Off-label use of muscular VSD device for closure of a rare congenital portosystemic shunt.

BACKGROUND: Congenital portosystemic shunt (CPSS) is a vascular malformation in which portal blood drains toward the systemic circulation, leading to pulmonary hypertension. CASE PRESENTATION: A 10-year-old patient was brought for evaluation because of dyspnea on exertion. Echocardiography revealed a pulmonary hypertension of 75 mmHg, and multi-slice CT angiography revealed the presence of a CPSS. Closure was finally implemented using a muscular ventricular septal defect device. Follow-up of the patient revealed a gradual decline in pulmonary hypertension. CONCLUSIONS: CPSS is an overlooked cause of reversible pulmonary hypertension (PH). Closure of such lesions and reversal pulmonary hypertension are possible via catheterization. The preferred device type depends largely on the intervening team. Plugs are the first choice for interventional radiologists, while ventricular and atrial septal occluder devices and duct occluders are preferred by pediatric cardiologists.

How the COVID-19 Pandemic Contributed to Diagnostic Bias.

Diagnosis bias in the medical field is a recognized entity that can contribute to misdiagnoses and incorrect management. It remains a constant challenge that must be recognized and addressed. Several factors play a role in the formation of preconceptions which influence the physicians' decision-making process. The aim of this paper is to present a case that was misdiagnosed and mistakenly managed due to diagnosis bias during the coronavirus disease 2019 (COVID-19) pandemic. We also suggest two ways to reduce the risk of diagnosis bias. Multi-inflammatory syndrome of children (MIS-C) was described during the COVID-19 pandemic. The rise in the incidence of MIS-C masked the diagnosis of other diseases that present in a similar fashion. In this paper, we describe the case of a seven-year-old girl, who presented in 2020, with acute onset respiratory distress. Her chest images were suggestive of COVID-19 pneumonitis which prompted the physicians to complete the MIS-C workup by performing an echocardiogram. A large aneurysm of the left main artery was seen which led to a preliminary diagnosis of MIS-C. A repeat echocardiography, 48 hours after the initiation of MIS-C treatment, was suggestive of a large coronary fistula complicated by infective endocarditis and multiple septic pulmonary emboli. It can be inferred that the misdiagnosis occurred as a result of availability and premature-closure biases. Efforts to decrease such biases include group decision-making and using checklists during the assessment of a patient.

Predictors of protein losing enteropathy after Fontan completion: An 8-year retrospective study at Sheikh Khalifa Medical City.

BACKGROUND: The Fontan procedure is the final stage of a three-stage palliation process in patients born with a univentricular heart as part of hypoplastic left heart syndrome (HLHS) or other pathologies with a univentricular heart. As essential as this procedure has proven to be for such cases, the Fontan physiology diminishes cardiac output and expands systemic venous pressure, which then leads to venous congestion that can be complicated by protein-losing enteropathy (PLE). This retrospective study aimed to identify the predictors of such complications in all patients who underwent completion of the Fontan procedure at our center (Sheikh Khalifa Medical City/SKMC) in the past eight years. METHODS: This study examined the medical records of patients who underwent completion of Fontan repair at our center since the inauguration of the cardiac surgery program of SKMC in the United Arab Emirates (UAE) - 01 Jan 2012 to 31 Dec 2020. Exclusion criteria included the absence of any of the undermentioned data in patient files. Patients were divided into two groups: those who developed PLE and those who did not. For each group, the following data were collected: demographics data (current age and age at completion of Fontan), clinical and laboratory data (oxygen saturation, serum albumin), echocardiographic data (classification of original cardiac diagnosis, degree of atrio-ventricular valve regurgitation, ventricular functions), hemodynamic data (mean pressures of superior vena cava and pulmonary arteries before Fontan completion), operative data (type of initial palliation, type of Fontan, presence of fenestrations and its size) and the need for any cardiac intervention prior to Fontan completion, such as atrio-ventricular valve repair, peripheral pulmonary stenting and arch balloon dilatation. RESULTS: Of the 48 included patients,13 (25%) developed PLE. Multivariate regression analysis proved that the best predictors of PLE were superior vena cava mean pressure (P = 0.012) and the degree of atrio-ventricular valve regurgitation (P = 0.013). An oxygen saturation <83% prior to Fontan completion was 92% sensitive in predicting PLE after Fontan completion. CONCLUSION: This is a single-center study of the predictors of PLE after Fontan procedure and, as expected from similar studies, SVC pressure higher than 11 mmHg and moderate-to-severe atrio-ventricular valve regurgitation were predictors of Fontan failure. The higher prevalence of PLE in our cohort, as well as lower cut-offs of SVC pressure that can predict complications, may be related to the predominance of hypoplastic left heart in the operated patients, which has been the main referral center for cardiac surgeries in UAE in the last decade.

New Strategies in the Treatment of Advanced Heart Failure in Children and the Current Consensus of Cairo University Children Hospital Heart Failure Working Group.

The long-term treatment of congestive heart failure (CHF) in children includes digoxin, diuretics and afterload reduction with angiotensin-converting enzyme (ACE) inhibitors. In spite of the wide use of these drugs being the standard, yet, pediatric heart failure (PHF) continued to be an important cause of morbidity and mortality in childhood. Introduction of new drugs has elevated the level of tolerance of these patients and played a role in delaying their urgent need to have heart transplant or Mechanical circulatory support (MCS). Together with a patient by patient tailored combination of different diuretics. We aim to present and discuss these new drugs and the combinations of regular drugs to reach the best outcome, as well as the consensus of our pediatric heart failure working group in Egypt.

The role of miRNAs in viral myocarditis, and its possible implication in induction of mRNA-based COVID-19 vaccines-induced myocarditis.

Background: Several reports of unheeded complications secondary to the current mass international rollout of SARS-COV-2 vaccines, one of which is myocarditis occurring with the FDA fully approved vaccine, Pfizer, and others. Main body of the abstract: Certain miRNAs (non-coding RNA sequences) are involved in the pathogenesis in viral myocarditis, and those miRNAs are interestingly upregulated in severe COVID-19. We hypothesize that the use of mRNA-based vaccines may be triggering the release of host miRNAs or that trigger the occurrence of myocarditis. This is based on the finding of altered host miRNA expression promoting virus-induced myocarditis. Short conclusion: In conclusion, miRNAs are likely implicated in myocarditis associated with mRNA vaccines. Our hypothesis suggests the use of miRNA as a biomarker for the diagnosis of mRNA vaccine-induced myocarditis. Additionally, the interplay between viral miRNA and the host immune system could alter inflammatory profiles, hence suggesting the use of therapeutic inhibition to prevent such complications.

Cardiac autonomic neuropathy linked to left ventricular dysfunction in type 1 diabetic patients.

Type 1 diabetes is a major cause of cardiovascular death; diabetic cardiomyopathy (DCM) is the most important cause of mortality among diabetic patients. There is an increasing body of evidence that the most important inducer of DCM is microvascular injury. The aim of this study is to establish a potential relationship between low frequency/high frequency (LF/HF) ratio and DCM and to set a possible predictive cutoff of LF:HF ratio for early detection of DCM. Methods: 75 type 1 diabetic patients together with 75 controls were assessed using tissue Doppler imaging for left ventricular (LV) and right ventricular (RV) diastolic function, and heart rate variability (HRV) indices including LF/HF ratio. Type 1 diabetic patients were also assessed for parameters of glycemic and lipid profile control. Results: Cases showed a statistically significant increase in LF/HF ratio compared to controls reflecting reduced HRV. Also, LV and RV diastolic function were reduced in cases compared to controls, there was a significant correlation between LV E/E' ratio (ratio of early transmitral velocity and average early mitral annular and basal septal velocities) and LF/HF ratio. LF/HF ratio was able to predict LV diastolic dysfunction as expressed by the LV E/E' ratio with a sensitivity of 96%. Conclusion: HRV indices notably LF/HF ratio seem to be an early and sensitive predictor of DCM, the latter finding not only underlines the role of microvascular injury in the induction of DCM but might help also for the early detection and reversal of it.

From HIV to COVID-19, Molecular mechanisms of pathogens' trade-off and persistence in the community, potential targets for new drug development.

Background: On the staggering emergence of the Omicron variant, numerous questions arose about the evolution of virulence and transmissibility in microbes. Main body of the abstract: The trade-off hypothesis has long speculated the exchange of virulence for the sake of superior transmissibility in a wide array of pathogens. While this certainly applies to the case of the Omicron variant, along with influenza virus, various reports have been allocated for an array of pathogens such as human immunodeficiency virus (HIV), malaria, hepatitis B virus (HBV) and tuberculosis (TB). The latter abide to another form of trade-off, the invasion-persistence trade-off. In this study, we aim to explore the molecular mechanisms and mutations of different obligate intracellular pathogens that attenuated their more morbid characters, virulence in acute infections and invasion in chronic infections. Short conclusion: Recognizing the mutations that attenuate the most morbid characters of pathogens such as virulence or persistence can help in tailoring new therapies for such pathogens. Targeting macrophage tropism of HIV by carbohydrate-binding agents, or targeting the TMPRSS2 receptors to prevent pulmonary infiltrates of COVID-19 is an example of how important is to recognize such genetic mechanisms.

Meary angle for the prediction of mitral valve prolapse risk in non-syndromic patients with pes planus, a cross-sectional study.

OBJECTIVES: Mitral Valve Prolapse (MVP) is a common valvular abnormality accounting for 2% of the population. There is a reported association between pes planus (PP) and MVP in some syndromes such as Marfan. However, this association has not been tested in non-syndromic cases. The primary outcome of this study is to measure the prevalence of MVP in a population of patients with PP. The secondary outcome parameter is to determine if the Meary angle (MA), a measure of the severity of flat foot, can be effectively used in the prediction of the presence of MVP. Forty-one patients with PP were screened using a lateral x-ray foot to determine MA while echocardiography was utilized to identify the presence and grade of MVP. RESULTS: 88% of screened patients were diagnosed with MVP. MA was correlated with the grade of MVP and showed high diagnostic accuracy (sensitivity 100% and specificity 90%) in predicting MVP risk when higher than 5. Children with PP are at a higher risk for MVP than the general population. Accordingly, the utilization of MA in such a specific population for the determination of patients at a higher need for echocardiography seems to be a worthwhile strategy in diagnosing MVP.

Blalock-Taussig Shunt versus Ductal Stent in the Palliation of Duct Dependent Pulmonary Circulation; A Systematic Review and Metanalysis.

In infants with ductal dependent pulmonary blood flow, Blalock-Taussig (BT) shunt and Patent Ductus Arteriosus (PDA) stent, are two palliative procedures aimed to restore circulation. A systematic review and metanalysis was performed on studies comparing PDA stents and BT shunts, in accordance with PRISMA guidelines. Meta-analysis revealed the following; (1) a reduced risk of mortality [RR = 0.585 [0.399-0.859], (P = 0.006)], (2) a reduced risk of complications [RR = 0.523 [0.318-0.860], (P = 0.011), and (3) a reduced risk of ECMO use [R = 0.267 [0.101-0.706] (P = 0.008)], all in the stent group. Additionally, stent group showed higher post procedure oxygen saturation [SMD = 1.307 [95% CI 1.065-1.550], (P < 0.001)], and Nakata index [SMD = 0.679 95% CI [0.513 to 0.845], (P < 0.001)]. PDA stenting presents a viable alternative to BT shunt procedure with better post procedure stability.

Advanced Echocardiography Techniques: The Future Stethoscope of Systemic Diseases.

Cardiovascular disease (CVD) has been showing patterns of extensive rise in prevalence in the contemporary era, affecting the quality of life of millions of people and leading the causes of death worldwide. It has been a provocative challenge for modern medicine to diagnose CVD in its crib, owing to its etiological factors being attributed to a large array of systemic diseases, as well as its non-binary hideous nature that gradually leads to functional disability. Novel echocardiography techniques have enabled the cardiac ultrasound to provide a comprehensive analysis of the heart in an objective, feasible, time- and cost-effective manner. Speckle tracking echocardiography, contrast echocardiography, and 3D echocardiography have shown the highest potential for widespread use. The uses of novel modalities have been elaborately demonstrated in this study as a proof of concept that echocardiography has a place in routine general practice with supportive evidence being as recent as its role in the concurrent COVID-19 pandemic. Despite such evidence, many uses remain off-label and unexploited in practice. Generalization of echocardiography at the point of care can become a much-needed turning point in the clinical approach to case management. To actualize such aspirations, we recommend further prospective and interventional studies to examine the effect of implementing advanced techniques at the point of care on the decision-making process and evaluate their effectiveness in prevention of cardiovascular morbidities and mortalities.

Early onset left ventricular remodeling in juvenile systemic lupus erythematosus; Insight from 3-dimensional speckle tracking echocardiography.

BACKGROUND: Early diagnosis and treatment of myocardial affection in patients with systemic lupus erythematosus (SLE) are crucial. OBJECTIVES: To evaluate the ventricular systolic function in juvenile-onset systemic lupus erythematosus (j-SLE) patients by 3-D speckle tracking echocardiography (3D-STE) and to determine the predictors of left ventricular (LV) dysfunction if present. METHODS: Twenty-six SLE patients without heart failure and 21 healthy controls were studied by standard echocardiogram and 3D-STE. Conventional parameters included LV ejection fraction (EF), fractional shortening (FS), and mitral annular plane systolic excursion (MAPSE). Global LV strain (GLS) and global area strain (GAS) were obtained by 3D-STE. Medical records, including diagnosis criteria, duration of disease, and SLE disease activity index (SLEDAI) were evaluated. RESULTS: The mean age was similar in patients and controls 11.42 vs 11.48 years p = 0.93. The mean duration of the disease was 1.87 ± 1.02 years and SLEDAI ranged from 0 to 9. By conventional and tissue Doppler imaging echocardiography, only MAPSE was significantly lower in SLE patients compared to controls (14.56 vs 18.46 mm, p < 0.001). By 3D speckle tracking echocardiography, GLS and GAS were significantly reduced in SLE patients compared to controls (-15.07 vs -19.9.4%, -34.6% vs -39.7%, respectively, p < 0.001). Multiple linear regression and ROC analyses indicated that the SLEDAI score was the only predictive factor for the left ventricular remodeling. CONCLUSIONS: These results indicate that early subclinical LV dysfunction occur in jSLE patients even with normal EF and SLE disease activity might be a potential driver for LV deformation.

The potential role of inhaled nitric oxide for postexposure chemoprophylaxis of COVID-19.

BACKGROUND: Several vaccines have been fast-tracked in an attempt to decrease the morbidity and mortality of COVID-19. However, post-exposure prophylaxis has been overlooked in battling COVID-19. MAIN TEXT: Inhaled nitric oxide is a potential tool in post-exposure prophylaxis of COVID-19. It decreases cytosolic calcium levels, which impairs the action of Furin. SARS-CoV-2 uses Furin to replicate in the respiratory tract. SHORT CONCLUSION: Inhaled nitric oxide could decrease the viral load in the upper respiratory tract, abort clinically symptomatic infection, and prevent subsequent complications. Nitric oxide might be a tool for post-exposure chemoprophylaxis in at-risk groups, especially medical personnel.

Salivary markers and coronavirus disease 2019: insights from cross-talk between the oral microbiome and pulmonary and systemic low-grade inflammation and implications for vascular complications.

To date, coronavirus disease 2019 (COVID-19) has affected over 6.2 million individuals worldwide, including 1.46 million deaths. COVID-19 complications are mainly induced by low-grade inflammation-causing vascular degeneration. There is an increasing body of evidence that suggests that oral dysbiotic taxa are associated with worse prognosis in COVID-19 patients, especially the Prevotella genus, which was retrieved from nasopharyngeal and bronchoalveolar lavage samples in affected patients. Oral dysbiosis may act by increasing the likelihood of vascular complications through low-grade inflammation, as well as impairing respiratory mucosal barrier mechanisms against SARS-CoV-2. Salivary markers can be used to reflect this oral dysbiosis and its subsequent damaging effects on and the lungs and vasculature. Salivary sampling can be self-collected, and is less costly and less invasive, and thus may be a superior option to serum markers in risk stratification of COVID-19 patients. Prospective studies are needed to confirm such hypothesis. Video Abstract: http://links.lww.com/CAEN/A28.

Novel biomarkers for subtle myocardial involvement in type I diabetes mellitus.

BACKGROUND: Evaluation of certain biomarkers could be used to predict left ventricular (LV) and right ventricular (RV) function impairment in children with type 1 diabetes mellitus. The aim of this study was to determine the best cardiac biomarker for prediction of diabetic cardiomyopathy. METHODOLOGY: This study was designed as case-control study. A total of 55 children with type 1 diabetes mellitus (group/G1) and 55 healthy controls (G2) were subjected to echocardiography including 3D-Speckle Tracking Echocardiography and tissue Doppler imaging for assessment of RV and LV systolic and diastolic functions. As well as HbA1c, troponin I, brain natriuretic peptide (BNP), plasma cardiotrophin (CT-1), activin-A, transforming growth factor-ß, and human insulin-like growth factor binding protein-7 (IGFBP-7) measurements. RESULTS: Diabetic patients showed RV and LV systo-diastolic dysfunction compared to controls, the best predictor of LV systolic dysfunction was CT-1 (sensitivity: 69%, while IGFBP-7 was found to be the best predictor of RV systolic dysfunction (sensitivity: 63%). BNP was found to the best predictor of diastolic RV and LV dysfunction (sensitivity: 82% for both). CONCLUSION: CT-1 has proven to be a diagnostic superiority in LV systolic dysfunction whilst BNP continues to prove every day through our study and through many others that it is the chief marker of diastolic dysfunction and HFpEF. This potential accuracy and the increasing availability of BNP in the outpatient setting make it clear that it should be used as a screening test for diabetic patients.

JAK out of the Box; The Rationale behind Janus Kinase Inhibitors in the COVID-19 setting, and their potential in obese and diabetic populations.

The adaptive use of Janus kinase (JAK)-inhibitors has been suggested by rheumatology experts in the management of COVID-19. We recount the rationale behind their use in this setting, and the current evidence for and against their use in this review. JAK-inhibitors role in COVID-19 infection appears to be multifaceted, including preventing viral endocytosis and dampening the effect of excessive chemokines. This drug class may be able to achieve these effects at already preapproved dosages. Concerns arise regarding reactivation of latent viral infections and the feasibility of their use in those with severe disease. Most interestingly, JAK-Inhibitors may also have an additional advantage for diabetic and obese populations, where the dysregulation of JAK-signal transducer and activator of transcription pathway may be responsible for their increased risk of poor outcomes. Targeting this pathway may provide a therapeutic advantage for these patient groups.

PPAR agonists as effective adjuvants for COVID-19 vaccines, by modifying immunogenetics: a review of literature.

BACKGROUND: Several coronavirus vaccine have been fast-tracked to halt the pandemic, the usage of immune adjuvants that can boost immunological memory has come up to the surface. This is particularly of importance in view of the rates of failure of seroconversion and re-infection after COVID-19 infection, which could make the vaccine role and response debatable. Peroxisome proliferator-activated receptors (PPARs) have an established immune-modulatory role, but their effects as adjuvants to vaccination have not been explored to date. It is increasingly recognized that PPAR agonists can upregulate the levels of anti-apoptotic factors such as MCL-1. Such effect can improve the results of vaccination by enhancing the longevity of long-lived plasma cells (LLPCs). The interaction between PPAR agonists and the immune system does not halt here, as T cell memory is also stimulated through enhanced T regulatory cells, antagonizing PD-L1 and switching the metabolism of T cells to fatty acid oxidation, which has a remarkable effect on the persistence of T memory cells. What is even of a more significant value is the effect of PPAR gamma on ensuring a profound secretion of antibodies upon re-exposure to the offending antigen through upregulating lipoxin B4, therefore potentially assisting the vaccine response and deterring re-infection. SHORT CONCLUSION: In view of the above, we suggest the use of PPAR as adjuvants to vaccines in general especially the emerging COVID-19 vaccine due to their role in enhancing immunologic memory through DNA-dependent mechanisms.

The potential use of lactate blockers for the prevention of COVID-19 worst outcome, insights from exercise immunology.

Following the decline in Physical Activity (PA) due to COVID-19 restrictions in the form of government mandated lockdowns and closures of public spaces, the modulatory effect of physical exercise on immunity is being heavily revisited. In an attempt to comprehend the wide discrepancy in patient response to COVID-19 and the factors that potentially modulate it, we summarize the findings relating PA to inflammation and immunity. A distinction is drawn between moderate intensity and high intensity physical exercise based on the high lactate production observed in the latter. We hypothesize that, the lactate production associated with high intensity anaerobic exercise is implicated in the modulation of several components of the innate and adaptive immunity. In this review, we also summarize these immunomodulatory effects of lactate. These include increasing serum IL-6 levels, the main mediator of cytokine storms, as well as affecting NK cells, Macrophages, Dendritic cells and cytotoxic T-lymphocytes. The implications of high lactate levels in athletic performance are highlighted where athletes should undergo endurance training to increase VO2 max and minimize lactate production. Tumor models of hypoxia were also reported where lactate levels are elevated leading to increased invasiveness and angiogenesis. Accordingly, the novel lactate blocking strategy employed in cancer treatment is evaluated for its potential benefit in COVID-19 in addition to the readily available beta-blockers as an antagonist to lactate. Finally, we suggest the diagnostic/prognostic purpose of the elevated lactate levels that can be determined through sweat lactate testing. It is the detrimental effect of lactate on immunity and its presence in sweat that qualify it to be used as a potential non-invasive marker of poor COVID-19 outcome.

Hypoxia-inducible factor (HIF): The link between obesity and COVID-19.

The COVID-19 death toll has involved to date more than 1 million confirmed deaths. The death rate is even higher in the obese COVID-19 patients, as a result of hypoxia, due to the interplay between adipose tissue hypoxia and obstructive sleep apnea. The discrepancy of manifestations seen in COVID-19 seems to be mediated by a differential immune response rather than a differential viral load. One of the key players of the immune response is HIF. HIF-1ß is a stable constitutively expressed protein in the nucleus; and under hypoxic changes, its activity is unaffected, whereas the HIF-α subunit has a short half-life and because of its degradation by an enzyme known as propyl hydroxylase; under hypoxic conditions, propyl hydroxylase gets deactivated thus leading to the stabilization of HIF-1α. As mentioned before, HIF-1α expression is triggered by hypoxic states, this crippling condition will aggravate the pro-inflammatory characteristics of HIF-1α. The vast majority of decompensated COVID19 cases manifest with drastic lung injury and severe viral pneumonia, the infection-induced hypoxia will the existing hypoxia in obesity. This will additionally augment HIF-1α levels that will provoke the already existing cytokines' storm to fulminant. Consequently, this will directly correlate the effect of a hypoxic environment with the increase of HIF-1α level. HIFɑ exists in two main isoforms HIF-1α and HIF-2α. HIF-1α and HIF-2α act in distinct ways in how they work on different target genes. For example, HIF-2α may act on hemopoietin genes (heme-regulating genes); while HIF-1α acts on EPO. HIF-1α release seems to be markedly augmented in obesity due to adipose tissue hypoxia and obstructive sleep apnea resulting in cyclic hypoxia. HIF-1α can also be secreted by direct viral proteolytic effects. Whereas, HIF-2α is stimulated by chronic hypoxia. HIF-1α exerts detrimental effects on the immune system, characterized by unopposed pro-inflammation at the macrophages, dendritic cells, T cells, and complement levels resulting in cytokines' storm, which is linked to the poor outcomes of COVID-19. On the other hand, HIF-2α role is regulatory and largely opposes the actions mediated by HIF-1α. In view of this, inhibiting HIF-1α release or switching its production to HIF-2α by natural products such as resveratrol or by synthetic drugs, offer a good therapeutic strategy that can prevent COVID-19 worst outcome in infected patients. The approach of breaking the vicious circle between lung damage-induced hypoxia and HIF-1α pro-inflammatory stimulant through drugs is considered to be extremely promising as a therapeutic manner to combat further deterioration of COVID19 cases.