Mirizzi Syndrome: A Case Report and Review of the Literature.

Mirizzi syndrome (MS) is a rare complication of chronic gallstones. Mirizzi syndrome is characterized by a set of symptoms that results from obstruction of the common hepatic or common bile duct (CBD). This may be due to extrinsic compression from an impacted gallstone in the gallbladder neck or cystic duct because of inflammatory changes secondary to chronic gallstone cholecystitis. We present a case of an 86-year-old patient with chronic gallstones who presented with abdominal pain and jaundice. The patient was diagnosed with MS type V after endoscopic retrograde cholangiopancreatography (ERCP). CBD stone fragments/debris were removed, and the patient was referred for surgical intervention for the repair of cholecystoduodenal fistula. MS must be in the differential diagnosis in elderly patients with chronic gallstone cholecystitis presenting with obstructive jaundice. Multiple diagnostic and therapeutic approaches are required to diagnose and manage the different types of MS. We aim to present the case to highlight and raise awareness of MS, particularly in patients with chronic gallstones.

Review of COVID-19 Variants and COVID-19 Vaccine Efficacy: What the Clinician Should Know?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta coronavirus that belongs to the Coronaviridae family. SARS-CoV-2 is an enveloped spherical-shaped virus. The ribonucleic acid (RNA) is oriented in a 5'-3'direction which makes it a positive sense RNA virus, and the RNA can be read directly as a messenger RNA. The nonstructural protein 14 (nsp14) has proofreading activity which allows the rate of mutations to stay low. A change in the genetic sequence is called a mutation. Genomes that differ from each other in genetic sequence are called variants. Variants are the result of mutations but differ from each other by one or more mutations. When a phenotypic difference is demonstrated among the variants, they are called strains. Viruses constantly change in two different ways, antigenic drift and antigenic shift. SARS-CoV-2 genome is also prone to various mutations that led to antigenic drift resulting in escape from immune recognition. The Center of Disease Control and Prevention (CDC) updates the variant strains in the different classes. The classes are variant of interest, variant of concern and variant of high consequence. The current variants included in the variant of interest by the USA are: B.1.526, B.1.525, and P.2; and those included in the variant of concern by the USA are B.1.1.7, P.1, B.1.351, B.1.427, and B.1.429. The double and triple mutant variants first reported in India have resulted in a massive increase in the number of cases. Emerging variants not only result in increased transmissibility, morbidity and mortality, but also have the ability to evade detection by existing or currently available diagnostic tests, which can potentially delay the diagnosis and treatment, exhibit decreased susceptibility to treatment including antivirals, monoclonal antibodies and convalescent plasma, possess the ability to cause reinfection in previously infected and recovered individuals, and vaccine breakthrough cases in fully vaccinated individuals. Hence, continuation of precautionary measures, genomic surveillance and vaccination plays an important role in the prevention of spread, early identification of variants, prevention of mutations and viral replication, respectively.

Review of COVID-19 Vaccines Approved in the United States of America for Emergency Use.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus causing a global pandemic. Coronaviruses are a large family of single-stranded ribonucleic acid (RNA) viruses. The virus has four essential structural proteins which include the spike (S) glycoprotein, matrix (M) protein, nucleocapsid (N) protein and small envelope (E) protein. Different technologies are being used for vaccine development to battle the pandemic. There are messenger ribonucleic acid (mRNA)-based vaccines, deoxyribonucleic acid (DNA) vaccines, inactivated viral vaccines, live attenuated vaccines, protein subunit-based vaccines, viral vector-based vaccines and virus-like particle-based vaccines. Vaccine development has five stages. In the clinical developmental stage, vaccine development can be sped up by combining phase 1 and 2. The vaccines can also be approved more swiftly on an emergent basis and released sooner for usage. The United States Food and Drug Administration (USFDA) has approved Pfizer-BioNTech, Moderna and Janssen coronavirus disease 2019 (COVID-19) vaccines for emergency use. There are other vaccines that have been approved around the world. The mRNA vaccines have been created using a novel technology and they contain a synthetically created RNA sequence of virus fragments encoding the S-protein which is injected. These vaccines have a relatively low cost of production and faster manufacturing time but can have comparatively lower immunogenicity and more than one dose of vaccine may be required. In the case of viral vector-based vaccines, genes encoding the SARS-CoV-2 S protein are isolated and following gene sequencings are introduced into the adenovirus vector. These vaccines have a relatively fast manufacturing time but the efficacy of the vaccine is variable based on the host's immune response to the viral vector. At the time of this paper, there were 81 vaccines in clinical development stage and 182 vaccines in preclinical development stage. Vaccines are an essential tool in our battle against COVID-19. Some of the COVID-19 vaccines have completed their phase III trials while many other potential vaccines are still in developmental stages. It used to take close to a decade for a vaccine to be developed and undergo rigorous testing until its production and availability to the public, but over the past year, we have seen multiple vaccines in different phases of testing against SARS-CoV-2 virus.

Purpuric Rash and Thrombocytopenia After the mRNA-1273 (Moderna) COVID-19 Vaccine.

The mRNA-1273 vaccine, popularly called the "Moderna vaccine" is being widely administered in the United States for the prevention of COVID-19 infection since December 2020. Mild to moderate intensity side effects like low-grade fever, myalgia, chills and malaise were reported in the trials related to the vaccine. With this case report, we report a case of purpuric rash and thrombocytopenia after receiving the first dose of the m-RNA-1273 vaccine. The patient, in this case, is a 60-year-old male patient who received the first vaccine dose and within two days, he developed diffuse papular rash associated with some thrombocytopenia. He had a history of tobacco use, Hepatitis C liver cirrhosis, chronic kidney disease stage 4, untreated hypertension and systolic congestive heart failure at the baseline. With review of the limited literature related to the vaccine and its side effect profile and with no other etiology explaining the sudden onset of rash, we attribute this thrombocytopenia and purpuric rash as the side effects of the mRNA-1273 vaccine.

A case series of vestibular symptoms in positive or suspected COVID-19 patients.

Respiratory symptoms are the most common presentation of an acute COVID-19 infection, but thromboembolic phenomena, encephalopathy and other neurological symptoms have been reported. With these case series, we present multiple presentations of COVID-19 induced vestibular symptoms namely dizziness, vertigo and nystagmus. The patients reported in this case series are from different parts of the world, belong to different age groups and had manifested these symptoms in different periods of the pandemic. The pathophysiology of vestibular neuritis induced by COVID-19 is similar to any other viral infection. Whether in the inpatient or outpatient settings, COVID-19 should be considered in the differential diagnosis for patients presenting with these symptoms, irrespective of the presence of respiratory symptoms or hypoxia.

Review of COVID-19 viral vector-based vaccines and COVID-19 variants.

The concept of viral vector-based vaccine was introduced in 1972 by Jackson et al and in 1982 Moss et al introduced the use of vaccinia virus as a transient gene expression vector. The technology has been used to make Ebola vaccines and now COVID-19 vaccines. There are two types of viral vector-based vaccines i.e. replicating and non-replicating. Non-replicating viral vector-based vaccines use replication-deficient viral vectors to deliver genetic material of a particular antigen to the host cell to induce immunity against the desired antigen. Replicating vector vaccines produce new viral particles in the cells they enter, which then go on to enter more new cells which will also make the vaccine antigen. Non-replicating vector-based vaccines are more commonly utilized. Adenovirus, vesicular stomatitis virus, vaccinia virus, adenovirus associated virus, retrovirus, lentivirus, cytomegalovirus, and sendai virus have been used as vectors. Current adenovirus vector-based vaccines being administered against SARS-CoV-2 infection are JNJ-78435735 by Johnson and Johnson (Janssen) along with Beth Israel Deaconess Medical Center, AZD1222 by Oxford-AstraZeneca, Sputnik V and Sputnik Light by Gamaleya Research Institute of Epidemiology and Microbiology, and Convidecia vaccine by CanSino Biologics. Of the five vaccines, the United States Food and Drug Administration (FDA) has approved Janssen vaccine for emergency use. Efficacy against COVID-19 variants has been found in all but the Convidecia vaccine so far. Heterologous prime-boost COVID-19 vaccination regimen may be the new face and more efficient immunization approach for enhanced immunity against COVID-19.

Efficacy and Cardiovascular Safety of GLP-1 Receptor Analogues.

Glucagon-like peptide- 1 receptor analogs (GLP-1RAs) are incretin mimetics with potent glucose-dependent insulinotropic action that translates to glycemic control in people with type- -2 diabetes mellitus (T2DM). These agents potentially have the ability to stimulate proliferation or prevent apoptosis of pancreatic ß-cells, induce weight-loss and provide vascular benefits in patients with T2DM. Newer GLP-1RA, semaglutide has shown a robust reduction in HbA1c up to 1.5 - 1.8%. However, individual differences exist between the different GLP-1RAs, in terms of efficacy, pharmacokinetics, tolerability, and vascular protection. The potential of vascular protection offered by newer anti-diabetic agents has generated a lot of excitement in the field of diabetes, and to a large extent, is now driving treatment decisions. So far, six cardiovascular outcome trials of GLP-1 RAs have been published, analyzing lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), long-acting exenatide (EXSCEL), dulaglutide (REWIND), and oral semaglutide (PIONEER 6) with a follow-up duration of 2-4 years. LEADER, REWIND and SUSTAIN-6 trials have demonstrated a reduction in rates of major adverse cardiovascular events with active GLP-1 RA treatment, but ELIXA, PIONEER 6 and EXSCEL, have been neutral. In this review, we discuss the available evidence from randomized controlled trials (RCTs) analyzing the cardiovascular effects of various GLP-1 RAs with the aim of comparing individual drugs. We have also summarized the general aspects of GLP-1RAs that can be applied in clinical practice.

A Comprehensive Review of Congenital Platelet Disorders, Thrombocytopenias and Thrombocytopathies.

Platelets play an important role in hemostasis through platelet plug formation by a phenomenon of adhesion; activation; secretion and aggregation. Defects in platelet hemostatic mechanisms can be congenital or acquired. Congenital platelet disorders are rare and manifestations range from asymptomatic to sometimes severe bleeding. The disorders arise due to diverse mechanisms. Congenital platelet disorders include thrombocytopathies and thrombocytopenia (platelet count <150 x 109/L) or thrombocytosis (platelet count > 450 x 109/L). Congenital thrombocytopathies include disorders of adhesion like von Willebrand's disease or Bernard-Soulier syndrome. The disorders of aggregation include congenital afibrinogenemia and Glanzmann thrombasthenia. Disorders of storage granules are gray platelet syndrome and Quebec platelet disorder. Congenital thrombocythopathy and thrombocytopenia often occur in conjunction. In this article, we have a detailed literature review of these rare thrombocytopathies, their presentation and treatment.