The Use of CRISPR-Cas9 Genetic Technology in Cardiovascular Disease: A Comprehensive Review of Current Progress and Future Prospective.

Over the last century, there have been major landmark developments in the field of medicine, enabling us to control and cure various diseases on a larger scale. A few of these include the discovery of antibiotics, the development of vaccines, and the origin of organ and tissue transplants. The continued quest for innovation in microbiology and medicine has helped humankind save millions of lives and decrease morbidity at the global level. Genetic medicine has grown significantly in the last two decades and appears to be the next frontier of curative therapies for chronic diseases. One important landmark in genetic medicine is the development of CRISPR (clustered, regularly interspaced short palindromic repeats) technology. In this article, we describe the basic structure and function of the CRISPR-Cas9 system, which, simply put, consists of an RNA part and a protein. It works as a molecular scissor that can perform targeted cuts followed by repairs in and around the genes of interest to attain favorable translational outcomes. We focused on summarizing recent studies using CRISPR-Cas9 technology in diagnosing and treating cardiovascular disease. These studies are primarily experimental and limited to animal models. However, their results are promising enough to anticipate that this technology will undoubtedly be available in clinical medicine in the coming years. CRISPR-Cas9-mediated gene editing has been used to study and potentially treat congenital heart disease, hyperlipidemias, arrhythmogenic cardiomyopathies, and the prevention of ischemia-reperfusion injury. Despite the current progress, we recognize the several challenges this technology faces, including funding for research, improving precision and reproducible results for human subjects, and establishing protocols for ethical compliance so that it is acceptable to the scientific community and the general public.

Reversible Cerebral Vasoconstriction Syndrome Associated With Oxybutynin Use; a Brief Review of Pathophysiology.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by reversible vasospasm of the central nervous system vasculature. It usually presents as a classic thunderclap headache, but complications like a stroke, seizure, or intracranial hemorrhage may occur at the onset. Most cases are linked temporally to secondary agents. The most common suggested mechanism underlying the RCVS is vascular tone dysregulation. Our report describes the RCVS incidence associated with oxybutynin use in a young female. We aim to describe the potential pathophysiology linking oxybutynin use and RCVS.

Arrhythmogenic Left Ventricular Cardiomyopathy Associated With a Phospholamban Gene Mutation in a Young Female: A Case Report and Literature Review.

Arrhythmogenic cardiomyopathy (ACM) is a myocardium disease characterized by phenotypic features of myocardial scarring due to fibrofatty myocardial replacement often associated with global or regional ventricular dysfunction. For years after arrhythmogenic right ventricular cardiomyopathy (ARVC) was first described, the left ventricle (LV) was generally considered normal or minimally involved. In recent years, however, LV involvement has been recognized. It usually presents with early-on arrhythmias more than heart failure symptoms compared to dilated cardiomyopathy. It can be right ventricular, biventricular, or left ventricular. The underlying pathophysiology involves either desmosomal or non-desmosomal mutations. Phospholamban (PLN) mutation is one of those and is associated with more severe arrhythmias and SCD. Primary prevention with ICD implantation should be considered in these patients, even the ones with an ejection fraction greater than 35%. In addition, if such patients progress to Stage D heart failure, they need to be evaluated for advanced heart failure therapies.

Pembrolizumab-Induced Broken Heart Syndrome, Pneumonitis, and Hypophysitis Occurring Concurrently; A Deadly Triad.

Immune checkpoint inhibitors are novel medications used to treat a wide range of solid organ tumors and work by stimulating the cellular immune response. With their increasing use, more and more multiorgan side effects are reported in the literature. Prompt recognition of these findings is vital for the safe clinical use of these agents. Most side effects are immune-mediated injury, and the treatment involves stopping the ICI drug and systemic steroids. We report a case of a 72-year-old female treated with pembrolizumab monotherapy for non-small cell lung cancer. She presented for dyspnea and generalized weakness after the second session of pembrolizumab. She was found to have a triad of Takotsubo cardiomyopathy, hypophysitis, and pneumonitis. The patient was discharged home on steroids and heart failure treatment with the discontinuation of further sessions of pembrolizumab.

Pakistan's Healthcare System: A Review of Major Challenges and the First Comprehensive Universal Health Coverage Initiative.

Each country's healthcare system has a different structure and functioning designed to meet the needs of its people utilizing the available resources. Due to ever-growing population needs and constantly emerging public health problems, it is vital for any healthcare system to be ready to adapt, recognize its limitations, and improve its flaws by learning from other healthcare models across the globe. In this article, we analyzed the significant challenges faced by Pakistan's healthcare system (PHS) and the first comprehensive initiative taken for universal health coverage in Pakistan. Inequitable distribution of resources, inadequate healthcare spending, non-adherence to preventative healthcare and brain drain are the major problems in the PHS. On the other hand, the recently introduced universal health coverage initiative, the Sehat Sahulat Program (SSP), can be considered one of the biggest achievements of the country's healthcare system.

A novel opportunity to improve heart failure care: focusing on subcutaneous furosemide.

The prevalence of heart failure (HF) continues to rise in developed nations. Symptomatic congestion is the most common reason for patients to seek medical attention, and management often requires intravenous (IV) diuretic administration in the hospital setting. Typically, the number of admissions increases as the disease progresses, not only impacting patient survival and quality of life but also driving up healthcare expenditures. pH-neutral furosemide delivered subcutaneously using a proprietary, single-use infusor system (Furoscix) has a tremendous potential to transition in-hospital decongestive therapy to the outpatient setting or to the patient's home. This review is aimed at providing an overview of the pharmacodynamic and pharmacokinetic profile of the novel pH-neutral furosemide in addition to the most recent clinical trials demonstrating its benefit when used in the home setting. Given the newest data and approval by the Food and Drug Administration in the US, it has the potential to revolutionize the care of patients with decompensated HF. Undoubtedly, it will lead to improved quality of life as well as significantly reduced healthcare costs related to hospital admissions.

Angioedema in the Absence of C1 Esterase Inhibitor Deficiency in a Young Patient With Anti-dsDNA Negative Lupus Nephritis.

Hereditary angioedema (HAE) is an autosomal dominant condition marked by a lack of functioning C1 esterase inhibitor (C1-INH). In contrast, acquired angioedema (AAE) due to a deficiency of C1 esterase inhibitor (AAE-C1-INH) may be the manifestation of an underlying lymphoproliferative, neoplastic, or autoimmune condition. Both are potentially fatal. The C1q protein is normal in HAE but low in AAE. A third mechanism has been reported to cause angioedema, especially in systemic lupus erythematosus (SLE) patients. AAE, which happens in association with SLE, may respond well to steroids. Here we present a case of AAE in a young female with SLE that led to upper airway compromise, requiring endotracheal intubation. Early detection and treatment of such cases can lead to an outstanding prognosis by preventing airway compromise and anoxic brain injury. Even though it is a condition of either very young or middle-aged patients, practitioners must be aware of this uncommon disease linked with SLE in adolescents and young adults.

Panhypopituitarism and Central Hypothyroidism Presenting as Myoclonus and Hyperreflexia.

Panhypopituitarism may present with symptoms of predominantly one or more hormonal deficiencies. Central hypothyroidism usually presents with typical symptoms of hypothyroidism, such as fatigue, weight gain, menstrual abnormalities, bradycardia, thick, coarse skin, muscle fasciculations, and hyporeflexia, among others. Herein we present a case of central hypothyroidism along with panhypopituitarism presenting with unusual symptoms of tongue fasciculation, hyperreflexia, and myoclonic jerks.

Management and Follow-Up of Biventricular Thrombi.

A thrombus is the most common intracardiac lesion. Isolated thrombi usually occur in the setting of ventricular dysfunction, such as a dyskinetic or hypokinetic myocardial wall, following an acute myocardial infarction (MI) or in cardiomyopathies (CM). Concurrent biventricular thrombus formation is rare. There are no clear guidelines for the treatment of biventricular thrombus. In this report, we describe our experience of the successful treatment of a case of biventricular thrombus with warfarin and rivaroxaban.

Substance Use-Associated Mortality among Heart Donors after the COVID-19 National Emergency Increased but Did Not Affect Peri-Transplant Outcomes.

INTRODUCTION: The COVID-19 pandemic and consequent social isolation prompted a surge in mental health disorders and substance use in the general population and, therefore, in potential organ donors. We aimed to evaluate if this led to a change in donor characteristics, including the mechanism and circumstance of death, and how this may have affected clinical outcomes following heart transplantation. METHODS: We identified all heart donors from the SRTR database between 18 October 2018 and 31 December 2021, excluding those who donated immediately after the US national emergency declaration. Donors were stratified into pre-COVID-19 (Pre-Cov; through 12 March 2020) and post-COVID-19 national emergency declaration cohorts (Post-Cov; 1 August 2020 through 31 December 2021) based on the heart procurement date. Relevant demographics, cause of death, and substance use history were collected in addition to graft cold ischemic time, the incidence of primary graft dysfunction (PGD), and recipient survival at 30 days post-transplant. RESULTS: A total of 10,314 heart donors were identified; 4941 were stratified into the Pre-Cov and 5373 into the Post-Cov cohorts. There was no difference in demographics, but illicit drug use was significantly higher in the Post-Cov group, leading to an increased incidence of death from drug intoxication. Fatal gunshot wounds were also more common. Despite these changes, the incidence of PGD remained similar (p = 0.371), and there was no difference in 30 days recipient survival (p = 0.545). CONCLUSION: Our findings confirm that COVID-19 had a major impact on mental health and psychosocial life with an associated increase in illicit substance use and fatal intoxication rates in heart transplant donors. These changes did not alter peri-operative mortality following heart transplantation. Future studies are needed to ensure that long-term outcomes remain unaffected.

ST-Elevation Myocardial Infarction Precipitated by Disseminated Intravascular Coagulation: A Therapeutic Challenge.

Acute coronary syndrome (ACS) can manifest as ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA). Common etiologies for STEMI include atherosclerotic plaque disruption or erosion manifesting as type 1 myocardial ischemia (MI). Causes of type 2 MI presenting as STEMI may include spontaneous coronary artery dissection, coronary artery spasm, and coronary embolism. STEMI is an emergency mandating immediate coronary intervention. We present a case of STEMI as a complication of disseminated intravascular coagulation (DIC). This case highlights the unique challenge of managing STEMI with active DIC.

Diagnostic and Therapeutic Challenges Associated With Left Ventricular Tumors.

Cardiac tumors are uncommon. Sometimes it is challenging to differentiate non-invasively between different kinds of cardiac tumors and thrombi, which is critical to dictate the subsequent treatment. In addition, not all high-risk cardiac tumors are amenable to surgical resection posing a therapeutic challenge. We report a case of cardiac papillary fibroelastoma in the left ventricular cavity with a 10-year follow-up, with no embolic complications.

Thyroid Cancer Presenting as Aspiration Pneumonia: A Tale of Retrosternal Goiters.

Abnormal enlargement of the thyroid gland is called goiter. Structurally, it can be nodular or diffuse. Usually, it presents as an anterior cervical mass; however, less commonly, it presents as a retrosternal mass causing symptoms of compression on the surrounding structures. Most patients with goiter are asymptomatic due to the euthyroid nature of the disease. However, sometimes they can be hypo or hyperthyroid depending on the etiology of the goiter. Here, we present the case of a patient without any previously known goiter who presented to the hospital with shortness of breath and was found to have hypoxic respiratory failure as his first noticed sign of thyroid disease. Diagnostic workup revealed retrosternal goiter causing compression effect on the esophagus and trachea resulting in dysphagia and aspiration. The patient was treated with feeding tube placement, followed by surgical resection of the mediastinal mass.

Ceftriaxone-Associated Severe Acute Hepatitis.

Drug-induced liver injury (DILI) is a common entity. Ceftriaxone is a well-tolerated parenteral antibiotic widely used for various bacterial infections. We report a patient who developed severe acute hepatitis following a single dose of 2 g ceftriaxone within one day. Apart from a fever of 101.9 F, no other insult was noted to explain his severe hepatocellular injury around the time of presentation. On stopping further ceftriaxone, his symptoms resolved, and liver enzymes normalized within a week. His Roussel Uclaf Causality Assessment Method (RUCAM) score was 6 which suggested DILI be a probable cause of his acute hepatitis. Further surveillance at a larger scale is needed to support evidence for this rare side effect.

Asymptomatic Pulmonic Valve Mass: A Diagnostic and Therapeutic Dilemma.

Cardiac masses are not common but remain important in cardiology practice as they can cause havoc to a patient's life through obstructive and arrhythmogenic symptoms. These lesions mostly include vegetation, thrombi, and tumors. Myxomas are the most common primary cardiac tumor, primarily arising from the left heart chambers. It is exceedingly rare for a myxoma to emerge from the right-sided cardiac valves. The standard treatment is surgical resection, regardless of size, which is not always possible. We report a unique case of a male with multiple co-morbidities who presented with an incidental finding of a pulmonary valve mass suspicious of being a myxoma. The myxomatous mass was asymptomatic with no right ventricular outflow tract obstruction. Echocardiogram can help identify and characterize these lesions, but this may not be easy, especially in the case of atypical location or morphology of the mass. Similarly, in some cases, the patient may not be able to undergo surgical excision. In such cases, there is no consensus or guidelines to help clinicians best manage the patients medically, creating a diagnostic and therapeutic dilemma.

Impact of Storage Lesion on Post-transfusion Rise in Hemoglobin.

BACKGROUND: The storage lesion is defined as the set of changes that occur in red blood cells (RBCs) during storage. Studies have shown that a prolonged storage period of RBCs is associated with increased destruction after transfusion. The aim of this study is to determine the impact of the storage lesion on the efficacy of RBC transfusions by comparing the mean rise in the hemoglobin of patients who received new vs old blood. METHODS: We did a retrospective chart review of all patients who received a single unit of pure red blood cell (PRBC) transfusion in a three-month period. Patients with hemolytic anemia and active bleeding were excluded. The storage lesion was estimated by calculating the number of days to expiration on the day of transfusion. Median days to expiration was calculated to be 11 days. Patients were divided into two groups based on days to expiration. Group A included patients who received old blood (days to expiration: 0-11) and group B included patients who received new blood (days to expiration: 11-38). The mean rise in hemoglobin between the two groups was compared using the paired t-test. RESULTS: The baseline characteristics of both groups were similar. There was no statistically significant difference in the mean rise in hemoglobin (1.01 vs 1.08- p-value 0.298), hematocrit (3.37 vs 3.61- p-value 0.249), and RBC count (0.42 vs 0.44- p-value 0.097) in the group that received old blood vs new blood, respectively. CONCLUSION: An RBC transfusion with a shorter storage period does not increase hemoglobin more than RBC with a longer storage period.

Spindle Cell Carcinoma of the Lung/Pleura: An Incidental Finding.

A 59-year-old male with a medical history of abdominal aortic dissection underwent a follow-up computed tomography (CT) scan abdomen, which showed an incidental pleural-based mass in the left lung base. The patient underwent an ultrasound (US)-guided biopsy and the histology was consistent with spindle cell carcinoma (SpCC). Staging workup was concerning for a metastatic lesion on the adrenal gland. The patient refused surgery and was subsequently started on chemotherapy. SpCC is a rare histological variant of sarcomatoid carcinoma. The prognosis is generally poor and treatment is the same as for other non-small cell lung cancers (NSCLC). The literature on disease progression and treatment is limited.