-
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 -
Journal of Clinical Oncology : Official... Jun 2024Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase 2 LUMINOSITY trial (NCT03539536)...
Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Non-Squamous EGFR-Wildtype NSCLC in the Phase 2 LUMINOSITY Trial.
PURPOSE
Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase 2 LUMINOSITY trial (NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage 1) and expand the selected group for efficacy evaluation (stage 2). Stage 2 enrolled patients with non-squamous epidermal growth factor receptor ()-wildtype NSCLC.
METHODS
Eligible patients had locally advanced/metastatic c-Met protein-overexpressing NSCLC and ≤2 prior lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in non-squamous -wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%-<50%]). Teliso-V was administered at 1.9 mg/kg every 2 weeks. Primary endpoint was overall response rate (ORR) by independent central review.
RESULTS
In total, 172 patients with non-squamous -wildtype NSCLC received Teliso-V in stages 1 and 2. ORR was 28.6% (95% CI, 21.7-36.2; c-Met high, 34.6% [24.2-46.2]; c-Met intermediate, 22.9% [14.4-33.4]). Median duration of response was 8.3 months (95% CI, 5.6-11.3; c-Met high, 9.0 [4.2-13.0]; c-Met intermediate: 7.2 [5.3-11.5]). Median overall survival was 14.5 months (95% CI, 9.9-16.6; c-Met high, 14.6 [9.2-25.6]; c-Met intermediate, 14.2 [9.6-16.6]). Median progression-free survival was 5.7 months (95% CI, 4.6-6.9; c-Met high, 5.5 [4.1-8.3]; c-Met intermediate: 6.0 [4.5-8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 was peripheral sensory neuropathy (7%).
CONCLUSION
Teliso-V was associated with durable responses in c-Met protein-overexpressing non-squamous -wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.
PubMed: 38843488
DOI: 10.1200/JCO.24.00720 -
Muscle & Nerve Jun 2024Active-duty service members (ADSM) and military Veterans represent a population with increased occupational risk for nerve injuries sustained both during training... (Review)
Review
Active-duty service members (ADSM) and military Veterans represent a population with increased occupational risk for nerve injuries sustained both during training operations and wartime. Mechanisms of war-related nerve injuries have evolved over time, from the musket ball-related traumas described by S.W. Mitchell to complex blast injuries and toxic exposures sustained during Middle East conflicts in the 21st century. Commonly encountered nerve injury etiologies in this population currently include compression, direct trauma, nutritional deficits, traumatic limb amputation, toxic chemical exposures, or blast-related injuries. Expeditious identification and comprehensive, interdisciplinary treatment of combat-associated neuropathies, as well as prevention of these injuries whenever possible is critical to reduce chronic morbidity and disability for service members and to maintain a well-prepared military. However, diagnosis of a combat-associated nerve injury may be particularly challenging due to comorbid battlefield injuries or delayed presentation of neuropathy from military toxic exposures. Advances in imaging for nerve injury, including MRI and ultrasound, provide useful tools to compliment EMG in establishing a diagnosis of combat-associated nerve injury, particularly in the setting of anatomic disruption or edema. Surgical techniques can improve pain control or restoration of function. In all cases, comprehensive interdisciplinary rehabilitation provides the best framework for optimization of recovery. Further work is needed to prevent combat-associated nerve injuries and promote nerve recovery following injury.
PubMed: 38837797
DOI: 10.1002/mus.28168 -
Pediatric Pulmonology Jun 2024This investigation aimed to delineate the clinical manifestations associated with high-altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) in pediatric...
OBJECTIVE
This investigation aimed to delineate the clinical manifestations associated with high-altitude pulmonary edema (HAPE) and acute mountain sickness (AMS) in pediatric populations and find the risk factors of HAPE.
METHODS
We conducted a retrospective analysis of clinical data from children under 18 years diagnosed with HAPE and AMS at an average altitude of 3000 m. The clinical data between these two groups were compared.
RESULTS
The study encompassed 74 pediatric patients, 27 with AMS and 47 with HAPE. HAPE presentations included classic HAPE (55.3%), reentry HAPE (27.7%), and high-altitude resident pulmonary edema (HARPE, 17.0%). Notably, 87.2% of HAPE cases were male, and 68.1% had a high body mass index (BMI). HARPE instances followed viral infections, prominently SARS-CoV-2. HAPE cases exhibited higher BMI, respiratory tract infections within 1 week preceding symptom onset, an increase in white blood cell counts (WBCs), lower peripheral arterial oxygen saturation (SpO), and higher heart rate compared to the AMS group. Multivariate logistic regression pinpointed high BMI as an independent HAPE risk factor (odds ratio = 19.389, 95% confidence interval: 1.069-351.759, p = .045).
CONCLUSION
HAPE occurs predominantly in males, with high BMI identified as a critical independent risk factor. The study underscores the need for heightened awareness and preventive strategies against HAPE in children at high altitudes.
PubMed: 38837645
DOI: 10.1002/ppul.27101 -
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