scholarly journals Mevalonate Kinase-Associated Diseases: Hunting for Phenotype–Genotype Correlation

2021 ◽  
Vol 10 (8) ◽  
pp. 1552
Author(s):  
Guilaine Boursier ◽  
Cécile Rittore ◽  
Florian Milhavet ◽  
Laurence Cuisset ◽  
Isabelle Touitou
Keyword(s):  
Severe Disease ◽  
Compound Heterozygous ◽  
Mevalonate Kinase ◽  
Kinase Gene ◽  
New Associations ◽  
Associated Diseases ◽  
Ocular Symptoms ◽  
Disseminated Superficial Actinic Porokeratosis ◽  
Increased Risk ◽  
Genotype Correlation

Mevalonate kinase-associated diseases (MKAD) are caused by pathogenic mutations in the mevalonate kinase gene (MVK) and encompass several phenotypically different rare and hereditary autoinflammatory conditions. The most serious is a recessive systemic metabolic disease called mevalonic aciduria, and the most recently recognized is disseminated superficial actinic porokeratosis, a dominant disease limited to the skin. To evaluate a possible correlation between genotypes and (1) the different MKAD clinical subtypes or (2) the occurrence of severe manifestations, data were reviewed for all patients with MVK variants described in the literature (N = 346), as well as those referred to our center (N = 51). The genotypes including p.(Val377Ile) (homozygous or compound heterozygous) were more frequent in mild systemic forms but were also sometimes encountered with severe disease. We confirmed that amyloidosis was more prevalent in patients compound heterozygous for p.(Ile268Thr) and p.(Val377Ile) than in others and revealed new associations. Patients homozygous for p.(Leu264Phe), p.(Ala334Thr) or compound heterozygous for p.(His20Pro) and p.(Ala334Thr) had increased risk of severe neurological or ocular symptoms. All patients homozygous for p.(Leu264Phe) had a cataract. The variants associated with porokeratosis were relatively specific and more frequently caused a frameshift than in patients with other clinical forms (26% vs. 6%). We provide practical recommendations focusing on phenotype–genotype correlation in MKAD that could be helpful for prophylactic management.

scholarly journals Clinical and Mutational Spectrum of Xeroderma Pigmentosum in Egypt: Identification of Six Novel Mutations and Implications for Ancestral Origins

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 295
Author(s):  
Eman Rabie ◽  
Khalda Amr ◽  
Suher Zada ◽  
Heba El-Sayed ◽  
Mohamad El Darouti ◽  
...  
Keyword(s):  
Xeroderma Pigmentosum ◽  
Autosomal Recessive ◽  
The Body ◽  
Genetic Profiling ◽  
Oral Cancers ◽  
Ocular Symptoms ◽  
Increased Risk ◽  
Migration Flows ◽  
Skin Photosensitivity ◽  
Genotype Correlation

Xeroderma pigmentosum is a rare autosomal recessive skin disorder characterized by freckle-like dry pigmented skin, photosensitivity, and photophobia. Skin and ocular symptoms are confined to sun exposed areas of the body. Patients have markedly increased risk for UV-induced skin, ocular, and oral cancers. Some patients develop neurodegenerative symptoms, including diminished tendon reflexes and microcephaly. In this study, we describe clinical and genetic findings of 36 XP patients from Egypt, a highly consanguineous population from North Africa. Thorough clinical evaluation followed by Sanger sequencing of XPA and XPC genes were done. Six novel and seven previously reported mutations were identified. Phenotype-genotype correlation was investigated. We report clinical and molecular findings consistent with previous reports of countries sharing common population structure, and geographical and historical backgrounds with implications on common ancestral origins and historical migration flows. Clinical and genetic profiling improves diagnosis, management, counselling, and implementation of future targeted therapies.

Edible Mushrooms: Novel Medicinal Agents to Combat Metabolic Syndrome and Associated Diseases

2020 ◽  
Vol 26 (39) ◽  
pp. 4970-4981
Author(s):  
Yu-Tang Tung ◽  
Chun-Hsu Pan ◽  
Yi-Wen Chien ◽  
Hui-Yu Huang
Keyword(s):  
Metabolic Syndrome ◽  
Unsaturated Fatty Acids ◽  
Edible Mushroom ◽  
Biologically Active ◽  
Edible Mushrooms ◽  
Beta Glucan ◽  
Medicinal Mushrooms ◽  
Associated Diseases ◽  
Increased Risk

Metabolic syndrome is an aggregation of conditions and associated with an increased risk of developing diabetes, obesity and cardiovascular diseases (CVD). Edible mushrooms are widely consumed in many countries and are valuable components of the diet because of their attractive taste, aroma, and nutritional value. Medicinal mushrooms are higher fungi with additional nutraceutical attributes having low-fat content and a transisomer of unsaturated fatty acids along with high fiber content, biologically active compounds such as polysaccharides or polysaccharide β-glucans, alkaloids, steroids, polyphenols and terpenoids. In vitro experiments, animal models, and even human studies have demonstrated not only fresh edible mushroom but also mushroom extract that has great therapeutic applications in human health as they possess many properties such as antiobesity, cardioprotective and anti-diabetic effect. They are considered as the unmatched source of healthy foods and drugs. The focus of this report was to provide a concise and complete review of the novel medicinal properties of fresh or dry mushroom and extracts, fruiting body or mycelium and its extracts, fiber, polysaccharides, beta-glucan, triterpenes, fucoidan, ergothioneine from edible mushrooms that may help to prevent or treat metabolic syndrome and associated diseases.

scholarly journals A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

2021 ◽  
Vol 22 (2) ◽  
pp. 889
Author(s):  
Ava Kwong ◽  
Cecilia Y. S. Ho ◽  
Vivian Y. Shin ◽  
Chun Hang Au ◽  
Tsun Leung Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Brca1 Gene ◽  
Pathogenic Mutation ◽  
Compound Heterozygous ◽  
Strong Family History ◽  
Breast And Ovarian Cancer ◽  
Pathogenic Mutations ◽  
Increased Risk ◽  
History Of

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.

scholarly journals Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e049967
Author(s):  
Karen Sól Saevarsdóttir ◽  
Hildur Ýr Hilmarsdóttir ◽  
Ingibjörg Magnúsdóttir ◽  
Arna Hauksdóttir ◽  
Edda Bjork Thordardottir ◽  
...  
Keyword(s):  
Severe Disease ◽  
Symptom Burden ◽  
Cross Sectional Study ◽  
Illness Severity ◽  
University Education ◽  
Adjusted Relative Risk ◽  
Sectional Study ◽  
Cross Sectional ◽  
Symptoms Of Depression ◽  
Increased Risk

ObjectiveTo test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity.DesignPopulation-based cross-sectional study.SettingIceland.ParticipantsA total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19.Main outcome measuresSymptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities.ResultsCompared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44).ConclusionsSevere disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19.

scholarly journals 491. Aerosol-Generating Medical Procedures: Transmission of SARS-CoV-2 and Emerging Viruses

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S312-S312
Author(s):  
Seth D Judson ◽  
Vincent J Munster
Keyword(s):  
High Risk ◽  
Severe Disease ◽  
Experimental Studies ◽  
Virus Transmission ◽  
Nosocomial Transmission ◽  
Medical Procedures ◽  
Emerging Viruses ◽  
Zoonotic Viruses ◽  
Increased Risk ◽  
Hospital Acquired

Abstract Background During the pandemic of coronavirus disease 2019 (COVID-19), many questions arose regarding risks for hospital-acquired or nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aerosol generating medical procedures (AGMPs), techniques that can generate infectious, virus-laden aerosols, could potentially amplify transmission among healthcare workers (HCWs). Thus, it was widely recommended that HCWs use airborne precautions when performing AGMPs. However, in clinical settings it is often unclear what procedures constitute AGMPs and how the risk varies by procedure or pathogen. We set out to further define AGMPs and assess the risk for nosocomial transmission of SARS-CoV-2 and other high-risk viruses via AGMPs. Methods We identified potential AGMPs and emerging viruses that were high-risk for nosocomial transmission through reviewing experimental and clinical data. Potential AGMPs were those associated with previous virus transmission or mechanically capable of transmission. High-risk viruses were defined as those that cause severe disease in humans for which limited therapies or interventions exist, are infectious via aerosols in humans or non-human primates (NHPs), found in the respiratory tract of infected humans or NHPs, and had previous evidence of nosocomial transmission. Results We identified multiple potential AGMPs, which could be divided into those that generate aerosols or induce a patient to form aerosols, as well as eight families of high-risk viruses. All of the viruses were emerging zoonotic RNA viruses. In the family Coronaviridae, we identified potential evidence for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 transmission via AGMPs. SARS-CoV-1 and SARS-CoV-2 were also found to be similarly stable when aerosolized. Conclusion Multiple emerging zoonotic viruses pose a high risk for nosocomial transmission through a variety of AGMPs. Given the similar stability of SARS-CoV-2 with SARS-CoV-1 when aerosolized and prior nosocomial transmission of SARS-CoV-1 via AGMPs, we suspect that certain AGMPs pose an increased risk for SARS-CoV-2 transmission. Additional experimental studies and on-site clinical sampling during AGMPs are necessary to further risk stratify AGMPs. Disclosures All Authors: No reported disclosures

scholarly journals Diabetes and COVID19: a bidirectional relationship

2021 ◽  
Author(s):  
Ranjit Unnikrishnan ◽  
Anoop Misra
Keyword(s):  
Clinical Care ◽  
Severe Disease ◽  
Respiratory Involvement ◽  
Pancreatic Damage ◽  
Increased Risk ◽  
Bidirectional Relationship ◽  
Rapid Spread ◽  
Relationship Of ◽  
The Relationship ◽  
New Onset

AbstractThe advent and rapid spread of the coronavirus disease-2019 (COVID19) pandemic across the world has focused attention on the relationship of commonly occurring comorbidities such as diabetes on the course and outcomes of this infection. While diabetes does not seem to be associated with an increased risk of COVID19 infection per se, it has been clearly demonstrated that the presence of hyperglycemia of any degree predisposes to worse outcomes, such as more severe respiratory involvement, ICU admissions, need for mechanical ventilation and mortality. Further, COVID19 infection has been associated with the development of new-onset hyperglycemia and diabetes, and worsening of glycemic control in pre-existing diabetes, due to direct pancreatic damage by the virus, body’s stress response to infection (including cytokine storm) and use of diabetogenic drugs such as corticosteroids in the treatment of severe COVID19. In addition, public health measures taken to flatten the pandemic curve (such as lockdowns) can also adversely impact persons with diabetes by limiting their access to clinical care, healthy diet, and opportunities to exercise. Most antidiabetic medications can continue to be used in patients with mild COVID19 but switching over to insulin is preferred in severe disease.

scholarly journals Baseline T-lymphocyte subset absolute counts can predict both outcome and severity in SARS-CoV-2 infected patients: a single center study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marco Iannetta ◽  
Francesco Buccisano ◽  
Daniela Fraboni ◽  
Vincenzo Malagnino ◽  
Laura Campogiani ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
T Lymphocyte ◽  
Lymphocyte Subsets ◽  
Severe Disease ◽  
Laboratory Data ◽  
Lymphocyte Subset ◽  
Multivariable Logistic Regression Analysis ◽  
Double Positive ◽  
Increased Risk ◽  
T Lymphocyte Subset

AbstractThe aim of this study was to evaluate the role of baseline lymphocyte subset counts in predicting the outcome and severity of COVID-19 patients. Hospitalized patients confirmed to be infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were included and classified according to in-hospital mortality (survivors/nonsurvivors) and the maximal oxygen support/ventilation supply required (nonsevere/severe). Demographics, clinical and laboratory data, and peripheral blood lymphocyte subsets were retrospectively analyzed. Overall, 160 patients were retrospectively included in the study. T-lymphocyte subset (total CD3+, CD3+ CD4+, CD3+ CD8+, CD3+ CD4+ CD8+ double positive [DP] and CD3+ CD4− CD8− double negative [DN]) absolute counts were decreased in nonsurvivors and in patients with severe disease compared to survivors and nonsevere patients (p < 0.001). Multivariable logistic regression analysis showed that absolute counts of CD3+ T-lymphocytes < 524 cells/µl, CD3+ CD4+ < 369 cells/µl, and the number of T-lymphocyte subsets below the cutoff (T-lymphocyte subset index [TLSI]) were independent predictors of in-hospital mortality. Baseline T-lymphocyte subset counts and TLSI were also predictive of disease severity (CD3+  < 733 cells/µl; CD3+ CD4+ < 426 cells/µl; CD3+ CD8+ < 262 cells/µl; CD3+ DP < 4.5 cells/µl; CD3+ DN < 18.5 cells/µl). The evaluation of peripheral T-lymphocyte absolute counts in the early stages of COVID-19 might represent a useful tool for identifying patients at increased risk of unfavorable outcomes.

scholarly journals Diabetes and COVID19: a bidirectional relationship

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ranjit Unnikrishnan ◽  
Anoop Misra
Keyword(s):  
Clinical Care ◽  
Severe Disease ◽  
Respiratory Involvement ◽  
Pancreatic Damage ◽  
Increased Risk ◽  
Bidirectional Relationship ◽  
Rapid Spread ◽  
Relationship Of ◽  
The Relationship ◽  
New Onset

AbstractThe advent and rapid spread of the coronavirus disease-2019 (COVID19) pandemic across the world has focused attention on the relationship of commonly occurring comorbidities such as diabetes on the course and outcomes of this infection. While diabetes does not seem to be associated with an increased risk of COVID19 infection per se, it has been clearly demonstrated that the presence of hyperglycemia of any degree predisposes to worse outcomes, such as more severe respiratory involvement, ICU admissions, need for mechanical ventilation and mortality. Further, COVID19 infection has been associated with the development of new-onset hyperglycemia and diabetes, and worsening of glycemic control in pre-existing diabetes, due to direct pancreatic damage by the virus, body’s stress response to infection (including cytokine storm) and use of diabetogenic drugs such as corticosteroids in the treatment of severe COVID19. In addition, public health measures taken to flatten the pandemic curve (such as lockdowns) can also adversely impact persons with diabetes by limiting their access to clinical care, healthy diet, and opportunities to exercise. Most antidiabetic medications can continue to be used in patients with mild COVID19 but switching over to insulin is preferred in severe disease.

scholarly journals Ethnic disparities in COVID-19: increased risk of infection or severe disease?

The Lancet ◽  
2021 ◽  
Vol 398 (10298) ◽  
pp. 389-390
Author(s):  
Daniel Pan ◽  
Christopher A Martin ◽  
Joshua Nazareth ◽  
Clareece R Nevill ◽  
Jatinder S Minhas ◽  
...  
Keyword(s):  
Severe Disease ◽  
Ethnic Disparities ◽  
Risk Of Infection ◽  
Increased Risk

scholarly journals Renin-angiotensin system blocker and outcomes of COVID-19: a systematic review and meta-analysis

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-215322
Author(s):  
Hyun Woo Lee ◽  
Chang-Hwan Yoon ◽  
Eun Jin Jang ◽  
Chang-Hoon Lee
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Severe Disease ◽  
Renin Angiotensin System ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Receptor Blockers

BackgroundThe association of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) with disease severity of patients with COVID-19 is still unclear. We conducted a systematic review and meta-analysis to investigate if ACEI/ARB use is associated with the risk of mortality and severe disease in patients with COVID-19.MethodsWe searched all available clinical studies that included patients with confirmed COVID-19 who could be classified into an ACEI/ARB group and a non-ACEI/ARB group up until 4 May 2020. A meta-analysis was performed, and primary outcomes were all-cause mortality and severe disease.ResultsACEI/ARB use did not increase the risk of all-cause mortality both in meta-analysis for 11 studies with 12 601 patients reporting ORs (OR=0.52 (95% CI=0.37 to 0.72), moderate certainty of evidence) and in 2 studies with 8577 patients presenting HRs. For 12 848 patients in 13 studies, ACEI/ARB use was not related to an increased risk of severe disease in COVID-19 (OR=0.68 (95% CI=0.44 to 1.07); I2=95%, low certainty of evidence).ConclusionsACEI/ARB therapy was not associated with increased risk of all-cause mortality or severe manifestations in patients with COVID-19. ACEI/ARB therapy can be continued without concern of drug-related worsening in patients with COVID-19.

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