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Mayo Clin Proc ; 95(7): 1354-1368, 2020 07.
Article in English | MEDLINE | ID: covidwho-1500136


OBJECTIVE: To explore the transcriptomic differences between patients with hypertrophic cardiomyopathy (HCM) and controls. PATIENTS AND METHODS: RNA was extracted from cardiac tissue flash frozen at therapeutic surgical septal myectomy for 106 patients with HCM and 39 healthy donor hearts. Expression profiling of 37,846 genes was performed using the Illumina Human HT-12v3 Expression BeadChip. All patients with HCM were genotyped for pathogenic variants causing HCM. Technical validation was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. This study was started on January 1, 1999, and final analysis was completed on April 20, 2020. RESULTS: Overall, 22% of the transcriptome (8443 of 37,846 genes) was expressed differentially between HCM and control tissues. Analysis by genotype revealed that gene expression changes were similar among genotypic subgroups of HCM, with only 4% (1502 of 37,846) to 6% (2336 of 37,846) of the transcriptome exhibiting differential expression between genotypic subgroups. The qRT-PCR confirmed differential expression in 92% (11 of 12 genes) of tested transcripts. Notably, in the context of coronavirus disease 2019 (COVID-19), the transcript for angiotensin I converting enzyme 2 (ACE2), a negative regulator of the angiotensin system, was the single most up-regulated gene in HCM (fold-change, 3.53; q-value =1.30×10-23), which was confirmed by qRT-PCR in triplicate (fold change, 3.78; P=5.22×10-4), and Western blot confirmed greater than 5-fold overexpression of ACE2 protein (fold change, 5.34; P=1.66×10-6). CONCLUSION: More than 20% of the transcriptome is expressed differentially between HCM and control tissues. Importantly, ACE2 was the most up-regulated gene in HCM, indicating perhaps the heart's compensatory effort to mount an antihypertrophic, antifibrotic response. However, given that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 for viral entry, this 5-fold increase in ACE2 protein may confer increased risk for COVID-19 manifestations and outcomes in patients with increased ACE2 transcript expression and protein levels in the heart.

Betacoronavirus , Cardiomyopathy, Hypertrophic/genetics , Cardiomyopathy, Hypertrophic/virology , Coronavirus Infections/complications , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/complications , Adolescent , Adult , Aged , Angiotensin-Converting Enzyme 2 , COVID-19 , Cardiomyopathy, Hypertrophic/metabolism , Case-Control Studies , Child , Genotype , Humans , Middle Aged , Myocardium/metabolism , Pandemics , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Young Adult
Int J Rehabil Res ; 43(3): 285-286, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1483689


We report, to the best of our knowledge, the first case of a probable COVID-19 infection in a 28-year-old man with Charcot-Marie-Tooth disease. The diagnosis was established through a remote interaction with the patient after early discharge from outpatient therapy due to upcoming traveling restrictions. The COVID-19 disease appeared mild, without major respiratory problems, and no obvious neuromuscular deterioration was reported or observed. Telerehabilitation provided an opportunity to continue with hand rehabilitation after tendon transfer surgery, perform an ad-hoc online evaluation, and advise the patient how to prevent the spread of infection and cope with restrictions limiting outpatient visits. This experience seems valuable for further development of telerehabilitation in anticipation of future pandemics or adversarial events since it allows reaching out to patients unable to travel and overcomes the need for regular outpatient visits.

Betacoronavirus , Charcot-Marie-Tooth Disease/surgery , Coronavirus Infections/complications , Pneumonia, Viral/complications , Telerehabilitation , Adult , COVID-19 , Charcot-Marie-Tooth Disease/complications , Humans , Male , Pandemics , SARS-CoV-2
J Med Ethics ; 46(8): 505-507, 2020 08.
Article in English | MEDLINE | ID: covidwho-1467731


COVID-19 is reducing the ability to perform surgical procedures worldwide, giving rise to a multitude of ethical, practical and medical dilemmas. Adapting to crisis conditions requires a rethink of traditional best practices in surgical management, delving into an area of unknown risk profiles. Key challenging areas include cancelling elective operations, modifying procedures to adapt local services and updating the consenting process. We aim to provide an ethical rationale to support change in practice and guide future decision-making. Using the four principles approach as a structure, Medline was searched for existing ethical frameworks aimed at resolving conflicting moral duties. Where insufficient data were available, best guidance was sought from educational institutions: National Health Service England and The Royal College of Surgeons. Multiple papers presenting high-quality, reasoned, ethical theory and practice guidance were collected. Using this as a basis to assess current practice, multiple requirements were generated to ensure preservation of ethical integrity when making management decisions. Careful consideration of ethical principles must guide production of local guidance ensuring consistent patient selection thus preserving equality as well as quality of clinical services. A critical issue is balancing the benefit of surgery against the unknown risk of developing COVID-19 and its associated complications. As such, the need for surgery must be sufficiently pressing to proceed with conventional or non-conventional operative management; otherwise, delaying intervention is justified. For delayed operations, it is our duty to quantify the long-term impact on patients' outcome within the constraints of pandemic management and its long-term outlook.

Coronavirus Infections/complications , Decision Making/ethics , Ethics, Medical , General Surgery/ethics , Health Equity/ethics , Pandemics/ethics , Patient Selection/ethics , Pneumonia, Viral/complications , Betacoronavirus , COVID-19 , Coronavirus Infections/virology , Cost-Benefit Analysis , England , Ethical Analysis , Ethical Theory , Humans , Informed Consent/ethics , Moral Obligations , Pneumonia, Viral/virology , Practice Guidelines as Topic , Principle-Based Ethics , Risk Assessment , SARS-CoV-2 , State Medicine , Surgeons , Surgical Procedures, Operative
Dtsch Arztebl Int ; 117(29-30): 492, 2020 07 20.
Article in English | MEDLINE | ID: covidwho-1456276
Repert. med. cir ; 29((Núm. Supl.1.)): 10-14, 2020.
Article in English, Spanish | LILACS (Americas) | ID: covidwho-1436545


Actualmente el mundo atraviesa una de las peores crisis a nivel salud secundario a la infección por un nuevo coronavirus de alta transmisibilidad y mortalidad, que ha impactado múltiples aspectos. Se ha establecido de forma general que la severidad de la infección está asociada con edad avanzada y comorbilidades como hipertensión y diabetes. Por otro lado, la obesidad en este momento representa una de las mayores amenazas del sector salud, por su gran relación con morbimortalidad a nivel cardiometabólico, esto conlleva a un alto costo de la enfermedad. Este artículo busca alertar sobre lo que han llamado algunos expertos el "choque de dos pandemias", esto dado al aumento de la prevalencia de obesidad a nivel mundial, donde nuestro país no está exento, que podría relacionarse con un número mayor de personas vulnerables a la infección por COVID-19 y sus complicaciones respiratorias y de esta manera evitar desenlaces catastróficos.

Currently the world is going through one of the worst health crises secondary to the infection by a new highly transmissible and deadly coronavirus, which has impacted multiple aspects. It has been generally established that the severity of the infection is associated with old age and comorbidities such as hypertension and diabetes. On the other hand, obesity at this time represents one of the greatest threats to the health sector, due to its strong relationship with morbidity and mortality at the cardiometabolic level which leads to a high cost of the disease. This article seeks to warn about what some experts have called the "clash of two pandemics", this given the increasing prevalence of obesity worldwide, where our country is not exempt, which could be related with a greater number of people vulnerable to COVID-19 infection and related respiratory complications and thus avoid catastrophic outcomes.

Humans , Coronavirus Infections/complications , Obesity , Inflammation
Pharmazie ; 75(8): 375-380, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-1435671


Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c and/or irregular blood glucose levels. Diabetic patients' mortality rates with COVID-19 are higher than those of cardiovascular or cancer patients. Recently, Bacillus Calmette-Guérin (BCG) vaccine has shown successful results in reversing diabetes in both rats and clinical trials based on different mechanisms from aerobic glycolysis to beta cells regeneration. BCG is a multi-face vaccine that has been used extensively in protection from tuberculosis (TB) and leprosy and has been repositioned for treatment of bladder cancer, diabetes and multiple sclerosis. Recently, COVID-19 epidemiological studies confirmed that universal BCG vaccination reduced morbidity and mortality in certain geographical areas. Countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies that have shown low numbers of reported COVID-19 cases. Some countries have started clinical trials that included a single dose BCG vaccine as prophylaxis from COVID-19 or an attempt to minimize its side effects. This proposed research aims to use BCG vaccine as a double-edged weapon countering both COVID-19 and diabetes, not only as protection but also as therapeutic vaccination. The work includes a case study of regenerated pancreatic beta cells based on improved C-peptide and PCPRI laboratory findings after BCG vaccination for a 9 year old patient. The patient was re-vaccinated based on a negative tuberculin test and no scar at the site of injection of the 1st BCG vaccination at birth. The authors suggest and invite the scientific community to take into consideration the concept of direct BCG re-vaccination (after 4 weeks) because of the reported gene expressions and exaggerated innate immunity consequently. As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet® while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.

BCG Vaccine/administration & dosage , Coronavirus Infections/immunology , Diabetes Mellitus/immunology , Insulin-Secreting Cells/cytology , Pneumonia, Viral/immunology , Animals , BCG Vaccine/immunology , COVID-19 , Child , Coronavirus Infections/complications , Diabetes Mellitus/physiopathology , Humans , Male , Pandemics , Pneumonia, Viral/complications , Rats , Regeneration/immunology , Risk Factors , Vaccination/methods