Cardiovascular disease: extraintestinal manifestation of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a spectrum of diseases characterized by the interplay of the aberrant immune system, genetic factors, environmental factors, and intestinal microbiota, resulting in relapsing inflammation of the gastrointestinal tract. Underlying pro-inflammatory state and immune dysregulation act as a catalyst for increasing the likelihood of developing extraintestinal manifestations, including cardiovascular diseases (CVD) like atherosclerosis, pericarditis, myocarditis, venous and arterial thromboembolism, arrhythmias, despite a lower prevalence of classic CVD risk factors, like high body mass index or dyslipidemia compared to the general population. Chronic inflammation damages endothelium resulting in the recruitment of inflammatory cells, which induce cytotoxicity, lipoprotein oxidation, and matrix degradation, which increases the risk of atherosclerosis. Additionally, intestinal dysbiosis disrupts the intestinal mucosal barrier, releasing endotoxins and lipopolysaccharides into circulation, further exaggerating the atherosclerotic process. Abnormal collagen metabolism and alteration of nitric oxide-mediated vasodilation lead to blood pressure dysregulation in patients with IBD. Therefore, it is essential to make lifestyle modifications like smoking cessation, dietary changes, and increasing physical activity with adherence to medication to mitigate the risk of developing CVD in patients with IBD. This article reviews the potential links between IBD and the increased risk of CVD in such individuals.

Cardiac MRI: An Overview of Physical Principles With Highlights of Clinical Applications and Technological Advancements.

The purpose of this review is to serve as a concise learning tool for clinicians interested in quickly learning more about cardiac magnetic resonance imaging (CMR) and its physical principles. There is heavy coverage of the basic physical fundamentals of CMR as well as updates on the history, clinical indications, cost-effectiveness, role of artificial intelligence in CMR, and examples of common late gadolinium enhancement (LGE) patterns. This literature review was performed by searching the PubMed database for the most up-to-date literature regarding these topics. Relevant, less up-to-date articles, covering the history and physics of CMR, were also obtained from the PubMed database. Clinical indications for CMR include adult congenital heart disease, cardiac ischemia, cardiomyopathies, and heart failure. CMR has a projected cost-benefit ratio of 0.58, leading to potential savings for patients. Despite its utility, CMR has some drawbacks including long image processing times, large space requirements for equipment, and patient discomfort during imaging. Artificial intelligence-based algorithms can address some of these drawbacks by decreasing image processing times and may have reliable diagnostic capabilities. CMR is quickly rising as a high-resolution, non-invasive cardiac imaging modality with an increasing number of clinical indications. Thanks to technological advancements, especially in artificial intelligence, the benefits of CMR often outweigh its drawbacks.

Protobothrops jerdonii (Jerdon's pit viper) and Protobothrops himalayanus (Himalayan lance-headed pit viper) bites: Clinical report on envenomings from North-East India, managed through remote consultation by a national-level Poison control center.

Members of the genus Protobothrops are amongst the more than twenty-eight range-restricted Indian pit viper species. Their bites and envenomings are rarely documented from India. Pit viper envenomings can be challenging to treat in the Indian setting, since available antivenoms do not satisfactorily neutralize their venoms. Herein, we present the first Indian reports on bites and envenoming by Protobothrops jerdonii and Protobothrops himalayanus resulting in local effects, coagulopathy and acute kidney injury in the case of the former and possible mild, isolated coagulopathy in the case of the latter; and discuss management-related challenges in the context of absent specific antivenoms.

A plain language summary of the TROPHY-U-01 study: sacituzumab govitecan use in people with locally advanced or metastatic urothelial cancer.

WHAT IS THIS SUMMARY ABOUT?: Sacituzumab govitecan (brand name: TRODELVY®) is a new treatment being studied for people with a type of bladder cancer, called urothelial cancer, that has progressed to a locally advanced or metastatic stage. Locally advanced and metastatic urothelial cancer are usually treated with platinum-based chemotherapy. Metastatic urothelial cancer is also treated with immune checkpoint inhibitors. There are few treatment options for people whose cancer gets worse after receiving these treatments. Sacituzumab govitecan is a suitable treatment option for most people with urothelial cancer because it aims to deliver an anti-cancer drug directly to the cancer in an attempt to limit the potential harmful side effects on healthy cells. This is a summary of a clinical study called TROPHY-U-01, focusing on the first group of participants, referred to as Cohort 1. All participants in Cohort 1 received sacituzumab govitecan. WHAT ARE THE KEY TAKEAWAYS?: All participants received previous treatments for their metastatic urothelial cancer, including a platinum-based chemotherapy and a checkpoint inhibitor. The tumor in 31 of 113 participants became significantly smaller or could not be seen on scans after sacituzumab govitecan treatment; an effect that lasted for a median of 7.2 months. Half of the participants were still alive 5.4 months after starting treatment, without their tumor getting bigger or spreading further. Half of them were still alive 10.9 months after starting treatment regardless of tumor size changes. Most participants experienced side effects. These side effects included lower levels of certain types of blood cells, sometimes with a fever, and loose or watery stools (diarrhea). Side effects led 7 of 113 participants to stop taking sacituzumab govitecan. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: The study showed that sacituzumab govitecan had significant anti-cancer activity. Though most participants who received sacituzumab govitecan experienced side effects, these did not usually stop participants from continuing sacituzumab govitecan. Doctors can help control these side effects using treatment guidelines, but these side effects can be serious. Clinical Trial Registration: NCT03547973 (ClinicalTrials.gov) (TROPHY-U-1).

JAK-STAT signaling maintains homeostasis in T cells and macrophages.

Immune cells need to sustain a state of constant alertness over a lifetime. Yet, little is known about the regulatory processes that control the fluent and fragile balance that is called homeostasis. Here we demonstrate that JAK-STAT signaling, beyond its role in immune responses, is a major regulator of immune cell homeostasis. We investigated JAK-STAT-mediated transcription and chromatin accessibility across 12 mouse models, including knockouts of all STAT transcription factors and of the TYK2 kinase. Baseline JAK-STAT signaling was detected in CD8+ T cells and macrophages of unperturbed mice-but abrogated in the knockouts and in unstimulated immune cells deprived of their normal tissue context. We observed diverse gene-regulatory programs, including effects of STAT2 and IRF9 that were independent of STAT1. In summary, our large-scale dataset and integrative analysis of JAK-STAT mutant and wild-type mice uncovered a crucial role of JAK-STAT signaling in unstimulated immune cells, where it contributes to a poised epigenetic and transcriptional state and helps prepare these cells for rapid response to immune stimuli.

Correlation of oxygenation indices in invasive mechanical ventilated adult patients.

BACKGROUND: Mechanical ventilation is essential for managing acute respiratory failure, but traditional methods of assessing oxygenation, like the PaO2/FiO2 ratio, pose challenges due to invasiveness and cost. OBJECTIVE: This single-centre prospective observational study aimed to assess the potential of the non-invasive Oxygen Saturation Index (OSI), utilising SpO2 measurements, to diagnose hypoxemia in mechanically ventilated adults. The study sought to establish correlations between OSI, oxygenation index (OI), PaO2/FiO2 ratio and SpO2/FiO2 ratio. METHODS: From August 2022 to July 2023, data was collected from 1055 mechanically ventilated intensive care unit patients. Statistical analysis included correlation tests, receiver operating curve (ROC) analysis and cut-off value determination for hypoxemia diagnosis. RESULTS: We found that the P/F ratio had a statistically significant negative correlation with OI (correlation coefficient -0.832, P value: 0.000 in hypoxemic group and correlation coefficient -0.888, P value: 0.000 in the non-hypoxemic group), and OSI (correlation coefficient -0.746, P value: 0.000 in hypoxemic group and correlation coefficient -0.629, P value: 0.000 in non-hypoxemic group) and has a positive correlation with P/F ratio (correlation coefficient 0.92, P value: 0.000 in hypoxemic group and correlation coefficient -0.67, P value: 0.000 in non-hypoxemic group). OI and OSI had a statistically significant correlation (correlation coefficient 0.955, P value: 0.000 in hypoxemic group and correlation coefficient 0.815, P value: 0.000 in non-hypoxemic group). on ROC analysis P/F ratio was the most accurate in predicting hypoxia followed by OI and OSI. with a cut-off value, of OI being 7.07, and that for OSI being 3.90, at an 80% sensitivity level to diagnose hypoxemia. CONCLUSION: OSI can serve as a dependable surrogate for OI, simplifying ARDS severity assessment. The P/F ratio is the most accurate predictor of hypoxia. Further research, especially in larger multicentre studies, is needed to validate these findings and explore the long-term clinical implications of using OSI for oxygenation monitoring in mechanically ventilated patients.

Harmonizing Hearts: Exploring the Impact of Music Therapy on Cardiovascular Health.

Music therapy (MT) is a music intervention involving a credentialed professional and a client, which has gained increasing recognition in current practices as an adjunct therapy for various conditions, including cardiovascular diseases (CVDs). MT demonstrates notable physiological as well as psychological effects leading to lowered anxiety, depression, and systolic blood pressure in patients with CVDs as well as having effects on heart rate and heart rate variability in healthy subjects. MT emerges as a promising adjunct in the prevention and rehabilitation of CVDs and its holistic impact on physiological and psychological parameters underscores its potential as a noninvasive, cost-effective intervention. Existing literature shows heterogeneity in methods in the studies such as the genre and quality of music utilized as well outcomes. While further research is warranted to optimize protocols and assess long-term effects, the current evidence highlights MT's substantial benefits in cardiovascular health care, making it a promising asset in modern therapeutic approaches. This comprehensive review explores the multifaceted role of MT in CVDs, discussing its mechanisms and clinical applications.

Unveiling the Silent Intruder: H. pylori's Hidden Link to Ischemic Heart Disease.

Cardiovascular disease is the leading cause of death. In addition to the well-known risk factors associated with cardiovascular disease, such as age, diabetes mellitus, smoking, hypertension, and obesity, there has been a growing concern regarding cardiac complications stemming from the Gram-negative bacteria Helicobacter pylori. While H. pylori is most commonly associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric lymphoma, it has also been implicated in extra gastric manifestations, encompassing cardiac, neurologic, ocular, and dermatologic issues. Key virulent factors for coronary artery disease include the vacuolating cytotoxin gene A and the cytotoxin-associated gene A. The most likely pathogenic mechanism of the relationship between H. pylori and coronary artery disease is initiating a chronic inflammatory process associated with infection and the modifications of classic risk factors. These alterations lead to the creation of prothrombotic and procoagulant environments. Here, we review the cardiac manifestations of H. pylori and the underlying pathophysiological mechanisms.

Evaluating Mass Spectrometry-Based Hydroxyl Radical Protein Footprinting of a Benchtop Flash Oxidation System against a Synchrotron X-ray Beamline.

Hydroxyl radical protein footprinting (HRPF) using synchrotron X-ray radiation (XFP) and mass spectrometry is a well-validated structural biology method that provides critical insights into macromolecular structural dynamics, such as determining binding sites, measuring affinity, and mapping epitopes. Numerous alternative sources for generating the hydroxyl radicals (•OH) needed for HRPF, such as laser photolysis and plasma irradiation, complement synchrotron-based HRPF, and a recently developed commercially available instrument based on flash lamp photolysis, the FOX system, enables access to laboratory benchtop HRPF. Here, we evaluate performing HRPF experiments in-house with a benchtop FOX instrument compared to synchrotron-based X-ray footprinting at the NSLS-II XFP beamline. Using lactate oxidase (LOx) as a model system, we carried out •OH labeling experiments using both instruments, followed by nanoLC-MS/MS bottom-up peptide mass mapping. Experiments were performed under high glucose concentrations to mimic the highly scavenging conditions present in biological buffers and human clinical samples, where less •OH are available for reaction with the biomolecule(s) of interest. The performance of the FOX and XFP HRPF methods was compared, and we found that tuning the •OH dosage enabled optimal labeling coverage for both setups under physiologically relevant highly scavenging conditions. Our study demonstrates the complementarity of FOX and XFP labeling approaches, demonstrating that benchtop instruments such as the FOX photolysis system can increase both the throughput and the accessibility of the HRPF technique.

The Rising Use of E-Cigarettes: Unveiling the Health Risks and Controversies.

The use of e-cigarettes has tremendously increased in recent times due to the widespread availability of e-cigarettes in diverse flavors, reduced cost compared to regular cigarettes, and misconception of being comparatively safe, which have led to around 2.55 million US middle and high school students smoking e-cigarettes. These devices use a nicotine-rich liquid, which is aerosolized electronically, producing vapors that may also include hazardous chemicals and heavy metals. E-cigarettes are associated with e-cigarette or vaping-associated lung injury, which presents as an acute respiratory ailment mirroring various pulmonary diseases. Additionally, it causes endothelial dysfunction, alters blood lipid profile by elevating circulating levels of low-density lipoprotein cholesterol, increases sympathetic tone, and is found to correlate with arterial stiffening, hence negatively affecting respiratory, cardiovascular, and overall health. We aim to provide a comprehensive analysis of the data on e-cigarettes and their harmful effects on health in comparison to conventional cigarette use by highlighting the pathophysiology of e-cigarette-induced adverse effects and critically analyzing the data both in favor and against its use. Our review concludes that no matter how much nicotine an e-cigarette contains, evidence shows that using it increases the risk of cardiovascular disease, albeit maybe not as much as smoking regular tobacco. Nonetheless, it is crucial to note that the long-term effects of e-cigarette usage are still not fully understood, and existing data have provided opposing viewpoints.

Lab testing overload: a comprehensive analysis of overutilization in hospital-based settings.

Overuse of laboratory tests has been a growing problem in the inpatient hospital setting for years, which adds to the rising cost of care. Various factors come into play, such as clinical routines, lack of cost transparency, and the convenience of electronic health record-based ordering. The financial ramifications of the overuse are significant, as lab costs drive most medical decisions. Eliminating unnecessary testing with clinical decision support and best practices is associated with marked cost savings, improved outcomes, and decreased patient distress. The excessive use of laboratory tests highly affects patients, resulting in hospital-induced anemia, low patient satisfaction, and poor outcomes. Tackling lab overuse requires a multifaceted approach that includes education, technology, and policy changes. In the era of precision healthcare, optimizing test utilization can reduce costs, decrease waste, and improve patient care.

The cardio-oncology continuum: Bridging the gap between cancer and cardiovascular care.

Cancer and cardiovascular disease are two of the leading causes of death worldwide. Although cancer has historically been viewed as a condition characterized by abnormal cell growth and proliferation, it is now recognized that cancer can lead to a variety of cardiovascular diseases. This is due to the direct impact of cancer on the heart and blood vessels, which can cause myocarditis, pericarditis, and vasculitis. Additionally, cancer patients frequently experience systemic effects such as oxidative stress, inflammation, and metabolic dysregulation, which can contribute to the development of cardiovascular risk factors such as hypertension, dyslipidemia, and insulin resistance. It is important to closely monitor patients with cancer, especially those undergoing chemotherapy or radiation therapy, for cardiovascular risk factors and promptly address them. This article aims to explore the clinical implications of the underlying mechanisms connecting cancer and cardiovascular diseases. Our analysis highlights the need for improved cooperation between oncologists and cardiologists, and specialized treatment for cancer survivors.

Arrhythmias and Hypertrophic Cardiomyopathy: Unravelling the Connection.

Hypertrophic cardiomyopathy (HCM) results from gene mutations affecting cardiac sarcomeres and is inherited in an autosomal dominant manner. With a prevalence of 1:200-1:500 in the general population, HCM is characterised by a hypertrophied and non-dilated left ventricle with predominant involvement of the interventricular septum. The myocardium's structural and intracellular factors, combined with triggers such as physical exertion, autonomic dysfunction, and ischemia, can lead to reentry events, and atrial and ventricular arrhythmias, including atrial fibrillation (AF) which is common among HCM patients. To manage the increased risk of mortality arising from congestive heart failure and thromboembolism, in patients with AF long-term anticoagulation and antiarrhythmic drugs are employed. HCM patients may also encounter supraventricular and ventricular arrhythmias, such as nonsustained ventricular tachycardia and ventricular premature beats, which can potentially lead to sudden cardiac death and necessitate treatment with implanted defibrillators. Physicians must comprehensively analyse clinical, anatomical, hemodynamic, rhythmic, functional, and genetic characteristics to identify HCM patients at high risk of sudden death. This article aims to discuss the pathophysiology of arrhythmia in HCM and clinical recommendations for various ventricular and atrial fibrillation including catheter ablation and implantable cardioverter-defibrillator (ICD).

A comprehensive analysis of different types of clinical rounds in hospital medicine.

Table rounds and bedside rounds are two methods healthcare professionals employ during clinical rounds for patient care and medical education. Bedside rounds involve direct patient engagement and physical examination, thus significantly impacting patient outcomes, such as improving communication and patient satisfaction. Table rounds occur in a conference room without the patient present and involve discussing patient data, which is more effective in fostering structured medical education. Both bedside and table rounds have pros and cons, and healthcare professionals should consider the specific requirements of their patients and medical trainees when deciding which approach to use. This research utilized a comprehensive search to identify relevant resources, such as university website links, as well as a PubMed search using relevant keywords such as 'bedside rounding,' 'table rounding,' and 'patient satisfaction.' Relevance, publication date, and study design were the basis for inclusion criteria. This study compared the effectiveness of these two methods based on physician communication, medical education, patient care, and patient satisfaction.

Protein supplementation: the double-edged sword.

Protein supplements are widely consumed by athletes as well as young adults and teenagers going to the gym and are an excellent source to increase protein intake, build muscle mass, and enhance recovery. They are available in the form of powders, gummies, protein bars, and ready-to-drink shakes and have been shown to have effects on almost every system in the body. Subjects consuming whey protein-based supplements regularly show significantly lower systolic blood pressure, while subjects who consume soy-based protein supplements have been reported to show a significant decrease in their systolic and diastolic blood pressures. Favorable effects of soy protein consumption have been observed on the serum lipid profile, with significant decreases in serum low-density lipoprotein and triglyceride levels. Lower postprandial glucose levels have been observed in diabetic subjects as well, which can be attributed to the lower glycemic index of these supplements. This can lead to an indirect decrease in diabetes-related complications. While these supplements affect the body positively, caution has to be exercised while consuming them in excess, as they have been shown to cause hyperfiltration and increased urinary calcium excretion which can, in turn, lead to chronic kidney disease development. This article focuses on the effects of protein supplementation on the human body, with emphasis on the cardiovascular, endocrine, and renal systems.

Synergistic strategies: Optimizing outcomes through a multidisciplinary approach to clinical rounds.

Multidisciplinary rounds (MDR) constitute a patient-centered care model wherein professionals from diverse disciplines collaborate in real time to provide specialized expertise. The MDR team, encompassing care partners, hospitalists, nurses, pharmacists, and more, employs a collaborative approach that optimizes patient care through shared goals, electronic record access, regular reviews, and patient involvement. MDRs have evolved to reduce patient mortality, complications, length of stay, and readmissions, and they enhance patient satisfaction and utilization of ancillary services. Family engagement in MDRs further transforms relationships from adversarial to collaborative, leading to improved comprehension of treatment strategies and smoother navigation of challenging conversations. Despite challenges such as time constraints, limited patient coverage, and hierarchical barriers, MDRs are being increasingly conducted across healthcare settings, with positive outcomes.

Age-Related Orthostatic Hypotension: A Comprehensive Analysis of Prevalence, Mechanisms, and Management in the Geriatric Population.

Geriatric patients frequently encounter orthostatic hypotension (OH), a multifaceted condition characterized by a significant drop in blood pressure upon assuming an upright position. As the elderly population is particularly susceptible to OH, our review endeavors to comprehensively explore the complex nature of this condition and various factors contributing to its development. We investigate the impact of comorbidities, polypharmacy, age-related physiological changes, and autonomic dysfunction in the pathogenesis of OH. Geriatric patients with OH are faced with an elevated risk of falls, syncope, a decline in their overall quality of life, and hence increased mortality. These implications require careful consideration, necessitating a thorough examination of therapeutic strategies. We evaluate various pharmaceutical and nonpharmacological therapies, delving into the effectiveness and safety of each approach in managing OH within geriatric populations. We explore the role of pharmacotherapy in alleviating symptoms and mitigating OH-related complications, as well as the potential benefits of volume expansion techniques to augment blood volume and stabilize blood pressure. We place particular emphasis on the significance of lifestyle changes and nonpharmacological interventions in enhancing OH management among the elderly. These interventions encompass dietary modifications, regular physical activity, and postural training, all tailored to the unique needs of the individual patient. To optimize outcomes and ensure patient safety, we underscore the importance of individualized treatment plans that take into account the geriatric patient's overall health status, existing comorbidities, and potential interactions with other medications. This review aims to improve clinical practice and patient outcomes by advocating for early detection, properly tailored management, and targeted interventions to address OH in the elderly population. By raising awareness of OH's prevalence and complexities among healthcare professionals, we hope to foster a comprehensive understanding of OH and contribute to the overall wellness and quality of life of this vulnerable demographic.

Cardiovascular Challenges Beyond Earth: Investigating the Impact of Space Travel on Astronauts' Cardiovascular Health.

In the coming decades, as humanity aims to establish a presence on Mars, there is a growing significance in comprehending, monitoring, and controlling the diverse health challenges arising from space exploration. The extended exposure to microgravity during space missions leads to various physical alterations in astronauts, such as shifts in bodily fluids, reduced plasma volume, loss of bone density, muscle wasting, and cardiovascular deconditioning. These changes can ultimately lead to orthostatic intolerance, underscoring the increasing importance of addressing these health risks. Astronauts are exposed to cosmic radiation consisting of high-energy particles from various sources, including solar cosmic rays and galactic cosmic rays. These radiations can impact the electrical signals in the heart, potentially causing irregular heart rhythms. Understanding the risks to the heart and blood circulation brought on by exposure to space radiation and the overall stress of spaceflight is essential and this article reviews the cardiovascular effects of space travel on astronauts.

Shedding light on weight loss: A narrative review of medications for treating obesity.

Obesity and overweight are the major risk factors for numerous chronic diseases, including cardiovascular diseases such as heart disease and stroke, which are the leading causes of death worldwide. The prevalence of obesity has dramatically risen in both developed and developing countries, making it a significant public health concern and a global crisis. Despite lifestyle modifications being the first-line treatment, the high risk of relapse has led to a growing interest in non-invasive pharmacotherapeutic interventions to achieve and maintain weight loss and reverse the growth of the obesity epidemic. Cardiovascular diseases and cancer account for the highest mortality rates among other comorbidities associated with obesity and overweight. Excess and abnormally deposited adipose tissue secretes various inflammatory mediators, leading to cardiovascular diseases and cancers. Weight loss of 5-10% significantly reduces cardiometabolic risk. Medications currently approved in the USA for long-term management of obesity are orlistat, naltrexone, bupropion, phentermine/topiramate, and Glucagon Like Peptide-1 (GLP-1) agonists such as liraglutide and semaglutide. The benefit-to-risk of medications, comorbidities, and individual responses should guide the treatment decisions. The article provides a comprehensive overview and discussion of several weight loss medications used previously and currently, including their efficacy, mechanisms of action, and side effects.

PrECOG PrE0807: A Phase 1b Feasibility Trial of Neoadjuvant Nivolumab Without and with Lirilumab in Patients with Muscle-invasive Bladder Cancer Ineligible for or Refusing Cisplatin-based Neoadjuvant Chemotherapy.

BACKGROUND AND OBJECTIVE: Neoadjuvant cisplatin-based chemotherapy prior to radical cystectomy (RC) improves overall survival (OS) in muscle-invasive bladder cancer (MIBC). However, many patients are cisplatin ineligible; therefore, new treatment options are needed. Nivolumab without/with lirilumab prior to RC was investigated in cisplatin-ineligible patients in this phase 1b trial (NCT03532451) to determine its safety/feasibility. METHODS: Patients with localized MIBC received two doses of nivolumab (480 mg) alone (cohort 1) or with lirilumab (240 mg; cohort 2) prior to RC. Cohorts were enrolled sequentially. The key eligibility criteria were cT2-4aN0-1M0 stage and cisplatin ineligibility/refusal. The primary endpoint was the rate of grade (G) ≥3 treatment-related adverse events (TRAEs) as per Common Terminology Criteria for Adverse Events version 5.0. The key secondary endpoints included the proportion of patients who underwent RC >6 wk after the last dose, CD8+ T-cell density change between pretreatment transurethral resection of bladder tumor (TURBT) and post-treatment RC, ypT0N0, 6 wk. In cohorts 1 and 2, ypT0N0 rates for patients with MIBC and RC were 17% and 21%,