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Medicine Dec 2022Severe insulin receptor gene (INSR)-related insulin resistance syndromes (SIR) include Donohue syndrome (DS), Rabson-Mendenhall syndrome (RMS), and type A insulin...
RATIONALE
Severe insulin receptor gene (INSR)-related insulin resistance syndromes (SIR) include Donohue syndrome (DS), Rabson-Mendenhall syndrome (RMS), and type A insulin resistance. The incidence of DS is about 1 in 4 million births. We identified novel INSR mutations (c.2246delG and c.2646 + 5G > A) in a patient with SIR, which expanded the variant spectrum and helped to improve the understanding of the diagnosis and treatment of this condition.
PATIENT CONCERNS
A 10-year-old Chinese boy was admitted to the hospital for deepening skin color. He presented with growth retardation, peculiar facial features, acanthosis nigricans, hypertrichosis, extremely high insulin levels, fasting hypoglycemia, and postprandial hyperglycemia, Whole-exome gene testing suggested compound heterozygous mutations in INSR (c.2246delG and c.2646 + 5G > A).
DIAGNOSIS
The diagnosis was SIR. What's more, based on the phenotypic and biographical results, this child did not present typical RMS and DS but rather an intermediate phenotype between the 2 conditions.
INTERVENTIONS
On the basis of a sensible diet and exercise, the patient was prescribed metformin (250 mg) at breakfast and lunch, which was increased to 500 mg after 1 month.
OUTCOMES
After 2 months of treatment, the patient's glycated hemoglobin (HbA1c) levels decreased to 6% but his insulin resistance did not improve significantly.
LESSONS
In children who are not obese but with severe insulin resistance, growth retardation, hirsutism, and hyperglycemia, genetic testing should be performed for early diagnosis, active treatment, and follow-up.
Topics: Humans; Male; Antigens, CD; Donohue Syndrome; East Asian People; Growth Disorders; Insulin Resistance; Metabolic Syndrome; Mutation; Receptor, Insulin; Child
PubMed: 36626508
DOI: 10.1097/MD.0000000000032266 -
Pediatric Critical Care Medicine : a... Feb 2019To develop a postoperative mortality case-mix adjustment model to facilitate assessment of cardiac ICU quality of care, and to describe variation in adjusted cardiac ICU... (Observational Study)
Observational Study
OBJECTIVE
To develop a postoperative mortality case-mix adjustment model to facilitate assessment of cardiac ICU quality of care, and to describe variation in adjusted cardiac ICU mortality across hospitals within the Pediatric Cardiac Critical Care Consortium.
DESIGN
Observational analysis.
SETTING
Multicenter Pediatric Cardiac Critical Care Consortium clinical registry.
PARTICIPANTS
All surgical cardiac ICU admissions between August 2014 and May 2016. The analysis included 8,543 admissions from 23 dedicated cardiac ICUs.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
We developed a novel case-mix adjustment model to measure postoperative cardiac ICU mortality after congenital heart surgery. Multivariable logistic regression was performed to assess preoperative, intraoperative, and immediate postoperative severity of illness variables as candidate predictors. We used generalized estimating equations to account for clustering of patients within hospital and obtain robust SEs. Bootstrap resampling (1,000 samples) was used to derive bias-corrected 95% CIs around each predictor and validate the model. The final model was used to calculate expected mortality at each hospital. We calculated a standardized mortality ratio (observed-to-expected mortality) for each hospital and derived 95% CIs around the standardized mortality ratio estimate. Hospital standardized mortality ratio was considered a statistically significant outlier if the 95% CI did not include 1. Significant preoperative predictors of mortality in the final model included age, chromosomal abnormality/syndrome, previous cardiac surgeries, preoperative mechanical ventilation, and surgical complexity. Significant early postoperative risk factors included open sternum, mechanical ventilation, maximum vasoactive inotropic score, and extracorporeal membrane oxygenation. The model demonstrated excellent discrimination (C statistic, 0.92) and adequate calibration. Comparison across Pediatric Cardiac Critical Care Consortium hospitals revealed five-fold difference in standardized mortality ratio (0.4-1.9). Two hospitals had significantly better-than-expected and two had significantly worse-than-expected mortality.
CONCLUSIONS
For the first time, we have demonstrated that variation in mortality as a quality metric exists across dedicated cardiac ICUs. These findings can guide efforts to reduce mortality after cardiac surgery.
Topics: Age Factors; Cardiac Surgical Procedures; Child, Preschool; Critical Care; Extracorporeal Membrane Oxygenation; Female; Heart Defects, Congenital; Hospital Mortality; Humans; Infant; Infant, Newborn; Intensive Care Units, Pediatric; Logistic Models; Male; Respiration, Artificial; Retrospective Studies; Risk Adjustment; Risk Factors; Severity of Illness Index
PubMed: 30489488
DOI: 10.1097/PCC.0000000000001776 -
Journal of Alzheimer's Disease : JAD 2019Adults with Down syndrome (DS) are at very high risk for Alzheimer's disease (AD). Neurofilament light (NF-L) has emerged as a potential blood-based biomarker of...
BACKGROUND
Adults with Down syndrome (DS) are at very high risk for Alzheimer's disease (AD). Neurofilament light (NF-L) has emerged as a potential blood-based biomarker of neurodegeneration due to AD.
OBJECTIVE
To understand the relationship between plasma NF-L with age, brain amyloid, and tau pathology, neurodegeneration as well as cognitive and functional performance.
METHODS
We analyzed imaging data as well as cognitive measures in relation to plasma NF-L in adults with DS, ages 30 to 60 who were enrolled in the Down Syndrome Biomarker Initiative.
RESULTS
We found significant correlations between NF-L plasma concentrations and amyloid pathology (r = 0.73, p = 0.007, pa = 0.041) and significant inverse correlations with regional glucose metabolism in 5 of 6 regions examined, which were Anterior cingulate (r = -0.55, p = 0.067, pa = 0.067), Posterior cingulate r = -0.90, p < 0.001, pa < 0.001), Lateral Temporal (r = -0.78, p = 0.004, pa = 0.012), Frontal cortex (r = -0.90, p < 0.001, p pa < 0.001), Parietal cortex (r = -0.82, p = 0.002, pa = 0.008), Precuneus (r = -0.73, pa = 0.010, pa = 0.020), and with hippocampal volume (r = -0.52, p = 0.084, pa = 0.084); and an inverse correlation with direct measures of cognition: CAMCOG (r = -0.66 p = 0.022, pa = 0.066) and positive correlation with CANTAB Paired Associates Learning (PAL) error rate (r = 0.68, p = 0.015, pa = 0.060). Finally, we found inverse relationships with informant-based functional measures (r = -0.57, p = 0.059, pa = 0.084) and OMQ-PF (r = -0.74, p = 0.008, pa = 0.041).
CONCLUSION
Plasma NF-L is associated with progressive neurodegeneration as well as with declines in cognitive and functional measures in adults with DS.
Topics: Adult; Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Brain; Cognition; Down Syndrome; Female; Humans; Male; Middle Aged; Neurofilament Proteins; Neuropsychological Tests; Positron-Emission Tomography; tau Proteins
PubMed: 31156181
DOI: 10.3233/JAD-190322 -
Connecticut Medicine May 2015Since the introduction of combination antiretroviral therapy (cART) as the standard of care for HIV disease, there has been a precipitous decline in the death rate due... (Observational Study)
Observational Study
OBJECTIVES
Since the introduction of combination antiretroviral therapy (cART) as the standard of care for HIV disease, there has been a precipitous decline in the death rate due to HIV/ AIDS. The purpose of this study was to report the prevalence of metabolic syndrome in HIV infected patients.
METHODS
Retrospective, cross-sectional, observational study of 259 patients with HIV infection treated with cART from an urban community hospital. Metabolic syndrome prevalence was defined using the International Diabetes Federation (IDF) and the U.S. National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. Study patients were included regardless of the duration of cART.
RESULTS
The prevalence of metabolic syndrome was 27% using IDF criteria and 26% using ATP III criteria. Logistic regression analysis found an association between treatment with the protease inhibitor darunavir and metabolic syndrome. (OR 3.32 with 95% confidence interval between 1.54 and 7.15).
CONCLUSION
There is a high prevalence of metabolic syndrome and obesity in HIV patients treated with cART, especially those taking the protease inhibitor darunavir.
Topics: Adult; Antiretroviral Therapy, Highly Active; Comorbidity; Cross-Sectional Studies; Female; HIV Infections; Humans; Male; Metabolic Syndrome; Middle Aged; Obesity; Prevalence; Retrospective Studies; Risk Factors
PubMed: 26245015
DOI: No ID Found -
Cardiology in the Young Apr 2018Children with single-ventricle disease experience high mortality and complex care. In other life-limiting childhood illnesses, paediatric palliative care may mitigate... (Randomized Controlled Trial)
Randomized Controlled Trial
Children with single-ventricle disease experience high mortality and complex care. In other life-limiting childhood illnesses, paediatric palliative care may mitigate maternal stress. We hypothesised that early palliative care in the single-ventricle population may have the same benefit for mothers. In this pilot randomised trial of early palliative care, mothers of infants with prenatal single-ventricle diagnoses completed surveys measuring depression, anxiety, coping, and quality of life at a prenatal visit and neonatal discharge. Infants were randomised to receive early palliative care - structured evaluation, psychosocial/spiritual, and communication support before surgery - or standard care. Among 56 eligible mothers, 40 enrolled and completed baseline surveys; 38 neonates were randomised, 18 early palliative care and 20 standard care; and 34 postnatal surveys were completed. Baseline Beck Depression Inventory-II and State-Trait Anxiety Index scores exceeded normal pregnant sample scores (mean 13.76±8.46 versus 7.0±5.0 and 46.34±12.59 versus 29.8±6.35, respectively; p=0.0001); there were no significant differences between study groups. The early palliative care group had a decrease in prenatal to postnatal State-Trait Anxiety Index scores (-7.6 versus 0.3 in standard care, p=0.02), higher postnatal Brief Cope Inventory positive reframing scores (p=0.03), and a positive change in PedsQL Family Impact Module communication and family relationships scores (effect size 0.46 and 0.41, respectively). In conclusion, these data show that mothers of infants with single-ventricle disease experience significant depression and anxiety prenatally. Early palliative care resulted in decreased maternal anxiety, improved maternal positive reframing, and improved communication and family relationships.
Topics: Adaptation, Psychological; Adult; Female; Follow-Up Studies; Heart Defects, Congenital; Heart Ventricles; Humans; Infant, Newborn; Mother-Child Relations; Mothers; Palliative Care; Pregnancy; Psychiatric Status Rating Scales; Stress, Psychological; Time Factors
PubMed: 29316996
DOI: 10.1017/S1047951117002761 -
BMC Pediatrics May 2024Donohue syndrome (DS), also referred to as leprechaunism, is a remarkably uncommon autosomal recessive disorder that primarily affects the endocrine system. Its...
INTRODUCTION
Donohue syndrome (DS), also referred to as leprechaunism, is a remarkably uncommon autosomal recessive disorder that primarily affects the endocrine system. Its incidence rate is exceedingly low, with only 1 case reported per 4 million live births. The syndrome is distinguished by a series of characteristic clinical features.
CASE PRESENTATION
We present a case of a twenty-month-old male with DS who experienced a range of dysmorphic and clinical features with the involvement of multiple systems. These features include skin hyperpigmentation, hypertrichosis, distinct facial features, abdominal distension, and microcephaly, with the involvement of the endocrine, renal, respiratory, and cardiac systems.
CONCLUSION
The primary features of DS involve severe insulin resistance and growth abnormalities, the association with pulmonary hypertension (PHTN) has not been reported before. This finding adds more complexity to the condition. To the best of the author's knowledge, this is the first report for a patient with DS who has PHTN. Further investigation is required since the mechanisms behind the development of PHTN in DS are not entirely understood. Shedding light on this association will contribute to better management strategies and outcomes for affected patients.
Topics: Humans; Male; Hypertension, Pulmonary; Infant; Donohue Syndrome
PubMed: 38773407
DOI: 10.1186/s12887-024-04714-1 -
Frontiers in Neuroscience 2022Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) artificially oxygenates and circulates blood retrograde from the femoral artery, potentially exposing...
Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) artificially oxygenates and circulates blood retrograde from the femoral artery, potentially exposing the brain to asymmetric perfusion. Though ECMO patients frequently experience brain injury, neurologic exams and imaging are difficult to obtain. Diffuse correlation spectroscopy (DCS) non-invasively measures relative cerebral blood flow (rBF) at the bedside using an optical probe on each side of the forehead. In this study we observed interhemispheric rBF differences in response to mean arterial pressure (MAP) changes in adult ECMO recipients. We recruited 13 subjects aged 21-78 years (7 with cardiac arrest, 4 with acute heart failure, and 2 with acute respiratory distress syndrome). They were dichotomized Glasgow Coma Scale Motor score (GCS-M) into comatose (GCS-M ≤ 4; = 4) and non-comatose (GCS-M > 4; = 9) groups. Comatose patients had greater interhemispheric rBF asymmetry (ASYM) vs. non-comatose patients over a range of MAP values (29 vs. 11%, = 0.009). ASYM in comatose patients resolved near a MAP range of 70-80 mmHg, while rBF remained symmetric through a wider MAP range in non-comatose patients. Correlations between post-oxygenator pCO or pH vs. ASYM were significantly different between comatose and non-comatose groups. Our findings indicate that comatose patients are more likely to have asymmetric cerebral perfusion.
PubMed: 35478849
DOI: 10.3389/fnins.2022.858404 -
Endocrinologia Y Nutricion : Organo de... Jan 2016
Topics: Donohue Syndrome; Humans; Infant; Infant, Newborn; Insulin Resistance; Male; Receptor, Insulin
PubMed: 26619761
DOI: 10.1016/j.endonu.2015.10.002 -
Open Forum Infectious Diseases Aug 2023The influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA level and presence of infectious virus on symptom occurrence is poorly understood,...
BACKGROUND
The influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA level and presence of infectious virus on symptom occurrence is poorly understood, particularly among nonhospitalized individuals.
METHODS
The study included 85 nonhospitalized, symptomatic adults, who were enrolled from September 2020 to November 2021. Data from a longitudinal cohort studied over 28 days was used to analyze the association of individual symptoms with SARS-CoV-2 viral RNA load, or the presence or level of infectious (culturable) virus. Presence of infectious virus and viral RNA load were assessed daily, depending on specimen availability, and amount of infectious virus was assessed on the day of maximum RNA load. Participants were surveyed for the start and end dates of 31 symptoms at enrollment and at days 9, 14, 21, and 28; daily symptom presence was determined analytically. We describe symptoms and investigate their possible association with viral determinants through a series of single or pooled (multiple days across acute period) cross-sectional analyses.
RESULTS
There was an association between viral RNA load and the same-day presence of many individual symptoms. Additionally, individuals with infectious virus were more than three times as likely to have a concurrent fever than individuals without infectious virus, and more than two times as likely to have concurrent myalgia, chills, headache, or sore throat.
CONCLUSIONS
We found evidence to support the association of viral RNA load and infectious virus on some, but not all symptoms. Fever was most strongly associated with the presence of infectious virus; this may support the potential for symptom-based isolation guidance for COVID-19.
PubMed: 37636517
DOI: 10.1093/ofid/ofad396 -
The American Journal of Tropical... Aug 2021Evaluating cases of reinfection may offer some insight into areas for further investigation regarding durability of immune response to severe acute respiratory syndrome...
Evaluating cases of reinfection may offer some insight into areas for further investigation regarding durability of immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sixty cases of reinfection with viral sequencing were identified in PubMed, Embase, Web of Science, and medRxiv before May 1, 2021.Episodes of infection were separated by a median of 116 days. Severity of illness was greater among individuals reinfected within 90 days of initial infection, no asymptomatic initial cases developed severe reinfection, nearly half of cases had suspected escape variants, and nearly all individuals tested following reinfection were found to have detectable levels of anti-SARS-CoV-2 antibodies. This analysis is limited by the heterogeneous methods used among reports. Reinfection continues to be relatively rare. As the case rate presumably increases over time, this review will inform measurements to determine the natural history and causal determinants of reinfection in more rigorous observational cohort studies and other standardized surveillance approaches.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Viral; COVID-19; COVID-19 Nucleic Acid Testing; Female; Humans; Male; Middle Aged; Reinfection; SARS-CoV-2; Sequence Analysis
PubMed: 34370705
DOI: 10.4269/ajtmh.21-0365