Tachy-brady syndrome: Electrophysiology and evolving principles of management.

Sudden alterations in the heart rate may be associated with diverse symptoms. Sinus node dysfunction (SND), also known as sick sinus syndrome, is a sinoatrial (SA) node disorder. SND is primarily caused by the dysfunction of the pacemaker, as well as impaired impulse transmission resulting in a multitude of abnormalities in the heart rhythms, such as bradycardia-tachycardia, atrial bradyarrhythmias, and atrial tachyarrhythmias. The transition from bradycardia to tachycardia is generally referred to as "tachy-brady syndrome" (TBS). Although TBS is etiologically variable, the manifestations remain consistent throughout. Abnormal heart rhythms have the propensity to limit tissue perfusion resulting in palpitations, fatigue, lightheadedness, presyncope, and syncope. In this review, we examine the physiology of tachy-brady syndrome, the practical approach to its diagnosis and management, and the role of adenosine in treating SND.

Glucocorticoid Receptor Antagonism and Cardiomyocyte Regeneration Following Myocardial Infarction: A Systematic Review.

Myocardial regeneration has been a topic of interest in literature and research in recent years. An evolving approach reported is glucocorticoid (GC) receptor antagonism and its role in the regeneration of cardiomyocytes. The authors of this study aim to explore the reported literature on GC receptor antagonism and its effects on cardiomyocyte remodeling, hypertrophy, scar formation, and ongoing cardiomyocyte death following cardiac injury. This article overviews cellular biology, mechanisms of action, clinical implications, challenges, and future considerations. The authors of this study conducted a systematic review utilizing the Cochrane methodology and PRISMA guidelines. This study includes data collected and interpreted from 30 peer-reviewed articles from 3 databases with the topic of interest. The mammalian heart has regenerative potential during its embryonic and fetal phases which is lost during its developmental processes. The microenvironment, intrinsic molecular mechanisms, and systemic and external factors impact cardiac regeneration. GCs influence these aspects in some cases. Consequently, GC receptor antagonism is emerging as a promising potential target for stimulating endogenous cardiomyocyte proliferation, aiding in cardiomyocyte regeneration following a cardiac injury such as a myocardial infarction (MI). Experimental studies on neonatal mice and zebrafish have shown promising results with GC receptor ablation (or brief pharmacological antagonism) promoting the survival of myocardial cells, re-entry into the cell cycle, and cellular division, resulting in cardiac muscle regeneration and diminished scar formation. Transient GC receptor antagonism has the potential to stimulate cardiomyocyte regeneration and help prevent the dreaded complications of MI. More trials based on human populations are encouraged to justify their applications and weigh the risk-benefit ratio.

Gene Editing as the Future of Cardiac Amyloidosis Therapeutics.

Cardiac Amyloidosis (CA) is a manifestation of a systemic disorder resulting from the deposition of transthyretin (TTR) in the myocardium. This leads to a myriad of manifestations ranging from conduction defects to heart failure. Previously CA was considered a rare disease, but recent advances in diagnostics and therapeutics have revealed the prevalence to be higher than estimated. There are two major classes of treatments for TTR cardiac amyloidosis (ATTR-CA): TTR stabilizers, such as tafamidis and AG10, and RNA interference (siRNA), such as patisiran and vutrisiran. Clustered regularly interspaced short palindromic repeats of genetic information-Cas9 endonuclease (CRISPR-Cas9) utilizes an RNA-guided endonuclease to target specific locations in the genome. Until recently, CRISPR-Cas9 was studied in small animal models for its ability to decrease extracellular deposition and accumulation of amyloid in tissues. Gene editing has demonstrated some early clinical promise as an emerging therapeutic modality in the treatment of CA. In an introductory human trial involving 12 subjects with TTR amyloidosis and amyloid cardiomyopathy (ATTR-CM), CRISPR-Cas9 therapy has demonstrated a reduction in approximately 90% of serum TTR proteins after 28 days. In this article, the authors review the current literature on therapeutic gene editing as a prospective curative treatment modality for CA.

The potential association between psychiatric symptoms and the use of levonorgestrel intrauterine devices (LNG-IUDs): A systematic review.

BACKGROUND: Levonorgestrel (LNG)-intrauterine devices (IUDs) are an effective method of contraception; however, there is growing evidence regarding potential psychiatric side effects such as depressive symptoms, anxiety, and suicidal thoughts. Therefore, we conducted this systematic review to summarise the psychiatric effects of using LNG-IUDs. METHODS: We searched six databases (MEDLINE, Web of Science, Scopus, Science Direct, Cochrane Library, and PsycInfo), and we included all study designs. The included studies were extracted, quality assessed, and qualitatively summarised. RESULTS: Out of the screened studies, only 22 were finally included. While ten studies showed increased depressive symptoms, two studies showed reduced symptoms. Moreover, one study showed increased anxiety, another one reported an increased risk of suicide, four studies concluded no association with depressive symptoms, and four other studies showed uncertainty about a potential association but mentioned other psychiatric symptoms. CONCLUSION: Despite unreliable data, many studies report psychiatric symptoms associated with LNG-IUDs, predominantly depression. Gynaecologists, general practitioners, and psychiatrists should therefore be aware of these potential risks, especially depressive symptoms and suicidality. Counselling patients about these risks should be mandatory. Further studies should investigate the absolute risk of mental disorders associated with LNG-IUDs and other hormonal contraceptives.KEY MESSAGESMany researchers are reporting adverse psychiatric events associated with levonorgestrel intrauterine devices (LNG-IUDs).Despite their effectiveness, a proper psychiatric assessment should be done before inserting LNG-IUDs.Proper counselling regarding the depressive symptoms and suicidality should be done by the treating obstetrician.Further studies should investigate the absolute risk of mental disorders associated with LNG-IUDs and other hormonal contraceptives.

Overview of lenvatinib as a targeted therapy for advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Patients commonly present with advanced/unresectable HCC where several treatment options are not effective. In this review, the authors discuss the indications and usage of lenvatinib, a multikinase inhibitor, as first-line therapy for advanced/unresectable HCC, its mode of action, efficacy, drug reactions, response to treatment and adverse effects. Since its approval in 2007, sorafenib has been used as first-line therapy for unresectable HCC. In 2018, a phase III multinational REFLECT trial on subjects with unresectable HCC (Child-Pugh class A) demonstrated that lenvatinib was non-inferior compared to sorafenib for overall survival, with a controllable toxicity profile, leading to its approval. In addition, our review discusses studies that compare the safety and efficacy profile of lenvatinib especially in patients who have a decline in their liver function to Child-Pugh class B. A current real world analysis of lenvatinib approval for unresectable HCC worldwide is reported.

Epidemiology, Pathogenesis, and Clinical Manifestations of Acute Esophageal Necrosis in Adults.

Acute esophageal necrosis (AEN), also termed "black esophagus," is a unique and uncommon occurrence observed in severely sick patients. Other terminologies include acute necrotizing esophagitis and Gurvits syndrome. This condition is described as a darkened distal third of the esophagus observed on endoscopy and presents as an upper gastrointestinal (GI) bleed, difficulty swallowing, abdominal pain, fever, syncope, nausea, and vomiting. The etiology of AEN has been linked to several possibilities, such as excessive gastric acid reflux, hypoperfusion, and ischemia due to impaired vascular supply and hemodynamic instability. Risk factors include increased age, sex (male), heart disease, hemodynamic insufficiency, alcohol use, gastric outlet obstruction, diabetic ketoacidosis (DKA), malnutrition, renal disease, and trauma which also have the propensity to complicate disease course. An esophageal biopsy is not warranted. Treatment of AEN is comprised of supportive management with intravenous fluids, proton pump inhibitors (PPI), sucralfate, parenteral nutrition, and antacids. Management of preexisting comorbidities associated with AEN is crucial to prevent exacerbation of the disease course that could result in a poor prognosis and increased mortality rates. This literature review article comprises epidemiology, etiology, pathogenesis, diagnosis, and management of AEN.

Tozinameran (BNT162b2) Vaccine: The Journey from Preclinical Research to Clinical Trials and Authorization.

Vaccination development and production was an essential question for the prevention and global control of COVID-19. The strong support from governing authorities such as Operation Warp Speed and robust funding has led to the development and authorization of the tozinameran (BNT162b2) vaccine. The BNT162b2 vaccine is a lipid nanoparticle-encapsulated mRNA that encodes for SARS-CoV-2 spike protein, the main site for neutralizing antibodies. Once it binds with the host cells, the lipid nanoparticles enable the transfer of the RNA, causing S antigens' expression of the SARS-CoV-2, conferring immunity. The vaccine is administered as a 2-dose regime 21 days apart for individuals 16 years and older. Pfizer-BioNTech's BNT162b2 vaccine was the first candidate to receive FDA-Emergency Use Authorization (EUA) on December 11, 2020. During phase 2/3 clinical trials, 95% efficacy was reported among 37,706 participants over the age of 16 who received the BNT162b2 vaccination; additionally, 52% efficacy was noted 12 days following the administration of the first dose of BNT162b2, reflecting early protection of COVID-19. The BNT162b2 vaccine has exhibited 100% efficacy in clinical trials of adolescents between the ages of 12 and 15. Clinical trials in pregnant women and children under the age of 12 are expected to also exhibit promising results. This review article encompasses tozinameran (BNT162b2) vaccine journey, summarizing the BNT162b1 and BNT162b2 vaccines from preclinical studies, clinical trial phases, dosages, immune response, adverse effects, and FDA-EUA.

The Neurological Complexities and Prognosis of COVID-19.

Several neurological manifestations and complications linked to SARS-CoV-2 have been reported along with well-known respiratory pathology. The global active transmission of SARS-CoV-2 and its unexplained characteristics has led to a pandemic. Since its rapid emergence from Wuhan, China, in December 2019, several studies have reported the impacts of COVID-19 on the CNS and PNS and its implications. This comprehensive review article comprises case reports, case series, metaanalysis, cohort studies, retrospective studies, and narrative reviews focusing on COVID-19-associated CNS and PNS complexities. The authors searched for over 200 articles and used 52 publications related to the neurological complexities of COVID-19 affecting the CNS and PNS as part of the literature review process. The predominant CNS symptoms noted in COVID-19 patients were headaches and dizziness, and the most common PNS symptoms were alterations in smell and taste. Case reports on headache/dizziness, intracerebral hemorrhage, acute hemorrhagic necrotizing encephalopathy, meningitis/encephalitis, encephalopathy, cerebrovascular events, chemosensory dysfunction, Guillain-Barre syndrome, and acute transverse myelitis/acute necrotizing myelitis in PCR-confirmed SARS-CoV-2 subjects are also reported. New-onset neurological symptoms were also observed in children with PCR-confirmed SARS-CoV-2 that developed pediatric multisystem inflammatory syndrome (PIMS). This comprehensive review article will assist the clinicians and researchers to gain information about the neurological manifestations and complications associated with COVID-19 and develop planning to treat these symptoms in concerned patients of all ages. However, it is unclear whether SARS-CoV2-associated neurological effects are due to primary infections or secondary response to the possible mechanisms discussed in this review.