Nanotechnology: The Future for Diagnostic and Therapeutic Intervention in Cardiovascular Diseases is Here.

With advances in technology and medicine over the last 3 decades, cardiovascular medicine has evolved tremendously. Nanotechnology provides a promising future in personalized precision medicine. In this review, we delve into the current and prospective applications of nanotechnology and nanoparticles in cardiology. Nanotechnology has allowed for point-of-care testing such as high-sensitivity troponins, as well as more precise cardiac imaging. This review is focused on 3 diseases within cardiology: coronary artery disease, heart failure, and valvular heart disease. The use of nanoparticles in coronary stents has shown success in preventing in-stent thrombosis, as well as using nanosized drug delivery medications to prevent neointimal proliferation in a way that spares systemic toxicity. In addition, by using nanoparticles as drug delivery systems, nanotechnology can be utilized in the delivery of goal-directed medical therapy in heart failure patients. It has also been shown to improve cell therapy in this patient population by helping in cell retention of grafts. Finally, the use of nanoparticles in the manufacturing of bioprosthetic valves provides a promising future for the longevity and success of cardiac valve repair and replacement.

The Interplay of Microbiome Dysbiosis and Cardiovascular Disease.

The intricate ecosystem of the mammalian gut, which hosts a diverse microbiome, plays a vital role in various physiological functions. Trillions of bacteria within the gut contribute to host metabolism, immune modulation, energy homeostasis, and more. Emerging research highlights the gut microbiota's significant impact on cardiovascular diseases (CVDs), with intestinal dysbiosis identified as a risk factor for conditions such as obesity and diabetes, both linked to atherosclerosis. Chronic inflammation, pivotal in atherosclerosis, is influenced by the gut microbiome, where microbial signals, such as lipopolysaccharides, can translocate from the gut to trigger inflammatory responses. Diet has major effects on the gut microbiota, with the Western diet, rich in saturated fats, contributing to dysbiosis and elevated cardiovascular risks. Probiotics and prebiotics offer therapeutic potential in CVD management. Probiotics, or live microorganisms, exhibit antioxidant, anti-inflammatory, and cholesterol-lowering effects. Probiotics are most effective when given with prebiotics, with the former acting on the latter as substrate. Understanding the dynamic interplay between diet, gut microbiota, and CVD provides insights into preventive and therapeutic strategies.

Paradoxical Reaction and Parastomal Pyoderma Gangrenosum Emergence With Secukinumab Therapy.

Paradoxical reactions are characterized by the emergence or worsening of a pathological condition that typically responds to the administered drug while treating the patient for another condition. Certain drugs, such as tumor necrosis factor inhibitors, can induce pyoderma gangrenosum. Recently, the drug secukinumab has been implicated in a few case reports as a potential cause of pyoderma gangrenosum after initiation. We report the first case of biologic-refractory ulcerative colitis presenting with parastomal pyoderma gangrenosum after the initiation of secukinumab. While these associations are still being investigated, they highlight the importance of monitoring patients for possible adverse skin reactions when starting new medications.

Native Aortic Valve Endocarditis Secondary to Gastric Antral Vascular Ectasia Manipulation During Endoscopic Argon Plasma Coagulation.

Gastric antral vascular ectasia (GAVE) is an uncommon cause of upper gastrointestinal (GI) bleeds. Due to the high vascularity of the region, transient bacteremia due to manipulation of the GI tract can very rarely cause the translocation of bacteria. We present a rare case in which endoscopic manipulation to treat GAVE led to native valve infective endocarditis (IE). Our patient had a prior history of GAVE and presented with worsening dizziness and shortness of breath (SOB). After an esophagogastroduodenoscopy (EGD) and subsequent argon plasma coagulation (APC) for active preantral bleeding, the patient was noted to have repeated fevers, a new cardiac murmur, and positive blood cultures for Staphylococcus epidermidis, leading to a diagnosis of native infective endocarditis. With high clinical suspicion and early recognition of a new cardiac murmur, a transesophageal echocardiogram (TEE) was key in identifying vegetation. This case highlights the importance of combining history, a physical exam, and diagnostic lab tests and imaging to identify endocarditis. Management included two months of intravenous (IV) vancomycin and repeat TEE for close monitoring of vegetation improvement.

Titin: The Missing Link in Cardiac Physiology.

Titin, an extraordinary protein known for its colossal size and multifaceted roles, is a cornerstone in the structural and functional dynamics of striated muscle tissues, including the heart and skeletal muscles. Its sheer enormity, with a molecular weight exceeding 3000 kDa, is paralleled only by the immense influence it exerts on muscle physiology. This review will delve into the remarkable structural organization of Titin and the genetics of this molecule, including the common mutations resulting in various cardiomyopathies. We will delve deeper into its role in dilated cardiomyopathy, familial restrictive cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction cardiomyopathy. This review culminates by discussing the prospects of therapeutic strategies targeting Titin. While these interventions remain primarily theoretical, the possibilities are intriguing. Patients with Titin truncation mutations present unique challenges, but innovative approaches like gene therapy or preemptive treatments with drugs such as angiotensin-converting enzyme inhibitors or beta-blockers offer hope. This multi-pronged approach highlights the significance of understanding Titin's multifaceted role and its potential as a target for future therapeutic interventions.

An Unusual Hiccup: Severe Singultus as a Symptom in Ulcerative Colitis.

Inflammatory bowel disease encompasses a group of chronic inflammatory conditions associated with both intestinal and extraintestinal manifestations. We present a 26-year-old man with a history of ulcerative colitis who presented with a disease exacerbation associated with severe intractable hiccups. We report a unique clinical symptom associated with severe ulcerative colitis and the diagnostic dilemma associated with this presentation. This case highlights the importance of recognizing unusual symptoms that can be associated with inflammatory bowel disease exacerbations and demonstrates the therapeutic potential of effective therapy of the underlying inflammatory disease.

Tumefactive Multiple Sclerosis: Challenges With Treatment Modalities.

Tumefactive multiple sclerosis comprises a rare subset of multiple sclerosis that often poses a diagnostic challenge to physicians. It is unique in its presentation as a solitary lesion, usually larger than 2 cm, with surrounding vasogenic edema, commonly mimicking a primary intracranial malignancy. We present a case of a 25-year-old female with no significant past medical history who presented to our institution with homonymous superior quadrantanopia. During her admission, she underwent a magnetic resonance imaging (MRI) of the brain, which revealed a large lesion in the left temporal area surrounded by marked edema. A thorough workup revealed a diagnosis of tumefactive multiple sclerosis. Subsequently, she was initiated on intravenous immunoglobulin rather than stress dose steroids, given the concern for a superimposed infection. Interestingly, the patient had a paradoxical progression of her symptoms as well as expansion of the vasogenic edema on a repeat MRI. In our case, we highlight the key differences in tumefactive multiple sclerosis diagnosis and management.

Distributive Shock in Erythrodermic Psoriasis Treated With Norepinephrine and Vasopressin: A Case Report.

Distributive shock and hypothermia are two unusual and potentially fatal complications of erythroderma, a rare complication of psoriasis. Very few cases of erythrodermic psoriasis have been reported, particularly in the United States, which may pose a diagnostic challenge for internists. We present a case report of distributive hemodynamic instability and hypothermia in a 61-year-old female who initially presented with acute altered mental status thought to be related to an infectious etiology.

Distribution and postnatal development of chondroitin sulfate proteoglycans in the perineuronal nets of cholinergic motoneurons innervating extraocular muscles.

Fine control of extraocular muscle fibers derives from two subpopulations of cholinergic motoneurons in the oculomotor-, trochlear- and abducens nuclei. Singly- (SIF) and multiply innervated muscle fibers (MIF) are supplied by the SIF- and MIF motoneurons, respectively, representing different physiological properties and afferentation. SIF motoneurons, as seen in earlier studies, are coated with chondroitin sulfate proteoglycan rich perineuronal nets (PNN), whereas MIF motoneurons lack those. Fine distribution of individual lecticans in the composition of PNNs and adjacent neuropil, as well as the pace of their postnatal accumulation is, however, still unknown. Therefore, the present study aims, by using double immunofluorescent identification and subsequent morphometry, to describe local deposition of lecticans in the perineuronal nets and neuropil of the three eye movement nuclei. In each nucleus PNNs were consequently positive only with WFA and aggrecan reactions, suggesting the dominating role of aggrecan is PNN establishment. Brevican, neurocan and versican however, did not accumulate at all in PNNs but were evenly and moderately present throughout the neuropils. The proportion of PNN bearing motoneurons appeared 76% in oculomotor-, 72.2% in trochlear- and 78.3% in the abducens nucleus. We also identified two morphological subsets of PNNs, the focal and diffuse nets of SIF motoneurons. The process of CSPG accumulation begins just after birth, although considerable PNNs occur at week 1 age around less than half of the motoneurons, which ratio doubles until 2-month age. These findings may be related to the postnatal establishment of the oculokinetic network, performing different repertoires of voluntary eye movements in functionally afoveolate and foveolate animals.

A Literature Review of Major Clinical Trials That Contributed to Treatment Protocols of Irritable Bowel Syndrome With Diarrhea.

The most common reason for seeing a gastroenterologist is irritable bowel syndrome (IBS). IBS was thought to be a functional disease; however, there are now numerous alternative pathophysiologic pathways that can explain the symptoms. The pathophysiology of IBS is diverse and not well understood. Most current first-line treatments for IBS target the primary symptom and mainly impact one symptom in the symptom complex. The purpose of this study was to summarize the data on new medicines used to treat IBS. We conducted a bibliographic search in Google Scholar and PubMed focused on medication clinical trials in IBS with diarrhea. New medications for IBS with diarrhea target important pathways in the pathophysiology of these disorders, improving both the abnormal bowel habit and other significant symptoms such as abdominal pain and bloating.

A Review of Trikafta: Triple Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator Therapy.

Cystic fibrosis (CF) is a potentially fatal genetic disease that causes serious lung damage. With time, researchers have a more complete understanding of the molecular-biological defects that underlie CF. This knowledge is leading to alternative approaches regarding the treatment of this condition. Trikafta is the third FDA-approved drug that targets the F508del mutation of the CFTR gene. The drug is a combination of three individual drugs which are elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA). This trio increases the activity of the cystic fibrosis transmembrane conductance regulator (CFTR) protein and reduces the mortality and morbidity rates in CF patients. The effectiveness of Trikafta, seen in clinical trials, outperforms currently available therapies in terms of lung function, quality of life, sweat chloride reduction, and pulmonary exacerbation reduction. The safety and efficacy of CFTR modulators in children with CF have also been studied. Continued evaluation of patient data is needed to confirm its long-term safety and efficacy. In this study, we will focus on reviewing data from clinical trials regarding the benefits of CFTR modulator therapy. We address the impact of Trikafta on lung function, pulmonary exacerbations, and quality of life. Adverse events of the different CFTR modulators are discussed.

A Review of Clinical Trials That Contributed to Chronic Obstructive Pulmonary Disease Treatment Protocols.

Chronic obstructive pulmonary disease (COPD) has remained a leading cause of death worldwide and is expected to increase its burden on the healthcare system in the coming future. Numerous clinical trials have been conducted over the years and as a result, many drugs became a part of the treatment protocols of COPD. Currently, there are also several drugs under development. This review will help future researchers to grasp salient features of previous studies and use them in their future trials in order to reduce the morbidity and mortality of COPD. Randomized control trials provide strong evidence for any hypothesis in a research study. This review focuses on major COPD trials in the last two decades including TORCH, UPLIFT, POET, WISDOM, and TIOSPIR. It showcases the main clinical question, primary outcome, and result of these five trials.

Epidemiology and Outcomes of Hospitalizations Due to Hepatocellular Carcinoma.

Background Hepatocellular Carcinoma (HCC) is a severe complication of cirrhosis and the incidence of HCC has been increasing in the United States (US). We aim to describe the trends, characteristics, and outcomes of hospitalizations due to HCC across the last decade. Methods We derived a study cohort from the Nationwide Inpatient Sample (NIS) for the years 2008-2017. Adult hospitalizations due to HCC were identified using the International Classification of Diseases (9th/10th Editions) Clinical Modification diagnosis codes (ICD-9-CM/ICD-10-CM). Comorbidities were also identified by ICD-9/10-CM codes and Elixhauser Comorbidity Software (Agency for Healthcare Research and Quality, Rockville, Maryland, US). Our primary outcomes were in-hospital mortality and discharge to the facility. We then utilized the Cochran-Armitage trend test and multivariable survey logistic regression models to analyze the trends, outcomes, and predictors. Results A total of 155,436 adult hospitalizations occurred due to HCC from 2008-2017. The number of hospitalizations with HCC decreased from 16,754 in 2008 to 14,715 in 2017. Additionally, trends of in-hospital mortality declined over the study period but discharge to facilities remained stable. Furthermore, in multivariable regression analysis, predictors of increased mortality in HCC patients were advanced age (OR 1.1; 95%CI 1.0-1.2; p< 0.0001), African American (OR 1.3; 95%CI 1.1-1.4;p< 0.001), Rural/ non-teaching hospitals (OR 2.7; 95%CI 2.4-3.3; p< 0.001), uninsured (OR 1.9; CI 1.6-2.2; p< 0.0001) and complications like septicemia and pneumonia as well as comorbidities such as hypertension, diabetes mellitus, and renal failure. We observed similar trends in discharge to facilities. Conclusions In this nationally representative study, we observed a decrease in hospitalizations of patients with HCC along with in-hospital mortality; however, discharge to facilities remained stable over the last decade. We also identified multiple predictors significantly associated with increased mortality, some of which are potentially modifiable and can be points of interest for future studies.