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Radiology Case Reports Aug 2024Sarcoidosis is a systemic granulomatous disease that can affect multiple organ systems. Although many sarcoidosis patients are asymptomatic, the variable clinical...
Sarcoidosis is a systemic granulomatous disease that can affect multiple organ systems. Although many sarcoidosis patients are asymptomatic, the variable clinical progression of symptomatic patients and the nonspecific presentation make diagnosis difficult in certain cases. Musculoskeletal and sinonasal involvement of sarcoidosis are uncommon manifestations, and they are often only seen in patients with widespread disease. Diagnosis of osseous sarcoidosis, sarcoid arthropathy, and sarcoid rhinosinusitis are typically based on a combination of clinical history, radiological findings, and pathologic specimens. Although there are classic image findings, such as lacelike honeycomb appearance of small bones of the hands or hilar/mediastinal lymphadenopathy, sole reliance on image findings for the diagnosis of sarcoidosis is unreasonable as many findings are nonspecific. However, failure to include sarcoidosis in the differential diagnosis often leads to a delay in recognition of musculoskeletal or sinonasal involvement and results in ineffective treatment plan. Even in patients with biopsy-proven sarcoidosis, some image findings in isolation that may represent granulomatous infiltrates are disregarded as nonspecific without raising the possibility of sarcoidosis due to its rare occurrence. Here we discuss a case of multisystemic sarcoidosis in a 42-year-old female with a constellation of classic and rare findings of biopsy-proven sarcoidosis.
PubMed: 38957650
DOI: 10.1016/j.radcr.2024.05.032 -
Frontiers in Immunology 2024Hemophagocytic lymphohistiocytosis (HLH) is an immune dysfunction characterized by an exaggerated and pathological inflammatory response, potentially leading to systemic... (Review)
Review
Hemophagocytic lymphohistiocytosis (HLH) is an immune dysfunction characterized by an exaggerated and pathological inflammatory response, potentially leading to systemic inflammatory reactions and multiple-organ failure, including renal involvement. HLH can be classified as primary or secondary, with primary HLH associated with genetic mutations affecting cell degranulation capacity, and secondary HLH often linked to infections, tumors, and autoimmune diseases. The pathogenesis of HLH is not fully understood, but primary HLH is typically driven by genetic defects, whereas secondary HLH involves the activation of CD8+ T cells and macrophages, leading to the release of inflammatory cytokines and systemic inflammatory response syndrome (SIRS). The clinical presentation of HLH includes non-specific manifestations, making it challenging to differentiate from severe sepsis, particularly secondary HLH due to infections. Shared features include prolonged fever, hepatosplenomegaly, hematopenia, hepatic dysfunction, hypertriglyceridemia, and hypofibrinogenemia, along with histiocytosis and hemophagocytosis. However, distinctive markers like dual hemocytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated sCD25 levels may aid in differentiating HLH from sepsis. Indeed, no singular biomarker effectively distinguishes between hemophagocytic lymphohistiocytosis and infection. However, research on combined biomarkers provides insights into the differential diagnosis. Renal impairment is frequently encountered in both HLH and sepsis. It can result from a systemic inflammatory response triggered by an influx of inflammatory mediators, from direct damage caused by these factors, or as a consequence of the primary disease process. For instance, macrophage infiltration of the kidney can lead to structural damage affecting various renal components, precipitating disease. Presently, tubular necrosis remains the predominant form of renal involvement in HLH-associated acute kidney injury (HLH-AKI). However, histopathological changes may also encompass interstitial inflammation, glomerular abnormalities, microscopic lesions, and thrombotic microangiopathy. Treatment approaches for HLH and sepsis diverge significantly. HLH is primarily managed with repeated chemotherapy to eliminate immune-activating stimuli and suppress hypercellularity. The treatment approach for sepsis primarily focuses on anti-infective therapy and intensive symptomatic supportive care. Renal function significantly influences clinical decision-making, particularly regarding the selection of chemotherapy and antibiotic dosages, which can profoundly impact patient prognosis. Conversely, renal function recovery is a complex process influenced by factors such as disease severity, timely diagnosis, and the intensity of treatment. A crucial aspect in managing HLH-AKI is the timely diagnosis, which plays a pivotal role in reversing renal impairment and creating a therapeutic window for intervention, may have opportunity to improve patient prognosis. Understanding the clinical characteristics, underlying causes, biomarkers, immunopathogenesis, and treatment options for hemophagocytic lymphohistiocytosis associated with acute kidney injury (HLH-AKI) is crucial for improving patient prognosis.
Topics: Lymphohistiocytosis, Hemophagocytic; Humans; Acute Kidney Injury; Critical Care; Biomarkers
PubMed: 38957461
DOI: 10.3389/fimmu.2024.1396124 -
BMC Health Services Research Jul 2024Nearly three out of four older people will use the emergency department (ED) during their last year of life. However, most of them do not benefit from palliative care....
BACKGROUND
Nearly three out of four older people will use the emergency department (ED) during their last year of life. However, most of them do not benefit from palliative care. Providing palliative care is a real challenge for ED clinicians who are trained in acute, life-saving medicine. Our aim is to understand the ED's role in providing palliative care for this population.
METHODS
We designed a qualitative study based on 1) interviews - conducted with older patients (≥ 75 years) with a palliative profile and their informal caregivers - and 2) focus groups - conducted with ED and primary care nurses and physicians. Palliative profiles were defined by the Supportive and Palliative Indicators tool (SPICT). Qualitative data was collected in French-speaking Belgium between July 2021 and July 2022. We used a constant inductive and comparative analysis.
RESULTS
Five older patients with a palliative profile, four informal caregivers, 55 primary and ED caregivers participated in this study. A priori, the participants did not perceive any role for the ED in palliative care. In fact, there is widespread discomfort with caring for older patients and providing palliative care. This is explained by multiple areas of tensions. Palliative care is an approach fraught with pitfalls, i.e.: knowledge and know-how gaps, their implementation depends on patients'(co)morbidity profile and professional values, experiences and type of practice. In ED, there are constant tensions between emergency and palliative care requirements, i.e.: performance, clockwork and needs for standardised procedures versus relational care, time and diversity of palliative care projects. However, even though the ED's role in palliative care is not recognised at first sight, we highlighted four roles assumed by ED caregivers: 1) Investigator, 2) Objectifier, 3) Palliative care provider, and 4) Decision-maker on the intensity of care. A common perception among participants was that ED caregivers can assist in the early identification of patients with a palliative profile.
CONCLUSIONS
Currently, there is widespread discomfort regarding ED caregivers caring for older patients and providing palliative care. Nonetheless, ED caregivers play four roles in palliative care for older patients. In the future, ED caregivers might also perform the role of early identifier.
Topics: Humans; Palliative Care; Qualitative Research; Aged; Emergency Service, Hospital; Female; Male; Aged, 80 and over; Dementia; Belgium; Focus Groups; Caregivers; Frailty; Interviews as Topic; Frail Elderly
PubMed: 38956595
DOI: 10.1186/s12913-024-11242-2 -
BMC Infectious Diseases Jul 2024Alveolar echinococcosis (AE) primarily affects the liver and potentially spreads to other organs. Managing recurrent AE poses significant challenges, especially when it...
BACKGROUND
Alveolar echinococcosis (AE) primarily affects the liver and potentially spreads to other organs. Managing recurrent AE poses significant challenges, especially when it involves critical structures and multiple major organs.
CASE PRESENTATION
We present a case of a 59-year-old female with recurrent AE affecting the liver, heart, and lungs following two previous hepatectomies, the hepatic lesions persisted, adhering to major veins, and imaging revealed additional diaphragmatic, cardiac, and pulmonary involvement. The ex vivo liver resection and autotransplantation (ELRA), first in human combined with right atrium (RA) reconstruction were performed utilizing cardiopulmonary bypass, and repairs of the pericardium and diaphragm. This approach aimed to offer a potentially curative solution for lesions previously considered inoperable without requiring a donor organ or immunosuppressants. The patient encountered multiple serious complications, including atrial fibrillation, deteriorated liver function, severe pulmonary infection, respiratory failure, and acute kidney injury (AKI). These complications necessitated intensive intraoperative and postoperative care, emphasizing the need for a comprehensive management strategy in such complicated high-risk surgeries.
CONCLUSIONS
The multidisciplinary collaboration in this case proved effective and yielded significant therapeutic outcomes for a rare case of advanced hepatic, cardiac, and pulmonary AE. The combined approach of ELRA and RA reconstruction under extracorporeal circulation demonstrated distinct advantages of ELRA in treating complex HAE. Meanwhile, assessing diaphragm function during the perioperative period, especially in patients at high risk of developing pulmonary complications and undergoing diaphragmectomy is vital to promote optimal postoperative recovery. For multi-resistant infection, it is imperative to take all possible measures to mitigate the risk of AKI if vancomycin administration is deemed necessary.
Topics: Humans; Middle Aged; Female; Liver Transplantation; Heart Atria; Transplantation, Autologous; Echinococcosis; Liver; Plastic Surgery Procedures; Echinococcosis, Hepatic
PubMed: 38956482
DOI: 10.1186/s12879-024-09545-0 -
Clinical Epidemiology 2024Electronic healthcare records (EHRs) are used to document diagnoses, symptoms, tests, and prescriptions. Though not primarily collected for research purposes, owing to...
BACKGROUND
Electronic healthcare records (EHRs) are used to document diagnoses, symptoms, tests, and prescriptions. Though not primarily collected for research purposes, owing to the size of the data as well as the depth of information collected, they have been used extensively to conduct epidemiological research. The Clinical Practice Research Datalink (CPRD) is an EHR database containing representative data of the UK population with regard to age, sex, race, and social deprivation measures. Fibrotic conditions are characterised by excessive scarring, contributing towards organ dysfunction and eventual organ failure. Fibrosis is associated with ageing as well as many other factors, it is hypothesised that fibrotic conditions are caused by the same underlying pathological mechanism. We calculated the prevalence of fibrotic conditions (as defined in a previous Delphi survey of clinicians) as well as the prevalence of fibrotic multimorbidity (the proportion of people with multiple fibrotic conditions).
METHODS
We included a random sample of 993,370 UK adults, alive, and enrolled at a UK general practice, providing data to the CPRD Aurum database as of 1st of January 2015. Individuals had to be eligible for linkage to hospital episode statistics (HES) and ONS death registration. We calculated the point prevalence of fibrotic conditions and multi-morbid fibrosis on the 1st of January 2015. Using death records of those who died in 2015, we investigated the prevalence of fibrosis associated death. We explored the most commonly co-occurring fibrotic conditions and determined the settings in which diagnoses were commonly made (primary care, secondary care or after death).
RESULTS
The point prevalence of any fibrotic condition was 21.46%. In total, 6.00% of people had fibrotic multimorbidity. Of the people who died in 2015, 34.82% had a recording of a fibrotic condition listed on their death certificate.
CONCLUSION
The key finding was that fibrotic multimorbidity affects approximately 1 in 16 people.
PubMed: 38952572
DOI: 10.2147/CLEP.S463499 -
Journal of Inflammation Research 2024Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS is of clinical importance for...
PURPOSE
Capillary leak syndrome (CLS) is an intermediary phase between severe acute pancreatitis (SAP) and multiple organ failure. As a result, CLS is of clinical importance for enhancing the prognosis of SAP. Plakophilin2 (PKP2), an essential constituent of desmosomes, plays a critical role in promoting connections between epithelial cells. However, the function and mechanism of PKP2 in CLS in SAP are not clear at present.
METHODS
We detected the expression of PKP2 in mice pancreatic tissue by transcriptome sequencing and bioinformatics analysis. PKP2 was overexpressed and knocked down to assess its influence on cell permeability, the cytoskeleton, tight junction molecules, cell adhesion junction molecules, and associated pathways.
RESULTS
PKP2 expression was increased in the pancreatic tissues of SAP mice and human umbilical vein endothelial cells (HUVECs) after lipopolysaccharide (LPS) stimulation. PKP2 overexpression not only reduced endothelial cell permeability but also improved cytoskeleton relaxation in response to acute inflammatory stimulation. PKP2 overexpression increased levels of ZO-1, occludin, claudin1, β-catenin, and connexin43. The overexpression of PKP2 in LPS-induced HUVECs counteracted the inhibitory effect of SB203580 (a p38/MAPK signaling pathway inhibitor) on the p38/MAPK signaling pathway, thereby restoring the levels of ZO-1, β-catenin, and claudin1. Additionally, PKP2 suppression eliminated the enhanced levels of ZO-1, β-catenin, occludin, and claudin1 induced by dehydrocorydaline. We predicted that the upstream transcription factor PPARγregulates PKP2 expression, and our findings demonstrate that the PPARγactivator rosiglitazone significantly upregulates PKP2, whereas its antagonist GW9662 down-regulates PKP2. Administration of rosiglitazone significantly reduced the increase in HUVECs permeability stimulated by LPS. Conversely, PKP2 overexpression counteracted the GW9662-induced reduction in ZO-1, phosphorylated p38/p38, and claudin1.
CONCLUSION
The activation of the p38/MAPK signaling pathway by PKP2 mitigates CLS in SAP. PPARγactivator rosiglitazone can up-regulate PKP2. Overall, directing efforts toward PKP2 could prove to be a feasible treatment approach for effectively managing CLS in SAP.
PubMed: 38952564
DOI: 10.2147/JIR.S459449 -
Nature Communications Jul 2024ANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a causative gene for KBG syndrome, a rare developmental disorder characterized by multiple organ...
ANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a causative gene for KBG syndrome, a rare developmental disorder characterized by multiple organ abnormalities, including cardiac defects. However, the role of ANKRD11 in heart development is unknown. The neural crest plays a leading role in embryonic heart development, and its dysfunction is implicated in congenital heart defects. We demonstrate that conditional knockout of Ankrd11 in the murine embryonic neural crest results in persistent truncus arteriosus, ventricular dilation, and impaired ventricular contractility. We further show these defects occur due to aberrant cardiac neural crest cell organization leading to outflow tract septation failure. Lastly, knockout of Ankrd11 in the neural crest leads to impaired expression of various transcription factors, chromatin remodelers and signaling pathways, including mTOR, BMP and TGF-β in the cardiac neural crest cells. In this work, we identify Ankrd11 as a regulator of neural crest-mediated heart development and function.
Topics: Animals; Neural Crest; Mice, Knockout; Mice; Heart; Repressor Proteins; Heart Defects, Congenital; Gene Expression Regulation, Developmental; Chromatin; Signal Transduction; Myocardium; Female
PubMed: 38951500
DOI: 10.1038/s41467-024-48955-1 -
Zhonghua Nei Ke Za Zhi Jul 2024A 19-year-old male patient with high-risk acute B-cell lymphoblastic leukemia received haploidentical stem cell transplantation. He developed anemia repeatedly and...
A 19-year-old male patient with high-risk acute B-cell lymphoblastic leukemia received haploidentical stem cell transplantation. He developed anemia repeatedly and parvovirus B19 nucleic acid was positive in blood plasma. The patient was diagnosed with cold agglutinin syndrome and multiple organ dysfunction including respiratory failure and hepatitis. In the conflict between viral infection and the treatment of cold agglutinin syndrome, we provided supportive treatment, complement inhibitors to control hemolysis, and antiviral therapy. After timely glucocorticoid and immunosuppressant therapy, the patient had achieved a good response.
Topics: Humans; Male; Parvovirus B19, Human; Young Adult; Multiple Organ Failure; Parvoviridae Infections; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
PubMed: 38951100
DOI: 10.3760/cma.j.cn112138-20231210-00376 -
Critical Care Research and Practice 2024Critically ill COVID-19 patients hospitalized in intensive care units (ICU) are immunosuppressed due to SARSCoV-2-related immunological effects and are administered...
Incidence of Carbapenem-Resistant Gram-Negative Bacterial Infections in Critically Ill Patients with COVID-19 as Compared to Non-COVID-19 Patients: A Prospective Case-Control Study.
INTRODUCTION
Critically ill COVID-19 patients hospitalized in intensive care units (ICU) are immunosuppressed due to SARSCoV-2-related immunological effects and are administered immunomodulatory drugs. This study aimed to determine whether these patients carry an increased risk of multi-drug resistant (MDR) and especially carbapenem-resistant Gram-negative (CRGN) bacterial infections compared to other critically ill patients without COVID-19.
MATERIALS AND METHODS
A prospective case-control study was conducted between January 2022 and August 2023. The ICU patients were divided into two groups (COVID-19 and non-COVID-19). Differences in the incidence of CRGN infections from e, spp., and were investigated. In addition, an indicator of the infection rate of the patients during their ICU stay was calculated. Factors independently related to mortality risk were studied.
RESULTS
Forty-two COVID-19 and 36 non-COVID-19 patients were analyzed. There was no statistically significant difference in the incidence of CRGN between COVID-19 and non-COVID-19 patients. The infection rate was similar in the two groups. Regarding the aetiological agents of CRGN infections, was significantly more common in non-COVID-19 patients (=0.007). COVID-19 patients had longer hospitalisation before ICU admission (=0.003) and shorter ICU length of stay (LOS) (=0.005). ICU COVID-19 patients had significantly higher mortality ( < 0.001) and sequential organ failure assessment (SOFA) score ( < 0.001) compared to non-COVID-19 patients. Μortality secondary to CRGN infections was also higher in COVID-19 patients compared to non-COVID-19 patients (=0.033). Male gender, age, ICU LOS, and hospital LOS before ICU admission were independent risk factors for developing CRGN infections. Independent risk factors for patients' mortality were COVID-19 infection, obesity, SOFA score, total number of comorbidities, WBC count, and CRP, but not infection from CRGN pathogens.
CONCLUSIONS
The incidence of CRGN infections in critically ill COVID-19 patients is not different from that of non-COVID-19 ICU patients. The higher mortality of COVID-19 patients in the ICU is associated with higher disease severity scores, a higher incidence of obesity, and multiple underlying comorbidities, but not with CRGN infections.
PubMed: 38947882
DOI: 10.1155/2024/7102082 -
World Journal of Gastroenterology Jun 2024Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory... (Review)
Review
Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.
Topics: Humans; COVID-19; Liver; SARS-CoV-2; Liver Diseases; Hepatocytes
PubMed: 38947288
DOI: 10.3748/wjg.v30.i22.2866