The Ross Procedure: Imaging, Outcomes and Future Directions in Aortic Valve Replacement.

The Ross procedure is gaining recognition as a significant option for aortic valve replacement (AVR), and is particularly beneficial in specific patient groups. Although categorized as a class IIb recommendation in the 2020 American College of Cardiology (ACC)/American Heart Association (AHA), and the European Society of Cardiology (ESC) management guidelines on valvular heart disease, recent studies bolster its credibility. Research, including a propensity-matched study, underlines the Ross procedure's association with enhanced long-term survival and reduced adverse valve-related events compared to other AVR types. This positions the Ross procedure as a primary option for AVR in young and middle-aged adults within specialized centers, and potentially the only choice for children and infants requiring AVR. This review meticulously examines the Ross procedure, covering historical perspectives, surgical techniques, imaging, and outcomes, including hemodynamic performance and quality of life, especially focusing on pediatric and young adult patients. It explores contemporary techniques and innovations like minimally invasive approaches and tissue engineering, underscoring ongoing research and future directions. A summarization of comparative studies and meta-analyses reiterates the Ross procedure's superior long-term outcomes, valve durability, and preservation of the left ventricular function, accentuating the crucial role of patient selection and risk stratification, and pinpointing areas for future research.

Unlocking insights in bicuspid aortic valve management in adult patients: the vital role of cardiac imaging.

The bicuspid aortic valve (BAV) presents a multifaceted clinical challenge due to its diverse morphologies and associated complications. This review aims to elucidate the critical role of cardiac imaging in guiding optimal management strategies for BAV patients. BAV, with a prevalence of 1-2%, has genetic underpinnings linked to the NOTCH1 gene mutation. Variability in BAV morphology necessitates tailored surgical approaches. The three primary types of BAV morphology - right-left cusp fusion, right-noncoronary cusp fusion, and left-noncoronary cusp fusion - demand nuanced considerations due to their distinct implications. Valvular dysfunction results in aortic stenosis or regurgitation, attributed to altered valve structure and turbulent hemodynamics. Cardiac imaging modalities, including echocardiography, magnetic resonance imaging, and computerized tomography, are instrumental in assessing valve function, aortic dimensions, and associated complications. Imaging helps predict potential complications, enabling informed treatment decisions. Regular follow-up is crucial to detecting alterations early and intervening promptly. Surgical management options encompass aortic valve repair or replacement, with patient-specific factors guiding the choice. Post-surgical surveillance plays a vital role in preventing complications and optimizing patient outcomes. The review underscores the significance of advanced cardiac imaging techniques in understanding BAV's complexities, facilitating personalized management strategies, and improving patient care. By harnessing the power of multimodal imaging, clinicians can tailor interventions, monitor disease progression, and ultimately enhance the prognosis and quality of life for individuals with BAV.

Role of three-dimensional transesophageal echocardiography in cardiac myxomas: an imaging challenge.

Nowadays, the diagnosis of cardiac myxomas (CM), particularly the histological types, remains a challenge. Two-dimensional (2D) transthoracic (TT) and transesophageal (TEE)  echocardiography (ECHO) represent the first steps in the imaging pathway. 3D ECHO,  implemented in imaging practice, appears to be an emerging diagnostic technique that overcomes some of the limitations of 2D ECHO while integrating the information provided by magnetic resonance (MRI). However, its role in the imaging arena is still debatable. Analyzing 17 myxomas in 13 patients, the study uncovers a diverse anatomical spectrum. Classical CM morphology is a minority, with most myxomas being sessile and originating from unexpected locations (right ventricular outflow tract and left atrial appendage). Texture and size variations are also noted. Comparing imaging, 2D TEE outperforms 2D TT in visualizing anatomical features, especially attachment types. 3D TEE confirms 2D TT findings and offers more detailed assessments, identifying peduncles missed in four cases by 2D TEE. Two small recurrent myxomas were exclusively detected by 3D TEE, not by 2D TEE or MRI. Two patients have papillary myxomas, one has an embolism. Another patient with a solid myxoma also suffers an embolism, with a clot found at the apex during surgery. Our study showed that CM has a wide anatomical spectrum beyond the typical features, making the diagnosis challenging. Therefore, a multimodality imaging approach is essential for distinguishing CM from other cardiac masses and differentiating myxoma histological types. These findings stress the importance of incorporating 3D ECHO alongside other imaging techniques for a comprehensive evaluation.

QcrB inhibition as a potential approach for the treatment of tuberculosis: A review of recent developments, patents, and future directions.

The unmet medical need for drug-resistant tuberculosis (DRTB) is a significant concern. Accordingly, identifying new drug targets for tuberculosis (TB) treatment and developing new therapies based on these drug targets is one of the strategies to tackle DRTB. QcrB is an innovative drug target to create treatments for DRTB. This article highlights QcrB inhibitors and their therapeutic compositions for treating TB. The literature for this article was gathered from PubMed and free patent databases utilizing different keywords related to QcrB inhibitor-based inventions. The data was collected from the conceptualization of telacebec (2010) QcrB to December 2022. A little interesting and encouraging research has been performed on QcrB inhibitors. Telacebec and TB47 are established QcrB inhibitors in the clinical trial. The inventive QcrB inhibitor-based drug combinations can potentially handle DRTB and reduce the TB therapy duration. The authors anticipate great opportunities in fostering QcrB inhibitor-based patentable pharmaceutical inventions against TB. Drug repurposing can be a promising strategy to get safe and effective QcrB inhibitors. However, developing drug resistance, drug tolerance, and selectivity of QcrB inhibitors for Mtb will be the main challenges in developing effective QcrB inhibitors. In conclusion, QcrB is a promising drug target for developing effective treatments for active, latent, and drug-resistant TB. Many inventive and patentable combinations and compositions of QcrB inhibitors with other anti-TB drugs are anticipated as future treatments for TB.

Computer-assisted discovery of safe and effective DprE1/ aaRSs Inhibitors against TB utilizing Drug Repurposing approach.

BACKGROUND: The emergence of various drug-resistant strains of Mycobacterium tuberculosis compelled medicinal chemists to expedite the discovery of novel, safer alternatives to present regimens. Decaprenylphosphoryl-ß-d-ribose 2'-epimerase (DprE1), an essential component of arabinogalactan biosynthesis, has been considered a novel target for developing new inhibitors against Tuberculosis. We aimed to discover DprE1 inhibitors utilizing the drug repurposing approach. METHODS: A structure-based virtual screening of FDA and world-approved drugs database was carried out, and initially, 30 molecules were selected based on their binding affinity. These compounds were further analyzed by molecular docking with extra-precision mode, MMGBSA binding free energy estimation, and prediction of ADMET profile. RESULTS: Based on the docking results and MMGBSA energy values- ZINC000006716957, ZINC000011677911, and ZINC000022448696 were identified to be the top three hit molecules with good binding interactions inside the active site of DprE1. These hit molecules were subjected to molecular dynamics (MD) simulation for a period of 100 ns to study the dynamic nature of the binding complex. MD results were in accordance with molecular docking and MMGBSA analysis showing protein-ligand contacts with key amino acid residues of DprE1. CONCLUSION: Based on their stability throughout the 100 ns simulation, ZINC000011677911 was the best in silico hit with an already known safety profile. This molecule could lead to future optimization and development of new DprE1 inhibitors.

Predictors of Illness Severity in COVID-19 Cases in Saudi Arabia.

PURPOSE: Multiple studies worldwide have reported the clinical and epidemiological features of coronavirus disease 2019 (COVID-19), with limited reports from the Middle East. This study describes the clinical and epidemiological features of COVID-19 cases in the Eastern Province of Saudi Arabia and identified factors associated with the severity of illness. PATIENTS AND METHODS: This was an observational study of 341 COVID-19 cases. These cases were reported in the first three months after the first case in the country was identified. Clinical and demographic data were analyzed and described to identify the effects of age, sex, and ethnicity on illness severity. In addition, the duration of viral shedding and cycle threshold (Ct) values of real-time PCR were evaluated as predictors of severity. RESULTS: The median age was 45 years. Males were twice as likely to be infected than females (p <0.0001). The duration of viral shedding ranged from 9 to 36 days. The most common clinical presentations include fever, shortness of breath, cough, myalgia, sore throat, vomiting, and headache. Critical cases were significantly higher in men (23% vs 8.7%), senior adults (>65 years), individuals of Bengali ethnicity, and in patients with comorbidities including diabetes, hypertension, and dyslipidemia (p =0.001). The case fatality rate was found to be 10%. The fatality was significantly higher in males than females (13.8% vs 2.6%), and in Asians (17.9%) than Arabs (6%) and Africans (0) (p =0.002). No association was found between viral load, represented by the RT-PCR cycle threshold (Ct) values, and severity of illness. CONCLUSION: Age, sex, and ethnicity are important predictors of COVID-19 severity. The cycle threshold (Ct) of the SARS-CoV-2 RT-PCR test cannot be used as a predictor of the criticality of illness.

Vitamin B12 deficiency and the knowledge and practice of physicians regarding screening for vitamin B12 deficiency among type 2 diabetic patients on metformin in selected hospitals in Riyadh, Saudi Arabia.

BACKGROUND/AIM: The worldwide prevalence of diabetes is high including Saudi Arabia. One standard first-line treatment for diabetes is metformin, which was reported to increase the risk for vitamin B12 deficiency. We wanted to determine the prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes mellitus patients. METHODS: We conducted a cross-sectional study at the diabetic clinics of four hospitals in Riyadh, Saudi Arabia. Type 2 diabetes mellitus patients who were on metformin for at least 1 year were included in the study. Associations between B12 deficiency and age, duration of type 2 diabetes mellitus (T2DM), duration of use and dosage of metformin, and use of proton pump inhibitors (PPIs) were determined. RESULTS: Of 363 T2DM patients, 206 (56.7%) were males and 157 (43.3%) were females, mean age was 53.72 ± 11.31 years, the mean duration of T2DM was 9.89 ± 7.32 years, and the mean duration of metformin use was 9.84 ± 7.29 years. There were 205 patients 56.5% who had a daily dose of 750 mg of metformin. The most commonly used oral hypoglycemic agent was gliclizide only in 138 (38.4%) of patients. There were 107 patients (29.5%) who were on PPIs. There were 210 patients (57.9%) who were on vitamin B12 supplementation, of which 111 (30.6%) had a daily dose of 200 mcg. The use of vitamin B12 supplement, duration of T2DM and duration of metformin use was significantly higher among females. The use of vitamin B12 supplement was significant among patients who were 46 years old and above. There were only 16 patients (4.4%) who had available serum vitamin B12 levels. Only 44.0% of the physician respondents know the current recommendation of American Diabetes Association on vitamin B12 screening and supplementation among diabetic patients, and 21.0% never prescribe vitamin B12 to their patients. CONCLUSION: Routine testing for serum vitamin B12 level is not practiced in our institution. A large percentage of physicians are not aware of the current recommendations of the American Diabetic Association (ADA) regarding vitamin B12 supplementation and screening. Thus, there is a need for doctors involved in the management of diabetes to keep abreast with guidelines and current recommendations and routinely monitor vitamin B12 levels particularly those who were on long-term takers of metformin and the elderly patients to optimize management of diabetes and its complications.