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Cureus Apr 2024Thrombocytopenia, anasarca (edema, pleural effusion, and ascites), fever, reticulin fibrosis/renal dysfunction, and organomegaly (TAFRO) syndrome is a rare and severe...
A Case of Thrombocytopenia, Anasarca (Edema, Pleural Effusion, and Ascites), Fever, Reticulin Fibrosis/Renal Dysfunction, and Organomegaly (TAFRO) Syndrome Initially Not Presenting With Thrombocytopenia: A Role of Immature Platelet Fraction.
Thrombocytopenia, anasarca (edema, pleural effusion, and ascites), fever, reticulin fibrosis/renal dysfunction, and organomegaly (TAFRO) syndrome is a rare and severe systemic disease. The emergence of thrombocytopenia, however, may be preceded by other signs or symptoms, which could delay the diagnosis of the disease. We reported a case in which an increased immature platelet fraction (IPF), a surrogate marker for megakaryocytic activity, preceded the development of thrombocytopenia, and finally, we diagnosed the patient with TAFRO syndrome. A 79-year-old male with a previous history of uninephrectomy due to bladder and ureteral cancer was admitted to our hospital because of massive edema and progressive impairment in renal function. On admission, inguinal lymphadenopathy, elevated C-reactive protein (CRP), bilateral pleural effusion, and ascites were observed, and the lymph node biopsy showed that atrophic lymphoid follicles and germinal centers were observed along with prominent glomeruloid vascular proliferation and the expansion of the interfollicular spaces consistent with the feature of Castleman's disease. The peripheral platelet count did not reach the level of the criteria for TAFRO syndrome (13.9×10/µL), but the immature platelet fraction was increased (11.6%), and bone marrow biopsy revealed hyperplasia of megakaryocytes. During the course of the preemptive treatment with prednisolone and tocilizumab, thrombocytopenia was uncovered, and the patient was finally diagnosed as having TAFRO syndrome. Thus, the present case may offer valuable information on the role of the immature platelet fraction in the establishment of the early diagnosis of TAFRO syndrome.
PubMed: 38779246
DOI: 10.7759/cureus.58772 -
Case Reports in Rheumatology 2024Generalized morphea is a rare fibrosing skin illness that progresses from erythematous, violet-colored skin patches to sclerotic plaques. Another uncommon...
BACKGROUND
Generalized morphea is a rare fibrosing skin illness that progresses from erythematous, violet-colored skin patches to sclerotic plaques. Another uncommon immune-mediated connective tissue disease called eosinophilic fasciitis (EF) evolves to cause sclerosis and woody skin induration. The coexistence of the two is extremely rare and has a poorer prognosis. Our case report is one of the first to report burn injuries as a trigger factor for EF and generalized morphea overlap. . A 36-year-old man presented with acute onset of rapidly progressing skin thickening, tender edema, and skin contractures involving all extremities, shortly after enduring burn injuries from a gasoline explosion. Workup was remarkable for peripheral eosinophilia, hypergammaglobulinemia, and elevated C-reactive protein. Skin biopsy demonstrated sclerodermoid changes and sclerotic thickening of subcutaneous fibrous septa associated with stromal mucin, dermal perivascular, diffuse lymphoplasmacytic infiltrate with eosinophils, decreased CD34 expression, and increased factor XIIIa. He was subsequently diagnosed with an overlap of generalized morphea and eosinophilic fasciitis. The patient had only limited improvement with steroids, methotrexate, mycophenolate mofetil, and intralesional triamcinolone acetonide injections.
CONCLUSION
Generalized morphea with concomitant EF indicates some degree of therapeutic resistance and poor prognosis with a low quality of life. Burn injuries can be a trigger factor for this overlap syndrome. Prompt identification of at-risk individuals and initiating aggressive management are necessary.
PubMed: 38774817
DOI: 10.1155/2024/3123953 -
Journal of Parasitology Research 2024Comorbidities that involve infectious and noninfectious diseases, such as malaria and cancer, have been described. Cancer and malaria induce changes in the nociceptive...
Comorbidities that involve infectious and noninfectious diseases, such as malaria and cancer, have been described. Cancer and malaria induce changes in the nociceptive and inflammatory responses through similar pathophysiological mechanisms. However, it is unclear whether malaria and antimalarial treatment can change the inflammatory and nociceptive responses induced by solid cancer. Therefore, the present study experimentally evaluated the effect of infection by strain ANKA and chloroquine treatment on the nociceptive and inflammatory responses induced by the solid Ehrlich tumor in male BALB/c mice. On the 1 experimental day, mice were infected with and injected with tumor cells in the left hind paw. From the 7 to the 9 experimental day, mice were treated daily with chloroquine. The parasitemia was evaluated on the 7 and 10 days after infection. On the 11 experimental day, mice were evaluated on the von Frey filament test, the hot plate test, and the paw volume test. At the end of the experimental tests on the 11th day, the peripheral blood of all mice was collected for dosing of IL-1 and TNF-. The blood parasitemia significantly increased from the 7 to the 10 day. The chloroquine treatment significantly decreased the parasitemia on the 10 day. The presence of the tumor did not significantly change the parasitemia on the 7 and 10 days in mice treated and nontreated with chloroquine. On the 11 day, the mechanical and thermal nociceptive responses significantly increased in mice with tumors. The treatment with antimalarial significantly reduced the mechanical nociceptive response induced by tumors. The hyperalgesia induced by tumors did not change with malaria. The mechanical and thermal hyperalgesia induced by the tumor was significantly reduced in mice treated and healed from malaria. On the 11 day, the volume of the paw injected by the tumor was significantly increased. The mice treated with chloroquine, infected with malaria, or healed of malaria showed reduced paw edema induced by the tumor. Mice with tumors did not show a change in IL- and TNF- serum levels. Mice with tumors showed a significant increase in serum levels of IL-1 but not TNF- when treated with chloroquine, infected with malaria, or healed of malaria. In conclusion, the results show that malaria infection and chloroquine treatment can influence, in synergic form, the nociceptive and inflammatory responses induced by the solid tumor. Moreover, the mechanical antinociception, the thermal hyperalgesia, and the antiedema effect observed in mice treated with chloroquine and healed from malaria can be related to the increase in the serum level of IL-1.
PubMed: 38774541
DOI: 10.1155/2024/3771926 -
BMC Cardiovascular Disorders May 2024Acute heart failure is the rapid onset of new or worsening symptoms and signs of heart failure. Despite the increasing burden of heart failure in developing countries... (Observational Study)
Observational Study
BACKGROUND
Acute heart failure is the rapid onset of new or worsening symptoms and signs of heart failure. Despite the increasing burden of heart failure in developing countries like Ethiopia, there is a paucity of comprehensive data regarding the clinical characteristics, treatment patterns, and outcomes of acute heart failure, especially in the selected study area. Therefore, this study aimed to assess the clinical characteristics, treatment patterns, and outcomes of hospitalized patients with acute heart failure at Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia.
METHODS
This is a retrospective cross-sectional study of 303 acute heart failure patients who were admitted to the medical wards and intensive care unit of Yekatit 12 Hospital Medical College, Addis Ababa, central Ethiopia, from July 1, 2022, to July 1, 2023. A pretested data abstraction format was used for data extraction from electronic medical records, and SPSS version 26 was used for data analysis. Descriptive analysis was used to summarize sociodemographic data, clinical characteristics, treatment patterns, and outcomes of acute heart failure. Bivariate and multivariate logistic regression models were fitted to identify factors associated with in-hospital mortality. The odds ratio (OR) with the corresponding 95% confidence interval (CI) was calculated to show the strength of the association.
RESULTS
Of the 303 patients, 51.5% were females, and the mean age was 56.7 years. The most frequent symptom and sign were dyspnea (98.7%) and peripheral edema (79%), respectively. The commonest underlying cause and precipitating factor of acute heart failure were cor pulmonale (22.8%) and pneumonia (35.3%), respectively. The commonest anti-remodeling medications prescribed on discharge were beta-blockers (47.9%), followed by mineralocorticoid receptor antagonists (42.8%) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (38.6%), and the least prescribed were sodium-glucose cotransporter 2 inhibitors (8.3%). The in-hospital mortality rate was 8.6%, and the median length of hospital stay was 9 days. Based on the multivariate logistic regression analysis, the most important predictors of in-hospital mortality were systolic blood pressure (SBP) < 115 mmHg (adjusted odds ratio [AOR] = 6.28; 95% CI: 1.99, 19.78), chloride level < 96 mg/dL (AOR = 4.88; 95% CI: 1.30, 18.33), blood urea nitrogen (BUN) > 20 mg/dl (AOR = 5.48; 95% CI: 1.47, 20.49), and presence of dyslipidemia (AOR = 3.73, 95% CI: 1.15, 12.07).
CONCLUSIONS
This study has shown that systolic blood pressure (SBP) < 115 mmHg, blood urea nitrogen (BUN) > 20 mg/dL, chloride (Cl) level < 96 mg/dL, and the presence of dyslipidemia were statistically significant factors associated with in-hospital mortality among patients with acute heart failure. Hence, healthcare providers should stratify patients with acute heart failure upon admission based on their risk of in-hospital mortality and address those potential negative prognostic indicators accordingly.
Topics: Humans; Retrospective Studies; Heart Failure; Ethiopia; Male; Female; Middle Aged; Cross-Sectional Studies; Hospital Mortality; Aged; Acute Disease; Treatment Outcome; Risk Factors; Adult; Risk Assessment; Time Factors; Practice Patterns, Physicians'; Aged, 80 and over; Hospitalization
PubMed: 38773412
DOI: 10.1186/s12872-024-03905-z -
Seminars in Arthritis and Rheumatism Aug 2024The ORAL Surveillance trial, a postmarketing safety clinical trial, found an increased risk of adverse cardiovascular events and venous thromboembolism (VTE) in patients...
OBJECTIVES
The ORAL Surveillance trial, a postmarketing safety clinical trial, found an increased risk of adverse cardiovascular events and venous thromboembolism (VTE) in patients treated with Janus Kinase (JAK) inhibitors compared to tumor necrosis factor (TNF) inhibitors. However, additional studies yielded mixed results and data on other JAK inhibitors are limited.
METHODS
A retrospective, pharmacovigilance study using the FDA adverse event reporting system (FAERS) to assess reporting of adverse cardiovascular events following treatment with JAK inhibitors in rheumatoid arthritis (RA) patients between January 2015 and June 2023. To identify disproportionately increased reporting, an adjusted reporting odds ratio (adj.ROR) was calculated with a multivariable logistic regression model.
RESULTS
We identified safety reports of 75,407 RA patients treated with JAK inhibitors (tofacitinib, n = 52,181; upadacitinib, n = 21,006; baricitinib, n = 2,220) and 303,278 patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs; TNF inhibitors, rituximab, and tocilizumab). The mean age was 61.2(±12) and 59.0(±13), respectively; 82 % and 81 % were women. Compared to bDMARDs, JAK inhibitors were associated with an increased reporting of VTE [n = 1,393, adj.ROR=2.11 (1.97-2.25)], stroke [n = 973, adj.ROR=1.25 (1.16-1.34)], ischemic heart disease [IHD, n = 999, adj.ROR=1.23 (1.13-1.33)], peripheral edema [n = 2699, adj.ROR=1.22 (1.17-1.28)], and tachyarrhythmias [n = 370, adj.ROR=1.15 (1.00-1.33)]. Most of the events occurred in the first year after treatment initiation. When different JAK inhibitors were compared, VTE, stroke, and IHD were more frequently reported with upadacitinib and baricitinib than tofacitinib. When stratified by age category, all safety signals were statistically significant in patients aged≤65 years.
CONCLUSION
In this global postmarketing study, JAK inhibitors are associated with increased reporting of VTE, stroke, IHD, and tachyarrhythmias. These adverse events were reported following all JAK inhibitors that were studied, suggesting a class effect.
Topics: Humans; Arthritis, Rheumatoid; Janus Kinase Inhibitors; Female; Male; Middle Aged; Aged; Antirheumatic Agents; Retrospective Studies; Cardiovascular Diseases; Azetidines; Pyrimidines; Piperidines; Pharmacovigilance; Pyrazoles; Purines; Adult; Sulfonamides; Adverse Drug Reaction Reporting Systems; Product Surveillance, Postmarketing; Heterocyclic Compounds, 3-Ring; Venous Thromboembolism
PubMed: 38772185
DOI: 10.1016/j.semarthrit.2024.152461 -
Zhen Ci Yan Jiu = Acupuncture Research May 2024Lumbar intervertebral disc herniation (LDH) is a common and frequently-occurring disease, which usually causes lumbar and leg pain. Studies have shown that acupuncture... (Review)
Review
Lumbar intervertebral disc herniation (LDH) is a common and frequently-occurring disease, which usually causes lumbar and leg pain. Studies have shown that acupuncture can improve the symptoms of LDH patients. In the present paper, we summarize the progress of researches on the mechanisms of acupuncture underlying improvement of symptoms of LDH in recent 10 years from 1) delaying the intervertibral disc degeneration (by down-regulating the expressions of matrix metalloproteinase [MMP]-3 and MMP-4, up-regulating the expressions of diosaccharides and polyglycoprotein, inhibiting apoptosis and promoting mitochondrial autophagy of nucleus pulposus cells, etc.), 2) maintaining spinal column stability (by relieving rachiasmus and improving lumbar flexor and extensor muscle strength, lowering the degree of polyfidus edema and fat infiltration, and restoring the biomechanics of the spine), 3) regulating inflammation (by inhibiting the production of proinflammatory factors and increasing the production of anti-inflammatory factors, etc.), 4) regulating immune response (by promoting the activity of T cells and other immune cells, lowering serum levels of MMP-3, transforming growth factor-β1 and prostaglandin E2, raising serum levels of IgA, IgG and IgM to improve immune function ), 5) modulating neural structure and function (by promoting myelin regeneration of sciatic nerve fibers, and reducing the edema of Schwann cells' cytoplasm and mitochondria, and improving neural ultrastructure, and sensory and motor functions of peripheral nerves, etc.), 6) relieving lumbar pain (by down-regulating expression of Ca/calmodulin-dependent protein kinase and activation of lumbar spinal cord glial cells, blocking nociceptive signal conduction, regulating the levels of pain-related factors, etc.), and 7) improving local microcirculation. These results may provide scientific evidence for acupuncture treatment of LDH.
Topics: Humans; Acupuncture Therapy; Intervertebral Disc Displacement; Animals; Lumbar Vertebrae
PubMed: 38764125
DOI: 10.13702/j.1000-0607.20230129 -
Lung Cancer (Amsterdam, Netherlands) Jun 2024Dysregulated MET is an established oncogenic driver in non-small cell lung cancer (NSCLC). MET signaling may also suppress anticancer immune responses. Concomitant MET...
INTRODUCTION
Dysregulated MET is an established oncogenic driver in non-small cell lung cancer (NSCLC). MET signaling may also suppress anticancer immune responses. Concomitant MET inhibition with capmatinib (a MET inhibitor) synergistically enhanced the efficacy of immunotherapies in murine cancer models, regardless of tumor dependency to MET signaling. Here, we report results of a multicenter, open-label, phase 2 study of capmatinib plus nivolumab (a PD-1 inhibitor) in patients with EGFR wild-type advanced NSCLC, previously treated with platinum-based chemotherapy.
METHODS
Patients were allocated into high-MET or low-MET groups according to MET expression determined by immunohistochemistry, MET gene copy number as assessed by fluorescence in-situ hybridization, and presence of MET exon 14 skipping mutation, then received capmatinib 400 mg, oral, twice daily in combination with nivolumab 3 mg/kg intravenously every 2 weeks. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate per RECIST v1.1.
RESULTS
The primary endpoint was met in both the high-MET (N = 16) and low-MET (N = 30) groups. In the high-MET and low-MET groups, respectively, the estimated mean 6-month PFS rate (95 % credible interval) by Bayesian analysis was 68.9 % (48.5-85.7) and 50.9 % (35.6-66.4). The Kaplan-Meier median PFS (95 % CI) was 6.2 months (3.5-19.2) and 4.2 months (1.8-7.4). The overall response rate (95 % CI) was 25.0 % (7.3-52.4) and 16.7 % (5.6-34.7). Most frequent treatment-related adverse events (≥30 % any grade, N = 46) were nausea (52.2 %), peripheral edema (34.8 %), and increased blood creatinine (30.4 %).
CONCLUSIONS
Capmatinib plus nivolumab showed clinical activity and manageable safety in pretreated patients with advanced EGFR wild-type NSCLC, independent of MET status.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02323126.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Nivolumab; Female; Lung Neoplasms; Male; Middle Aged; Aged; Antineoplastic Combined Chemotherapy Protocols; ErbB Receptors; Benzamides; Adult; Proto-Oncogene Proteins c-met; Aged, 80 and over; Acrylamides; Imidazoles; Triazines
PubMed: 38763104
DOI: 10.1016/j.lungcan.2024.107820 -
Pediatric Rheumatology Online Journal May 2024Vitamin C deficiency, or scurvy, is rare but poses risks for children with poor diets, limited resources, or malabsorption issues. It may also be common in children with...
BACKGROUND
Vitamin C deficiency, or scurvy, is rare but poses risks for children with poor diets, limited resources, or malabsorption issues. It may also be common in children with restrictive or selective dietary habits in children with global developmental delay, autism spectrum disorder, and physical disabilities. Symptoms include fatigue, irritability, joint and muscle pain, joint swellings, edema, swollen gums, easy bruising, and delayed wound healing. Early recognition and prompt intervention are essential to prevent the progression of symptomatic vitamin C deficiency in children.
CASE PRESENTATION
We present a case of a 13-year-old boy with developmental delay secondary to Lennox Gastaut syndrome referred for suspected recurrent, severe, and atypical IgA vasculitis. He presented with irritability, loss of appetite, petechial and ecchymotic lower limb lesions, unilateral gum swelling, severe arthritis, peripheral oedema, severe weight loss, anaemia, and raised inflammatory markers. Multiple investigations were performed before the diagnosis of scurvy was made. A surgical finding of friable gingival tissue with multiple loose teeth, a skin biopsy with follicular hyperkeratosis and extravasated perifollicular red blood cells, and a typical X-ray finding led to the diagnosis of scurvy.
CONCLUSION
Scurvy should be given careful consideration as a differential diagnosis in patients presenting with musculoskeletal issues, mucocutaneous complaints, and constitutional symptoms such as malaise, asthenia, irritability, and loss of appetite. A focused and detailed dietary history looking for a lack of good sources of vitamin C can be an easy indicator of this differential. Imaging studies revealing the typical features can also help make the diagnosis. Pathology of the skin revealing pathognomonic features can add to the certainty of the diagnosis. In the absence of all else, the rapid response to treatment with an appropriate dose of vitamin C has a diagnostic and therapeutic role.
Topics: Humans; Scurvy; Male; Adolescent; Diagnosis, Differential; Ascorbic Acid; IgA Vasculitis
PubMed: 38760753
DOI: 10.1186/s12969-024-00992-2 -
Neuro-ophthalmology (Aeolus Press) 2024A 15-year-old female presented with headaches and bilateral vision loss. Fundoscopic examination revealed bilateral optic nerve oedema as well as peripheral retinal...
A 15-year-old female presented with headaches and bilateral vision loss. Fundoscopic examination revealed bilateral optic nerve oedema as well as peripheral retinal haemorrhages. Magnetic resonance imaging of the brain showed findings consistent with bilateral optic neuritis. The patient was started on high dose intravenous corticosteroids but her vision failed to improve. The presence of retinal haemorrhages raised concern that a vasculitis was underlying her symptoms, prompting an extensive work-up, which was unrevealing. Plasmapheresis was initiated and the patient's vision eventually improved to 20/20 in both eyes. Ultimately, she was found to be positive for myelin oligodendrocyte glycoprotein (MOG) antibodies, consistent with a diagnosis of MOG-associated optic neuritis. The patient's course was typical for MOG-associated optic neuritis but her peripheral retinal haemorrhages were atypical, which created diagnostic uncertainty. It is important to be aware of the possibility of retinal findings in this disease. We also review potential causes for retinal haemorrhages in optic neuritis.
PubMed: 38756341
DOI: 10.1080/01658107.2023.2290540 -
Ophthalmology. Retina Apr 2024To describe and quantify the structural and functional consequences of retinal vasculopathy with cerebral leukoencephalopathy (RVCL) on the neurosensory retina.
OBJECTIVE
To describe and quantify the structural and functional consequences of retinal vasculopathy with cerebral leukoencephalopathy (RVCL) on the neurosensory retina.
DESIGN
Cross sectional descriptive study from December 2021 to December 2022.
PARTICIPANTS
Retinal vasculopathy with cerebral leukoencephalopathy patients (n = 9, 18 eyes) recruited from the RVCL Research Center at Washington University in St. Louis.
METHODS
Retinal vasculopathy with cerebral leukoencephalopathy patients underwent comprehensive ophthalmological evaluation including OCT, OCT angiography (OCTA), ultrawidefield fundus imaging, retinal autofluorescence, dark adaptation, electroretinography (ERG), Goldmann kinetic perimetry, and fluorescein angiography (FA).
MAIN OUTCOME MEASURES
Comprehensive characterization from various modalities including best-corrected visual acuity, central subfield thickness (μm) from OCT, foveal avascular zone (mm) from OCTA, dark adaptation rod intercept (seconds), cone response in ERG, and presence or absence of vascular abnormalities, leakage, neovascularization, and nonperfusion on FA.
RESULTS
A total of 18 eyes from 9 individuals were included in this study. The best-corrected visual acuity ranged from 20/15 to 20/70. The mean central subfield thickness from OCT was 275.8 μm (range, 217-488 μm). The mean foveal avascular zone (FAZ) from OCTA was 0.65 (range, 0.18-1.76) mm. On dark adaptometry, the mean time was 5.02 (range, 2.9-6.5) minutes, and 1 individual had impaired dark adaptation. Electroretinography demonstrated mild cone response impairment in 4 eyes. On FA, there was evidence of macular and peripheral capillary nonperfusion in 16 of 18 eyes and notable areas of vascular leakage and retinal edema in 5 of the 18 eyes.
CONCLUSIONS
This study illustrates the phenotypic spectrum of disease and may be clinically valuable for aiding diagnosis, monitoring disease progression, and further elucidating the pathophysiology of RVCL to aid in the development of therapies.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Humans; Male; Female; Cross-Sectional Studies; Tomography, Optical Coherence; Adult; Fluorescein Angiography; Visual Acuity; Electroretinography; Middle Aged; Multimodal Imaging; Leukoencephalopathies; Visual Fields; Retinal Diseases; Retinal Vessels; Young Adult; Fundus Oculi; Adolescent
PubMed: 38752998
DOI: 10.1016/j.oret.2023.10.013