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Journal of Autoimmunity Oct 2023Sarcoidosis is a sterile non-necrotizing granulomatous disease without known causes that can involve multiple organs with a predilection for the lung and thoracic lymph...
Sarcoidosis is a sterile non-necrotizing granulomatous disease without known causes that can involve multiple organs with a predilection for the lung and thoracic lymph nodes. Worldwide it is estimated to affect 2-160/100,000 people and has a mortality rate over 5 years of approximately 7%. For sarcoidosis patients, the cause of death is due to sarcoid in 60% of the cases, of which up to 80% are from advanced cardiopulmonary failure (pulmonary hypertension and respiratory microbial infections) in all races except in Japan were greater than 70% of the sarcoidosis deaths are due to cardiac sarcoidosis. Scadding stages for pulmonary sarcoidosis associates with clinical outcomes. Stages I and II have radiographic remission in approximately 30%-80% of cases. Stage III only has a 10%-40% chance of resolution, while stage IV has no change of resolution. Up to 40% of pulmonary sarcoidosis patients progress to stage IV disease with lung parenchyma fibroplasia, bronchiectasis with hilar retraction and fibrocystic disease. These patients are at highest risk for the development of precapillary pulmonary hypertension, which may occur in up to 70% of these patients. Sarcoid patients with pre-capillary pulmonary hypertension can respond to targeted pulmonary arterial hypertension medications. Stage IV fibrocytic sarcoidosis with significant pulmonary physiologic impairment, >20% fibrosis on HRCT or pre-capillary pulmonary hypertension have the highest risk of mortality, which can be >40% at 5-years. First line treatment for patients who are symptomatic (cough and dyspnea) with parenchymal infiltrates and abnormal pulmonary function testing (PFT) is oral glucocorticoids, such as prednisone with a typical starting dose of 20-40 mg daily for 2 weeks to 2 months. Prednisone can be tapered over 6-18 months if symptoms, spirometry, PFTs, and radiographs improve. Prolonged prednisone may be required to stabilize disease. Patients requiring prolonged prednisone ≥10 mg/day or those with adverse effects due to glucocorticoids may be prescribed second and third line treatements. Second and third line treatments include immunosuppressive agents (e.g., methotrexate and azathioprine) and anti-tumor necrosis factor (TNF) medication; respectively. Effective treatments for advanced fibrocystic pulmonary disease are being explored. Despite different treatments, relapse rates range from 13% to 75% depending on the stage of sarcoid, number of organs involved, socioeconomic status, and geography. CONCLUSION: The mortality rate for sarcoidosis over a 5 year follow up is approximately 7%. Unfortunately, 10%-40% of patients with sarcoidosis develop progressive pulmonary disease, and >60% of deaths resulting from sarcoidosis are due to advance cardiopulmonary disease. Oral glucocorticoids are the first line treatment, while methotrexate and azathioprine are considered second and anti-TNF agents are third line treatments that are used solely or as glucocorticoid sparing agents for symptomatic extrapulmonary or pulmonary sarcoidosis with infiltrates on chest radiographs and abnormal PFT. Relapse rates have ranged from 13% to 75% depending on the population studied.
PubMed: 37865579
DOI: 10.1016/j.jaut.2023.103107 -
Allergy Aug 2023The potential benefit of inducing delayed-type hypersensitivity (DTH) reaction in healthy volunteers (HVs) as experimental models to study skin inflammatory disorders... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The potential benefit of inducing delayed-type hypersensitivity (DTH) reaction in healthy volunteers (HVs) as experimental models to study skin inflammatory disorders was recently reported using bulk molecular technologies. Immunophenotype of skin T cells, including cellular source of Type 1, 2, and 3 cytokines, in a local DTH reaction and their modulation by oral drugs remain to be investigated.
METHOD
Purified protein derivative (PPD), nickel, diphencyprone (DPCP), or house dust mite (HDM) was administered as sensitizer to 40 HVs. In addition, 20 HVs were randomized to receive oral prednisone or placebo before DPCP challenge. We characterized the immunophenotype and cytokine profile of CD3 T cell infiltrate, and examined the modulation by oral prednisone at single-cell level using multiparameter flow cytometry and unsupervised analysis.
RESULTS
PPD was biased toward a Th1 and Tc1 response, and HDM a Th2/Th17 and Tc2. Nickel and DPCP displayed a mixed Th1/Th2/Th17 and Tc1 response. CD4 CD25 FoxP3 regulatory T cells (Tregs), the minor CD4 CD25 FoxP3 ICOS PD-1 (activated PD-1 Th), and CD103 tissue resident memory (TRM) cells were detected in all groups. DPCP uniquely elicited rare CD8 CD103 CD25 RoRγt PD-1 ICOS IFNγ T cells (activated CD8 IFNγ PD-1 TRM). Oral prednisone decreased frequencies of activated PD-1 Th and CD8 IFNγ PD-1 TRM subsets relative to placebo in DPCP reaction. The latter was positively correlated with improvement of clinical parameters with prednisone.
CONCLUSION
DTH and skin CD3 T cell profiles elicited by common sensitizers can be modulated by oral drugs. Corticosteroids reduce the frequencies of activated PD-1 Th and CD8 IFNγ PD-1 TRM cells after DPCP exposure.
Topics: Humans; Prednisone; Programmed Cell Death 1 Receptor; Nickel; Forkhead Transcription Factors
PubMed: 37163280
DOI: 10.1111/all.15764 -
American Journal of Hematology Feb 2024For elderly frail patients with diffuse large B-cell lymphoma (DLBCL), an attenuated chemo-immunotherapy strategy of rituximab, cyclophosphamide, doxorubicin,...
For elderly frail patients with diffuse large B-cell lymphoma (DLBCL), an attenuated chemo-immunotherapy strategy of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-miniCHOP) was introduced as a treatment option as from 2014 onward in the Netherlands. Although R-miniCHOP is more tolerable, reduction of chemotherapy could negatively affect survival compared to R-CHOP. The aim of this analysis was to assess survival of patients treated with R-miniCHOP compared to R-CHOP. DLBCL patients ≥65 years, newly diagnosed in 2014-2020, who received ≥1 cycle of R-miniCHOP or R-CHOP were identified in the Netherlands Cancer Registry, with survival follow-up through 2022. Patients were propensity-score-matched for baseline characteristics. Main endpoints were progression-free survival (PFS), overall survival (OS), and relative survival (RS). The use of R-miniCHOP in DLBCL increased from 2% in 2014 to 15% in 2020. In total, 384 patients treated with R-miniCHOP and 384 patients treated with R-CHOP were included for comparison (median age; 81 years, stage 3-4; 68%). The median number of R-(mini)CHOP cycles was 6 (range, 1-8). The 2-year PFS, OS and RS were inferior for patients treated with R-miniCHOP compared to R-CHOP (PFS 51% vs. 68%, p < .01; OS 60% vs. 75%, p < .01; RS 69% vs. 86%, p < .01). In multivariable analysis, patients treated with R-miniCHOP had higher risk of all-cause mortality compared to patients treated with R-CHOP (HR 1.73; 95%CI, 1.39-2.17). R-miniCHOP is effective for most elderly patients. Although survival is inferior compared to R-CHOP, the use of R-miniCHOP as initial treatment is increasing. Therefore, fitness needs to be carefully weighed in treatment selection.
Topics: Humans; Aged; Rituximab; Antibodies, Monoclonal, Murine-Derived; Vincristine; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Cyclophosphamide; Lymphoma, Large B-Cell, Diffuse; Prednisone; Treatment Outcome
PubMed: 38014799
DOI: 10.1002/ajh.27151 -
Blood Mar 2024
Topics: Humans; Aged; Hodgkin Disease; Vinblastine; Bendamustine Hydrochloride; Prednisone; Doxorubicin
PubMed: 38483406
DOI: 10.1182/blood.2023023125 -
The World Journal of Men's Health Jul 2024This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in...
Comparison of Short-Term Outcomes and Safety Profiles between Androgen Deprivation Therapy+Abiraterone/Prednisone and Androgen Deprivation Therapy+Docetaxel in Patients with Metastatic Hormone-Sensitive Prostate Cancer.
PURPOSE
This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
MATERIALS AND METHODS
A web-based database system was established to collect prospective cohort data for patients with mHSPC in Korea. From May 2019 to November 2022, 928 patients with mHSPC from 15 institutions were enrolled. Among these patients, data from 122 patients who received ADT+abiraterone/prednisone or ADT+docetaxel as the primary systemic treatment for mHSPC were collected. The patients were divided into two groups: ADT+abiraterone/prednisone group (n=102) and ADT+docetaxel group (n=20). We compared the demographic characteristics, medical histories, baseline cancer status, initial laboratory tests, metastatic burden, oncological outcomes for mHSPC, progression after mHSPC treatment, adverse effects, follow-up, and survival data between the two groups.
RESULTS
No significant differences in the demographic characteristics, medical histories, metastatic burden, and baseline cancer status were observed between the two groups. The ADT+abiraterone/prednisone group had a lower prostate-specific antigen (PSA) progression rate (7.8% 30.0%; p=0.011) and lower systemic treatment discontinuation rate (22.5% 45.0%; p=0.037). No significant differences in adverse effects, oncological outcomes, and total follow-up period were observed between the two groups.
CONCLUSIONS
ADT+abiraterone/prednisone had lower PSA progression and systemic treatment discontinuation rates than ADT+docetaxel. In conclusion, further studies involving larger, double-blinded randomized trials with extended follow-up periods are necessary.
PubMed: 38164028
DOI: 10.5534/wjmh.230104 -
Cureus Jul 2023Whipple's disease is a rare systemic disease caused by a infection. Although older literature reports a low rate of incidence, case reports continue to rise due to...
Whipple's disease is a rare systemic disease caused by a infection. Although older literature reports a low rate of incidence, case reports continue to rise due to increased awareness of the disease. Classic Whipple's disease presents as weight loss, diarrhea, and arthralgia and may involve the heart, central nervous system (CNS), or any other organ system. Some patients with Whipple's disease do not have the classic signs and symptoms of the disease. We present a case of Whipple's disease in a patient with poor appetite, weight loss, and granulomatous inflammation of various organs, including the kidneys and spleen, mimicking sarcoidosis. She had presented three years earlier with acute kidney injury (AKI) and hypercalcemia. The renal biopsy revealed diffuse granulomatous interstitial nephritis. Both AKI and hypercalcemia resolved with prednisone; however, her weight loss and decreased appetite continued. The initial positron emission tomography (PET) scan showed increased fluorodeoxyglucose (FDG) avidity in the spleen and large intestine, and the splenic biopsy revealed non-caseating granulomas. A diagnosis of sarcoidosis was made, and she was started on methotrexate with prednisone. Nevertheless, the weight loss and poor appetite were relentless. A repeat PET scan showed increased FDG avidity in loops of the small and large intestines. A small intestinal biopsy revealed positive periodic acid-Schiff (PAS) and negative acid-fast bacilli (AFB) revealing the diagnosis of Whipple's disease. Whipple's disease should be considered in the differential diagnosis of sarcoidosis, especially in those patients worsening on standard immunosuppression.
PubMed: 37575808
DOI: 10.7759/cureus.41839 -
Pediatric Neurology Sep 2023To describe the clinical features of patients with childhood-onset myasthenia gravis (MG) (CMG) and explore predictors affecting the treatment outcomes.
BACKGROUND
To describe the clinical features of patients with childhood-onset myasthenia gravis (MG) (CMG) and explore predictors affecting the treatment outcomes.
METHODS
A retrospective observational cohort analysis of 859 patients with CMG with disease onset before age 14 years was performed at Tongji Hospital.
RESULTS
Patients in the pubertal-onset group (n = 148) had a worse disease course than those in the prepubertal group (n = 711), including a higher incidence of generalized MG (GMG) at presentation, generalization of ocular MG (OMG), and more severe Myasthenia Gravis Foundation of America (MGFA) classification. All patients were initially treated with pyridostigmine, 657 with prednisone, and 196 with immunosuppressants (ISs). However, 226 patients were resistant to prednisone treatment. Multivariate analysis revealed that thymic hyperplasia, higher MGFA class, disease duration before prednisone administration, and thymectomy before prednisone administration were independent predictors of prednisone resistance. At the last visit, 121 of the 840 patients with OMG had developed GMG after a median of 10.0 years from symptom onset and 186 patients (21.7%) achieved complete stable remission (CSR). In multivariable analysis, age at onset, thymic hyperplasia, prednisone, and IS treatment were associated with generalization, whereas age at onset, disease duration, anti-acetylcholine receptor antibodies (AChR-ab), MGFA class II, short-term prednisone treatment, and IS treatment were associated with CSR.
CONCLUSIONS
The majority of patients with CMG have mild clinical symptoms and favorable outcomes, especially those with earlier onset age, shorter disease duration, and negative AChR-ab. In addition, early prednisone and ISs are shown to be effective and safe for most patients with CMG.
Topics: Humans; Adolescent; Prednisone; Thymus Hyperplasia; Prognosis; Retrospective Studies; East Asian People; Myasthenia Gravis; Treatment Outcome; Immunosuppressive Agents; Thymectomy
PubMed: 37421800
DOI: 10.1016/j.pediatrneurol.2023.06.008 -
Journal of Zhejiang University.... Aug 2023Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry,... (Review)
Review
Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (), isocitrate dehydrogenase 2 (), Ras homolog gene family, member A (), splicing factor 3B subunit 1 (), and tumor protein p53 () mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and , , and mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.
Topics: Humans; Rituximab; Vincristine; Prednisone; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Neoplasm Recurrence, Local; Lymphoma, T-Cell; Cyclophosphamide; Lymphoma, Large B-Cell, Diffuse; Doxorubicin; Lymphadenopathy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37551557
DOI: 10.1631/jzus.B2300181 -
Central nervous system prophylaxis in diffuse large B-cell lymphoma: What does the evidence tell us?Blood Reviews Sep 2023Secondary involvement of the central nervous system (CNS) by diffuse large b-cell lymphoma (DLBCL) is a rare yet often catastrophic event for DLBCL patients. As standard... (Review)
Review
Secondary involvement of the central nervous system (CNS) by diffuse large b-cell lymphoma (DLBCL) is a rare yet often catastrophic event for DLBCL patients. As standard first-line therapy for DLBCL with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) does not cross the blood-brain barrier, one approach to lessen the risk of CNS relapse has been to include additional agents, primarily methotrexate, directed at the CNS with standard R-CHOP although the timing, dose, and mode of administration differs widely across treating physicians. This practice derives from decades of non-randomized, often retrospective data with inconsistent outcomes. The current available tools and risk models are imprecise in their ability to predict which patients are truly at risk of secondary CNS relapse and more recent, large-scale real-world analyses call into question these longstanding practices. In a field lacking any prospective, randomized studies, this review synthesizes the available data investigating the utility of CNS prophylaxis in patients with DLBCL receiving 1st line therapy.
Topics: Humans; Retrospective Studies; Prospective Studies; Central Nervous System Neoplasms; Neoplasm Recurrence, Local; Antineoplastic Combined Chemotherapy Protocols; Rituximab; Cyclophosphamide; Prednisone; Vincristine; Central Nervous System; Doxorubicin; Lymphoma, Large B-Cell, Diffuse; Recurrence
PubMed: 37258362
DOI: 10.1016/j.blre.2023.101101 -
Revista Espanola de Enfermedades... Jun 2024We report the case of a 58-year-old male patient presenting with clinical and laboratory findings indicative of acute hepatitis. Abdominal ultrasound excluded biliary...
We report the case of a 58-year-old male patient presenting with clinical and laboratory findings indicative of acute hepatitis. Abdominal ultrasound excluded biliary tract abnormalities. Two weeks prior, the patient had contracted COVID-19. Viral hepatitis was ruled out, and the presence of autoantibodies was confirmed. Liver biopsy findings were consistent with autoimmune hepatitis and grade 1 fibrosis. Initial treatment with budesonide was ineffective, leading to a switch to prednisone, with maintenance therapy comprising prednisone and azathioprine. COVID-19 infection may act as a trigger for the development of autoimmune hepatitis.
PubMed: 38832588
DOI: 10.17235/reed.2024.10532/2024