-
Endocrine Journal Feb 2022This report of a working group established by the Japan Diabetes Society proposes a new classification and diagnostic criteria for insulin resistance syndrome. Insulin...
This report of a working group established by the Japan Diabetes Society proposes a new classification and diagnostic criteria for insulin resistance syndrome. Insulin resistance syndrome is defined as a condition characterized by severe attenuation of insulin action due to functional impairment of the insulin receptor or its downstream signaling molecules. This syndrome is classified into two types: genetic insulin resistance syndrome, caused by gene abnormalities, and type B insulin resistance syndrome, caused by autoantibodies to the insulin receptor. Genetic insulin resistance syndrome includes type A insulin resistance as well as Donohue and Rabson-Mendenhall syndromes, all of which are caused by abnormalities of the insulin receptor gene; conditions such as SHORT syndrome caused by abnormalities of PIK3R1, which encodes a regulatory subunit of phosphatidylinositol 3-kinase; conditions caused by abnormalities of AKT2, TBC1D4, or PRKCE; and conditions in which a causative gene has not yet been identified. Type B insulin resistance syndrome is characterized by severe impairment of insulin action due to the presence of insulin receptor autoantibodies. Cases in which hypoglycemia alone is induced by autoantibodies that stimulate insulin receptor were not included in Type B insulin resistance syndrome.
Topics: Diabetes Mellitus; Donohue Syndrome; Humans; Hypoglycemia; Insulin Resistance; Metabolic Syndrome; Receptor, Insulin
PubMed: 35110500
DOI: 10.1507/endocrj.EJ21-0725 -
JAMA Jun 2023SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of...
IMPORTANCE
SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.
OBJECTIVE
To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.
DESIGN, SETTING, AND PARTICIPANTS
Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.
EXPOSURE
SARS-CoV-2 infection.
MAIN OUTCOMES AND MEASURES
PASC and 44 participant-reported symptoms (with severity thresholds).
RESULTS
A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.
CONCLUSIONS AND RELEVANCE
A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.
Topics: Female; Adult; Humans; Middle Aged; Male; SARS-CoV-2; COVID-19; Prospective Studies; Post-Acute COVID-19 Syndrome; Cohort Studies; Disease Progression; Fatigue
PubMed: 37278994
DOI: 10.1001/jama.2023.8823 -
The Pan African Medical Journal 2021
Topics: Abnormalities, Multiple; Donohue Syndrome; Growth Disorders; Humans
PubMed: 35178143
DOI: 10.11604/pamj.2021.40.232.31738 -
Paediatric Anaesthesia Jan 2018Donohue syndrome is a rare autosomal recessive disorder of insulin resistance, causing a functional defect in insulin receptor function, and affecting the ability of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Donohue syndrome is a rare autosomal recessive disorder of insulin resistance, causing a functional defect in insulin receptor function, and affecting the ability of the insulin to bind the receptor. Features include severe hyperinsulinism and fasting hypoglycemia, along with severe failure to thrive despite feeding. An accelerated fasting state results in muscle wasting, decreased subcutaneous fat, and an excess of thick skin. A reduced thoracic diameter is accentuated by increased abdominal distension, which impacts on respiratory reserve. Cardiac disease develops early in life, with progressive hypertrophic cardiomyopathy as a result of hyperinsulinism. Prognosis is poor with the majority of patients dying in infancy of sepsis. The aim of this review is to report our experience of providing anesthesia for patients with Donohue syndrome, and inform guidance for safe management of these children, based on a comprehensive literature review.
METHODS
A literature search was carried out using PubMed, Medline, and the Cochrane Library, and using the MESH search terms detailed below. Patients were identified by formal request to the department of pediatric endocrinology at Great Ormond Street Hospital. Each patient's notes were searched manually and electronically for both clinical presentation and outcome, and anesthesia records.
DISCUSSION
There is currently no published literature relating to anesthetic management of Donohue syndrome. We report a case series of 5 patients with Donohue syndrome who have presented to our institution. This small series of children with this complex disorder demonstrates a clearly increased risk of general anesthesia. Many of the risks relate to restrictive lung disease and abdominal distension which worsens with bag valve mask ventilation and limited respiratory reserve which leads to precipitous desaturation. During induction, a spontaneously breathing technique is recommended. If required, bag valve mask ventilation should be accompanied by constant gastric aspiration. Intubation is challenging, and a difficult airway plan, including a second experienced anesthetist and ENT support, should be in place. These children are predisposed to developing cardiomyopathy and therefore at risk of cardiovascular collapse under anesthesia.
Topics: Anesthesia; Cardiomyopathy, Hypertrophic; Donohue Syndrome; Humans; Infant; Infant, Newborn; Insulin Resistance; Sepsis
PubMed: 29148123
DOI: 10.1111/pan.13273 -
Indian Pediatrics Aug 2015
Topics: Donohue Syndrome; Fatal Outcome; Female; Humans; Infant, Newborn
PubMed: 26388649
DOI: No ID Found -
PloS One 2023SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of...
IMPORTANCE
SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis.
METHODS
RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms.
DISCUSSION
RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options.
REGISTRATION
NCT05172024.
Topics: Humans; COVID-19; Observational Studies as Topic; Post-Acute COVID-19 Syndrome; Prospective Studies; Retrospective Studies; SARS-CoV-2; Adolescent; Adult; Multicenter Studies as Topic
PubMed: 37352211
DOI: 10.1371/journal.pone.0286297 -
Biology Oct 2023The liver is a major metabolic organ that performs many essential biological functions such as detoxification and the synthesis of proteins and biochemicals necessary... (Review)
Review
The liver is a major metabolic organ that performs many essential biological functions such as detoxification and the synthesis of proteins and biochemicals necessary for digestion and growth. Any disruption in normal liver function can lead to the development of more severe liver disorders. Overall, about 3 million Americans have some type of liver disease and 5.5 million people have progressive liver disease or cirrhosis, in which scar tissue replaces the healthy liver tissue. An estimated 20% to 30% of adults have excess fat in their livers, a condition called steatosis. The most common etiologies for steatosis development are (1) high caloric intake that causes non-alcoholic fatty liver disease (NAFLD) and (2) excessive alcohol consumption, which results in alcohol-associated liver disease (ALD). NAFLD is now termed "metabolic-dysfunction-associated steatotic liver disease" (MASLD), which reflects its association with the metabolic syndrome and conditions including diabetes, high blood pressure, high cholesterol and obesity. ALD represents a spectrum of liver injury that ranges from hepatic steatosis to more advanced liver pathologies, including alcoholic hepatitis (AH), alcohol-associated cirrhosis (AC) and acute AH, presenting as acute-on-chronic liver failure. The predominant liver cells, hepatocytes, comprise more than 70% of the total liver mass in human adults and are the basic metabolic cells. Mitochondria are intracellular organelles that are the principal sources of energy in hepatocytes and play a major role in oxidative metabolism and sustaining liver cell energy needs. In addition to regulating cellular energy homeostasis, mitochondria perform other key physiologic and metabolic activities, including ion homeostasis, reactive oxygen species (ROS) generation, redox signaling and participation in cell injury/death. Here, we discuss the main mechanism of mitochondrial dysfunction in chronic liver disease and some treatment strategies available for targeting mitochondria.
PubMed: 37887021
DOI: 10.3390/biology12101311 -
Med (New York, N.Y.) Nov 2023Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease that requires hospitalization. It...
BACKGROUND
Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes.
METHODS
Here, we use data from an international consortium to study this question and assess whether differences between these groups are context specific. Data from 83,163 hospitalized COVID-19 patients (34,843 vaccinated, 48,320 unvaccinated) from 38 countries were analyzed.
FINDINGS
While typical symptoms were more often reported in unvaccinated patients, comorbidities, including some associated with worse prognosis in previous studies, were more common in vaccinated patients. Considerable between-country variation in both in-hospital fatality risk and vaccinated-versus-unvaccinated difference in this outcome was observed.
CONCLUSIONS
These findings will inform allocation of healthcare resources in future surges as well as design of longer-term international studies to characterize changes in clinical profile of hospitalized COVID-19 patients related to vaccination history.
FUNDING
This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z, and 220757/Z/20/Z); the Bill & Melinda Gates Foundation (OPP1209135); and the philanthropic support of the donors to the University of Oxford's COVID-19 Research Response Fund (0009109). Additional funders are listed in the "acknowledgments" section.
Topics: Humans; COVID-19; SARS-CoV-2; Hospitalization; Hospitals; Vaccination
PubMed: 37738979
DOI: 10.1016/j.medj.2023.08.005