scholarly journals High Prevalence of Pre-Existing Liver Abnormalities Identified Via Autopsies in COVID-19: Identification of a New Silent Risk Factor?

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1703
Author(s):  
Yuri Hirayama ◽  
Natasha Faye Daniels ◽  
Shelley Evans ◽  
David Clarke ◽  
Stephenie Purvis ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Hepatic Dysfunction ◽  
Outcome Data ◽  
Venous Congestion ◽  
High Prevalence ◽  
Function Test ◽  
Hospital Patients ◽  
Time Of Admission ◽  
Subsequent Literature

A high prevalence of hepatic pathology (in 17 of 19 cases) was reported in post-mortem (PM) examinations of COVID-19 patients, undertaken between March 2020 and February 2021 by a single autopsy pathologist in two English Coronial jurisdictions. The patients in our cohort demonstrated high levels of recognised COVID-19 risk factors, including hypertension (8/16, 50%), type 2 diabetes mellitus (8/16, 50%) and evidence of arteriopathy 6/16 (38%). Hepatic abnormalities included steatosis (12/19; 63%), moderate to severe venous congestion (5/19; 26%) and cirrhosis (4/19; 21%). A subsequent literature review indicated a significantly increased prevalence of steatosis (49%), venous congestion (34%) and cirrhosis (9.3%) in COVID-19 PM cases, compared with a pre-pandemic PM cohort (33%, 16%, and 2.6%, respectively), likely reflecting an increased mortality risk in SARS-CoV-2 infection for patients with pre-existing liver disease. To corroborate this observation, we retrospectively analysed the admission liver function test (LFT) results of 276 consecutive, anonymised COVID-19 hospital patients in our centre, for whom outcome data were available. Of these patients, 236 (85.5%) had significantly reduced albumin levels at the time of admission to hospital, which was likely indicative of pre-existing chronic liver or renal disease. There was a strong correlation between patient outcome (length of hospital admission or death) and abnormal albumin at the time of hospital admission (p = 0.000012). We discuss potential mechanisms by which our observations of hepatic dysfunction are linked to a risk of COVID-19 mortality, speculating on the importance of recently identified anti-interferon antibodies.

Premature ovarian ageing following heterozygous loss of Senataxin

2020 ◽  
Author(s):  
G N Subramanian ◽  
M Lavin ◽  
H A Homer
Keyword(s):  
Dna Damage ◽  
Neurodegenerative Disorder ◽  
Dna Helicase ◽  
Dna Integrity ◽  
Ovarian Activity ◽  
Homozygous Mutation ◽  
Female Mice ◽  
Mating Trial ◽  
High Prevalence

Abstract Premature loss of ovarian activity before 40 years of age is known as primary ovarian insufficiency (POI) and occurs in ∼1% of women. A more subtle decline in ovarian activity, known as premature ovarian ageing (POA), occurs in ∼10% of women. Despite the high prevalence of POA, very little is known regarding its genetic causation. Senataxin (SETX) is an RNA/DNA helicase involved in repair of oxidative stress-induced DNA damage. Homozygous mutation of SETX leads to the neurodegenerative disorder, ataxia oculomotor apraxia type 2 (AOA2). There have been reports of POI in AOA2 females suggesting a link between SETX and ovarian ageing. Here, we studied female mice lacking either one (Setx+/−) or both (Setx−/−) copies of SETX over a 12- to 14-month period. We find that DNA damage is increased in oocytes from 8-month-old Setx+/− and Setx−/− females compared with Setx+/+ oocytes leading to a marked reduction in all classes of ovarian follicles at least 4 months earlier than typically occurs in female mice. Furthermore, during a 12-month long mating trial, Setx+/− and Setx−/− females produced significantly fewer pups than Setx+/+ females from 7 months of age onwards. These data show that SETX is critical for preventing POA in mice, likely by preserving DNA integrity in oocytes. Intriguingly, heterozygous Setx loss causes an equally severe impact on ovarian ageing as homozygous Setx loss. Because heterozygous SETX disruption is less likely to produce systemic effects, SETX compromise could underpin some cases of insidious POA.

scholarly journals Treatment with a DPP-4 inhibitor at time of hospital admission for COVID-19 is not associated with improved clinical outcomes: data from the COVID-PREDICT cohort study in The Netherlands

2021 ◽  
Author(s):  
Rick I. Meijer ◽  
Trynke Hoekstra ◽  
Niels C. Gritters van den Oever ◽  
Suat Simsek ◽  
Joop P. van den Bergh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Hospital Admission ◽  
Clinical Outcomes ◽  
Primary Outcome ◽  
Infectious Complications ◽  
Glucose Lowering ◽  
Diabetes Severity ◽  
Outcome Mortality

Abstract Purpose Inhibition of dipeptidyl peptidase (DPP-)4 could reduce coronavirus disease 2019 (COVID-19) severity by reducing inflammation and enhancing tissue repair beyond glucose lowering. We aimed to assess this in a prospective cohort study. Methods We studied in 565 patients with type 2 diabetes in the CovidPredict Clinical Course Cohort whether use of a DPP-4 inhibitor prior to hospital admission due to COVID-19 was associated with improved clinical outcomes. Using crude analyses and propensity score matching (on age, sex and BMI), 28 patients using a DPP-4 inhibitor were identified and compared to non-users. Results No differences were found in the primary outcome mortality (matched-analysis = odds-ratio: 0,94 [95% confidence interval: 0,69 – 1,28], p-value: 0,689) or any of the secondary outcomes (ICU admission, invasive ventilation, thrombotic events or infectious complications). Additional analyses comparing users of DPP-4 inhibitors with subgroups of non-users (subgroup 1: users of metformin and sulphonylurea; subgroup 2: users of any insulin combination), allowing to correct for diabetes severity, did not yield different results. Conclusions We conclude that outpatient use of a DPP-4 inhibitor does not affect the clinical outcomes of patients with type 2 diabetes who are hospitalized because of COVID-19 infection.

scholarly journals Vitamin D, SARS-CoV-2 and Causal Associations in Transversal Studies: The Time-Series Analysis to Reveal Potential Confounders. Comment on Gaudio et al. Vitamin D Levels Are Reduced at the Time of Hospital Admission in Sicilian SARS-CoV-2-Positive Patients. Int. J. Environ. Res. Public Health 2021, 18, 3491

2021 ◽  
Vol 18 (13) ◽  
pp. 6793
Author(s):  
Cristiano Ialongo ◽  
Antonella Farina ◽  
Raffaella Labriola ◽  
Antonio Angeloni ◽  
Emanuela Anastasi
Keyword(s):  
Public Health ◽  
Vitamin D ◽  
Time Series ◽  
Severe Acute Respiratory Syndrome ◽  
Time Series Analysis ◽  
Hospital Admission ◽  
The State ◽  
Series Analysis ◽  
Vitamin D Levels ◽  
Time Of Admission

We read with great interest the paper by Gaudio and colleagues on vitamin D and on the state of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the time of admission [...]

scholarly journals High prevalence of previously unknown heart failure and left ventricular dysfunction in patients with type 2 diabetes

Diabetologia ◽  
2012 ◽  
Vol 55 (8) ◽  
pp. 2154-2162 ◽  
Author(s):  
L. J. M. Boonman-de Winter ◽  
F. H. Rutten ◽  
M. J. M. Cramer ◽  
M. J. Landman ◽  
A. H. Liem ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Left Ventricular Dysfunction ◽  
Ventricular Dysfunction ◽  
Left Ventricular ◽  
High Prevalence

404 Sleep-Disordered Breathing In Native Hawaiians/Pacific Islanders With Associated Comorbidities And Adherence To Therapy

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A160-A161
Author(s):  
Darin Ryujin ◽  
Krishna Sundar ◽  
Allyson Gilles
Keyword(s):  
Sleep Disordered Breathing ◽  
Demographic Data ◽  
Ethnic Origin ◽  
Pacific Islanders ◽  
Native Hawaiians ◽  
University Of Utah ◽  
High Prevalence ◽  
Artery Disease ◽  
Disordered Breathing

Abstract Introduction Sleep-disordered breathing in Native Hawaiians and Pacific Islanders (NHPIs), its relationship to type 2 diabetes mellitus (DM), chronic renal, and heart disease, is not well known. NHPIs comprise only 1.3% of Utah’s population, but have the highest rates of DM and deaths due to diabetic kidney disease in Utah. This study assessed the nature of sleep-disordered breathing, its association with demographic variables, and comorbidities, and adherence patterns to positive airway pressure (PAP) therapy. Methods University of Utah sleep clinics patient databases from 2014 were evaluated to identify NHPIs using first/last names. Electronic medical records were reviewed to confirm patient ethnic origin, demographic data, and comorbidities. The most recent PAP downloads were obtained. Results Of 106 NHPIs were identified, data available for 104 patients (71 males, 33 females) was analyzed. Mean age of males was 47 + 13 years and females 48±13 years. Prevalence rates of obesity were 13% (female 9%, male 15%) with BMI≥30, 33% (female 24%, male 23%) with BMI≥35, and 49% (female 58%, Male 23%) with BMI≥40). Majority of patients had severe OSA (61% males with AHI≥30; 39% females with ≥ 30), with overall mean AHI of 47±38. A high prevalence of comorbidities was noted: 61% hypertension (male 58%; female 67%), diabetes 54% (male 48%, female 67%), renal disease 20% (male 21%, female 18%), coronary artery disease 13% (male 14%, female 9%), and congestive heart failure 13% (male 15%, female 9%). Prevalence of lung disease was low 13% (male 9%, female 18%). Conclusion NHPIs evaluated for sleep-disordered breathing have high rates of obesity, severe OSA, and concerning comorbidities. PAP adherence in this group was poor compared to overall adherence for patients seen in University of Utah sleep clinics (~70%). Further research is required to assess the relationships between OSA, associated comorbidities, and disease outcomes. Addressing low rates of PAP adherence in this population may afford opportunities to improve health outcomes. Support (if any) n/a

scholarly journals Evaluating the contribution of rare variants to type 2 diabetes and related traits using pedigrees

2017 ◽  
Vol 115 (2) ◽  
pp. 379-384 ◽  
Author(s):  
Goo Jun ◽  
Alisa Manning ◽  
Marcio Almeida ◽  
Matthew Zawistowski ◽  
Andrew R. Wood ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mexican American ◽  
Complex Disease ◽  
Rare Variants ◽  
Whole Genome Analysis ◽  
Mexican American Families ◽  
Extended Pedigrees ◽  
High Prevalence ◽  
Study Designs

A major challenge in evaluating the contribution of rare variants to complex disease is identifying enough copies of the rare alleles to permit informative statistical analysis. To investigate the contribution of rare variants to the risk of type 2 diabetes (T2D) and related traits, we performed deep whole-genome analysis of 1,034 members of 20 large Mexican-American families with high prevalence of T2D. If rare variants of large effect accounted for much of the diabetes risk in these families, our experiment was powered to detect association. Using gene expression data on 21,677 transcripts for 643 pedigree members, we identified evidence for large-effect rare-variant cis-expression quantitative trait loci that could not be detected in population studies, validating our approach. However, we did not identify any rare variants of large effect associated with T2D, or the related traits of fasting glucose and insulin, suggesting that large-effect rare variants account for only a modest fraction of the genetic risk of these traits in this sample of families. Reliable identification of large-effect rare variants will require larger samples of extended pedigrees or different study designs that further enrich for such variants.

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