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Laboratory Animals Jun 2024Two healthy Landrace pigs anaesthetized with propofol suffered rapid onset of fatal sepsis. Clinical signs included severe arterial hypotension, loss of peripheral...
Two healthy Landrace pigs anaesthetized with propofol suffered rapid onset of fatal sepsis. Clinical signs included severe arterial hypotension, loss of peripheral oxygenation, low end-tidal CO, clinical onset of pulmonary oedema and cardiac dysfunction. Gross and histopathological examination revealed loss of vascular integrity with severe lung oedema and congestion, haemorrhages in several organs and fluid leakage into body cavities. Large numbers of Gram-negative bacteria, primarily sp., were present in the anaesthetic infusion containing propofol and were also cultured from internal organs of both pigs. The propofol was likely contaminated by bacteria after inappropriate handling and storage in the operating room. This report illustrates the potential for severe nosocomial infection when applying propofol in animals and humans and may serve as a reminder of the importance of strict aseptic practice in general, and specifically in the handling of this anaesthetic agent.
PubMed: 38863139
DOI: 10.1177/00236772231200524 -
Scientific Reports Jun 2024Acute pancreatitis (AP) is currently among the most prevalent digestive diseases. The pathogenesis of AP remains elusive, and there is no specific treatment. Therefore,...
Acute pancreatitis (AP) is currently among the most prevalent digestive diseases. The pathogenesis of AP remains elusive, and there is no specific treatment. Therefore, identifying novel therapeutic targets is imperative for effective management and prevention of AP. In this study, we conducted a comprehensive transcriptomic analysis of peripheral blood from patients with AP and the pancreatic tissue from a mouse model of AP. Our analyses revealed that mouse model of AP exhibited a higher enrichment of mitogen-activated protein kinase signaling, endocytosis, apoptosis and tight junction pathways than the control. Subsequent weighted gene co-expression network analysis identified 15 gene modules, containing between 50 and 1000 genes each, which demonstrated significant correlations within samples from patients with AP. Further screening identified four genes (ACSL4, GALNT3, WSB1, and IL1R1) that were significantly upregulated in severe acute pancreatitis (SAP) in both human and mouse samples. In mouse models of SAP, ACSL4 was significantly upregulated in the pancreas, whereas GALNT3, WSB1, and IL1R1 were not. Lastly, we found that a commercially available ACSL4 inhibitor, PRGL493, markedly reduced IL-6 and TNFα expression, alleviated pancreatic edema and necrosis, and diminished the infiltration of inflammatory cells. In conclusion, this study comprehensively depicts the key genes and signaling pathways implicated in AP and suggests the potential of ACSL4 as a novel therapeutic target for SAP. These findings provide valuable insights for further exploration of therapeutic strategies for SAP.
Topics: Animals; Pancreatitis; Humans; Mice; Disease Models, Animal; Male; Pancreas; Gene Expression Profiling; Signal Transduction; Acute Disease; Female
PubMed: 38862656
DOI: 10.1038/s41598-024-63898-9 -
The Egyptian Heart Journal : (EHJ) :... Jun 2024Myeloproliferative disorders, including monoclonal gammopathy of undetermined significance (MGUS), are often associated with amyloid light-chain (AL)-type cardiac...
BACKGROUND
Myeloproliferative disorders, including monoclonal gammopathy of undetermined significance (MGUS), are often associated with amyloid light-chain (AL)-type cardiac amyloidosis (CA) but occasionally with wild-type transthyretin (ATTR) CA. In recent years, ATTR amyloidosis has attracted necessity for its reliable diagnosis with the addition of new treatments. Usually, both wild-type ATTR CA and AL-type CA present with marked cardiac hypertrophy, but renal dysfunction is milder in wild-type ATTR amyloidosis than in AL-type amyloidosis. Peripheral neurologic and autonomic symptoms such as numbness and dysesthesia are moderately present in AL-type amyloidosis, but less so in wild-type ATTR amyloidosis. Furthermore, the prognosis of ATTR-type amyloidosis is better than that of AL-type amyloidosis.
CASE PRESENTATION
A 72-year-old man with cardiac hypertrophy presented with New York Heart Association functional class III dyspnea and leg edema. He had no history of carpal tunnel syndrome. An electrocardiogram showed atrial fibrillation and low voltage. The N-terminal pro-B-type natriuretic peptide level was 3310 pg/mL, and troponin T was elevated to 0.073 ng/mL. However, the glomerular filtration rate was only slightly decreased at 69.0 mL/min/1.73 m. The serum free light-chain assay revealed a significant increase in the kappa chain, with positive results in Bence Jones proteins and serum immunoelectrophoresis. Bone marrow examination confirmed the diagnosis of monoclonal gammopathy of undetermined significance (MGUS). AL-type amyloidosis associated with a myeloproliferative disorder was suspected, and the prognosis was initially predicted to be poor, classified as Mayo stage IV. Contrary to this prognosis, the patient showed a slow progression of heart failure. Further imaging modalities and cardiac tissue findings confirmed the diagnosis as transthyretin type amyloidosis, and a favorable prognosis was established with the use of tafamidis.
CONCLUSIONS
MGUS occasionally coexists with wild-type ATTR CA. Scant autonomic symptoms, mild renal dysfunction, and slow progression of heart failure might be clues that the CA associated with the myeloproliferative disease is wild-type ATTR amyloidosis.
PubMed: 38856864
DOI: 10.1186/s43044-024-00499-x -
Chest Jun 2024A 57-year-old man was admitted to our hospital via the ED presenting in reduced general condition because of an infection of unknown origin, generalized edema, and...
A 57-year-old man was admitted to our hospital via the ED presenting in reduced general condition because of an infection of unknown origin, generalized edema, and dyspnea at rest (peripheral capillary oxygen saturation, 89%) that required 2 L/min intranasal oxygen. Anamnesis was complicated by an infection-triggered delirium, but his wife reported an increasing physical decay that had led to bed confinement. The BP was reduced at 88/55 mm Hg with a normal heart rate of 86 beats/min. Lung auscultation showed mild bipulmonal rales. Previous comorbidities were a BMI of 42 kg/m, an insulin-dependent type 2 diabetes mellitus with a severe diabetes-related chronic kidney disease stage G4A3, and systemic arterial hypertension.
Topics: Humans; Male; Middle Aged; Pulmonary Artery; Vascular Calcification; Tomography, X-Ray Computed; Diagnosis, Differential
PubMed: 38852977
DOI: 10.1016/j.chest.2024.02.022 -
Medicine Jun 2024Nasopharyngeal carcinoma has a high incidence in East and Southeast Asia, often with distant metastasis. However, leptomeningeal metastasis (LM) is extremely rare and... (Review)
Review
RATIONALE
Nasopharyngeal carcinoma has a high incidence in East and Southeast Asia, often with distant metastasis. However, leptomeningeal metastasis (LM) is extremely rare and usually has a poor prognosis. This paper reports the clinical treatment of a patient with meningeal metastasis of nasopharyngeal carcinoma (NPC) in order to improve the clinician's understanding of the disease. Early diagnosis of the disease can alleviate the pain of patients and prolong their survival time.
PATIENT CONCERNS
We report the case of a 55-year-old female with a history of NPC with LM. Brain magnetic resonance imaging showed temporal lobe enhancement, peripheral edema, and enhancement of the adjacent meninges. Cerebrospinal fluid cytology suggests the presence of malignant tumor cells.
DIAGNOSES
The patient was diagnosed with LM from NPC.
INTERVENTIONS
The patients were regularly given targeted therapy with nimotuzumab, immunotherapy with karyolizumab, and lumbar intrathecal methotrexate chemotherapy and supportive treatment.
OUTCOMES
The patient had survived for 3 years since the diagnosis of LM and was in good condition and still under active antitumor treatment.
LESSONS
Leptomeningeal metastasis of NPC is a rare disease. Although there is currently no unified treatment plan, the neurological symptoms can still be controlled and the quality of life can be improved through active treatment.
Topics: Humans; Female; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Meningeal Neoplasms; Meningeal Carcinomatosis; Magnetic Resonance Imaging
PubMed: 38847717
DOI: 10.1097/MD.0000000000037853 -
European Journal of Case Reports in... 2024Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, characterised by multi-organ affections. Haematological involvement is a common manifestation of...
BACKGROUND
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, characterised by multi-organ affections. Haematological involvement is a common manifestation of SLE, consisting of autoimmune peripheral cytopenia. Autoimmune myelofibrosis (AIMF) is a rare cause of cytopenia in SLE; it could precede or be concurrent with the diagnosis of SLE. There are few studies that describe this association.
CASE DESCRIPTION
We report a case of AIMF revealing the diagnosis of SLE in 34-year-old female, presented with episodes of gingival bleeding associated with peripheral inflammatory polyarthralgia, photosensitivity and deterioration of general condition. Clinical examination revealed a soft pitting oedema in the lower limbs. Laboratory investigations showed a pancytopenia, inflammatory biological syndrome, with positive 24-hour proteinuria and anti-native DNA antibodies. A bone marrow biopsy showed diffuse myelofibrosis associated with maturation disorders and no tumour infiltrate. Renal biopsy revealed proliferative glomerulonephritis class III with immune deposits.
CONCLUSION
The association of AIMF with SLE has been rarely reported, and it could be another cause for cytopenia in SLE.
LEARNING POINTS
Autoimmune myelofibrosis can be associated with systemic lupus erythematosus (SLE), even though it is rare.This association should be considered when pancytopenia is not well controlled during SLE, prompting a bone marrow biopsy to confirm the diagnosis.The therapeutic management of this association is the same as that used in SLE.
PubMed: 38846662
DOI: 10.12890/2024_004511 -
Frontiers in Pediatrics 2024This article reports a case of neonatal incontinentia pigmenti onset in only one male monozygotic twin with characteristic skin lesions after birth followed by severe...
BACKGROUND
This article reports a case of neonatal incontinentia pigmenti onset in only one male monozygotic twin with characteristic skin lesions after birth followed by severe cerebrovascular lesions.
CASE PRESENTATION
A male infant, the first of monozygotic twins, was born with multiple yellow pustules all over his body, repeated new herpes at different sites during the course of the disease, aggravated by fusion, warty crusts, and hyperpigmentation; biopsy pathology suggested eosinophilic spongiform edema of the skin. Peripheral blood eosinophils were significantly elevated, and brain magnetic resonance imaging revealed diffuse multiple cystic and lamellar abnormal signal areas in the left frontal and parietal lobes. On day 30, the infant showed neurological symptoms, such as poor response and apnea, and an emergency cranial computed tomography scan revealed abnormal changes in the left cerebral hemisphere and bilateral cerebellum. After admission, he was given a potassium permanganate bath and topical mupirocin for 1 month, and the skin abnormalities improved. He was treated with mechanical ventilation and vasoactive drugs for 2 days after the cerebrovascular accident, and died the same day after the parents chose hospice care. No deletion variants or point mutations were detected in subsequent genetic tests, and chromosomal copy number variation tests revealed different degrees of chimeric duplications and deletions in different regions of chromosomes Y and 3. The parents were healthy, and his twin brother had normal growth and development with no abnormalities at multiple follow-up visits.
CONCLUSION
Neonatal incontinentia pigmenti in only one male monozygotic twin is extremely rare and the genetic diagnosis is challenging. Awareness of the combined cerebrovascular lesions needs to be enhanced, and potential prevention and treatment methods need to be explored to improve the prognosis.
PubMed: 38832002
DOI: 10.3389/fped.2024.1338054 -
Kidney Medicine Jun 2024Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for...
RATIONALE & OBJECTIVE
Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for focal segmental glomerulosclerosis (FSGS). In the DUET 8-week double-blind period, sparsentan resulted in greater proteinuria reduction versus irbesartan. We report the long-term efficacy and safety of sparsentan during the open-label extension over more than 4 years.
STUDY DESIGN
Patients were examined from their first sparsentan dose (double-blind period or open-label extension) through 4.6 years.
SETTING & PARTICIPANTS
Patients with FSGS, excluding secondary FSGS.
INTERVENTION
Sparsentan (200, 400, and 800 mg/d).
OUTCOMES
Urinary protein-creatinine ratio, FSGS partial remission endpoint (urinary protein-creatinine ratio ≤1.5 g/g and >40% reduction from baseline), estimated glomerular filtration rate, and blood pressure approximately every 12 weeks. Treatment-emergent adverse events by year and cases/100 patient-years.
RESULTS
109 patients were enrolled; 108 received ≥1 sparsentan dose; 103 entered the open-label extension (68 sparsentan, 35 irbesartan during the double-blind period). Sparsentan was ongoing in 45/108 patients (41.7%); median time to treatment discontinuation was 3.9 years (95% CI, 2.6-5.2). Mean percent proteinuria reduction from baseline was sustained through follow-up. Achieving partial remission within 9 months of first sparsentan dose (52.8% of patients) versus not achieving (47.2%) was associated with significantly slower rate of estimated glomerular filtration rate decline over the entire treatment period (-2.70 vs -6.56; = 0.03) and in the first 2 years (-1.69 vs -6.46; = 0.03). The most common treatment-emergent adverse events (>9 cases/100 patient-years) were headache, peripheral edema, upper respiratory infection, hyperkalemia, and hypotension. Peripheral edema and hypotension declined from year 1 (13.9% and 15.7% of patients, respectively) to ≤4% in years ≥2. There were no cases of heart failure and no patient deaths.
LIMITATIONS
The open-label extension does not include a comparison group.
CONCLUSIONS
Long-term sparsentan treatment showed sustained proteinuria reduction and a consistent safety profile.
PubMed: 38831932
DOI: 10.1016/j.xkme.2024.100833 -
Frontiers in Pain Research (Lausanne,... 2024Complex Regional Pain Syndrome (CRPS) is a chronic pain disorder characterized by a diverse array of symptoms, including pain that is disproportionate to the initial... (Review)
Review
Complex Regional Pain Syndrome (CRPS) is a chronic pain disorder characterized by a diverse array of symptoms, including pain that is disproportionate to the initial triggering event, accompanied by autonomic, sensory, motor, and sudomotor disturbances. The primary pathology of both types of CRPS (Type I, also known as reflex sympathetic dystrophy, RSD; Type II, also known as causalgia) is featured by allodynia, edema, changes in skin color and temperature, and dystrophy, predominantly affecting extremities. Recent studies started to unravel the complex pathogenic mechanisms of CRPS, particularly from an autoimmune and neuroimmune interaction perspective. CRPS is now recognized as a systemic disease that stems from a complex interplay of inflammatory, immunologic, neurogenic, genetic, and psychologic factors. The relative contributions of these factors may vary among patients and even within a single patient over time. Key mechanisms underlying clinical manifestations include peripheral and central sensitization, sympathetic dysregulation, and alterations in somatosensory processing. Enhanced understanding of the mechanisms of CRPS is crucial for the development of effective therapeutic interventions. While our mechanistic understanding of CRPS remains incomplete, this article updates recent research advancements and sheds light on the etiology, pathogenesis, and molecular underpinnings of CRPS.
PubMed: 38828388
DOI: 10.3389/fpain.2024.1385889 -
Cureus Apr 2024Leprosy has been known for its wide range of peripheral nerve and tissue involvement and causing disabilities. Early diagnosis and treatment with multi-drug therapy can...
Leprosy has been known for its wide range of peripheral nerve and tissue involvement and causing disabilities. Early diagnosis and treatment with multi-drug therapy can save lives and limbs and prevent disabilities. However, management and drug therapy are usually lengthy and full of ups and downs of side effects. Further, the lepra reaction is frequently noted during management, requiring immunosuppression and leading to associated side effects. Limb edema per se due to leprosy is unusual and mostly a symptom of a reactional state. There is no specific management for edema in such cases, and it subsides with improving reactionary states. Nevertheless, the edema may be persistent and bothersome. The present report highlights one such unusual case in a 40-year-old man, diagnosed with borderline-tuberculoid leprosy and experiencing a type-1 reaction. Owing to ocular complications, steroid therapy for the reaction was tapered abruptly, and his limb edema did not subside with the improving lepra reaction. Compression stockings helped to manage edema. This case also makes us ponder the possible use of compression stockings as an opioid-sparing aid in lepra reaction-related edema.
PubMed: 38800266
DOI: 10.7759/cureus.58893