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Cureus Sep 2023Cardiovascular disorders (CVDs) represent a global challenge and are regarded as one of the leading causes of mortality. The role of inflammation as a risk factor in... (Review)
Review
Cardiovascular disorders (CVDs) represent a global challenge and are regarded as one of the leading causes of mortality. The role of inflammation as a risk factor in these disorders has been studied, with the accelerated atherosclerotic process being a crucial factor in the pathogenesis. Several inflammatory biomarkers such as C-reactive protein (CRP), Interleukins (ILs), Tumor Necrosis Factor-alpha (TNF-α), and others have been identified that play a role in the atherosclerotic process, thus linking systemic inflammatory conditions with CVDs, including acute myocardial infarction (AMI), chronic heart failure (CHF), venous thromboembolism (VTE) and others. These markers could be used to predict the risk of CVDs. Understanding the precise mechanisms can lead to therapeutic strategies targeted at pro-inflammatory processes. We aim to provide an overview of the existing literature on the role of inflammation in various cardiovascular disorders and identify different inflammatory biomarkers and therapeutic targets in this comprehensive literature review. We reviewed 190 references published between 2013 and August 3, 2023, in well-reputed journals and analyzed eight selected papers in-depth. We describe the pathophysiologic pathways that lead to atherosclerosis and other cardiovascular pathologies. Several inflammatory cytokines encompassing various groups were identified to be causing endothelial dysfunction, leading to an increased risk for CVDs. Polymorphisms in the genes for different cytokines also led to different levels of susceptibility to CVDs. Nevertheless, future research detailing the inflammatory pathways and their link with CVDs would lead to better outcomes for patients with preexisting and new onset of CVDs as well as chronic inflammatory disorders.
PubMed: 37859889
DOI: 10.7759/cureus.45483 -
Frontiers in Immunology 2023Systemic therapy remains the primary therapeutic approach for advanced hepatocellular carcinoma (HCC). Nonetheless, its efficacy in achieving control of intrahepatic... (Review)
Review
The worthy role of hepatic arterial infusion chemotherapy in combination with anti-programmed cell death protein 1 monoclonal antibody immunotherapy in advanced hepatocellular carcinoma.
Systemic therapy remains the primary therapeutic approach for advanced hepatocellular carcinoma (HCC). Nonetheless, its efficacy in achieving control of intrahepatic lesions is constrained. Hepatic arterial infusion chemotherapy (HAIC) is a therapeutic approach that combines localized treatment with systemic antitumor effects, which aim is to effectively manage the progression of cancerous lesions within the liver, particularly in patients with portal vein tumor thrombosis (PVTT). Combining HAIC with anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody (mAb) immunotherapy is anticipated to emerge as a novel therapeutic approach aimed at augmenting the response inside the localized tumor site and achieving prolonged survival advantages. In order to assess the effectiveness, safety, and applicability of various therapeutic modalities and to address potential molecular mechanisms underlying the efficacy of HAIC-sensitizing immunotherapy, we reviewed the literature about the combination of HAIC with anti-PD-1 mAb therapies.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Treatment Outcome; Cisplatin; Fluorouracil; Venous Thrombosis; Immunotherapy; Cell Death
PubMed: 38022559
DOI: 10.3389/fimmu.2023.1284937 -
Cureus Aug 2023Systemic vasculitides encompass a cluster of autoimmune diseases that affect blood vessels, and are characterized by immune-mediated injury to either small- or... (Review)
Review
Systemic vasculitides encompass a cluster of autoimmune diseases that affect blood vessels, and are characterized by immune-mediated injury to either small- or large-sized blood vessels. Individuals afflicted with systemic vasculitides experience notable morbidity and mortality attributable to cardiovascular manifestations. Noteworthy among these are ischemic heart disease, venous thromboembolism, aortic involvement, valvular irregularities, myocarditis, and pericarditis. This narrative review investigated and evaluated the prevalent cardiovascular disturbances commonly associated with different types of vasculitides. This review also discusses the mechanisms that underlie these manifestations. It also provides a thorough explanation of the many diagnostic techniques essential for detecting the disease at its occult stage. It is essential for healthcare professionals to have knowledge of the cardiovascular complications caused by vasculitides, as this enables them to promptly recognize these symptoms and employ suitable diagnostic techniques early on. By doing so, timely detection can be ensured, which will subsequently aid in initiating appropriate treatment strategies that are vital for decreasing morbidity and mortality in patients with systemic vasculitides.
PubMed: 37791229
DOI: 10.7759/cureus.44417 -
Journal of Gastroenterology Dec 2023This substudy of the Cancer-VTE Registry estimated venous thromboembolism (VTE) incidence and risk factors in pancreatic cancer patients. (Observational Study)
Observational Study
BACKGROUND
This substudy of the Cancer-VTE Registry estimated venous thromboembolism (VTE) incidence and risk factors in pancreatic cancer patients.
METHODS
The Cancer-VTE Registry was an observational study that collected VTE data from patients with solid tumors across Japan. We measured baseline VTE prevalence, and at 1-year follow-up, the cumulative incidence of symptomatic and composite VTE (symptomatic VTE and incidental VTE requiring treatment), bleeding, cerebral infarction/transient ischemic attack (TIA)/systemic embolic event (SEE), and all-cause death.
RESULTS
Of 1006 pancreatic cancer patients, 86 (8.5%) had VTE at baseline, and seven (0.7%) had symptomatic VTE. Significant risk factors of baseline VTE were Eastern Cooperative Oncology Group performance status (ECOG PS) of 1, body mass index (BMI) ≥ 25 kg/m, history of VTE, D-dimer > 1.2 µg/mL, and hemoglobin < 10 g/dL. At 1-year follow-up, the cumulative incidence of events was higher for pancreatic cancer vs other cancers. Pancreatic cancer patients with VTE vs those without VTE had significantly higher incidences of bleeding, cerebral infarction/TIA/SEE, and all-cause death. No significant risk factors for composite VTE were identified.
CONCLUSIONS
The cumulative incidence of composite VTE during cancer treatment was higher in pancreatic cancer than in other cancer types. Some risk factors for VTE prevalence at cancer diagnosis were identified. Although VTE prevalence at cancer diagnosis did not predict the subsequent 1-year incidence of composite VTE, it was a significant predictor of other events such as all-cause death in pancreatic cancer patients.
TRIAL REGISTRATION
UMIN Clinical Trials Registry; UMIN000024942.
Topics: Humans; Incidence; Venous Thromboembolism; Ischemic Attack, Transient; Pancreatic Neoplasms; Registries; Cerebral Infarction; Risk Factors
PubMed: 37676492
DOI: 10.1007/s00535-023-02033-3 -
Open Access Rheumatology : Research and... 2024Rheumatoid arthritis (RA) is a systemic, chronic, immune-mediated inflammatory condition. Treatments options encompass conventional synthetic disease-modifying... (Review)
Review
Rheumatoid arthritis (RA) is a systemic, chronic, immune-mediated inflammatory condition. Treatments options encompass conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologic disease-modifying antirheumatic drugs (bDMARDs) like tumor necrosis factor (TNF) inhibitors (TNFis) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) including Janus Kinase inhibitors (JAKinibs). Orally administered JAKinibs have demonstrated comparable or, in specific cases, superior efficacy compared to bDMARDs in inflammatory conditions. However, the escalating clinical utilization has been accompanied by the emergence of serious adverse effects, including major adverse cardiac events (MACE), malignancies and venous thrombotic episodes (VTE), leading to regulatory restrictions imposed by health authorities in both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
PubMed: 38435420
DOI: 10.2147/OARRR.S436637 -
Medicina (Kaunas, Lithuania) Jul 2023According to Fick's principle, the total uptake of (or release of) a substance by tissues is the product of blood flow and the difference between the arterial and the... (Review)
Review
According to Fick's principle, the total uptake of (or release of) a substance by tissues is the product of blood flow and the difference between the arterial and the venous concentration of the substance. Therefore, the mixed or central venous minus arterial CO content difference depends on cardiac output (CO). Assuming a linear relationship between CO content and partial pressure, central or mixed venous minus arterial PCO differences (PCO and PCO) are directly related to CO. Nevertheless, this relationship is affected by alterations in the COHb dissociation curve induced by metabolic acidosis, hemodilution, the Haldane effect, and changes in CO production (VCO). In addition, PCO and PCO are not interchangeable. Despite these confounders, CO is a main determinant of PCO. Since in a study performed in septic shock patients, PCO was correlated with changes in sublingual microcirculation but not with those in CO, it has been proposed as a monitor for microcirculation. The respiratory quotient (RQ)-RQ = VCO/O consumption-sharply increases in anaerobic situations induced by exercise or critical reductions in O transport. This results from anaerobic VCO secondary to bicarbonate buffering of anaerobically generated protons. The measurement of RQ requires expired gas analysis by a metabolic cart, which is not usually available. Thus, some studies have suggested that the ratio of PCO to arterial minus central venous O content (PCO/CO) might be a surrogate for RQ and tissue oxygenation. In this review, we analyze the physiologic determinants of PCO and PCO/CO and their potential usefulness and limitations for the monitoring of critically ill patients. We discuss compelling evidence showing that they are misleading surrogates for tissue perfusion and oxygenation, mainly because they are systemic variables that fail to track regional changes. In addition, they are strongly dependent on changes in the COHb dissociation curve, regardless of changes in systemic and microvascular perfusion and oxygenation.
Topics: Humans; Carbon Dioxide; Blood Gas Analysis; Shock, Septic; Hemodynamics; Cardiac Output
PubMed: 37512072
DOI: 10.3390/medicina59071262 -
American Journal of Physiology. Heart... Feb 2024Pulmonary and systemic congestion as a consequence of heart failure are clinically recognized as alarm signals for clinical outcome and mortality. Although signs and...
Pulmonary and systemic congestion as a consequence of heart failure are clinically recognized as alarm signals for clinical outcome and mortality. Although signs and symptoms of congestion are well detectable in patients, monitoring of congestion in small animals with heart failure lacks adequate noninvasive methodology yet. Here, we developed a novel ultrasonography-based scoring system to assess pulmonary and systemic congestion in experimental heart failure, by using lung ultrasound (LUS) and imaging of the inferior vena cava (Cava), termed CavaLUS. CavaLUS was established and tested in a rat model of supracoronary aortic banding and a mouse model of myocardial infarction, providing high sensitivity and specificity while correlating to numerous parameters of cardiac performance and disease severity. CavaLUS, therefore, provides a novel comprehensive tool for experimental heart failure in small animals to noninvasively assess congestion. As thorough, noninvasive assessment of congestion is not available in small animals, we developed and validated an ultrasonography-based research tool to evaluate pulmonary and central venous congestion in experimental heart failure models.
Topics: Humans; Mice; Animals; Rats; Hyperemia; Lung; Ultrasonography; Heart Failure; Vena Cava, Inferior
PubMed: 38099848
DOI: 10.1152/ajpheart.00735.2023 -
Journal of Fungi (Basel, Switzerland) Jul 2023Systemic infections caused by rare yeasts are increasing given the rise in immunocompromised or seriously ill patients. Even though globally, the clinical significance... (Review)
Review
Systemic infections caused by rare yeasts are increasing given the rise in immunocompromised or seriously ill patients. Even though globally, the clinical significance of these emerging opportunistic yeasts is increasingly being recognized, less is known about the epidemiology of rare yeasts in Latin America. This review collects, analyzes, and contributes demographic and clinical data from 495 cases of infection caused by rare yeasts in the region. Among all cases, 32 species of rare yeasts, distributed in 12 genera, have been reported in 8 Latin American countries, with (49.5%), (11.1%), and (7.8%) the most common species found. Patients were mostly male (58.3%), from neonates to 84 years of age. Statistically, surgery and antibiotic use were associated with higher rates of infections, while central venous catheter, leukemia, and cancer were associated with higher rates of infections. From all cases, fungemia was the predominant diagnosis (50.3%). Patients were mostly treated with amphotericin B (58.7%). Crude mortality was 40.8%, with a higher risk of death from fungemia and infections. Culture was the main diagnostic methodology. Antifungal resistance to one or more drugs was reported in various species of rare yeasts.
PubMed: 37504735
DOI: 10.3390/jof9070747 -
CPT: Pharmacometrics & Systems... Dec 2023Limited information is available concerning infant exposure and safety when breastfed by mothers receiving chemotherapy. Whereas defining distribution to breast milk is...
Limited information is available concerning infant exposure and safety when breastfed by mothers receiving chemotherapy. Whereas defining distribution to breast milk is important to infer drug exposure, infant pharmacokinetics also determine to what extent the infant will be exposed to potential toxic effects. We aimed to assess the impact of chemotherapy containing breast milk on infants by predicting systemic and local (intestinal) exposure of paclitaxel and doxorubicin in infants through breast milk using a physiologically-based pharmacokinetic (PBPK) approach. Whole-body PBPK models of i.v. paclitaxel and doxorubicin were extended from the literature, with an oral absorption component to enable predictions in infants receiving paclitaxel or doxorubicin-containing breast milk. For safety considerations, worst-case scenarios were explored. Finally, paclitaxel and doxorubicin exposures in plasma and intestinal tissue of infants following feeding of breast milk from paclitaxel- or doxorubicin-treated mothers were simulated and breast milk discarding strategies were evaluated. The upper 95th percentile of the predicted peak concentrations in peripheral venous blood were 3.48 and 0.74 nM (0.4%-1.7% and 0.1%-1.8% of on-treatment) for paclitaxel and doxorubicin, respectively. Intestinal exposure reached peak concentrations of 1.0 and 140 μM for paclitaxel and doxorubicin, respectively. Discarding breast milk for the first 3 days after maternal chemotherapy administration reduced systemic and tissue exposures even further, to over 90% and 80% for paclitaxel and doxorubicin, respectively. PBPK simulations of chemotherapy exposure in infants after breastfeeding with chemotherapy containing breast milk suggest that particularly local gastrointestinal adverse events should be monitored, whereas systemic adverse events are not expected.
Topics: Infant; Female; Humans; Milk, Human; Paclitaxel; Breast Feeding; Doxorubicin; Mothers
PubMed: 37798909
DOI: 10.1002/psp4.13043