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Open Life Sciences 2024Castleman disease (CD) is a relatively rare lymphoproliferative disorder. Lesions predominantly originate on the chest and neck and rarely occur on the abdomen. A...
Castleman disease (CD) is a relatively rare lymphoproliferative disorder. Lesions predominantly originate on the chest and neck and rarely occur on the abdomen. A 34-year-old female presented to our hospital with an unexplained 10-year history of anemia. A pathological diagnosis of plasma cell-type CD was established. One cycle of chemotherapy (thalidomide, cyclophosphamide, and prednisolone) improved her anemia significantly. Prompt etiological diagnosis and early intervention are essential to address systemic manifestations in patients with CD, and it is crucial to consider CD as a differential diagnosis when intra-abdominal masses are detected.
PubMed: 38947769
DOI: 10.1515/biol-2022-0898 -
Cureus May 2024A 50-year-old man presented with fever and a generalized rash, with chronic fatigue and lymphadenopathy for a year and a half. Initial tests ruled out...
A 50-year-old man presented with fever and a generalized rash, with chronic fatigue and lymphadenopathy for a year and a half. Initial tests ruled out lymphoproliferative disorders, showing reactive hyperplasia and cytomegalovirus. Symptoms worsened after ampicillin treatment, leading to suspected drug-induced hypersensitivity syndrome (DIHS). Upon admission, amoxicillin was discontinued, and prednisolone and antiviral treatment were initiated. The patient's condition improved with this therapy. A drug-induced lymphocyte stimulation test confirmed hypersensitivity to both ampicillin and allopurinol. This case illustrates the diagnostic challenge of chronic and acute DIHS because of the rare presentation. It underscores the need for high suspicion of DIHS in patients with chronic lymphadenopathy and fatigue, particularly with recent drug exposure. Effective management involves recognizing symptoms, withdrawing the offending drug, and using corticosteroids. Viral infections like cytomegalovirus can complicate DIHS diagnosis and treatment, necessitating a comprehensive approach. This case highlights the importance of considering DIHS in differential diagnoses and the complexities of managing it alongside co-infections in rural healthcare settings.
PubMed: 38947678
DOI: 10.7759/cureus.61376 -
Cureus May 2024Varicella zoster virus (VZV) vasculopathy is a rare yet potentially severe neurological manifestation resulting from VZV reactivation, primarily affecting...
Varicella zoster virus (VZV) vasculopathy is a rare yet potentially severe neurological manifestation resulting from VZV reactivation, primarily affecting immunocompromised individuals. We present a case report of a 61-year-old male with VZV vasculopathy who initially presented with herpes zoster ophthalmicus, subsequently complicated by meningoencephalitis and an acute infarct in the territory of the left middle cerebral artery (MCA). Imaging revealed acute and chronic infarcts in the capsuloganglionic regions, accompanied by thickening and enhancement of the left MCA wall. Treatment involved a 14-day course of intravenous acyclovir, supplemented with oral prednisolone, resulting in modest clinical improvement. VZV vasculopathy represents an infrequently acknowledged neurological syndrome, particularly prevalent among immunocompromised individuals. Early recognition and appropriate intervention offer promise in ameliorating outcomes for affected patients. This case emphasizes the importance of including VZV vasculopathy in the differential diagnosis of neurological deficits, especially within high-risk populations.
PubMed: 38947631
DOI: 10.7759/cureus.61419 -
The Knee Jun 2024The average rate of patient dissatisfaction following total knee arthroplasty (TKA) is 10%. Multi-modal analgesia is the present standard of pain management after TKA....
BACKGROUND
The average rate of patient dissatisfaction following total knee arthroplasty (TKA) is 10%. Multi-modal analgesia is the present standard of pain management after TKA. Studies show that with multi-modal analgesia, approximately 60% of patients experience severe knee pain following surgery, while around 30% experience moderate pain. To date, there is no literature available on targeted pain management using bone cement.
OBJECTIVES
To investigate the feasibility of incorporating anti-inflammatory medications and identify the analgesic with the best release pharmacokinetics from bone cement for application in pain management.
METHODS
In an in-vitro study, 100 mg of five drugs (aceclofenac, diclofenac, naproxen, paracetamol and methyl prednisolone) were incorporated into bone cement (Palacos). Cement cubes holding each drug were made and allowed to harden for 30 min. Each drug-containing cube was placed in a beaker with saline for 72 h. Fractions of 10 ml were collected at 0, 6, 24, 48 and 72 h and analysed using high-pressure liquid chromatography to measure the percentage release of the drug from bone cement.
RESULTS
Naproxen showed superior elution from bone cement, with 10.9% at 24 h and 9.08% at 72 h. Paracetamol showed 4.9% at 24 h and 3.78% at 72 h, aceclofenac 0.2% at 24 h and 0.4% at 72 h, diclofenac 3.03% at 24 h and 1.99% at 72 h, and methylprednisolone 0.26% at 24 h and 0.32% at 72 h.
CONCLUSIONS
Polymethylmethacrylate bone cement can elute analgesics in vitro. Among the five drugs studied, naproxen had the best release kinematics from polymethylmethacrylate bone cement. Analgesic eluting bone cement is a novel approach for targeted postoperative pain management in TKA.
PubMed: 38943788
DOI: 10.1016/j.knee.2024.05.012 -
Circulation. Cardiovascular Imaging Jun 2024
PubMed: 38941554
DOI: 10.1161/CIRCIMAGING.124.016668 -
Cureus May 2024A case of a 43-year-old male with a history of Graves' disease treated with propylthiouracil was investigated for vasculitis and lymphoproliferative disease. However,...
Diagnostic Dilemma of a Complex Case of Cerebral Vasculitis: A Rare Probable Drug-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Large Vessel Involvement.
A case of a 43-year-old male with a history of Graves' disease treated with propylthiouracil was investigated for vasculitis and lymphoproliferative disease. However, his clinical picture was complicated by recurrent episodes of neurological symptoms resembling stroke syndrome, which widened the breadth of the diagnostic workup. Extensive investigations, including imaging and biopsies, excluded other possibilities. The patient was treated as probable cerebral vasculitis after identifying new narrowing in the left middle cerebral artery and was treated with pulsed intravenous methylprednisolone, followed by high-dose oral prednisolone and cyclophosphamide. Repeated brain imaging showed further narrowing of the large vessels, which reaffirmed the likelihood of vasculitis necessitating continuation of induction therapy with further maintenance treatment, which led to stabilization of neurological burden and symptom recovery. This case elucidates complexities in reaching the diagnosis of drug-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which can present heterogeneously and mimic other clinical entities such as stroke.
PubMed: 38939237
DOI: 10.7759/cureus.61254 -
Frontiers in Immunology 2024The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms...
BACKGROUND
The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorticoids (GCs) on cells of the innate immune system and the differences between patients with distinct immunotherapies have received little attention to date.
METHODS
We conducted immunophenotyping using flow cytometry on peripheral blood mononuclear cells of pwMS who received IVMP treatment during a relapse. We compared the impact of an IVMP treatment on a broad variety of immune cell subsets within three groups: twelve patients who were treatment-naïve to disease modifying therapies (wDMT) to ten patients on platform therapies (PT) and eighteen patients on fingolimod therapy (FTY).
RESULTS
We observed pronounced interindividual short- and intermediate-term effects of IVMP on distinct immune cells subsets. In addition to the well-documented decrease in T-helper cells (Th cells), we detected significant alterations after the first IVMP infusion within the innate immune response among neutrophil, eosinophil and basophil granulocytes, monocytes and plasmacytoid dendritic cells (pDCs). When comparing patients wDMT to the PT and FTY cohorts, we found that IVMP had a similar impact on innate immune cells across all treatment groups. However, we did not observe a significant further decline in T lymphocyte counts during IVMP in patients with pre-existing lymphopenia under FTY treatment. Although T cell apoptosis is considered the main mechanism of action of GCs, patients with FTY still reported symptom improvement following IVMP treatment.
CONCLUSION
In addition to T cell suppression, our data suggests that further immunoregulatory mechanisms of GC, particularly on cells of the innate immune response, are of greater significance than previously understood. Due to the regulation of the adaptive immune cells by DMTs, the impact of GC on these cells varies depending on the underlying DMT. Additional studies involving larger cohorts and cerebrospinal fluid samples are necessary to gain a deeper understanding of the immune response to GC in pwMS with different DMTs during relapse to define and explain differences in clinical response profiles.
Topics: Humans; Female; Male; Adult; Middle Aged; Multiple Sclerosis; Fingolimod Hydrochloride; Immunity, Innate; Methylprednisolone; Immunophenotyping; Leukocytes, Mononuclear; Adrenal Cortex Hormones; Immunosuppressive Agents; Glucocorticoids
PubMed: 38938576
DOI: 10.3389/fimmu.2024.1404316 -
Case Reports in Obstetrics and... 2024Autoimmune hemolytic anemia (AIHA) associated with solid tumors such as mature cystic teratomas is rare and poorly understood. Here, we report a successfully treated...
BACKGROUND
Autoimmune hemolytic anemia (AIHA) associated with solid tumors such as mature cystic teratomas is rare and poorly understood. Here, we report a successfully treated case of secondary AIHA in a mature cystic teratoma containing antibodies against red blood cells. . A 22-year-old woman was referred to our hospital with progressive anemia. Laboratory findings revealed hemolysis with a positive direct and indirect antiglobulin test. Imaging studies identified a left ovarian mass, suspected to be a mature cystic teratoma, which was later confirmed by histopathology after laparoscopic oophorocystectomy. The patient was treated with prednisolone, resulting in improved anemia. To examine the relationship between the tumor and AIHA, an indirect antiglobulin test was performed on the tumor contents. Stronger aggregations were observed at any concentration diluted by 10 times from 10 to 10,000 times of the tumor contents compared to the patient's serum. Additionally, immunofixation electrophoresis of the tumor contents revealed the presence of monoclonal immunoglobulin G-.
CONCLUSION
The presence of monoclonal IgG- in the tumor suggests intratumoral antibody production as a possible mechanism. Further research is necessary to elucidate the pathogenic relationship between such tumors and AIHA. The report also highlights the importance of considering secondary AIHA in patients with unexplained anemia and solid tumors.
PubMed: 38938323
DOI: 10.1155/2024/2223281 -
BMJ Case Reports Jun 2024In this paper, we report the case of a boy in early childhood who presented with iron-deficiency anaemia, initially thought to be nutritional, who had a subsequent...
In this paper, we report the case of a boy in early childhood who presented with iron-deficiency anaemia, initially thought to be nutritional, who had a subsequent diagnosis of idiopathic pulmonary haemosiderosis (IPH). This is a slowly progressive and life-threatening disorder and is of paramount importance that this is identified early and treated appropriately. His first chest CT was not typical for IPH, and this appearance should be highlighted (small cystic changes alone initially). He also had focal disease, which allowed us to make the diagnosis using CT-guided biopsy. During his treatment, he experienced an uncommon side effect to a commonly prescribed medication (bradycardia with methylprednisolone). Since starting azathioprine as a steroid-sparing agent, he has been doing well.
Topics: Humans; Hemosiderosis; Male; Hemosiderosis, Pulmonary; Lung Diseases; Tomography, X-Ray Computed; Anemia, Iron-Deficiency; Azathioprine; Diagnosis, Differential; Methylprednisolone
PubMed: 38937263
DOI: 10.1136/bcr-2024-261171 -
Transplant Immunology Jun 2024Despite the significant role of JAK3 in various autoimmune diseases, including graft-versus-host disease (GVHD), there has been a lack of potent and selective JAK3...
BACKGROUND
Despite the significant role of JAK3 in various autoimmune diseases, including graft-versus-host disease (GVHD), there has been a lack of potent and selective JAK3 inhibitors specifically studied for GVHD. In our preclinical investigations, we evaluated a novel JAK3 inhibitor called CS12192, which is already undergoing clinical investigation in autoimmune diseases.
METHODS
We evaluated the efficacy of CS12192 in GVHD through mixed lymphocyte reaction (MLR) in both mouse and human cells, as well as allogeneic bone marrow transplantation (BMT) in a murine model.
RESULTS
CS12192, starting at a concentration of 0.5 μM, dose-dependently reduced the intracellular positivity for cytokines TNF-α and IFN-γ in CD4+ T cells (p < 0.05 to p < 0.0001) and CD8+ T cells (p < 0.01 to p < 0.0001) during mouse allogeneic MLR assays. This effect was observed for both single and double positivity of the cytokines. Moreover, In MLR assays with three different human donors, CS12192 also demonstrated a dose-dependent reduction in the proportion of IFN-γ positive CD4+ T cells (p < 0.0001) and CD8+ T cells (p < 0.01 to p < 0.0001). Additionally, it suppressed T cell proliferation in the mouse MLR (p < 0.05 to p < 0.0001), but this effect was observed in only one human donor (p < 0.001 to p < 0.0001). Furthermore, the administration of CS12192 at 40 and 80 mg/kg BID significantly improved the survival rate in the BMT model, resulting in cumulative 62-day survival rates of 88.89% (p < 0.01) and 100% (p < 0.001), respectively, compared with prednisolone (p < 0.05).
CONCLUSIONS
CS12192 is a novel, potent and selective JAK3 inhibitor demonstrating great potential to mitigate acute GVHD.
PubMed: 38936745
DOI: 10.1016/j.trim.2024.102075