Acute cholangitis: a state-of-the-art review.

Acute cholangitis is a potentially life-threatening bacterial infection of the intra and/or extrahepatic bile ducts. It remains the second and third cause of community-acquired and hospital-acquired bacteremia, respectively, and is associated with mortality rates of up to 15%, despite advances in broad-spectrum antimicrobial therapy and improved access to emergency biliary tract decompression procedures. Even though not much has changed in recent years in terms of diagnosis or treatment, new data have emerged regarding multidrug-resistant bacteria that serve as etiologic agents of cholangitis. Moreover, different approaches in antibiotic regimes depending on severity grading and bile sample cultures as well as novel minimally invasive endoscopic procedures that can help when consecrated treatments such as endoscopic retrograde cholangiopancreatography (ERCP) fail, cannot be performed, or are unavailable have been proposed. This state-of-the-art review aims to offer a complete and updated assessment of the epidemiology, novel diagnostic and therapeutic methods, complications, and prognostic variables of acute cholangitis. The authors will review the prognostic implications of unusual complications, the relevance of regular bile samples and antibiograms, and their new role in guiding antibiotic therapy and limiting antibiotic resistance to present an organized and comprehensive approach to the care of acute cholangitis.

Overview of dyslipidemia and metabolic syndrome in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral blood. Subjects suffering from MPNs display a high burden of cardiovascular risk factors, and thrombotic events are often the cause of death in this population of patients. Herein, we provide a brief overview of dyslipidemia and metabolic syndrome and their epidemiology in MPNs and examine the common molecular mechanisms between dyslipidemia, metabolic syndrome, and MPNs, with a special focus on cardiovascular risk, atherosclerosis, and thrombotic events. Furthermore, we investigate the impact of dyslipidemia and metabolic syndrome on the occurrence and survival of thrombosis in MPN patients, as well as the management of dyslipidemia in MPNs, and the impact of MPN treatment on serum lipid concentrations, particularly as side/adverse effects reported in the context of clinical trials.

Acute myocardial infarction in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage. Affected individuals are at increased risk for cardiovascular and thrombotic events. Myocardial infarction (MI) may be one of the earliest clinical manifestations of MPNs or may be a thrombotic complication that develops during the natural course of the disease. In the present review, we examine the epidemiology, pathogenesis, clinical presentation, and management of MI in MPNs based on the available literature. Moreover, we review potential biomarkers that could mediate the MI-MPNs crosstalk, from classical biochemical tests, e.g., lactate dehydrogenase, creatine kinase and troponins, to pro-inflammatory cytokines, oxidative stress markers, and clonal hematopoiesis.

Stealth invaders: unraveling the mystery of neurotropic viruses and their elusive presence in cerebrospinal fluid - a comprehensive review.

Neurotropic viruses are a threat to human populations due to ongoing zoonosis. A wide array of neurological manifestations can occur most often including parkinsonism, encephalitis/encephalopathy, flaccid myelitis, and Guillain-Barré syndrome. Neuroinvasion occurs through: transneural transmission, blood brain barrier (BBB) dysfunction, and 'trojan horse' mechanism or infected immune cell trafficking into the central nervous system (CNS). Transneural transmission occurs through virus mediated hijacking of intracellular transport proteins allowing retrograde viral transport. BBB dysfunction occurs through cytokine storm increasing membrane permissibility. Increased chemokine expression allows leukocyte trafficking to the BBB. Virally infected leukocytes may successfully pass through the BBB allowing the pathogen to infect microglia and other CNS cell types. We define cerebrospinal fluid (CSF) nondetection as a virus' ability to evade direct CSF detection but still causing significant neurological symptoms and disease. Mechanisms of CSF nondetection include: transneuronal propagation through trans-synaptic transmission, and synaptic microfusion, as well as intrathecal antibody synthesis and virus neutralization. Direct virus detection in CSF is associated with an increased neurological disease burden. However, the lack of CSF detection does not exclude CNS involvement due to possible neuroevasive mechanisms.

Budd-Chiari syndrome in myeloproliferative neoplasms: A review of literature.

Myeloproliferative neoplasms (MPNs) are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs. Classical, Philadelphia-negative MPNs, i.e., polycythemia vera, essential thrombocythemia and primary myelofibrosis, exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites, e.g., portal, splanchnic or hepatic veins, the placenta or cerebral sinuses. The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury, stasis, elevated leukocyte adhesion, integrins, neutrophil extracellular traps, somatic mutations (e.g., the V617F point mutation in the JAK2 gene), microparticles, circulating endothelial cells, and other factors, to name a few. Herein, we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs, with a particular focus on its epidemiology, pathogenesis, histopathology, risk factors, classification, clinical presentation, diagnosis, and management.

Raynaud's Phenomenon: Reviewing the Pathophysiology and Management Strategies.

Raynaud's phenomenon (RP) is a multifactorial vasospastic disorder characterized by a transient, recurrent, and reversible constriction of peripheral blood vessels. RP is documented to affect up to 5% of the general population, but variation in its prevalence is commonly recognized owing to many factors, including varied definitions, gender, genetics, hormones, and region. Furthermore, RP may be idiopathic or be a clinical manifestation of an underlying illness. Patients with RP classically describe a triphasic discoloration of the affected area, beginning with pallor, followed by cyanosis, and finally ending with erythema. This change in color spares the thumb and is often associated with pain. Each attack may persist from several minutes to hours. Moreover, the transient cessation of blood flow in RP is postulated to be mediated by neural and vascular mechanisms. Both structural and functional alterations observed in the blood vessels contribute to the vascular abnormalities documented in RP. However, functional impairment serves as a primary contributor to the pathophysiology of primary Raynaud's. Substances like endothelin-1, angiotensin, and angiopoietin-2 play a significant role in the vessel-mediated pathophysiology of RP. The role of nitric oxide in the development of this phenomenon is still complex. Neural abnormalities resulting in RP are recognized as either being concerned with central mechanisms or peripheral mechanisms. CNS involvement in RP may be suggested by the fact that emotional distress and low temperature serve as major triggers for an attack, but recent observations have highlighted the importance of locally produced factors in this regard as well. Impaired vasodilation, increased vasoconstriction, and several intravascular abnormalities have been documented as potential contributors to the development of this disorder. RP has also been observed to occur as a side effect of various drugs. Recent advances in understanding the mechanism of RP have yielded better pharmacological therapies. However, general lifestyle modifications along with other nonpharmacological interventions remain first-line in the management of these patients. Calcium channel blockers, alpha-1 adrenoreceptor antagonists, angiotensin-converting enzyme inhibitors, nitric oxide, prostaglandin analogs, and phosphodiesterase inhibitors are some of the common classes of drugs that have been found to be therapeutically significant in the management of RP. Additionally, anxiety management, measures to avoid colder temperatures, and smoking cessation, along with other simple modifications, have proven to be effective non-drug strategies in patients experiencing milder symptoms.