Clinical Impact of Malnutrition According to the Global Leadership Initiative on Malnutrition Criteria Combined With Kidney Dysfunction to Determine Mortality in Inpatients.

OBJECTIVE: The clinical impact of malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in patients with kidney dysfunction remains poorly understood. This study investigated the usefulness of GLIM criteria for malnutrition in predicting mortality in patients with kidney dysfunction and different clinical renal states, including no kidney disease (NKD), acute kidney injury (AKI), and chronic kidney disease (CKD). METHODS: This single-center retrospective cohort study included 6,712 patients aged ≥18 admitted between 2018 and 2019. The relationship between the estimated glomerular filtration rate (eGFR) groups, nutritional status based on the GLIM criteria, and the incidence of all-cause mortality was evaluated using a multivariate Cox proportional hazards model. Malnutrition was defined as at least one phenotype (weight loss, low body mass index, or reduced muscle mass) and one etiological criterion (reduced intake/assimilation or disease burden/inflammation). RESULTS: Multivariate Cox proportional hazards model showed that eGFR ≤29 (vs. eGFR: 60-89, adjusted hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.52-2.22), 30-59 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.20-1.64), and ≥90 (vs. eGFR: 60-89, adjusted HR = 1.40, 95% CI: 1.14-1.71), moderate and severe malnutrition (vs. without malnutrition, adjusted HR = 1.38 [1.18-1.62] and 2.18 [1.86-2.54], respectively) were independently associated with the incidence of death. The all-cause mortality rate was higher in patients with malnutrition or eGFR ≤29 (adjusted HR, 3.31; 95% CI: 2.51-4.35) than in patients without malnutrition or eGFR 60-89. Furthermore, moderate and severe malnutrition (vs. no malnutrition) was independently associated with death in patients with NKD, AKI, and CKD. CONCLUSION: Malnutrition based on the GLIM criteria was associated with increased all-cause mortality in inpatients, and malnutrition combined with kidney dysfunction was associated with a higher risk of mortality. Furthermore, patients with NKD, AKI, and CKD showed an association between malnutrition based on GLIM criteria and mortality.

Predictors of damage accrual in patients with antineutrophil cytoplasmic antibody-associated vasculitis: A nationwide prospective study.

OBJECTIVES: This study elucidated the prognosis and risk factors associated with damage accrual during long-term remission maintenance therapy for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We obtained data from 120 patients registered in a nationwide prospective cohort study on remission induction therapy in Japanese patients with AAV and rapidly progressive glomerulonephritis (RemIT-JAV-RPGN), who achieved remission at 24 months after treatment initiation and were followed up for additional 24 months. The primary outcome was the vasculitis damage index (VDI) score at Month 48, and the secondary outcome included risk factors associated with increased total VDI at Month 48. RESULTS: The understudied patients comprised 52 men and 68 women aged 68 ± 13 years. Between Months 25 and 48, the patients' survival rate was 95% (114/120). End-stage renal disease developed in seven patients by Month 48, and 64 cases had increased VDI. The multivariable analysis results revealed that oral prednisolone (PSL) doses at Month 24 were associated with damage accrual between Months 24 and 48. CONCLUSIONS: VDI accrual was observed in more than half of patients with AAV during maintenance therapy, and increased VDI scores were associated with oral PSL doses 24 months after initiating remission induction therapy in Japan.

Association between reduced left ventricular ejection fraction and peritoneal dialysis related peritonitis: a single center retrospective cohort study in Japan.

We present a single-center retrospective analysis of 228 Japanese patients with peritoneal dialysis, in which we examined whether reduced left ventricular ejection fraction (LVEF) is a risk factor for peritonitis development. Time-dependent multivariable-adjusted Cox proportional hazards models revealed that reduced LVEF (LVEF < 50% vs. preserved LVEF ≥ 50%, hazard ratio (HR) 2.10; 95% confidence interval (CI) 1.16-3.82) was associated with peritonitis. Qualitatively, similar associations with reduced LVEF (< 50%) were observed for enteric peritonitis (adjusted HR 7.68; 95% CI 2.51-23.5) but not for non-enteric peritonitis (adjusted HR 1.15; 95% CI 0.54-2.44). Reduced LVEF is associated with a significantly higher risk of subsequent peritonitis, particularly enteric peritonitis. These results indicate that patients with reduced LVEF may be at risk of enteric peritonitis from bowel sources caused by intestinal involvement due to cardiac dysfunction.

Lymphopenia is a risk factor for severe infections in older patients with microscopic polyangiitis: a retrospective cohort study in Japan.

Objective: Previous studies have identified the predictors of severe infections in ANCA-associated vasculitis. However, lymphopenia has not been fully evaluated as a predictor of subsequent severe infections in patients with microscopic polyangiitis (MPA). The aim of this study was to assess the association between lymphopenia and severe infections requiring hospitalization after receiving immunosuppressive therapy for MPA. Methods: This single-centre retrospective cohort study included 130 consecutive patients with newly diagnosed MPA from Aichi Medical University Hospital, Japan, who received immunosuppressive therapy between March 2004 and December 2020. The relationship between lymphopenia and subsequent severe infections was assessed using time-dependent multivariate Cox proportional hazard models adjusted for clinically relevant factors. Results: During the follow-up period (median: 38 months; interquartile range: 15-63 months), 56 severe infectious episodes occurred in 51 patients (39.2%). Time-dependent multivariate Cox proportional hazard analyses identified older age [adjusted hazard ratio (HR) = 1.74 per 10 years, 95% CI: 1.13, 2.67], methylprednisolone pulse therapy (adjusted HR = 2.04, 95% CI: 1.03, 4.02), moderate lymphopenia (vs normal, adjusted HR = 7.17, 95% CI: 3.10, 16.6) and severe lymphopenia (vs normal, adjusted HR = 36.1, 95% CI: 11.8, 110.9) as significant predictors of severe infection. Conclusion: Lymphopenia is a predictor of subsequent severe infections in patients with MPA who receive immunosuppressive therapy. These results suggest the importance of sustained infection surveillance, particularly in older patients who develop lymphopenia during strong immunosuppressive therapy.

Malnutrition according to the GLIM criteria with kidney dysfunction is associated with increased mortality in hospitalized patients with cardiovascular disease: A retrospective cohort study.

BACKGROUND & AIMS: Cardiovascular disease (CVD) is a significant cause of mortality and rising healthcare costs, involving numerous chronic and nutritional risk. Although several studies have reported that malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria is associated with mortality in patients with CVD, they have not evaluated this association in terms of malnutrition severity (moderate or severe). Furthermore, the relationship between malnutrition combined with renal dysfunction, a risk factor for death in CVD patients, and mortality has not been previously evaluated. Thus, we aimed to assess the association between malnutrition severity and mortality, as well as malnutrition status stratified by kidney function and mortality, in patients hospitalized due to CVD events. METHODS: This single-centre, retrospective cohort study included 621 patients with CVD aged ≥18 years admitted to Aichi Medical University between 2019 and 2020. The relationship between nutritional status based on the GLIM criteria (without malnutrition, moderate malnutrition, or severe malnutrition) and the incidence of all-cause mortality was evaluated by multivariable Cox proportional hazards models. RESULTS: Patients with moderate and severe malnutrition were significantly more prone to mortality than those without malnutrition (adjusted hazard ratio [HR] of patients without, with moderate, and with severe malnutrition: 1.00 [reference], 1.94 [1.12-3.35], and 2.63 [1.53-4.50], respectively). Furthermore, we found the highest all-cause mortality rate in patients with malnutrition and a lower estimated glomerular filtration rate (eGFR <30 mL/min/1.73 m2) (adjusted HR, 10.1; confidence interval, 3.90-26.4) than in patients without malnutrition and normal eGFR (eGFR ≥60 mL/min/1.73 m2). CONCLUSIONS: The present study indicated that malnutrition according to the GLIM criteria was associated with increased all-cause mortality in patients with CVD, and malnutrition associated with kidney dysfunction was associated with a higher risk of mortality. These findings provide clinically relevant information to identify high mortality risk in patients with CVD and highlight the need for giving careful attention to malnutrition with kidney dysfunction among patients with CVD.

Granulomatosis with polyangiitis presenting as multiple renal masses: A case report with MRI findings.

It is extremely rare for granulomatosis with polyangiitis to form masses in the kidneys. Magnetic resonance imaging findings of renal masses caused by this disease have been infrequently reported. In this study, we report a case of renal masses caused by granulomatosis with polyangiitis with different findings. While on steroid treatment for a recently diagnosed granulomatosis with polyangiitis, a man in his 60s underwent computed tomography for a hepatic dysfunction. Computed tomography showed incidental findings of a 40 mm × 35 mm mass in the left kidney and two 8 mm × 8 mm masses in the right kidney; all masses were hypovascular. On magnetic resonance imaging, the left renal mass showed a hyperintense signal with slightly hypointense signal rim on T2-weighted imaging. The left renal mass showed a strong hypointense signal where the mass abutted the renal capsule. On diffusion-weighted imaging, the left renal mass showed an isointense signal with a hyperintense signal rim. Both right renal masses showed an isointense signal with slightly hypointense signal rim on T2-weighted imaging and hyperintense signal on diffusion-weighted imaging. Suspecting renal masses caused by the disease, the patient was then treated with steroids and methotrexate. After 6 months of treatment, both right renal masses resolved; however, the left renal mass shrank but abnormal signal remained. Based on the treatment course, it is conceivable that the renal masses were caused by granulomatosis with polyangiitis.

Population pharmacokinetics and limited sampling strategy for therapeutic drug monitoring of mycophenolate mofetil in Japanese patients with lupus nephritis.

BACKGROUND: Mycophenolate mofetil (MMF), a prodrug of the immunosuppressive agent mycophenolic acid (MPA), is difficult to administer because of the pharmacokinetic complexity of MPA. Although dosage adjustment according to the 12-h area under the concentration-time curve (AUC0-12) is thought to be desirable, multiple blood samplings for AUC calculation may pose a clinical challenge. A limited sampling strategy (LSS) would provide a solution; however, little is known about MPA pharmacokinetics in lupus nephritis patients, especially in those with Asian backgrounds, or few, if any, LSSs are reported for them. METHODS: Thirty-four adult Japanese patients receiving MMF for lupus nephritis were examined retrospectively. MPA pharmacokinetics were investigated, and a PPK model was developed using Phoenix® NLME™ software. Single and double blood sampling strategies from Bayesian estimation using the PPK model and from multiple linear regression were compared. Tolerability was also evaluated. RESULTS: In the pharmacokinetic analysis, renal function and serum albumin had significant effects on dose-normalized AUC0-12; and serum albumin, concomitant proton pump inhibitor (PPI) and iron/magnesium oxide did on dose-normalized maximum concentration. As a PPK model, a two-compartment model was developed with a transit absorption model and first-order elimination, in which creatinine clearance and serum albumin were covariates for MPA clearance. The double sampling strategy at 1 and 4 h by multiple linear regression showed the best agreement with the observed AUC0-12 (r2 = 0.885). Of the single sampling strategies, the one at 6 h by Bayesian estimation performed best (r2 = 0.769). The tolerability evaluation showed that correlations were suggested for gastrointestinal involvement. CONCLUSIONS: The present study developed the first PPK model of MPA for Japanese lupus nephritis patients. As for LSSs, a double sampling strategy at 1 and 4 h by multiple linear regression would work best; when only a single blood sampling is allowed, a strategy at 6 h by Bayesian estimation using the PPK model developed in this study would be best. The LSSs good enough for clinical use may facilitate safer, more effective, and individualized therapy.

A case of 2,8-DHA crystalline nephropathy caused by adenine phosphoribosyltransferase deficiency: diagnosis and treatment.

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder that leads to the accumulation of poorly soluble 2,8-dihydroxyadenine (DHA) in the kidneys, resulting in a variety of renal presentations including nephrolithiasis, acute kidney injury, and chronic kidney disease (CKD) caused by crystal nephropathy. Here, we report a case of a 43-year-old man with 2,8-DHA crystalline nephropathy caused by APRT deficiency strongly suspected by renal biopsy results and definitively diagnosed by a urine gas chromatography-mass spectrometry (GC/MS)-based plasma metabolomic assessment. This case represents the importance of awareness and recognition of the signs and symptoms of this rare condition and its progression to CKD, which can be prevented by the early administration of xanthine oxidoreductase inhibitors.

Nation-wide cohort study of remission induction therapy using rituximab in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: Effectiveness and safety in the first 6 months.

OBJECTIVES: The aim of this article is to evaluate the effectiveness and safety of rituximab (RTX) for microscopic polyangiitis and granulomatosis with polyangiitis in Japan. METHODS: In this prospective observational study, all patients with microscopic polyangiitis and granulomatosis with polyangiitis administered RTX were enrolled at each institution. During the observation period of 2 years, data up to 6 months were analysed. Cox proportional hazards analysis was used to assess the factors associated with an outcome. RESULTS: Of the 75 patients who received RTX for remission induction therapy, 53 achieved remission by the sixth month and 50 were in remission at the sixth month. During therapy, 38 serious adverse events were observed in 24 patients, 21 serious infections in 16 patients, and 9 patients died. No factors were associated with remission; however, there was a significant difference between patients with and without remission in serious adverse events (22.6% vs. 54.5%), serious infections (11.3% vs. 45.4%), and death (1.9% vs. 36.4%). The hazard ratio (95% confidence interval) for serious infection was 3.49 (1.29-9.74) for patients aged ≥ 75 years and 3.53 (1.31-9.53) for pulmonary complications. Four patients maintained remission for 6 months. CONCLUSIONS: The effectiveness and safety of RTX for microscopic polyangiitis and granulomatosis with polyangiitis for up to 6 months was demonstrated.

Mepolizumab administration for eosinophilic granulomatosis with polyangiitis in an elderly patient with an abrupt onset of limb ischaemia and peripheral neuropathy: A case-based literature review.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of anti-neutrophil cytoplasmic antibody-associated vasculitis characterised by small- to medium-sized vessel vasculitis and is typically associated with eosinophilic granulomatous inflammation. EGPA can affect any organ system, most commonly the lungs, skin, and the nervous system. However, limb ulcers are rare complications and have only been described in few case reports. Furthermore, no documented cases of EGPA have been treated with mepolizumab. Herein, we report a case of an 86-year-old Japanese woman with anti-neutrophil cytoplasmic antibody-negative EGPA, who had an abrupt onset of upper limb ulcers and bilateral foot drop due to multiple mononeuropathy. Clinicopathological sural nerve biopsy showed eosinophil-associated vascular damage. The patient was administered steroids, intravenous immunoglobulin, vasodilators, and mepolizumab; this resulted in clinical improvement of her finger ulcers and peripheral neuropathy without any adverse effects. In cases of an abrupt onset of limb ischaemia and peripheral neuropathy, physicians should consider the possibility of EGPA as a differential diagnosis. Furthermore, the early administration of mepolizumab might yield better outcomes in terms of improving limb ischaemia and peripheral neuropathy.

Time to normalisation of CRP and incidence of relapse in microscopic polyangiitis: A medical records review study in Japan.

OBJECTIVES: Despite the identification of risk factors for relapses in anti-neutrophil cytoplasmic antibody-associated vasculitis, the relationship between changes in C-reactive protein levels after initial treatment and incidence of relapse remains unknown. This study aimed to assess the association between the time taken for normalisation of C-reactive protein levels and the incidence of relapse in Japanese adult patients with microscopic polyangiitis. METHODS: This study included 85 consecutive patients with newly diagnosed microscopic polyangiitis who achieved remission after six months of immunosuppressive treatment at the Aichi Medical University Hospital, between 2009 and 2017. The relationship between the time to normalisation of C-reactive protein after initial immunosuppressive treatment and relapse incidences was evaluated using multivariable Cox proportional hazard models. RESULTS: During the follow-up period, 13 (30.2%), 7 (41.2%), and 16 (64.0%) patients relapsed (P=0.025) within 1-14, 15-28, and ≥29 days of normalisation, respectively. Hazard ratios (95% confidence intervals) of the time to normalisation of C-reactive protein of 1-14, 15-28, and ≥29 days were 1.00 (reference), 2.42 (95%CI: 0.92-6.39), and 3.48 (95%CI: 1.56-7.76), respectively. CONCLUSIONS: A significant association between the time to normalisation of C-reactive protein and relapse incidence in Japanese patients with microscopic polyangiitis was observed.

Association between renal-limited vasculitis and relapse of antineutrophil cytoplasmic antibody-associated vasculitis: A single-center retrospective cohort study in Japan.

BACKGROUND: Several previous studies have evaluated the predictors of relapse in antineutrophil cytoplasmic antibody-associated vasculitis. Nonetheless, the association between renal-limited vasculitis and relapse has not been evaluated. OBJECTIVE: To assess the association between renal-limited vasculitis and the incidence of relapse in Japan among patients with microscopic polyangiitis/renal-limited vasculitis. METHODS: This retrospective cohort study included consecutive patients in remission at 6 months, with renal-limited vasculitis (n = 24, renal-limited vasculitis group) and microscopic polyangiitis with renal and extra-renal involvement (n = 56, non-renal-limited vasculitis group) between 2004 and 2020. RESULTS: During the median follow-up period of 35 (range, 15‒57) months, 28 (35.0%) patients had a relapse. Multivariable Cox proportional hazards models revealed that the lower estimated glomerular filtration rate (per -10 mL/min/1.73 m2; adjusted hazard ratio = 0.87, 95% confidence interval: 0.76-0.99; P =  0.043), renal-limited vasculitis (adjusted hazard ratio =  0.23, 95% confidence interval: 0.08-0.68; P =  0.008), and glucocorticoid combined with intravenous cyclophosphamide or rituximab (adjusted HR = 0.32, 95% CI: 0.11-0.96; P = 0.042) were associated with a decreased risk of relapse. Glucocorticoid dose during the observation period was lower in the renal-limited vasculitis group than in the non-renal-limited vasculitis group. CONCLUSIONS: Renal-limited vasculitis was associated with a lower risk of relapse than non-renal-limited vasculitis. Our data may contribute to the development of optimal management for renal-limited vasculitis, which may assist in minimizing the adverse effects of immunosuppressive therapy.

A case of bilateral uveitis associated with seminoma/germinoma in thymus and pineal glands, two primary lesions.

Purpose: To report a case of bilateral ocular paraneoplastic syndrome by seminoma/germinoma in thymus and pineal glands, two primary lesions. Observations: A 18-year-old male presented at a local clinic complaining of just floaters in left eye without any other clinical signs and symptoms. The treating ophthalmologist found bilateral uveitis, and referred to our hospital. Bilateral retinal periphlebitis and optic disc swelling were shown. Vitreous opacity was found in left eye. We started ocular and systemic examinations to identify the cause of the uveitis, and also initiated oral steroid therapy. The survey using aqueous humor and blood samples showed no specific results for his uveitis. Computer tomography (CT) and magnetic resonance imaging (MRI) detected tumors in thymus and pineal glands. Five months after his first visit, the tumor in his thymus was resected, and was diagnosed as a seminoma/germinoma by pathological examination. Three months later, the tumor in the pineal gland was diagnosed as a germinoma by biopsy followed by chemotherapy and focal radiotherapy. Finally no abnormal ocular finding but slight optic disc atrophy was ascertained. Conclusions and importance: This is a case of ocular paraneoplastic syndrome induced by seminoma/germinoma in thymus and pineal glands, two primary lesions. Systemic screening by CT and MRI enables prompt diagnosis, treatment and favorable clinical course for such pathogenesis.

Association of alcohol consumption with the incidence of proteinuria and chronic kidney disease: a retrospective cohort study in Japan.

BACKGROUND: The difference in the clinical impact of alcohol consumption on kidney function based on sex remains to be elucidated. This study aimed to assess the association between the dose of alcohol consumption and the incidence of proteinuria and chronic kidney disease stratified by sex. METHODS: This retrospective cohort study included 26,788 workers (19,702 men and 7086 women) with normal renal function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2) at annual health examinations between January 2010 and March 2015 in Japan. The main exposure was alcohol consumption. The primary outcomes were the incidence of proteinuria (dipstick urinary protein ≥ 1) and incidence of low estimated glomerular filtration rate (eGFR; rate < 60 mL/min per 1.73 m2; decreased from the baseline eGFR by 25%). RESULTS: During a median observational period of 4 years (interquartile range: 2-6), 1993 (10.1%) men and 462 (6.5%) women developed proteinuria, whereas 667 (3.4%) men and 255 (3.6%) women developed low eGFR. After adjustment for clinically relevant factors using a Cox proportional hazards model, alcohol consumption of ≥ 46 g/day in females was significantly associated with the incidence of proteinuria (hazard ratio, 1.57; 95% confidence interval, 1.10-2.26) and low eGFR (hazard ratio, 1.62; 95% confidence interval, 1.04-2.53). However, no significant association between alcohol consumption and primary outcomes was observed in men. CONCLUSIONS: In conclusion, daily higher alcohol consumption was significantly associated with a higher incidence of proteinuria and low eGFR among women. Women might be prone to high alcohol consumption with kidney dysfunction.

Anti-neutrophil cytoplasmic antibody-associated vasculitis complicated by thrombotic microangiopathy with posterior reversible encephalopathy syndrome successfully treated with eculizumab: A case report.

Thrombotic microangiopathy is characterised by endothelial cell injury, intravascular platelet-fibrin thrombi, and vascular damage, leading to acute kidney injury, thrombocytopenia, and microangiopathic haemolytic anaemia. Among the autoimmune diseases related to thrombotic microangiopathy, anti-neutrophil cytoplasmic antibody-associated vasculitis-related thrombotic microangiopathy cases have been rarely reported; therefore, the optimal treatment for associated vasculitis-related thrombotic microangiopathy remains unknown. An 84-year-old woman without significant medical history presented with a 1-month history of general fatigue, fever, and deteriorating bilateral leg numbness and was admitted to our hospital. She had elevated myeloperoxidase anti-neutrophil cytoplasmic antibody levels, polyneuropathy, and rapid progressive glomerulonephritis because of pauci-immune crescentic glomerulonephritis, as revealed by a kidney biopsy. Accordingly, we diagnosed her with microscopic polyangiitis. After administering methylprednisolone pulse therapy, rituximab, and intravenous immunoglobulin, the patient's mental state deteriorated, presenting signs of thrombotic microangiopathy with posterior reversible encephalopathy syndrome. Intermittent haemodialysis and plasma exchange were initiated; however, her condition did not improve, and eculizumab administration was initiated thereafter. The patient's symptoms showed a remarkable response to eculizumab; thrombotic microangiopathy findings, kidney function, and neurological symptoms improved after only two doses of eculizumab, and she achieved sustained remission. The extremely effective course of eculizumab treatment indicated that overt complement activation affected the development of thrombotic microangiopathy. Anti-neutrophil cytoplasmic antibody-associated vasculitis-related thrombotic microangiopathy may be mediated by complement activation, and prompt induction of eculizumab therapy may be a superior strategy to prevent organ damage. Further studies should elucidate the role of complement activation in associated vasculitis-related thrombotic microangiopathy and the efficacy of eculizumab treatment.

Long-term good outcome of the fibrocavitary form of pulmonary Mycobacterium avium complex disease with concomitant abatacept monotherapy in a patient with rheumatoid arthritis.

A 53-year-old woman diagnosed with rheumatoid arthritis (RA) demonstrated thick-walled large cavities with consolidation in the left upper lobe on chest computed tomography (CT). Mycobacterium avium was isolated from sputum cultures, and she was diagnosed as having the fibrocavitary (FC) form of pulmonary Mycobacterium avium complex (MAC) disease. Clarithromycin-containing, multidrug, anti-MAC chemotherapy was started immediately. After 7 months, the cavitary lesions improved, and sputum cultures showed negative conversion. Thereafter, abatacept monotherapy was started due to high RA disease activity. Clinical remission of RA has been sustained and cavitary lesions disappeared by concomitant abatacept and anti-MAC therapy for more than 5 years. Immediate initiation of anti-MAC therapy and prior confirmed efficacy are needed for the treatment of the FC form. Abatacept and anti-MAC therapy could be continued, leading to the withdrawal of prednisolone, along with careful observation by strict chest CT evaluation and repeated sputum cultures. Biologics are generally contraindicated for pulmonary MAC disease, particularly the FC form. When there is a pre-existing lung lesion apparently of FC type, abatacept cannot be started without prior anti-MAC chemotherapy. This case suggests that abatacept may be carefully used to avoid progressive joint destruction after FC lesions of pulmonary MAC disease are resolved.

Case report: Thrombotic microangiopathy concomitant with macrophage activation syndrome in systemic lupus erythematosus refractory to conventional treatment successfully treated with eculizumab.

Thrombotic microangiopathy (TMA) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). Macrophage activation syndrome (MAS) is also a rare, life-threatening hyperinflammatory condition that is comorbid with SLE. However, the association between TMA and MAS in patients with SLE has rarely been assessed, and the difficulty of diagnosing these conditions remains prevalent. The efficacy of eculizumab has been reported for SLE patients whose conditions are complicated with TMA. However, no study has investigated the therapeutic efficacy of eculizumab for TMA concomitant with SLE-associated MAS. Herein, we report the first case of TMA concomitant with SLE-associated MAS that was initially refractory to conventional immunosuppressive therapy but showed remarkable recovery after eculizumab treatment. Furthermore, we evaluated serum syndecan-1 and hyaluronan levels, which are biomarkers of endothelial damage. We found that these levels decreased after the administration of eculizumab, suggesting that TMA was the main pathology of the patient. This case illustrates that it is important to appropriately assess the possibility of TMA during the course of SLE-associated MAS and consider the use of eculizumab as necessary.

Association between serum magnesium levels and abdominal aorta calcification in patients with pre-dialysis chronic kidney disease stage 5.

BACKGROUND: Several studies have revealed the relationship between serum magnesium levels and vascular calcification in chronic kidney disease patients. Despite excellent predictability of abdominal aorta calcification for cardiovascular disease events, the relationship between serum magnesium levels and abdominal aorta calcification, as evaluated by quantitative methods, in pre-dialysis patients remains unclear. This study aimed to determine the abdominal aorta calcification volume using computerized tomography and its association with serum magnesium levels in pre-dialysis chronic kidney disease stage 5 patients. METHODS: This single-center cross-sectional study included 100 consecutive patients with pre-dialysis chronic kidney disease stage 5 between January 2016 and May 2020 at Aichi Medical University Hospital, Japan. The relationships between serum magnesium levels and the abdominal aorta calcification volume were assessed using multiple linear regression models after adjusting for clinically relevant factors. We also assessed clinical factors that affect serum magnesium levels. RESULTS: The mean serum magnesium level was 2.0 mg/dL (interquartile range, 1.8 to 2.3). Multivariate analyses revealed that a higher serum magnesium level (stand. ß = -0.245, p = 0.010) was significantly associated with a reduced abdominal aorta calcification volume, and that a history of cardiovascular disease (stand. ß = 0.3792, p < 0.001) and older age (stand. ß = 0.278, p = 0.007) were significantly associated with an increased abdominal aorta calcification volume. Moreover, multivariate analysis showed that the use of proton pump inhibitor or potassium-competitive acid blocker was significantly associated with lower serum magnesium levels (stand. ß = -0.246, p = 0.019). CONCLUSIONS: The present study revealed that the higher Mg level was significantly associated with lower volume of abdominal aorta calcification in pre-dialysis chronic kidney disease stage 5 patients. Further studies should be undertaken to determine the appropriate magnesium level to suppress vascular calcification.

Association between body mass index and severe infection in older adults with microscopic polyangiitis: a retrospective cohort in Japan.

BACKGROUND: Although previous studies have evaluated risk factors for the incidence of severe infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), the relationship between body mass index (BMI) and severe infection in AAV has not been elucidated. We hypothesized that older adults with AAV and a low BMI would be at a higher risk of infection. We therefore investigated the association between underweight status at AAV diagnosis and subsequent occurrence of severe infection in older adults with AAV. METHODS: This single-center retrospective cohort study included 93 consecutive older adults with microscopic polyangiitis (MPA) treated at the Aichi Medical University Hospital in Japan between 2004 and 2018. The relationships between BMI at diagnosis and subsequent first severe infection were assessed using multivariate Cox proportional hazards models. The cumulative probability of the development of the first severe infection was calculated using the Kaplan-Meier method and the log-rank test. The level of statistical significance was set at P <  0.05. RESULTS: During the median follow-up period of 19 (6-53) months, 29 (31.2%) patients developed at least one severe infection. Older age (adjusted hazard ratio [HR] = 2.02, 95% confidence interval [CI]: 1.14-3.52, per 10 years; P =  0.016), low BMI (< 18.5 kg/m2 compared with normal BMI [18.5-23.0 kg/m2], adjusted HR =  2.63, 95% CI: 1.11-6.19; P =  0.027), and use of methylprednisolone pulse therapy (adjusted HR = 2.48, 95% CI: 1.07-5.76; P =  0.034) were found to be significant predictors of severe infection. CONCLUSIONS: Low BMI was associated with a higher risk of severe infection in older adults with MPA, suggesting that careful management may be required to prevent this complication in this vulnerable group. Further studies are needed to elucidate the optimal treatment strategy for these patients.

Primary cutaneous methotrexate-associated B-cell lymphoproliferative disorders other than EBV-positive mucocutaneous ulcer: clinical, pathological, and immunophenotypic features.

Methotrexate (MTX)-associated B-cell lymphoproliferative disorders (B-LPD) may first present in the skin. Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is now a well known disease listed in the 2017 World Health Organization classification. However, primary cutaneous MTX-associated B-LPD (pcMTX B-LPD), other than EBVMCU, appear to be underestimated, and their distinctiveness remains unproven. This study aimed to document the clinicopathological characteristics of nine patients with pcMTX B-LPD that were not EBVMCU to extend our understanding of this peculiar disease. The cohort included three males and six females, with a median age of 74 years (range 54-83 years). All patients were treated with MTX for RA. Of nine patients, four presented with a solitary lesion, and five had multiple lesions. Histologically, five cases showed a polymorphic pattern, and four showed a monomorphic pattern. Immunohistochemically, four cases showed positive EBER staining, and one showed positive CD5 staining. In eight cases, once pcMTX B-LPD was diagnosed, methotrexate was immediately withdrawn. All eight of these patients experienced spontaneous regression and achieved complete remission (CR), without relapse. The patient with CD5 positivity received cytotoxic chemotherapy as the initial treatment. This patient achieved a CR after the initial treatment, but eventually experienced disease relapse resulting in death. We also revealed that pcMTX B-LPD and MTX-associated EBVMCU exhibited similar biological behaviours. We concluded that most pcMTX B-LPD cases could be cured by stopping MTX treatment. We also highlighted the fact that pcMTX B-LPD and MTX-EBVMCU had overlapping features. This finding suggested that pcMTX B-LPD and MTX-EBVMCU might share an underlying mechanism.