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World Journal of Gastroenterology Jun 2024In this editorial we comment on the article published in a recent issue of the . Acute liver failure (ALF) is a critical condition characterized by rapid hepatocellular...
In this editorial we comment on the article published in a recent issue of the . Acute liver failure (ALF) is a critical condition characterized by rapid hepatocellular injury and organ dysfunction, and it often necessitates liver transplant to ensure patient survival. Recent research has elucidated the involvement of distinct cell death pathways, namely ferroptosis and pyroptosis, in the pathogenesis of ALF. Ferroptosis is driven by iron-dependent lipid peroxidation, whereas pyroptosis is an inflammatory form of cell death; both pathways contribute to hepatocyte death and exacerbate tissue damage. This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF, highlighting the role of key regulators such as silent information regulator sirtuin 1. Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways. Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.
Topics: Animals; Humans; Ferroptosis; Hepatocytes; Iron; Lipid Peroxidation; Liver; Liver Failure, Acute; Liver Transplantation; Pyroptosis; Signal Transduction; Sirtuin 1
PubMed: 38946877
DOI: 10.3748/wjg.v30.i23.2931 -
BMJ Case Reports Jun 2024Extranodal involvement in diffuse large B-cell lymphoma (DLBCL) is defined as disease outside of the lymph nodes and occurs in up to one-third of patients, though...
Extranodal involvement in diffuse large B-cell lymphoma (DLBCL) is defined as disease outside of the lymph nodes and occurs in up to one-third of patients, though multiorgan extranodal involvement is rare. Here, we describe a case of a patient presenting with widely metastatic lesions, including involvement of the lung, parotid gland, breast, pancreas, femur and multiple soft tissue masses, with initial concern for primary breast malignancy. Breast pathology and imaging were consistent with triple-expressor, double-hit stage IV high-grade B-cell lymphoma with extensive extranodal involvement. Extranodal involvement is a poor prognostic factor associated with high rates of treatment failure, and novel therapies targeting CD19 are currently being studied for relapsed and refractory DLBCL. Extranodal disease is a complex entity that can involve virtually any organ system and should be considered for new presentations of malignancy.
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Female; Middle Aged; Breast Neoplasms; Lung Neoplasms; Parotid Neoplasms; Pancreatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Fatal Outcome
PubMed: 38945554
DOI: 10.1136/bcr-2023-257416 -
Thrombosis Research Jun 2024Dysregulated host response to infection causes life-threatening organ dysfunction. Excessive inflammation and abnormal blood coagulation can lead to disseminated...
INTRODUCTION
Dysregulated host response to infection causes life-threatening organ dysfunction. Excessive inflammation and abnormal blood coagulation can lead to disseminated intravascular coagulation (DIC) and multiple-organ failure in the late sepsis stages. Platelet function impairment in sepsis contributes to bleeding, secondary infection, and tissue injury. Platelet transfusion is considered in patients with sepsis with DIC and bleeding; however, its benefits are limited and of low quality. Fibrinogen plays a crucial role in platelet function, and establishing a fibrin network binds to activated integrin αIIbβ3 and promotes outside-in signaling that amplifies platelet functions. However, the role of fibrinogen in sepsis-induced platelet dysfunction remains unclear.
MATERIALS AND METHODS
We evaluated the effects of fibrinogen on platelet hyporeactivity during septic shock in adult male Wistar rats using lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP) surgery. Changes in the hemodynamic, biochemical, and coagulation parameters were examined. Platelet activation and aggregation were measured using whole-blood assay, 96-well plate-based aggregometry, and light-transmission aggregometry. Additionally, platelet adhesion, spreading, and fibrin clot retraction were evaluated.
RESULTS
Rats with LPS- and CLP-induced sepsis displayed considerable decreases in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and clot retraction. The aggregation of platelets obtained from rats with sepsis was markedly augmented by fibrinogen supplementation. Additionally, fibrinogen administration improved platelet adhesion, spreading, and clot retraction in rats with sepsis.
CONCLUSIONS
Fibrinogen supplementation could serve as a potential therapeutic intervention for alleviating platelet hyporeactivity in patients with sepsis and bleeding.
PubMed: 38945093
DOI: 10.1016/j.thromres.2024.109072 -
The American Journal of Emergency... Jun 2024We aimed to investigate the prognostic factors of pediatric extracorporeal cardiopulmonary resuscitation (ECPR).
OBJECTIVE
We aimed to investigate the prognostic factors of pediatric extracorporeal cardiopulmonary resuscitation (ECPR).
METHODS
The retrospective study included a total of 77 pediatric cases (7 neonates and 70 children) who underwent ECPR after in-hospital and out-of-hospital cardiac arrest between July 2007 and December 2022. Primary endpoints were complications, while secondary endpoints included all-cause in-hospital mortality.
RESULTS
Among the 45 cases experiencing complications, 4 neonates and 41 children had multiple simultaneous complications, primarily neurological issues in 25 cases. Additionally, organ failure occurred in 11 cases, and immunodeficiency was present in two cases. Furthermore, 9 cases experienced bleeding events, and 13 cases showed thrombosis. Patients with complications had lower weight, shorter ECMO durations, and longer CPR durations. Non-survivors had longer CPR durations and shorter durations of ECMO, ICU stay, and mechanical ventilation compared to survivors. Complications were more prevalent in non-survivors, particularly organ failure and bleeding events.
CONCLUSION
Weight, CPR duration, and ECMO duration were associated with complications, suggesting areas for treatment optimization. The higher occurrence of complications in non-survivors underscores the importance of early detection and management to improve survival rates. Our findings suggest clinicians consider these factors in prognostic assessments to enhance the effectiveness of ECPR programs.
PubMed: 38943709
DOI: 10.1016/j.ajem.2024.06.034 -
Revista de La Facultad de Ciencias... Jun 2024Cerebral gas embolism is an unusual but extremely serious condition that occurs when air is introduced into the arterial or venous circulation of the brain. Although...
INTRODUCTION
Cerebral gas embolism is an unusual but extremely serious condition that occurs when air is introduced into the arterial or venous circulation of the brain. Although rare, it can lead to significant neurological deficits and even the death of the patient.
CLINICAL CASE
76-year-old patient with pre-existing diffuse interstitial lung disease, who experienced a massive stroke due to spontaneous pneumomediastinum. Her presentation included confusion, seizures, and motor weakness. Imaging tests revealed air bubbles in the cerebral sulci and hypodense areas in the cerebellum and parietooccipitals. In addition, pneumothorax and air in the upper mediastinum were noted on chest radiographs and chest CT scan. Despite therapeutic measures such as hyperbaric oxygen, the patient unfortunately died due to multiple organ failure.
DISCUSSION
The diagnosis of cerebral gas embolism generally involves performing a cerebral computed tomography, which is highly sensitive for detecting the presence of air in the cerebral vessels. Management includes monitoring of vital and neurological signs, as well as specific measures such as airway closure, venous catheter aspiration, Trendelenburg positioning, and hyperbaric oxygen.
CONCLUSION
Cerebral gas embolism is a potentially fatal condition that requires a brain computed tomography for diagnosis and it is vitally important to know the prevention measures to avoid the appearance of this complication and also to know the general measures to adopt when it occurs.
Topics: Humans; Male; Embolism, Air; Aged; Fatal Outcome; Lung Diseases, Interstitial; Intracranial Embolism; Tomography, X-Ray Computed; Hyperbaric Oxygenation
PubMed: 38941227
DOI: 10.31053/1853.0605.v81.n2.42414 -
CHEST Critical Care Jun 2024Acute brain dysfunction during sepsis, which manifests as delirium or coma, is common and is associated with multiple adverse outcomes, including longer periods of...
BACKGROUND
Acute brain dysfunction during sepsis, which manifests as delirium or coma, is common and is associated with multiple adverse outcomes, including longer periods of mechanical ventilation, prolonged hospital stays, and increased mortality. Delirium and coma during sepsis may be manifestations of alteration in systemic metabolism. Because access to brain mitochondria is a limiting factor, measurement of peripheral platelet bioenergetics offers a potential opportunity to understand metabolic changes associated with acute brain dysfunction during sepsis.
RESEARCH QUESTION
Are altered platelet mitochondrial bioenergetics associated with acute brain dysfunction during sepsis?
STUDY DESIGN AND METHODS
We assessed participants with critical illness in the ICU for the presence of delirium or coma via validated assessment measures. Blood samples were collected and processed to isolate and measure platelet mitochondrial oxygen consumption. We used Seahorse extracellular flux to measure directly baseline, proton leak, maximal oxygen consumption rate, and extracellular acidification rate. We calculated adenosine triphosphate-linked, spare respiratory capacity, and nonmitochondrial oxygen consumption rate from the measured values.
RESULTS
Maximum oxygen consumption was highest in patients with coma, as was spare respiratory capacity and extracellular acidification rate in unadjusted analysis. After adjusting for age, sedation, modified Sequential Organ Failure Assessment score without the neurologic component, and preexisting cognitive function, increased spare respiratory capacity remained associated with coma. Delirium was not associated with any platelet mitochondrial bioenergetics.
INTERPRETATION
In this single-center exploratory prospective cohort study, we found that increased platelet mitochondrial spare respiratory capacity was associated with coma in patients with sepsis. Future studies powered to determine any relationship between delirium and mitochondrial respiration bioenergetics are needed.
PubMed: 38938510
DOI: 10.1016/j.chstcc.2024.100076 -
Open Veterinary Journal May 2024Although relatively uncommon, lymphoma is the most prevalent haematopoietic neoplasia in horses, and multicentric lymphoma remains the most common presentation of the...
BACKGROUND
Although relatively uncommon, lymphoma is the most prevalent haematopoietic neoplasia in horses, and multicentric lymphoma remains the most common presentation of the disease. The pathogenesis of equine lymphoma is still poorly understood and the diagnosis is usually confirmed at an advanced stage of the disease, compromising the prognosis. This study investigated the clinical, pathological, and molecular features of a case of equine multicentric lymphoma.
CASE DESCRIPTION
An apparently healthy 5-year-old crossbreed mare hospitalized at the Centre of Animal Reproduction of Vairão, Portugal, suddenly presented clinical signs of supraorbital oedema and mandibular lymph node enlargement, developing fever, facial oedema, and generalized lymphadenopathy. The mare ended up dying twenty-four days after the first clinical signs due to multisystem organ failure. Haematological and biochemical analyses, necropsy, and microscopic and molecular evaluation of affected tissues were performed. At necropsy, the main findings were multiple multinodular lesions, distributed along the serous surface of oropharynx, trachea, pericardium, gastrointestinal tract, and mesentery. Microscopically, these consisted of solid proliferations of neoplastic round cells that exhibited immunopositivity for CD3 (T cells). Based on these findings, a medium-grade multicentric T-cell lymphoma was diagnosed.
CONCLUSION
There is still very little research regarding the molecular characterization of lymphoma in horses. As an entity itself is quite heterogeneous, it is important to describe the interspecies particularities to understand its development and behaviour.
Topics: Horses; Animals; Horse Diseases; Female; Fatal Outcome; Lymphoma; Portugal; Lymphoma, T-Cell
PubMed: 38938428
DOI: 10.5455/OVJ.2024.v14.i5.24 -
Journal of Translational Medicine Jun 2024Patient heterogeneity poses significant challenges for managing individuals and designing clinical trials, especially in complex diseases. Existing classifications rely...
BACKGROUND
Patient heterogeneity poses significant challenges for managing individuals and designing clinical trials, especially in complex diseases. Existing classifications rely on outcome-predicting scores, potentially overlooking crucial elements contributing to heterogeneity without necessarily impacting prognosis.
METHODS
To address patient heterogeneity, we developed ClustALL, a computational pipeline that simultaneously faces diverse clinical data challenges like mixed types, missing values, and collinearity. ClustALL enables the unsupervised identification of patient stratifications while filtering for stratifications that are robust against minor variations in the population (population-based) and against limited adjustments in the algorithm's parameters (parameter-based).
RESULTS
Applied to a European cohort of patients with acutely decompensated cirrhosis (n = 766), ClustALL identified five robust stratifications, using only data at hospital admission. All stratifications included markers of impaired liver function and number of organ dysfunction or failure, and most included precipitating events. When focusing on one of these stratifications, patients were categorized into three clusters characterized by typical clinical features; notably, the 3-cluster stratification showed a prognostic value. Re-assessment of patient stratification during follow-up delineated patients' outcomes, with further improvement of the prognostic value of the stratification. We validated these findings in an independent prospective multicentre cohort of patients from Latin America (n = 580).
CONCLUSIONS
By applying ClustALL to patients with acutely decompensated cirrhosis, we identified three patient clusters. Following these clusters over time offers insights that could guide future clinical trial design. ClustALL is a novel and robust stratification method capable of addressing the multiple challenges of patient stratification in most complex diseases.
Topics: Humans; Liver Cirrhosis; Male; Female; Cluster Analysis; Middle Aged; Prognosis; Acute Disease; Algorithms; Aged; Cohort Studies
PubMed: 38937846
DOI: 10.1186/s12967-024-05386-2 -
Nature Reviews. Disease Primers Jun 2024Multiple myeloma (MM) is a haematological lymphoid malignancy involving tumoural plasma cells and is usually characterized by the presence of a monoclonal immunoglobulin... (Review)
Review
Multiple myeloma (MM) is a haematological lymphoid malignancy involving tumoural plasma cells and is usually characterized by the presence of a monoclonal immunoglobulin protein. MM is the second most common haematological malignancy, with an increasing global incidence. It remains incurable because most patients relapse or become refractory to treatments. MM is a genetically complex disease with high heterogeneity that develops as a multistep process, involving acquisition of genetic alterations in the tumour cells and changes in the bone marrow microenvironment. Symptomatic MM is diagnosed using the International Myeloma Working Group criteria as a bone marrow infiltration of ≥10% clonal plasma cells, and the presence of at least one myeloma-defining event, either standard CRAB features (hypercalcaemia, renal failure, anaemia and/or lytic bone lesions) or biomarkers of imminent organ damage. Younger and fit patients are considered eligible for transplant. They receive an induction, followed by consolidation with high-dose melphalan and autologous haematopoietic cell transplantation, and maintenance therapy. In older adults (ineligible for transplant), the combination of daratumumab, lenalidomide and dexamethasone is the preferred option. If relapse occurs and requires further therapy, the choice of therapy will be based on previous treatment and response and now includes immunotherapies, such as bi-specific monoclonal antibodies and chimeric antigen receptor T cell therapy.
Topics: Multiple Myeloma; Humans; Dexamethasone; Lenalidomide; Antibodies, Monoclonal; Hematopoietic Stem Cell Transplantation; Melphalan; Thalidomide; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38937492
DOI: 10.1038/s41572-024-00529-7 -
Clinical and Experimental Medicine Jun 2024Patients with multiple myeloma (MM) have an increased risk of sepsis due to underlying disease- and treatment-related immunosuppression. However, data on sepsis... (Observational Study)
Observational Study
Comprehensive analysis of clinical outcomes, infectious complications and microbiological data in newly diagnosed multiple myeloma patients: a retrospective observational study of 92 subjects.
Patients with multiple myeloma (MM) have an increased risk of sepsis due to underlying disease- and treatment-related immunosuppression. However, data on sepsis incidence, causative pathogens, and impact on outcomes in newly diagnosed MM (NDMM) are limited. We conducted a retrospective observational study of 92 NDMM patients who developed sepsis between 2022 and 2023 at a tertiary care center in Italy. Patient characteristics, sepsis criteria [Quick Sequential Organ Failure Assessment, Systemic Inflammatory Response Syndrome (SIRS)], microbiology results, and associations with progression-free survival (PFS) were analyzed. In this cohort of 92 critically-ill patients, pathogenic organisms were identified via microbiological culture in 74 cases. However, among the remaining 18 culture-negative patients, 9 exhibited a SIRS score of 2 and another 9 had a SIRS score of 4, suggestive of a clinical presentation consistent with sepsis despite negative cultures. Common comorbidities included renal failure (60%), anemia (71%), and bone disease (83%). Gram-negative (28%) and Gram-positive (23%) bacteria were frequent causative organisms, along with fungi (20%). Cox Univariate analyses for PFS showed statically significant HR in patients with albumin ≥ 3.5 vs < 3.5 (HR = 5.04, p < 0.001), Karnofsky performance status ≥ 80 vs < 80 (HR = 2.01, p = 0.002), and early-stage vs late-stage disease by International Staging System (HR = 4.76 and HR = 12.52, both p < 0.001) and Revised International Staging System (R-ISS III vs R-ISS I, HR = 7.38, p < 0.001). Sepsis is common in NDMM and associated with poor outcomes. Risk stratification incorporating sepsis severity, comorbidities, and disease stage may help guide preventive strategies and optimize MM management.
Topics: Humans; Multiple Myeloma; Retrospective Studies; Male; Female; Aged; Middle Aged; Sepsis; Italy; Aged, 80 and over; Adult; Tertiary Care Centers
PubMed: 38937383
DOI: 10.1007/s10238-024-01411-2