Initial surgical performance in robot-assisted radical prostatectomy is associated with clinical outcomes and learning curves.

BACKGROUND: The association between surgical performance ratings and clinical outcomes in robotic surgery is poorly understood. Additionally, no studies have reported on the relationship between the surgeon's initial case-skill evaluation and the learning curve in robot-assisted surgery. We evaluated whether an objective surgical technique evaluation score for initial robot-assisted radical prostatectomy (RARP) was associated with clinical outcomes and surgeons' learning curves. METHODS: Six surgeons who were trained in and started to perform RARP at our institution were included. Anonymized, unedited videos of each surgeon's 10th RARP case were evaluated by three reviewers, using modified Objective Structured Assessment of Technical Skill (OSATS) scores. We then divided the surgeons into two groups on the basis of these OSATS scores. We retrospectively compared the clinical outcomes and learning curves of the console time of the two groups for consecutive RARPs, performed from March 2018 to July 2023. RESULTS: We analyzed 258 RARPs (43 cases/surgeon), including 129 cases performed by high-OSATS score surgeons (18.2-19.3 points) and 129 cases performed by low-OSATS score surgeons (11.9-16.0 points). Overall, the high-OSATS score group had significantly shorter operation and console times than the low-OSATS score group did (both P < 0.01) and their patients' rate of continence recovery by 3 months post-RARP was significantly higher (P = 0.03). However, complications, blood loss, and positive margins did not differ between the groups (P = 0.08, P = 0.51, and P = 0.90, respectively). The high-OSATS score group had a significantly shorter console time than the low-OSATS score group did after the 11-20 cases. CONCLUSIONS: The OSATS score in early RARP cases can predict subsequent surgical outcomes and surgeons' learning curves.

A Safer Method for Disinfection of Bacillus Calmette-Guerin-Containing Urine: A Prospective, Randomized Study.

INTRODUCTION: The aim of the study was to examine whether disinfection of bacillus Calmette-Guerin-containing urine with etaprocohol® (ethanol 76.9-81.4 vol % and isopropanol as an additive) is safer than disinfection with sodium hypochlorite. METHOD: In prospective research, safety and efficacy was analyzed in 5 patients in the etaprocohol® disinfection group and 5 patients in the sodium hypochlorite disinfection group. The primary endpoint was the temperature change after disinfection and the secondary endpoint was the unpleasantness of the odor caused by disinfection. Additionally, concentration of gas produced was also examined. Sensory tests were taken from staff who performed urine disinfection and the odor generated by disinfection was evaluated. As a safety protocol, post-BCG-treated urine is cultured to verify the negativity for mycobacteria. RESULTS: Mycobacteria were disinfected in all cases. The temperature rise following disinfection was significantly higher in the sodium hypochlorite group. The sensory test outcomes were significantly worse in the group disinfected with sodium hypochlorite. The concentration of gas generated immediately after disinfection in both groups reached the maximum value and declined quickly. CONCLUSIONS: Disinfection of bacillus Calmette-Guerin-containing urine with etaprocohol® was safer than disinfection with sodium hypochlorite, and an equivalent disinfection effect was achieved.

Immunological disease activity parameters at conception are risk factors for preterm birth and low birth weight in patients with systemic lupus erythematosus.

OBJECTIVE: This study aimed to identify which disease activity parameters may be risk factors for preterm birth (PB) and low birth weight (LBW) in patients with systemic lupus erythematosus (SLE). We also analyzed the extent to which these parameters affected PB and LBW. METHODS: We collected the SLE Disease Activity Index (SLEDAI), the rate of lupus low disease activity state (LLDAS) attainment, complement levels, and the titer of anti-double stranded DNA (dsDNA) antibody as disease activity parameters. We retrospectively analyzed the associations of these parameters with PB and LBW. RESULTS: Sixty pregnancies were included in this study. C3 levels and anti-dsDNA antibody titers at conception were strongly associated with PB (p = 0.03 and p = 0.01, respectively), whereas C3 and CH50 levels were associated with LBW (p = 0.02 and p = 0.03, respectively). A logistic regression analysis showed that the cutoff values of C3 and anti-dsDNA antibody for PB were 62.0 mg/dl and 5.4 IU/ml, respectively. The cutoff values of C3 and CH50 for LBW were 87.0 mg/dl and 41.8 U/ml, respectively. The risk of PB or LBW was increased when divided by the cutoff value, and the combination of these cutoff values showed a significantly higher risk of PB and LBW (p = 0.01 and p < 0.01, respectively). CONCLUSIONS: PB and LBW are strongly associated with disease activity parameters in patients with SLE. Therefore, strictly monitoring and controlling these disease activity parameters, with or without clinical manifestation, is important for women who want to become mothers.

Efficacy and safety of apremilast and its impact on serum cytokine levels in patients with Behçet's disease.

To evaluate the long-term clinical efficacy of apremilast in Behçet's disease (BD) and its effect on serum cytokine levels. This study included 15 BD patients who were treated with apremilast. The rates of change in oral and genital ulcers, skin lesions, arthritis, and arthralgia were evaluated every 3 months for 12 months. The efficacy of apremilast was compared between patients with and without oral ulcer remission. Changes in the serum levels of interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-10, IL-17A, IL-6, IL-8, and IL-23 between baseline and 3 months after apremilast initiation were compared. After 3 months, oral and genital ulcers disappeared in most cases. The skin and joint lesions tended to improve for up to 6 months; however, recurrence was observed after 9 months. The improvement of genital ulcers was earlier in the oral ulcer remission group than the oral ulcer non-remission group, with the genital ulcers disappearing within the first 3 months. The baseline levels of serum cytokines, analyzed in seven patients, did not exhibit significant associations with specific organ lesions. After administration of apremilast, the TNF-α and IL-23 levels significantly decreased; however, the IFN-γ, IL-6, IL-8, and IL-10 levels did not show significant changes. The rates of decrease in the serum IL-6, IFN-γ, and IL-10 levels were greater in patients with improved oral ulcers. Modulation of serum cytokine levels with apremilast might underlie the efficacy of apremilast in oral ulcers in BD patients.

Mechanism of hypertensive crisis during energy device ablation of the adrenal gland: An experimental animal study.

OBJECTIVE: To elucidate the mechanism of hypertensive crisis during energy device ablation of the adrenal gland. METHODS: Electrocoagulation on the adrenal glands of six pigs was carried out with the same energy device (VIO300D) using four methods: (i) monopolar coagulation; (ii) monopolar soft coagulation using IO-advanced ball-type electrodes; (iii) bipolar soft coagulation by pinching; and (iv) bipolar soft coagulation by non-pinching (surface contact) using Bipolar forceps Premium. After electrocoagulation for 5 s, blood pressure and pulse changes were monitored, and adrenal hormones were measured from a central vein. The adrenal glands were removed, and the degree of tissue damage was scored histologically. RESULTS: Hypertensive crisis occurred with electrocoagulation of the adrenal gland by the monopolar coagulation, monopolar soft coagulation and bipolar soft coagulation pinching methods. Blood pressure did not change with the bipolar soft coagulation non-pinching method. Pathologically, tissue damage to the adrenal medulla was associated with elevated blood pressure and adrenaline and noradrenaline release. CONCLUSIONS: Hypertensive crisis caused by energy device ablation to the adrenal gland is caused by the release of catecholamines due to heat damage to the adrenal medulla rather than the type of energy device. Proper use of an energy device that does not cause thermal degeneration of the medulla is required to prevent hypertensive crisis.

Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era.

OBJECTIVES: The efficacy and safety of sunitinib versus sorafenib in patients with advanced renal cell carcinoma with renal impairment remains poorly documented. PATIENTS AND METHODS: We assessed the efficacy and safety of sunitinib and sorafenib in patients with advanced renal cell carcinoma with an estimated glomerular filtration rate of 15-60 mL/min/1.73 m2 by reviewing the medical records of patients treated at Jichi Medical University Hospital, Japan, between May 2008 and August 2016. RESULTS: Twenty-seven patients were treated with sunitinib and 14 with sorafenib. Median progression-free survival in sunitinib- and sorafenib-treated patients was comparable, at 6.6 vs 5.8 months, respectively (HR, 1.618; 95% CI, 0.689-3.798; P = 0.2691). Median overall survival was also comparable, at 65.9 vs 58.0 months (HR, 0.985; 95% CI, 0.389-2.479; P = 0.9748). Grade 3 or higher adverse events were significantly more frequent in the sunitinib-treated than sorafenib-treated patients (P = 0.0357). Compared to pre-treatment values, estimated glomerular filtration rate at the discontinuation of treatment was not decreased in either group. In contrast, estimated glomerular filtration rate was decreased on long-term treatment, particularly in previously nephrectomized patients. CONCLUSIONS: Sunitinib and sorafenib had similar efficacy in patients with advanced renal cell carcinoma and severe renal impairment. Although renal function was not markedly impaired in either group, close attention to decreased renal function may be necessary in previously nephrectomized patients on long-term treatment.

Cancer detection rate of prebiopsy MRI with subsequent systematic and targeted biopsy are superior to non-targeting systematic biopsy without MRI in biopsy naïve patients: a retrospective cohort study.

BACKGROUND: To determine whether prebiopsy multiparametric magnetic resonance imaging (mpMRI) with subsequent systematic plus targeted biopsies for suspicious lesions improve prostate cancer detection compared with standard non-targeting systematic biopsies without mpMRI in biopsy-naïve patients. METHODS: Patients who underwent their first prostate biopsy due to suspicion of prostate cancer were analyzed retrospectively to compare the biopsy outcomes between patients who received prebiopsy mpMRI (215 patients) and those who did not (281 patients). mpMRI was performed to determine pre-biopsy likelihood of the presence of prostate cancer using a three-point scale (1 = low level of suspicion, 2 = equivocal, and 3 = high level of suspicion). Systematic biopsies were performed in both groups. Targeted biopsies were added for a high level of suspicious lesions on mpMRI. All biopsies were performed by transperineal biopsy technique. After biopsy, Prostate Imaging Reporting and Data System ver. 2 (PIRADS-2) scoring was performed to describe the mpMRI findings and predictive value of PIRADS-2 was evaluated. RESULTS: The detection rate of total and clinically significant prostate cancer was significantly higher in patients who received prebiopsy mpMRI than in those who did not (55.3 and 46.0% vs. 42.0 and 35.2%, respectively; p = 0.004 and p = 0.016). The clinically insignificant prostate cancer detection rate was similar between the two groups (9.3% vs. 6.8%; p = 0.32). Of 86 patients who underwent systematic plus targeted biopsy in the MRI cohort and were diagnosed with prostate cancer, seven patients were detected by addition of targeted biopsy whereas 29 patients were missed by targeted biopsy but detected by systematic biopsy. There was a correlation between the PIRADS-2 and prostate cancer detection rate, and a receiver-operator curve analysis yielded an area under the curve of 0.801 (p <  0.0001). CONCLUSIONS: Prebiopsy mpMRI with subsequent systematic plus targeted biopsies for suspicious lesions can yield a higher cancer detection rate than non-targeting systematic biopsies. PIRADS-2 scoring is useful for predicting the biopsy outcome.

Case of EGPA and Eosinophilic Chronic Rhinosinusitis Concomitant with IgG4 Related Disease.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis in patients with bronchial asthma and eosinophilic rhinosinusitis. Serum IgG4 levels are markedly elevated in patients with active EGPA, a disease which has been closely associated with IgG4-related disease (IgG4RD). A 68-year-old male with a history of asthma and eosinophilic rhinosinusitis developed vasculitis and orbital symptoms. The results of a laboratory examination showed eosinophilia (4,067/µl; 39%), while image evaluations revealed hypertrophy of the rectus muscles, trigeminal nerve, lachrymal gland, and bilateral submandibular glands. Biopsy of the paranasal sinus showed the prominent infiltration of eosinophils and IgG4-positive plasma cells. The patient was diagnosed with EGPA concomitant with IgG4RD and treated with systemic steroids. Although concomitant cases of EGPA with IgG4RD are extremely rare, clinical manifestations associated with both diseases are sometimes mixed. Therefore, systemic scrutiny may be required for cases of EGPA with high serum IgG4 levels and pathognomonic symptoms or findings of IgG4RD

[Rheumatoid arthritis and malignancy].

Rheumatoid arthritis (RA) is associated with excess mortality. Especially, malignancy is a major cause of mortality. According to previous reports, the overall incidence of malignancies in RA patients has been reported to be comparable or slightly higher than that in general population. The increased incidence of malignant lymphoma and lung cancer has been reported to be consistent in most studies. The use of some csDMARD was also reported as risk factors for malignancy. Recently, MTX associated lymphoproliferative disorder(MTX-LPD) is one of the important complications in RA treatment. We revealed the mean MTX dose was demonstrated to be an independent risk factor regarding MTX-LPD onset in RA patients. This data suggest that the treatment with higher MTX dose promotes LPD onset in Japanese RA patients.

A case of catastrophic antiphospholipid syndrome, which presented an acute interstitial pneumonia-like image on chest CT scan.

We report the case of catastrophic antiphospholipid syndrome (CAPS) complicated with mixed connective tissue disease (MCTD). A female patient was diagnosed with acute interstitial pneumonia (AIP) with MCTD by chest CT scan. Corticosteroid therapy was refractory for lung involvement, and she died due to acute respiratory failure. The autopsy revealed that AIP was compatible with lung involvement of CAPS. We therefore suggest that chest CT might reveal AIP-like findings in CAPS patients whose condition is complicated with pulmonary manifestations.

Comparison of different ANCA detection methods in a predominantly MPO-ANCA-associated vasculitis cohort.

We compared different antineutrophil cytoplasmic antibody (ANCA) detection methods using a predominantly myeloperoxidase (MPO)-ANCA-associated vasculitis cohort. Stored sera from 147 patients with untreated ANCA-associated vasculitis (AAV), including microscopic polyangiitis and granulomatosis with polyangiitis (n = 115 and 32, respectively), and 124 disease controls were tested for P-ANCA and C-ANCA with immunofluorescence (IIF), and for MPO-ANCA and proteinase 3 (PR3)-ANCA with different antigen-specific immunoassays: direct enzyme-linked immunosorbent assay (ELISA), chemiluminescent enzyme immunoassay (CLEIA), third-generation fluorescent enzyme immunoassay (FEIA), and latex turbidimetrical immunoassay (LTIA). In addition, MPO-ANCA and PR3-ANCA titers were calibrated using certified reference materials (CRMs). The sensitivities and specificities for AAV diagnoses were 95% and 94% (IIF), 86% and 98% (ELISA), 93% and 94% (CLEIA), 92% and 96% (FEIA), and 68% and 88% (LTIA). Dual IIF/antigen-specific immunoassay testing reduced diagnostic accuracies from 94% to 93%. The quantitative agreement between ANCA levels measured using CLEIA and FEIA and calibrated using CRMs was not good. In conclusion, this study demonstrated the high performance of antigen-specific immunoassays for AAV diagnosis in a predominantly MPO-ANCA-associated vasculitis cohort and suggested that the benefit of dual IIF/antigen-specific immunoassay testing is limited. Standardizing ANCA measurements using different immunoassays was difficult, even when using CRMs.

Nintedanib combined with immunosuppressive agents improves forced vital capacity in connective tissue disease-associated PF-ILD: a single-center study.

BACKGROUND: In 2020, Nintedanib (NTB), a tyrosine kinase inhibitor, was the first drug approved worldwide for treating progressive fibrosing interstitial lung disease (PF-ILD). This study evaluated the efficacy and safety of NTB in Japanese patients with CTD-associated PF-ILD in a real-world setting, as there are few reports on this topic. We also evaluated the efficacy and safety of combination therapy with NTB and immunosuppressive agents (IS). METHODS: CTD-associated PF-ILD patients receiving NTB at our institution were included in this retrospective study. To evaluate the efficacy and safety of NTB, we investigated changes in forced vital capacity (FVC) (%), diffusing capacity for carbon monoxide (DLCO) (%), monthly change in FVC (%/month), serum Krebs von den Lungen-6 (KL-6) levels (U/mL) before and after NTB treatment, and adverse events (AEs) during NTB treatment. Moreover, to evaluate the efficacy of the NTB + IS combination therapy, we divided the patients into two groups: one received only NTB (NTB group), and the other received both NTB and IS (NTB + IS group) following the diagnosis of CTD-associated PF-ILD. We analyzed the differences in the changes of these variables between the two groups. RESULTS: Twenty-six patients with CTD-associated PF-ILD were included. After NTB treatment, there were no significant deteriorations in FVC (%) and DLCO (%), while the monthly change in FVC (%/month) significantly increased (p < 0.001). The changes in FVC (%) and the monthly change in FVC (%/month) were significantly greater in the NTB + IS group than in the NTB group. Following NTB treatment, the mean serum KL-6 levels significantly decreased (p < 0.001). AEs associated with NTB in this study were similar to those in previous clinical trials, and there was no significant difference in the incidence of AEs between the two groups. CONCLUSIONS: This study demonstrates that NTB is an effective medication for slowing the progression of CTD-associated PF-ILD in real-world settings. NTB + IS combination therapy for CTD-associated PF-ILD may be more effective than NTB alone in slowing the progression of CTD-associated PF-ILD.

Colchicine-responsive chronic recurrent multifocal osteomyelitis associated with familial Mediterranean fever in the presence of MEFV mutation: A case report.

A 38-year-old female was referred with a history of fever, polyarthralgia, and bone pain. She was diagnosed with chronic recurrent multifocal osteomyelitis based on imaging and biopsy findings. Non-steroidal anti-inflammatory drugs and bisphosphonate caused no improvement. Then, she developed recurrent diarrhoea and abdominal pain. Genetic testing revealed MEFV mutation. Based on the symptoms and genetic mutation results that emerged during the course of these events, she was diagnosed with familial Mediterranean fever. All symptoms, including bone pain, improved with daily colchicine administration. This case was considered familial Mediterranean fever complicated with a clinical diagnosis of chronic recurrent multifocal osteomyelitis, which is included in the spectrum of pyrine autoinflammatory diseases. Considering this case, patients with chronic recurrent multifocal osteomyelitis with MEFV gene variants may respond to colchicine.

Pregnancy course and outcomes of patients with polymyositis and dermatomyositis (PM/DM) managed in a single center.

We aimed to determine the association between disease activity during pregnancy and pregnancy outcomes of women with polymyositis and dermatomyositis (PM/DM). Patients with PM/DM who were managed from pregnancy to delivery at Kagawa University Hospital from March 2006 to May 2021 were enrolled. Clinical data were retrospectively analyzed to evaluate the association between disease activity during pregnancy and pregnancy outcomes. Eight pregnancies in 5 women with PM/DM were analyzed. The mean age at conception was 28.3 ± 3.8 years, and mean disease duration was 6.3 ± 3.2 years. Four patients required an increased glucocorticoid dosage because of worsening disease activity (sustained elevation of creatine phosphokinase [CPK] concentration). Two patients who continuously received immunosuppressive drugs from conception to delivery showed no increase in disease activity and did not need increased glucocorticoid dosages. The pregnancy outcomes were 1 spontaneous abortion and 7 live births. The mean gestation length was 35.3 ± 5.2 weeks, and mean birthweight was 2297.7 ± 1041.4 g. Five adverse pregnancy outcomes (APOs) occurred (2 preterm births and 4 low birthweights); most of these cases had sustained elevation of CPK concentration and increased glucocorticoid dosages. No APOs occurred in the 2 patients who received continuous immunosuppressive medication. Continued use of pregnancy-compatible medications and control of disease activity with lower glucocorticoid dosages in pregnancies with PM/DM may be important to achieve good pregnancy outcomes.

A case of Degos disease successfully treated with corticosteroid combined with cyclophosphamide.

Degos disease is a rare disorder characterized by systemic vasculitis involving various organs. There is no established, effective treatment for the disorder, and its prognosis is still poor. Combination therapy with corticosteroid and cyclophosphamide is considered effective for vasculitides involving the small arteries such as ANCA-associated vasculitis. We present here a 42-year-old man who developed Degos disease over several months, and was successfully treated using combined treatment with corticosteroid and cyclophosphamide.

Longer preserved urethral length in robot-assisted radical prostatectomy significantly contributes to post-operative urinary continence recovery.

Objectives: To assess the relationship between the surgical procedure of robot-assisted radical prostatectomy (RARP) and urinary continence recovery by reviewing the video database. Methods: Video and data about men diagnosed with prostate cancer and underwent RARP were extracted and reviewed. Preserved urethral length (PUL) was semi-quantitatively measured using the lateral width of a 16-Fr urethral balloon catheter while cutting the urethra on a video screen. In addition, by reviewing intraoperative RARP video database, other surgical skill outcomes were also collected. Kaplan-Meier analysis with log-rank test was used to compare the urinary continence recovery rate, stratified by the PUL. Univariate and multivariate analyses were performed using the Cox proportional hazards model, and p-values of <0.05 were considered significant. Results: The number of patients included in this study was 213. In univariate analysis, a PUL of ≥16 mm, a body mass index of <23.1 kg/m2 and a resected prostate volume of <44.3 g were statistically significant factors that influenced urinary continence recovery [hazard ratio (HR) 1.58, p = 0.036; HR 0.67, p = 0.021; and HR 0.58, p = 0.005, respectively]. Those factors also remained statistically significant in the multivariate analysis (HR 1.87, p = 0.022; HR 0.54, p = 0.001; and HR 0.57, p = 0.005, respectively). One year post-operatively, the recovery rate from urinary continence was 79.0% for patients with a PUL of ≥16 mm and 66.5% for patients with a PUL of <16 mm. Conclusion: These results suggest that patients with longer PUL in RARP have a significantly higher rate of post-operative urinary continence recovery.

FDG-PET/CT imaging parameters for predicting spontaneous regression of methotrexate-associated lymphoproliferative disorder in patients with rheumatoid arthritis.

In this study, we investigated the usefulness of FDG-PET/CT for predicting spontaneous regression in methotrexate-associated lymphoproliferative disorder (MTX-LPD). Twenty patients with rheumatoid arthritis who were diagnosed with MTX-LPD were enrolled in the study. These patients were divided into those who showed spontaneous regression (SR group: ten patients) and those who received chemotherapy after discontinuation of MTX (CTx group: ten patients). Between-group differences in potential biomarkers were compared, including clinical markers at the onset of LPD [serum LDH and interleukin 2 receptor (sIL-2R)], change in absolute number of peripheral lymphocytes (ΔALC) over follow-up, and the FDG-PET/CT-derived parameters of maximum standardized uptake value (SUVmax), mean SUV (SUVmean), peak SUV (SUVpeak), sum of the metabolic tumor volume (MTVsum), and sum of total lesion glycolysis (TLGsum). The levels of sIL-2R, MTVsum, and TLGsum were significantly lower in the SR group than in the CTx group. In addition, ΔALC was higher in the SR group. In conclusion, MTV and TLG values measured by FDG-PET/CT may be suitable for use as predictors of SR in patients with MTX-LPD.

Systemic lupus erythematosus with various clinical manifestations in a patient with hereditary angioedema: a case report.

BACKGROUND: Hereditary angioedema (HAE) is an inherited disease characterized by recurrent angioedema without urticaria or pruritus. The most common types of HAE are caused by deficiency or dysfunction in C1 esterase inhibitor (C1-INH-HAE). The association between C1-INH-HAE and systemic lupus erythematosus (SLE) is known; however, variations in the underlying pathophysiology, disease course, and treatment in this population remain incompletely understood. CASE PRESENTATION: A 31-year-old Japanese woman with a prior diagnosis of HAE type 1 based on the episodes of recurrent angioedema, low C1 inhibitor antigen levels and function, and family history presented with new complaints of malar rash, alopecia, and arthralgias in her hands and elbows. She later developed fever, oral ulcers, lupus retinopathy, a discoid rash localized to her chest, and malar rash. Investigations revealed positive antinuclear antibody, leukopenia, thrombocytopenia, hypocomplementemia, and nephritis. Based on these findings, she was diagnosed with SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria. There did not appear to be a correlation between HAE disease activity and the timing of presentation with SLE, because HAE disease activity had been stable. The patient was able to achieve and maintain remission with immunosuppressive therapy including prednisolone, hydroxychloroquine, and tacrolimus. CONCLUSIONS: Our patient presented with a variety of symptoms, including fever and cytopenia in addition to mucocutaneous, joint, ocular, and renal lesions. It is important to better characterize the clinical characteristics of SLE in patients with C1-INH-HAE, and to clarify the mechanisms of SLE in this population.

Humoral immune response against BNT162b2 mRNA COVID-19 vaccine in patients with rheumatic disease undergoing immunosuppressive therapy: A Japanese monocentric study.

We investigated serum total antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain after BNT162b2 mRNA vaccination against coronavirus disease 2019 (COVID-19) in Japanese patients taking various immunosuppressive medications for rheumatic disease. In 212 outpatients with rheumatic diseases at Kagawa University Hospital and 43 healthy volunteers (controls), all of whom had received 2 doses of BNT162b2 vaccine, serum antibody titers of SARS-CoV-2 spike protein were analyzed at least 14 days after the second dose. Many of the patients were taking immunosuppressive agents to manage their rheumatic disease. The antibody titers against SARS-CoV-2 spike protein in these patients were significantly lower than those in controls. The analysis of therapeutic agents revealed that the antibody titers in patients treated with rituximab were much lower than those in controls. In patients treated with tacrolimus, baricitinib, azathioprine, mycophenolate mofetil, abatacept, tumor necrosis factor inhibitors, cyclosporine, interleukin-6 inhibitors, methotrexate, or glucocorticoids, antibody titers were moderately lower than those of controls. Interleukin-17 and interleukin-23 inhibitors did not impair the humoral response. In addition, the combination of methotrexate with various immunosuppressive agents reduced titers, although not significantly. In Japanese patients with rheumatic disease, many immunosuppressants impaired the immune response to the BNT162b2 vaccine. The degree of decline in antibody titers differed according to immunosuppressant. When used concomitantly with other immunosuppressants, methotrexate may impair the immune response to the BNT162b2 vaccine. However, immunomodulatory treatments such as interleukin-17 and -23 inhibitors may not attenuate this response in patients with rheumatic disease.

Preterm birth is strongly affected by the glucocorticoid dose during pregnancy in women complicated by systemic lupus erythematosus.

BACKGROUND: This study aimed to investigate the effect of glucocorticoid doses on adverse pregnancy outcomes (APOs) in women complicated by systemic lupus erythematosus (SLE). METHODS: We investigated 74 pregnancies complicated by SLE or SLE-dominant mixed connective tissue disease. The pregnancies were managed from conception to delivery in our institution. We retrospectively evaluated whether the mean glucocorticoid dose during pregnancy is associated with APOs, including preterm birth (PB), low birth weight (LBW), and light-for-date (LFD). We also calculated the cut-off dose of glucocorticoid that affected APOs. RESULTS: All APOs occurred in 35 (50.7%) patients, with 14 cases of PB, 23 cases of LBW, and 10 cases of LFD. Patients with all APOs or PB had a higher dose of glucocorticoid during pregnancy than patients without all APOs or with full-term birth (P = 0.03, P <  0.01, respectively). Logistic regression analysis for all APOs and PB showed that the cut-off values of the mean glucocorticoid dose were 6.5 and 10.0 mg/day, respectively. Patients who delivered LBW or LFD newborns showed no significant difference in the glucocorticoid dose used during pregnancy than patients without LBW or LFD newborns. Patients who delivered LBW newborns were more likely to have used glucocorticoids during pregnancy (P <  0.01). CONCLUSIONS: In pregnancies complicated by SLE, a relatively lower dose of glucocorticoid than previously reported is significantly related to APOs, especially PB. Therefore, the disease activity of patients with SLE should be managed with the appropriate lower dose of glucocorticoid during pregnancy.