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-congenital disorders of glycosylation (CDG; formerly CDG-IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N-glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2-CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild-type to mutant alleles in fibroblasts from affected individuals.

Rural and Urban Differences in the Adoption of New Health Information and Medical Technologies.

BACKGROUND: This statewide survey sought to understand the adoption level of new health information and medical technologies, and whether these patterns differed between urban and rural populations. METHODS: A random sample of 7,979 people aged 18-75 years, stratified by rural status and race, who lived in 1 of 34 Indiana counties with high cancer mortality rates and were seen at least once in the past year in a statewide health system were surveyed. RESULTS: Completed surveys were returned by 970 participants. Rural patients were less likely than urban to use electronic health record messaging systems (28.3% vs 34.5%, P = .045) or any communication technology (43.0% vs 50.8%, P = .017). Rural patients were less likely to look for personal health information for someone else's medical record (11.0% vs 16.3%, P = .022), look-up test results (29.5% vs 38.3%, P = .005), or use any form of electronic medical record (EMR) access (57.5% vs 67.1%, P = .003). Rural differences in any use of communication technology or EMRs were no longer significant in adjusted models, while education and income were significantly associated. There was a trend in the higher use of low-dose computed tomography (CT) scan among rural patients (19.1% vs 14.4%, P = .057). No significant difference was present between rural and urban patients in the use of the human papilloma virus test (27.1% vs 26.6%, P = .880). CONCLUSIONS: Differences in health information technology use between rural and urban populations may be moderated by social determinants. Lower adoption of new health information technologies (HITs) than medical technologies among rural, compared to urban, individuals may be due to lower levels of evidence supporting HITs.