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OBJECTIVES: To clarify clinical features of anti-Ro52 antibody (Ab)-positive polymyositis (PM)/dermatomyositis (DM). PATIENTS AND METHODS: We retrospectively examined clinical features and status of anti-Ro52 Ab in patients with PM/DM admitted at the University of Tsukuba Hospital between January 2019 and February 2023. We compared anti-Ro52 Ab-positive and -negative groups. RESULTS: A total of 40 patients were selected and analyzed. Median age at diagnosis was 61.5 (48.8-69.3) years and 34 cases were female. Twenty-three cases were PM and 17 cases were DM (including 6 clinically amyopathic dermatomyositis: CADM). Twenty-two cases were positive for anti-Ro52 Ab, 14 for anti-ARS Ab, and 6 for anti-MDA5 Ab. Interstitial lung disease (ILD) was detected in 29 cases, 9 of which were rapidly progressive. Glucocorticoid (GC)-resistant cardiomyopathy was detected in 6 cases, malignancy in 3 cases, and Sjögren's syndrome (SS) in 4 cases. Of the 22 anti-Ro52 Ab positive cases, only 3 were single-positive and the remaining 19 cases simultaneously had other autoantibodies. Comparing the anti-Ro52 Ab-positive and -negative groups, the frequencies of anti-ARS Ab positivity (63.6% vs. 0%), ILD (95.5% vs. 44.4%), GC-resistant cardiomyopathy (27.3% vs. 0%), concomitant use of immunosuppressants (95.5% vs. 55.6%), and levels of C-reactive protein (CRP) were significantly higher in the anti-Ro52 Ab-positive group (p<0.05). The frequencies of PM/DM, positivity of anti-MDA5 Ab, malignancies, and SS were comparable between groups. CONCLUSION: Anti-Ro52 Ab were frequently positive in PM/DM and anti-Ro52 Ab-positive patients showed significantly higher rates of anti-ARS Ab positivity and ILD, GC-resistant cardiomyopathy, concomitant use of immunosuppressants, and higher levels of CRP. Anti-Ro52 Ab may be useful as a severity marker in PM/DM.
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We report a case of fulminant hepatitis in a hepatitis B surface antigen (HBsAg)-positive patient with aggressive adult T-cell leukemia-lymphoma who received monotherapy with an anti-CCR4 monoclonal antibody, mogamulizumab, with decreased hepatitis B virus (HBV)- DNA levels by entecavir prophylaxis. Although HBV reactivation-related hepatitis was considered in the differential diagnosis, the patient did not meet the conventional criteria for HBV reactivation and was finally diagnosed with drug-induced hepatitis. Considering that the immunoenhancing effects of mogamulizumab can lead to HBV reactivation-related hepatitis in HBsAg-positive patients, we should differentiate drug-induced hepatitis from HBV reactivation, especially in patients receiving immunomodulatory drugs, if HBV-DNA levels are reduced by antiviral prophylaxis.
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IgG4-related disease (IgG4-RD) is a systemic condition in which IgG4+ plasma cell infiltration and fibrosis cause organ swelling and lead to diverse clinical manifestations. Although IgG4-RD typically responds to glucocorticoids (GCs), relapse during tapering occurs and an early GC-sparing approach might therefore be beneficial. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with multiple symptoms that is also treated with GCs as a first-line therapy. Recently, belimumab, a recombinant human IgG-1λ monoclonal antibody that inhibits B-cell activating factor, was approved, but reports of use for IgG4-RD are scarce. Here, we present a rare case of IgG4-RD complicated with SLE which was successfully treated with belimumab. A 67-year-old man was diagnosed with IgG4-RD based on a high serum IgG4 level and histopathological findings. Furthermore, he had pericardial effusion on echocardiography, and laboratory tests revealed thrombocytopenia, autoimmune hemolysis, positive anti-nuclear antibodies, positive anti-DNA antibodies, and hypocomplementemia. These data led to an SLE diagnosis. Treatment was started with prednisolone at 40 mg/day, plus hydroxychloroquine, which initially improved both the SLE and IgG4-RD symptoms. During the GC tapering, belimumab was added and clinical symptoms resolved completely. Our case and the literature review summarize reported rare overlapping cases of IgG4-RD and SLE and suggest that belimumab is a promising candidate for the treatment of IgG4-RD.
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Enfermedad Relacionada con Inmunoglobulina G4 , Lupus Eritematoso Sistémico , Masculino , Humanos , Anciano , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Glucocorticoides/uso terapéutico , Inmunoglobulina G , Inmunosupresores/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Invasive fungal infections (IFIs) represent a potentially fatal complication in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) if the initiation of therapy is delayed. Some guidelines recommend antifungal prophylaxis or preemptive therapy for these patients depending on the risk of IFIs following allogeneic HSCT. This retrospective study aimed to identify the group of patients who safely undergo allogeneic HSCT with low-dose fluconazole (FLCZ) prophylaxis (100 mg/day). METHODS: We retrospectively reviewed 107 patients who underwent their first allogeneic HSCT at Nagoya City University Hospital from January 1, 2010, to December 31, 2019. We analyzed the efficacy of low-dose FLCZ prophylaxis and investigated the relationship between major risk factors and antifungal prophylaxis failure (APF) within 100 days post-transplant. RESULTS: Of the 107 patients, 70 received low-dose FLCZ prophylaxis, showing a cumulative incidence of APF of 37.1% and a proven/probable IFI rate of 4.3%. There were no fungal infection-related deaths, including Aspergillus infections, in the FLCZ prophylaxis group. In a multivariable analysis, cord blood transplantation (CBT) (subdistribution hazard ratio (SHR), 3.55; 95% confidence interval (CI), 1.44-8.77; p = 0.006) and abnormal findings on lung CT before transplantation (SHR, 2.24; 95% CI, 1.02-4.92; p = 0.044) were independent risk factors for APF in the FLCZ prophylaxis group. CONCLUSION: Low-dose FLCZ prophylaxis is a useful and safe option for patients receiving allogeneic HSCT, except in those undergoing CBT or having any fungal risk features including history of fungal infections, positive fungal markers, and abnormal findings on lung CT before transplantation.
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Fluconazol , Trasplante de Células Madre Hematopoyéticas , Humanos , Fluconazol/efectos adversos , Estudios Retrospectivos , Antifúngicos/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Factores de RiesgoRESUMEN
We present the case of a 17-year-old woman with IgA vasculitis (IgAV) who presented with relapsing gastrointestinal (GI) symptoms that were refractory to glucocorticoid and combination therapy with cyclosporine A, azathioprine or mycophenolate mofetil (MMF). The patient responded well to remission induction with intravenous cyclophosphamide (IVCY) and was successfully maintained with MMF. Remission induction with IVCY followed by maintenance therapy with MMF was effective in a patient with multidrug-resistant IgAV with GI lesions.
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Vasculitis por IgA , Nefritis Lúpica , Femenino , Humanos , Adolescente , Ácido Micofenólico/uso terapéutico , Inmunosupresores/uso terapéutico , Ciclofosfamida/uso terapéutico , Azatioprina , Inducción de RemisiónRESUMEN
Because of its efficient and robust gene transfer capability, messenger RNA (mRNA) has become a promising tool in various research fields. The lipid nanoparticle (LNP) is considered to be a fundamental technology for an mRNA delivery system and has been used extensively for the development of RNA vaccines against SARS-CoV-2. We recently developed ssPalm, an environmentally responsive lipid-like material, as a component of LNP for mRNA delivery. In this study, a self-degradable unit (phenyl ester) that confers high transfection activity and an immune stimulating unit (vitamin E scaffold) for high immune activation were combined to design a material, namely, ssPalmE-Phe-P4C2, for vaccine use. To design a simple and user-friendly form of an RNA vaccine based on this material, a freeze-drying-based preparation method for producing a ready-to-use-type LNP (LNP(RtoU)) was used to prepare the LNPssPalmE-Phe. The optimization of the preparation method and the lipid composition of the LNPssPalmE-Phe(RtoU) revealed that dioleoyl-sn-glycero phosphatidylethanolamine (DOPE) was a suitable helper lipid for achieving a high vaccination activity of the LNPssPalmE-Phe(RtoU). Other findings indicated that to maintain particle properties and vaccination activity, a 40% cholesterol content was necessary. A single administration of the LNPssPalmE-Phe(RtoU) that contained mRNA-encoding Ovalbumin (mOVA-LNPssPalmE-Phe(RtoU)) demonstrated a significant suppression of tumor progression in a tumor-bearing mouse OVA-expressing cell line (E.G7-OVA). In summary, the LNPssPalmE-Phe(RtoU) is an easy-to-handle drug delivery system (DDS) for delivering mRNA antigens in immunotherapy.
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Based on the clinical success of an in vitro transcribed mRNA (IVT-mRNA) that is encapsulated in lipid nanoparticles (mRNA-LNPs), there is a growing demand by researchers to test whether their own biological findings might be applicable for use in mRNA-based therapeutics. However, the equipment and/or know-how required for manufacturing such nanoparticles is often inaccessible. To encourage more innovation in mRNA therapeutics, a simple method for preparing mRNA-LNPs is prerequisite. In this study, we report on a method for encapsulating IVT-mRNA into LNPs by rehydrating a Ready-to-Use empty freeze-dried LNP (LNPs(RtoU)) formulation with IVT-mRNA solution followed by heating. The resulting mRNA-LNPs(RtoU) had a similar intraparticle structure compared to the mRNA-LNPs prepared by conventional microfluidic mixing. In vivo genome editing, a promising application of these types of mRNA-LNPs, was accomplished using the LNPs(RtoU) containing co-encapsulated Cas9-mRNA and a small guide RNA.
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Liposomas , Nanopartículas , ARN Mensajero/genética , ARN Mensajero/química , Nanopartículas/química , Microfluídica , ARN Interferente Pequeño/genéticaRESUMEN
OBJECTIVES: The aim is to clarify the differences in magnetic resonance imaging (MRI) findings between rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP) and infliximab (IFX). METHODS: The study included RA patients who received CZP or IFX and were examined with low-field MRI (compacTscan; compact magnetic resonance imaging) at the beginning and again within 6 months of treatment initiation. Comparisons were made regarding background, clinical course, and differences in MRI findings following initiation of tumour necrosis factor inhibitors between the CZP and IFX treatment groups. MRI findings were evaluated by scoring erosion, bone marrow oedema (BME), and synovitis. RESULTS: Ten cases in CZP and 18 cases in IFX group were compared. The biologic disease-modifying antirheumatic drug-naïve rate in the IFX group was significantly higher than that in the CZP group. After 6 months, disease activities were significantly decreased from baseline in both groups. Erosion score did not change significantly in both groups after 6 months. BME score was significantly decreased in the CZP group after 6 months, whereas in the IFX group, there was no significant change. Synovitis score was significantly decreased in both groups after 6 months. CONCLUSIONS: The findings of our study suggest that, in patients with RA, CZP might improve BME more effectively than IFX.
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Antirreumáticos , Artritis Reumatoide , Sinovitis , Humanos , Certolizumab Pegol/uso terapéutico , Infliximab/uso terapéutico , Resultado del Tratamiento , Artritis Reumatoide/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Imagen por Resonancia Magnética , Sinovitis/tratamiento farmacológicoRESUMEN
Indoleamine 2,3-dioxygenase 1 (IDO), an enzyme that metabolizes tryptophan (Trp) to kynurenine (Kyn), is an important microenvironmental factor suppressing antitumor immunity. Here, we investigated the clinical impact of aberrant Trp metabolism in patients with multiple myeloma (MM) treated with lenalidomide (Len) and evaluated its effects on T cell immunity ex vivo. Kyn and Trp concentrations were quantified in sera from 72 patients with relapsed or refractory MM prior to the initiation of therapy with Len plus dexamethasone (Ld). Associations of the Kyn/Trp ratio with progression-free survival (PFS) and overall survival (OS) were analyzed. The expressions of IDO in tumor and stromal cells were evaluated during co-culture, and the effects of culture medium containing low Trp and high Kyn concentrations on T cells in the presence of Len were investigated. Patients with high serum Kyn/Trp ratios (≥46.0, n = 22) had significantly shorter PFS and OS than those with low ratios (4.9 vs. 12.6 months, and 15.5 vs. 45.7 months, respectively). MM cells promoted IDO expression in stromal cells during co-culture in both a direct contact and an indirect manner. Incubation in medium with a high Kyn/Trp ratio significantly inhibited T cell cytokine production and upregulated the expression of inhibitory immune receptors. These effects were sustained even in the presence of Len. In conclusion, a high serum Kyn/Trp ratio is associated with poor prognosis in patients with MM. We propose that aberrant Trp metabolism reduces anti-tumor immunity and the efficacy of Len therapy.
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Mieloma Múltiple , Triptófano , Humanos , Mieloma Múltiple/tratamiento farmacológico , Lenalidomida/uso terapéutico , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , QuinureninaRESUMEN
AIM: We retrospectively investigated patients with administration of nucleos(t)ide analogs (NAs) for prevention of or against hepatitis B virus (HBV) reactivation, and their clinical outcomes after cessation of the NA. METHODS: We enrolled 180 patients who were positive for HBsAg when they started immunosuppressive therapy or chemotherapy and an NA was administered to prevent HBV reactivation (HBV carrier group), and 82 patients with resolved HBV infection who started administration of an NA after HBV reactivation (de novo HBV group). Cessation of the NA depended on each physician's judgment without definite criteria. RESULTS: A total of 27 patients in the HBV carrier group and 22 in the de novo HBV group stopped NA therapy. In the HBV carrier group, 16 patients experienced virological relapse, which was defined as HBV DNA levels ≥20 IU/ml, and one with hematological disease had an alanine aminotransferase flare after cessation of NA. Of the 16 patients, the NA was reintroduced in three, whereas, the remaining 13 had low levels of HBV DNA and no alanine aminotransferase flare. In the de novo HBV group, virological relapse occurred in six patients, and one with hematological disease had an alanine aminotransferase flare after cessation of the NA. The NA was reintroduced in four of the six patients. CONCLUSIONS: We may be able to consider to cease NA therapy proactively in HBV carriers and resolved patients with non-hematological disease, if their primary diseases are under remission after completion of immunosuppressive therapy or chemotherapy. However, careful follow up is necessary after stopping NA therapy.
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OBJECTIVE: To clarify the efficacy and safety of intravenous abatacept for glandular and extraglandular involvements in Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). MATERIALS AND METHODS: We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials). The primary endpoint was the remission rate as measured by SDAI at 52 weeks. The secondary endpoints included the changes in the Saxon's test, Schirmer's test, ESSDAI and ESSPRI. Adverse events and adherence rates were also analyzed. RESULTS: 68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled. SDAI decreased significantly from 23.6 ± 13.2 at baseline to 9.9 ± 9.5 at 52 weeks. Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly at 24 weeks. Tear volume increased significantly at 52 weeks. Both ESSDAI and ESSPRI were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients. CONCLUSION: Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in SS associated with RA.
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Artritis Reumatoide , Síndrome de Sjögren , Humanos , Femenino , Abatacept/efectos adversos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/tratamiento farmacológico , Estudios Prospectivos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Administración IntravenosaRESUMEN
Recent studies have suggested that the clinical features of elderly-onset adult-onset Still's disease (AOSD) differ from those of young and middle-aged-onset patients, whereas the details remain unclear, and cytokine profiles of elderly-onset AOSD have not been reported. To clarify the clinical features and cytokine profiles of elderly-onset AOSD, we examined patients with AOSD who developed the disease between January 2006 and September 2021. We divided the patients into the young and middle-aged-onset group (aged < 65 years) and the elderly-onset group (aged ≥ 65 years) and compared the groups in terms of patient characteristics, clinical symptoms, laboratory findings including serum interleukin (IL)-6 and IL-18, treatment, and prognosis. A total of 48 patients were examined (10 in the elderly-onset group). In the elderly-onset group, atypical rash was significantly more frequent, typical rash and splenomegaly were significantly less frequent, white blood cell count and neutrophil ratio were significantly higher and serum IL-6 levels were significantly lower. Serum IL-6 showed a significantly negative correlation with age at onset. Treatment and relapse were comparable between the 2 groups, whereas infections were significantly more frequent in the elderly-onset group. The clinical features and cytokine profiles of elderly-onset AOSD might differ from those of young and middle-aged-onset AOSD.
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Exantema , Enfermedad de Still del Adulto , Adulto , Persona de Mediana Edad , Anciano , Humanos , Interleucina-6 , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
Adult onset Still disease (AOSD) is a systemic inflammatory disorder characterized by skin rash, spiking fever, arthritis, sore throat, lymphadenopathy, and hepatosplenomegaly. Although the etiology of this disease has not been fully clarified, both innate and acquired immune responses could contribute to its pathogenesis. Hyperactivation of macrophages and neutrophils along with low activation of natural killer (NK) cells in innate immunity, as well as hyperactivation of Th1 and Th17 cells, whereas low activation of regulatory T cells (Tregs) in acquired immunity are involved in the pathogenic process of AOSD. In innate immunity, activation of monocytes/macrophages might play central roles in the development of AOSD and macrophage activation syndrome (MAS), a severe life-threating complication of AOSD. Regarding the activation mechanisms of monocytes/macrophages in AOSD, in addition to type II interferon (IFN) stimulation, several pathways have recently been identified, such as the pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs)-pattern recognition receptors (PRRs) axis, and neutrophil extracellular traps (NETs)-DNA. These stimulations on monocytes/macrophages cause activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain (NLRP) 3 inflammasomes, which trigger capase-1 activation, resulting in conversion of pro-IL-1ß and pro-IL-18 into mature forms. Thereafter, IL-1ß and IL-18 produced by activated monocytes/macrophages contribute to various clinical features in AOSD. We identified placenta-specific 8 (PLAC8) as a specifically increased molecule in monocytes of active AOSD, which correlated with serum levels of CRP, ferritin, IL-1ß, and IL-18. Interestingly, PLAC8 could suppress the synthesis of pro-IL-1ß and pro-IL-18 via enhanced autophagy; thus, PLAC8 seems to be a regulatory molecule in AOSD. These findings for the activation mechanisms of monocytes/macrophages could shed light on the pathogenesis and development of a novel therapeutic strategy for AOSD.
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Síndrome de Activación Macrofágica , Enfermedad de Still del Adulto , Humanos , Interleucina-18/metabolismo , Síndrome de Activación Macrofágica/etiología , Síndrome de Activación Macrofágica/metabolismo , Macrófagos , Monocitos/metabolismo , Proteínas/metabolismoRESUMEN
BACKGROUNDS: A fully automated, novel, high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developing. The purpose of this study is to evaluate the efficacy of measuring HBcrAg, using that assay, to diagnose HBV reactivation in a multi-center setting, compared with ultra-high-sensitivity HBsAg (iTACT-HBsAg) and HBV DNA assays. METHODS: Forty-four patients with HBV reactivation from 2008 to 2020 were enrolled in four hospitals. Serial serum specimens from the patients were assessed retrospectively for their HBcrAg levels by iTACT-HBcrAg (lower limit of detection; 2.0 log U/mL) and HBsAg levels by iTACT-HBsAg (lower limit of detection; 0.0005 IU/mL); these were compared to the HBV DNA levels. HBV reactivation was defined as detection of serum HBV DNA, including unquantifiable detection. RESULTS: At HBV reactivation and/or thereafter, HBV DNA levels were quantified (≥ 1.3 log IU/mL) in the sera of 27 patients, and were below the level of quantification (< 1.3 log IU/mL) in the sera of 17 patients. Of the 27 patients with HBV reactivation and whose serum HBV DNA was quantified, the sera of 26 and 24 patients (96.3% and 88.9%) were positive by iTACT-HBcrAg and iTACT-HBsAg, respectively. HBcrAg was detectable by iTACT-HBcrAg before HBV DNA was quantifiable in 15 of the 27 patients. Of the 11 patients with HBV reactivation and undetectable HBcrAg by iTACT-HBcrAg at HBV reactivation and/or thereafter, 10 had unquantifiable HBV DNA and none developed HBV reactivation-related hepatitis. CONCLUSIONS: The iTACT-HBcrAg assay is useful for monitoring HBV reactivation to determine the initiation of treatment with nucleos(t)ide analogues.
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Antígenos del Núcleo de la Hepatitis B , Hepatitis B Crónica , Biomarcadores , ADN Viral , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Estudios RetrospectivosRESUMEN
Pleural effusion is a rare manifestation in synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, which is characterized by the presence of osteoarticular lesions and dermatological involvement. We herein report a 71-year-old man with pleural effusion resulting from SAPHO syndrome. He was successfully treated using corticosteroids and has experienced no recurrence for one year. We should consider SAPHO syndrome when encountering cases of anterior chest pain and pleural fluid.
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Acné Vulgar , Síndrome de Hiperostosis Adquirido , Hiperostosis , Osteítis , Derrame Pleural , Sinovitis , Acné Vulgar/patología , Síndrome de Hiperostosis Adquirido/complicaciones , Síndrome de Hiperostosis Adquirido/diagnóstico , Síndrome de Hiperostosis Adquirido/tratamiento farmacológico , Anciano , Humanos , Hiperostosis/patología , Masculino , Osteítis/patología , Derrame Pleural/diagnóstico por imagen , Derrame Pleural/etiología , Sinovitis/diagnóstico , Sinovitis/diagnóstico por imagenRESUMEN
AIMS: To prevent hepatitis B virus (HBV) reactivation-related hepatitis, we examined the clinical usefulness of a highly sensitive HB core-related antigen (iTACT-HBcrAg) assay in patients with resolved HBV infection after nucleos(t)ide analog (NA) treatment for HBV reactivation. METHODS: We retrospectively analyzed 27 patients with resolved HBV infection who experienced HBV reactivation (defined as HBV DNA levels of 1.3 log IU/ml or more), and who received systemic chemotherapies for hematological malignancies between 2008 and 2020. iTACT-HBcrAg, HBsAg-HQ, and antibodies against hepatitis B surface antigen (anti-HBs) were measured using samples stored after HBV reactivation. The lower limit of quantification for iTACT-HBcrAg was 2.0 log U/ml. RESULTS: HBV reactivation was diagnosed at a median HBV DNA level of 1.8 log IU/ml, and then all patients received NA treatment. No patient had HBV-related hepatitis with a median maximum HBV DNA level of 2.0 log IU/ml. The positivities of iTACT-HBcrAg and HBsAg-HQ were 96% and 52% after HBV reactivation, respectively. Of 25 patients with detectable iTACT-HBcrAg at the initiation of NA treatment, 17 (68%) achieved iTACT-HBcrAg loss. Median durations from NA treatment to HBV DNA loss and iTACT-HBcrAg loss or the last follow-up were 35 and 175 days, respectively. Recurrence of HBV reactivation after NA cessation was not observed in seven of eight patients who achieved iTACT-HBcrAg loss or seropositive for anti-HBs during follow-up, except for one without anti-HBs after allogeneic transplantation. CONCLUSIONS: iTACT-HBcrAg could be a potential surrogate marker for diagnosing early-stage HBV reactivation as well as safe cessation of NA treatment in patients with resolved HBV infection after HBV reactivation.
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Objective To identify factors associated with pneumomediastinum during management of connective tissue disease (CTD)-related interstitial lung disease (ILD). Methods Patients diagnosed with pneumomediastinum after the initiation of corticosteroid therapy for their CTD-ILD were enrolled. The baseline characteristics of patients who developed pneumomediastinum after the initiation of corticosteroid therapy (n=13, all occurring within 120 days) were compared to those of patients who did not develop pneumomediastinum (n=49). A multivariate logistic regression analysis was performed to identify factors associated with pneumomediastinum. A receiver operating characteristic (ROC) curve analysis was also performed to assess the predictive performance. Results The body mass index (BMI) [odds ratio (OR) (95% confidence interval (CI)) 0.482 (0.272-0.853)] and serum lactate dehydrogenase (LDH) [OR (95% CI) 1.013 (1-1.025)] levels at baseline were identified as independent factors associated with pneumomediastinum after corticosteroid initiation. The optimal cut-off points of the BMI and LDH levels for predicting pneumomediastinum development, as estimated by the Youden index, were 20.2 kg/m2 and 378 U/L, respectively. LDH showed a sensitivity of 61.5% and the highest specificity of 87.8%. Importantly, combining these markers resulted in the highest sensitivity of 100% and a specificity of 71.4%. Conclusion A low BMI and high serum LDH levels at baseline are useful predictive factors for pneumomediastinum development in CTD-ILD patients.
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Enfermedades del Tejido Conjuntivo , Enfermedades Pulmonares Intersticiales , Enfisema Mediastínico , Biomarcadores , Enfermedades del Tejido Conjuntivo/complicaciones , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/epidemiología , Enfisema Mediastínico/diagnóstico por imagen , Enfisema Mediastínico/etiología , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: The primary objective is to reveal the effect of hydroxychloroquine (HCQ) treatment on corrected QT (QTc) interval in patients with systemic lupus erythematosus (SLE). The secondary objective is to investigate factors that affect QTc prolongation. METHODS: SLE patients who had electrocardiograms between 2015 and 2020 were recruited and assigned to two groups based on whether they were treated with HCQ (HCQ group) or not (control group). Change of QTc before and after HCQ administration in the HCQ group was measured and compared with the control group. Patients treated with HCQ were further divided into two groups based on presence or absence of QTc prolongation and the characteristics were compared. RESULTS: In total, 126 patients were recruited, of whom 42 were treated with HCQ. In the HCQ group, the mean QTc significantly increased (p < .001), while there was no significant difference of mean QTc in the control group. Moreover, those in the HCQ group with QTc prolongation showed a significantly higher proportion of hypertension and longer SLE duration compared to those without QTc prolongation. However, the multiple logistic regression analysis showed that there were no significant differences among them. CONCLUSION: HCQ could induce QTc prolongation in SLE patients. It might be better that the possibility of QTc prolongation was taken into consideration when HCQ was administered in the patients with longer disease duration of SLE and coincidence of hypertension.
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Antirreumáticos , Síndrome de QT Prolongado , Lupus Eritematoso Sistémico , Antirreumáticos/efectos adversos , Electrocardiografía , Humanos , Hidroxicloroquina/efectos adversos , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológicoRESUMEN
OBJECTIVES: We compared large vessel vasculitis (LVV) clinical features between age groups. METHODS: We retrospectively examined clinical features and therapies in 41 LVV patients at our hospital from January 2010 to March 2020. We compared two patient groups, elderly (≥50 years) and young (<50 years). RESULTS: Of all patients, 29 were elderly and 12 were young. In the younger group, upper extremity symptoms (p <.05), bruits (p <.01), and cardiovascular complications (p <.01) were more common. Of the elderly group, 7 (24%) met classification criteria for giant cell arteritis while none of the younger group met these criteria; however, 10 (83%) of the younger group and 3 (10%) of the elderly group met the ACR classification criteria for Takayasu arteritis (p <.01). In the elderly group, 16 patients (66%) met no criteria (p <.01). There were no significant differences in laboratory findings but imaging showed a significantly higher incidence of head and neck artery lesions in the younger group (p <.05). The younger group was more likely to receive additional tocilizumab (p <.01) and cardiovascular complications were more likely to occur in younger patients (p < .01). CONCLUSION: LVV clinical features differed between elderly- and young-age-onset groups.