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International Journal of Cardiology.... Feb 2021To investigate the effect of the corona virus disease 2019 (COVID-19) pandemic on the acute treatment of patients with ST-segment elevation (STEMI) and Non-ST-segment...
BACKGROUND
To investigate the effect of the corona virus disease 2019 (COVID-19) pandemic on the acute treatment of patients with ST-segment elevation (STEMI) and Non-ST-segment elevation acute coronary syndrome (NSTE-ACS).
METHODS
We retrospectively identified patients presenting to the emergency department (ED) with suspected ACS. We evaluated the number of percutaneous coronary interventions (PCIs) for STEMI, NSTE-ACS, and elective PCI cases. In STEMI patients, we assessed the time from chest pain onset (cpo) to ED presentation, post-infarction left ventricular ejection fraction (LVEF), and time from ED presentation to PCI. We directly compared cases from two time intervals: January/February 2020 versus March/April 2020 (defined as 2 months before and after the COVID-19 outbreak). In a secondary analysis, we directly compared cases from March/April 2020 with patients from the same time interval in 2019.
RESULTS
From January to April 2020, 765 patients presented with acute chest pain to the ED. A dramatic reduction of ED presentations after compared to before the COVID-19 outbreak (31% relative reduction) was observed. Overall, 398 PCIs were performed, 220/398 PCIs (55.3%) before versus 178/398 PCIs (44.7%) after the outbreak. While numbers for NSTE-ACS and elective interventions declined by 21% and 31%, respectively, the number of STEMI cases remained stable. Time from cpo to ED presentation, post-infarction LVEF, and median door-to-balloon time remained unchanged.
CONCLUSIONS
In contrast to previous reports, our findings do not confirm the dramatic drop in STEMI cases and interventions in northwestern Switzerland as observed in other regions and hospitals around the world.
PubMed: 33335974
DOI: 10.1016/j.ijcha.2020.100686 -
Prenatal Diagnosis Sep 2020Conventional genetic tests (quantitative fluorescent-PCR [QF-PCR] and single nucleotide polymorphism-array) only diagnose ~40% of fetuses showing ultrasound...
OBJECTIVE
Conventional genetic tests (quantitative fluorescent-PCR [QF-PCR] and single nucleotide polymorphism-array) only diagnose ~40% of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, and rapid turnaround times. In this study, we implemented rES in prenatal care to increase diagnostic yield.
METHODS
We prospectively studied 55 fetuses. Inclusion criteria were: (a) two or more independent major fetal anomalies, (b) hydrops fetalis or bilateral renal cysts alone, or (c) one major fetal anomaly and a first-degree relative with the same anomaly. In addition to conventional genetic tests, we performed trio rES analysis using a custom virtual gene panel of ~3850 Online Mendelian Inheritance in Man (OMIM) genes.
RESULTS
We established a genetic rES-based diagnosis in 8 out of 23 fetuses (35%) without QF-PCR or array abnormalities. Diagnoses included MIRAGE (SAMD9), Zellweger (PEX1), Walker-Warburg (POMGNT1), Noonan (PTNP11), Kabuki (KMT2D), and CHARGE (CHD7) syndrome and two cases of Osteogenesis Imperfecta type 2 (COL1A1). In six cases, rES diagnosis aided perinatal management. The median turnaround time was 14 (range 8-20) days.
CONCLUSION
Implementing rES as a routine test in the prenatal setting is challenging but technically feasible, with a promising diagnostic yield and significant clinical relevance.
Topics: Abnormalities, Multiple; Adult; Diagnostic Tests, Routine; Feasibility Studies; Female; Fetus; Genetic Testing; Humans; Infant, Newborn; Male; Netherlands; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Prenatal Diagnosis; Prospective Studies; Ultrasonography, Prenatal; Exome Sequencing
PubMed: 32627857
DOI: 10.1002/pd.5781 -
European Heart Journal. Case Reports Sep 2019Acute coronary syndrome (ACS) can be a life-threatening condition. However, identification of patients with ACS can be challenging, especially among women, and clinical...
BACKGROUND
Acute coronary syndrome (ACS) can be a life-threatening condition. However, identification of patients with ACS can be challenging, especially among women, and clinical presentation can often overlap with other medical entities.
CASE SUMMARY
A 61-year-old woman with a history of stable bronchial asthma presented with worsening dyspnoea for spiroergometry. During bicycle exercise testing, she developed acute chest pain and her electrocardiogram showed significant ST-segment elevations. High-sensitivity cardiac troponin was elevated and a coronary angiography was performed showing normal coronary arteries. Cardiac magnetic resonance imaging showed no signs of myocardial infarction, myocarditis or Takotsubo cardiomyopathy but the incidental finding of a giant hiatal hernia impeding the filling of the left atrium. The giant hernia was surgically corrected, and the patient's exertional dyspnoea fully relieved during follow-up.
DISCUSSION
Hiatal hernia might compress cardiac structures, cause exertional dyspnoea and mimic ST-elevation myocardial infarction. 10.1093/ehjcr/ytz138_audio1 ytz138_audio1 6074443146001.
PubMed: 31425572
DOI: 10.1093/ehjcr/ytz138 -
Journal of Vascular Surgery Cases and... Sep 2021Endovascular management of aortic complications in patients with Marfan syndrome (MFS) is uncommon. We treated a patient with MFS with a diagnosis of a 75-mm aortic arch...
Successful repair of an arch aneurysm with acute aortic dissection in a patient with Marfan syndrome using a hybrid surgical approach and the stent-assisted balloon-induced intimal disruption and relamination in aortic dissection repair technique.
Endovascular management of aortic complications in patients with Marfan syndrome (MFS) is uncommon. We treated a patient with MFS with a diagnosis of a 75-mm aortic arch aneurysm and uncomplicated aortic type B dissection using single-stage hybrid surgery combining total arch replacement with elephant trunk and the STABILISE (stent-assisted balloon-induced intimal disruption and relamination in aortic dissection repair) technique for complete aortic remodeling. The repair was successful, and the aortic true lumen was completely expanded. At 6 months after surgery, clinical evaluation confirmed the early success of the intervention. This type of surgery must be studied further before it can become routine treatment for patients with MFS but it proved safe and feasible.
PubMed: 34278066
DOI: 10.1016/j.jvscit.2021.05.013 -
Biochimica Et Biophysica Acta.... Oct 2019Zellweger spectrum disorders (ZSDs) are autosomal recessive diseases caused by defective peroxisome assembly. They constitute a clinical continuum from severe early...
Zellweger spectrum disorders (ZSDs) are autosomal recessive diseases caused by defective peroxisome assembly. They constitute a clinical continuum from severe early lethal to relatively milder presentations in adulthood. Liver disease is a prevalent symptom in ZSD patients. The underlying pathogenesis for the liver disease, however, is not fully understood. We report a hypomorphic ZSD mouse model, which is homozygous for Pex1-c.2531G>A (p.G844D), the equivalent of the most common pathogenic variant found in ZSD, and which predominantly presents with liver disease. After introducing the Pex1-G844D allele by knock-in, we characterized homozygous Pex1-G844D mice for survival, biochemical parameters, including peroxisomal and mitochondrial functions, organ histology, and developmental parameters. The first 20 post-natal days (P20) were critical for survival of homozygous Pex1-G844D mice (~20% survival rate). Lethality was likely due to a combination of cholestatic liver problems, liver dysfunction and caloric deficit, probably as a consequence of defective bile acid biosynthesis. Survival beyond P20 was nearly 100%, but surviving mice showed a marked delay in growth. Surviving mice showed similar hepatic problems as described for mild ZSD patients, including hepatomegaly, bile duct proliferation, liver fibrosis and mitochondrial alterations. Biochemical analyses of various tissues showed the absence of functional peroxisomes accompanied with aberrant levels of peroxisomal metabolites predominantly in the liver, while other tissues were relatively spared. ur findings show that homozygous Pex1-G844D mice have a predominant liver disease phenotype, mimicking the hepatic pathology of ZSD patients, and thus constitute a good model to study pathogenesis and treatment of liver disease in ZSD patients.
Topics: ATPases Associated with Diverse Cellular Activities; Alleles; Animals; Disease Models, Animal; Female; Fibroblasts; Humans; Liver; Liver Diseases; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; Peroxisomes; Phenotype; Zellweger Syndrome
PubMed: 31207289
DOI: 10.1016/j.bbadis.2019.06.013 -
Annals of Indian Academy of Neurology 2021We report a newborn born to a consanguineous couple with antenatally detected dilatation of third ventricle, unilateral talipes, and intra uterine growth retardation. On...
We report a newborn born to a consanguineous couple with antenatally detected dilatation of third ventricle, unilateral talipes, and intra uterine growth retardation. On examination, there was facial dysmorphism, hypotonia, encephalopathy, joint laxity and muscle hypertrophy in addition to left foot talipes. On evaluation, there were renal cortical cysts, rhizomelia, chondrodysplasia punctata and elevated muscle enzymes, along with a dilated third ventricle. As the phenotype was not consistent with any of the muscular dystrophies or the peroxisomal disorders, an exome sequencing was requested. It revealed a combination of Zellweger syndrome and Ullrich congenital muscular dystrophy type 1.
PubMed: 35002136
DOI: 10.4103/aian.AIAN_1108_20 -
BMC Medical Genetics Nov 2020Peroxisome biogenesis disorders (PBDs) are a group of metabolic diseases caused by dysfunction of peroxisomes. Different forms of PBDs are described; the most severe one...
BACKGROUND
Peroxisome biogenesis disorders (PBDs) are a group of metabolic diseases caused by dysfunction of peroxisomes. Different forms of PBDs are described; the most severe one is the Zellweger syndrome (ZS). We report on an unusual presentation of Zellweger syndrome manifesting in a newborn with severe and fulminant sepsis, causing death during the neonatal period.
CASE PRESENTATION
A term male Caucasian neonate presented at birth with hypotonia and poor feeding associated with dysmorphic craniofacial features and skeletal abnormalities. Blood tests showed progressive leukopenia; ultrasounds revealed cerebral and renal abnormalities. He died on the fourth day of life because of an irreversible Gram-negative sepsis. Post-mortem tests on blood and urine samples showed biochemical alterations suggestive of ZS confirmed by genetic test.
CONCLUSIONS
ZS is an early and severe forms of PBDs. Peroxisomes are known to be involved in lipid metabolism, but recent studies suggest their fundamental role in modulating immune response and inflammation. In case of clinical suspicion of ZS it is important to focus the attention on the prevention and management of infections that can rapidly progress to death.
Topics: ATPases Associated with Diverse Cellular Activities; Fatal Outcome; Gene Expression; Gram-Negative Bacterial Infections; Humans; Immunity, Innate; Infant, Newborn; Male; Mutation; Peroxisomes; Sepsis; Zellweger Syndrome
PubMed: 33213396
DOI: 10.1186/s12881-020-01175-y -
Cells Dec 2020Genetic alterations in genes lead to peroxisome biogenesis disorder. In humans, they are associated with Zellweger spectrum disorders (ZSD). No validated treatment has...
Genetic alterations in genes lead to peroxisome biogenesis disorder. In humans, they are associated with Zellweger spectrum disorders (ZSD). No validated treatment has been shown to modify the dismal natural history of ZSD. Liver transplantation (LT) improved clinical and biochemical outcomes in mild ZSD patients. Hepatocyte transplantation (HT), developed to overcome LT limitations, was performed in a mild ZSD 4-year-old child with encouraging short-term results. Here, we evaluated low dose (12.5 million hepatocytes/kg) and high dose (50 million hepatocytes/kg) syngeneic male HT via intrasplenic infusion in the -G844D NMRI mouse model which recapitulates a mild ZSD phenotype. HT was feasible and safe in growth retarded ZSD mice. Clinical (weight and food intake) and biochemical parameters (very long-chain fatty acids, abnormal bile acids, etc.) were in accordance with ZSD phenotype but they were not robustly modified by HT. As expected, one third of the infused cells were detected in the liver 24 h post-HT. No liver nor spleen microchimerism was detected after 7, 14 and 30 days. Future optimizations are required to improve hepatocyte engraftment in -G844D NMRI mouse liver. The mouse model exhibited the robustness required for ZSD liver-targeted therapies evaluation.
Topics: Animals; Biomarkers; Disease Models, Animal; Hepatocytes; Humans; Liver; Male; Mice; Peroxisomes; Phenotype; Zellweger Syndrome
PubMed: 33396635
DOI: 10.3390/cells10010040 -
Journal of Clinical Medicine Jun 2021Most studies investigating early risk predictors in coronavirus disease 19 (COVID-19) lacked comparison with controls. We aimed to assess and directly compare outcomes...
Most studies investigating early risk predictors in coronavirus disease 19 (COVID-19) lacked comparison with controls. We aimed to assess and directly compare outcomes and risk predictors at time of emergency department (ED) presentation in COVID-19 and controls. Consecutive patients presenting to the ED with suspected COVID-19 were prospectively enrolled. COVID-19-patients were compared with (i) patients tested negative (overall controls) and (ii) patients tested negative, who had a respiratory infection (respiratory controls). Primary outcome was the composite of intensive care unit (ICU) admission and death at 30 days. Among 1081 consecutive cases, 191 (18%) were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 890 (82%) were tested negative (overall controls), of which 323 (30%) had a respiratory infection (respiratory controls). Incidence of the composite outcome was significantly higher in COVID-19 (23%) as compared with the overall control group (10%, adjusted-HR 2.45 (95%CI, 1.61-3.74), < 0.001) or the respiratory control group (10%, adjusted-HR 2.93 (95%CI, 1.66-5.17), < 0.001). Blood oxygen saturation, age, high-sensitivity troponin, c-reactive protein, and lactate dehydrogenase were identified as the strongest predictors of poor outcome available at time of ED presentation in COVID-19 with highly comparable prognostic utility in overall and respiratory controls. In conclusion, patients presenting to the ED with COVID-19 have a worse outcome than controls, even after adjustment for differences in baseline characteristics. Most predictors of poor outcome in COVID-19 were not restricted to COVID-19, but of comparable prognostic utility in controls and therefore generalizable to unselected patients with suspected COVID-19.
PubMed: 34204453
DOI: 10.3390/jcm10122672 -
Biochimica Et Biophysica Acta.... Nov 2020Zellweger spectrum disorders (ZSD) are inborn errors of metabolism caused by mutations in PEX genes that lead to peroxisomal biogenesis disorder (PBD). No validated...
Zellweger spectrum disorders (ZSD) are inborn errors of metabolism caused by mutations in PEX genes that lead to peroxisomal biogenesis disorder (PBD). No validated treatment is able to modify the dismal progression of the disease. ZSD mouse models used to develop therapeutic approaches are limited by poor survival and breeding restrictions. To overcome these limitations, we backcrossed the hypomorphic Pex1 p.G844D allele to NMRI background. NMRI mouse breeding restored an autosomal recessive Mendelian inheritance pattern and delivered twice larger litters. Mice were longitudinally phenotyped up to 6 months of age to make this model suitable for therapeutic interventions. ZSD mice exhibited growth retardation and relative hepatomegaly associated to progressive hepatocyte hypertrophy. Biochemical studies associated with RNA sequencing deciphered ZSD liver glycogen metabolism alterations. Affected fibroblasts displayed classical immunofluorescence pattern and biochemical alterations associated with PBD. Plasma and liver showed very long-chain fatty acids, specific oxysterols and C bile acids intermediates elevation in ZSD mice along with a specific urine organic acid profile. With ageing, C fatty acid and phytanic acid levels tended to normalize in ZSD mice, as described in patients reaching adulthood. In conclusion, our mouse model recapitulates a mild ZSD phenotype and is suitable for liver-targeted therapies evaluation.
Topics: ATPases Associated with Diverse Cellular Activities; Alleles; Animals; Bile Acids and Salts; Cell Membrane; Female; Glucose-6-Phosphatase; Hepatocytes; Longitudinal Studies; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Oxysterols; RNA-Seq; Zellweger Syndrome
PubMed: 32693164
DOI: 10.1016/j.bbadis.2020.165900