Late-onset Neutropenia after Rituximab Treatment for MPO-ANCA-associated Vasculitis.

An underestimated side effect of rituximab is late-onset neutropenia (R-LON), which often resolves spontaneously and rarely results in a severe infection. We herein report a case of febrile neutropenia due to R-LON in a 91-year-old woman with renal failure who was treated with rituximab to induce remission of MPO-ANCA-associated vasculitis. Fifty-four days after the last rituximab administration, the patient was hospitalized for febrile neutropenia due to R-LON, which improved with granulocyte colony-stimulating factor and antibiotics. Although R-LON may resolve spontaneously and remain unnoticed, it can cause severe infections in the elderly and patients with renal failure.

A case diagnosed with IgA nephropathy during a complete remission of minimal change nephrotic syndrome treated with rituximab.

We herein report a case of IgA nephropathy in a 20-year-old male who maintained a complete remission of minimal change nephrotic syndrome (MCNS) through the administration of rituximab (RTX). He was diagnosed with nephrotic syndrome at 4 years of age. After he relapsed frequently, he was diagnosed with MCNS at 8 years of age based on the findings of a kidney biopsy. At 13 years of age, RTX therapy was initiated to maintain a complete remission after steroid treatment. MCNS recurred twice, including the time in which the interval between the RTX administrations was long. Whenever he relapsed, remission induction was achieved using steroids, and remission maintenance was achieved using RTX. Five months after the 7th RTX administration, the serum IgA level started to increase. After the 9th RTX administration, he demonstrated microhematuria despite the urinary protein level indicating complete remission. At the 10th administration, the urinary protein and the red-blood cell casts were also observed. A renal biopsy was performed 84 months after the initial administration of RTX, and the patient was diagnosed with complications of IgA nephropathy. RTX is not considered to be a useful treatment for IgA nephropathy. The reasons for this are due to the fact that IgA1 does not decrease even following the administration of RTX, because B cells residing in the mucosa may not be deleted by RTX, and IgA production may also continue due to the presence of CD20- long-lived plasma cells. Even when administering RTX, if there are findings of glomerulonephritis on urine testing, the possibility of IgA nephropathy must be considered.

Oral Iron Absorption of Ferric Citrate Hydrate and Hepcidin-25 in Hemodialysis Patients: A Prospective, Multicenter, Observational Riona-Oral Iron Absorption Trial.

Oral ferric citrate hydrate (FCH) is effective for iron deficiencies in hemodialysis patients; however, how iron balance in the body affects iron absorption in the intestinal tract remains unclear. This prospective observational study (Riona-Oral Iron Absorption Trial, R-OIAT, UMIN 000031406) was conducted at 42 hemodialysis centers in Japan, wherein 268 hemodialysis patients without inflammation were enrolled and treated with a fixed amount of FCH for 6 months. We assessed the predictive value of hepcidin-25 for iron absorption and iron shift between ferritin (FTN) and red blood cells (RBCs) following FCH therapy. Serum iron changes at 2 h (ΔFe2h) after FCH ingestion were evaluated as iron absorption. The primary outcome was the quantitative delineation of iron variables with respect to ΔFe2h, and the secondary outcome was the description of the predictors of the body's iron balance. Generalized estimating equations (GEEs) were used to identify the determinants of iron absorption during each phase of FCH treatment. ΔFe2h increased when hepcidin-25 and TSAT decreased (-0.459, -0.643 to -0.276, p = 0.000; -0.648, -1.099 to -0.197, p = 0.005, respectively) in GEEs. FTN increased when RBCs decreased (-1.392, -1.749 to -1.035, p = 0.000) and hepcidin-25 increased (0.297, 0.239 to 0.355, p = 0.000). Limiting erythropoiesis to maintain hemoglobin levels induces RBC reduction in hemodialysis patients, resulting in increased hepcidin-25 and FTN levels. Hepcidin-25 production may prompt an iron shift from RBC iron to FTN iron, inhibiting iron absorption even with continued FCH intake.

EXTREME MACULAR SCHISIS-SIMULATING RETINAL DETACHMENT IN EYES WITH PATHOLOGIC MYOPIA.

PURPOSE: To determine the clinical and imaging characteristics, natural course, and surgical outcomes of pathologic myopic eyes with an extreme macular schisis simulating a retinal detachment (EMSSRD). METHODS: The data of 617 highly myopic eyes with myopic traction maculopathy were studied. The diagnosis of EMSSRD in the optical coherence tomography images was made based on a high elevation of the retina (>500 µ m), less obvious columnar structures, and the presence of thin remnants of outer retinal tissues above the retinal pigment epithelium. RESULTS: Among 617 eyes, 25 eyes had an EMSSRD. All of the eyes with an EMSSRD had macular atrophy caused by myopic macular neovascularization. In the five eyes they had progressed to MHRD, the retinal detachment started away from the macular atrophy. Among the 10 eyes which required surgery, there was no significant difference in the presurgical and postsurgical best-corrected visual acuity between the eyes operated because of a worsening of the EMSSRD and the eyes operated because of a progression to MHRD. CONCLUSION: In severely myopic eyes with macular neovascularization-related macular atrophy, a novel condition termed EMSSRD can be present. The optical coherence tomography images resemble those of a MHRD except the presence of thin remnants of the retina remaining on the retinal pigment epithelium.

Infrequent use of nighttime dialysis for emergency admission due to worsening heart failure in patients on maintenance hemodialysis.

In the emergency admission due to worsening heart failure (HF) in patients on maintenance hemodialysis, emergent dialysis may be indicated, which increases personnel expenses. To clarify the characteristics and in-hospital management of the patients, we conducted a multicenter retrospective study including 142 patients on maintenance hemodialysis emergently admitted for worsening HF (71.6 ± 9.2 years, 69.0% male, 44.4% HF with preserved [≥50%] ejection fraction). The interval between last hemodialysis and admission was long (median 55 h), suggesting that fluid accumulation triggered HF events. Although most patients (73.9%) were admitted in the nighttime (5 p.m. to 9 a.m.), only 17.9% of them needed nighttime dialysis and were managed medically until the first in-hospital dialysis, with the use of noninvasive positive pressure ventilation in 45.1% and oxygen supplementation in 95.8%. While patients on hemodialysis with worsening HF were frequently admitted in the nighttime, nighttime dialysis was indicated in a limited population.

Novel coronavirus disease in patients with end-stage kidney disease.

The novel coronavirus disease outbreak started in Wuhan, China, in December 2019 and has since spread rapidly worldwide. As almost all patients with end-stage kidney disease have been treated with HD in Japan, they have a higher risk of infection than the healthy population. Moreover, the complications of renal failure, such as hypertension and cardiovascular diseases, appear to be a risk factor of death owing to novel coronavirus disease. The reported morbidity and mortality rates of novel coronavirus disease are significantly higher in dialysis patients than in the healthy population. No treatment for novel coronavirus disease has yet been developed; thus, countermeasures to prevent the spread of coronavirus disease in dialysis facilities must be rapidly established. The latest findings on novel coronavirus disease in patients with end-stage kidney disease and the guidelines for countermeasures against the spread of novel coronavirus disease worldwide are summarized in this review.

Influence of acetaminophen on renal function: a longitudinal descriptive study using a real-world database.

PURPOSE: Long-term acetaminophen (APAP) use has poorly defined effects on renal function. We investigated these effects using a real-world database. METHODS: We used a database of health data routinely collected from 185 hospitals serving 20 million patients in Japan. Individuals with chronic pain were selected for the study. The primary outcome was the change in renal function, as measured by 1/serum creatinine (SCr) during the postindex period. RESULTS: After excluding individuals who did not meet the inclusion criteria, 241,167 patients were included in the analysis (median age 79.0, range 65-101 years; 111,252 were men). APAP was prescribed significantly more frequently to patients with a low renal function (P < 0.001). The annual changes in 1/SCr median and interquartile range (IQR) were - 0.038 (- 0.182 to 0.101) in patients receiving APAP, - 0.040 (- 0.187 to 0.082) in patients receiving non-steroidal anti-inflammatory drugs (NSAIDs), and - 0.025 (- 0.142 to 0.079) in nonmedicated control patients (P < 0.001). These changes were not significantly different among patients with a low renal function, with 0.003 (- 0.066 to 0.113) in the APAP group, 0.000 (- 0.089 to 0.090) in the NSAID group, and - 0.009 (- 0.086 to 0.089) in the control group (P = 0.327). CONCLUSION: Physicians tended to select APAP for individuals with a low renal function. The annual changes in 1/SCr were significantly different based on APAP and NSAID use or no analgesia, but the differences were not significant among patients with a low renal function. Overall, long-term use of APAP does not appear to exacerbate the renal function in a clinical setting.

FUNCTIONAL AND STRUCTURAL OUTCOMES AFTER FOVEA-SPARING INTERNAL LIMITING MEMBRANE PEELING FOR MYOPIC MACULAR RETINOSCHISIS BY MICROPERIMETRY.

PURPOSE: To determine the morphological and physiological outcomes and safety of vitrectomy with fovea-sparing internal limiting membrane peeling for myopic macular retinoschisis (MRS). METHODS: Highly myopic eyes (refractive error greater than -8.0 diopters or an axial length longer than 26.5 mm) with MRS that underwent vitrectomy with fovea-sparing internal limiting membrane peeling were analyzed retrospectively. The best-corrected visual acuity, retinal morphology, and the central and paracentral retinal sensitivities at 2°/6° by microperimetry were evaluated before and after the surgery. Postoperative microscotomas were also determined. RESULTS: Thirty-three eyes with MRS; 16 eyes with and 17 eyes without a foveal retinal detachment, were studied. All 33 eyes had an improvement of MRS and foveal retinal detachment partially or completely after surgery, and none developed a full thickness macular hole. The postoperative best-corrected visual acuity, the central retinal sensitivity, and the retinal sensitivity at 2° were significantly better than the preoperative values. Sixteen eyes developed postoperative microscotomas at paracentral 2° and/or 6°. CONCLUSION: The results showed that vitrectomy with fovea-sparing internal limiting membrane peeling is an effective and safe method to treat an MRS regardless of the presence of a foveal retinal detachment. However, careful follow-up should be performed to detect postoperative microscotomas.

DEVELOPMENT OF MACULAR ATROPHY AFTER PARS PLANA VITRECTOMY FOR MYOPIC TRACTION MACULOPATHY AND MACULAR HOLE RETINAL DETACHMENT IN PATHOLOGIC MYOPIA.

PURPOSE: To determine the incidence and long-term outcome of macular atrophy (MA) after pars plana vitrectomy (PPV) in pathologic myopia. METHODS: Highly myopic patients who underwent PPV for myopic traction maculopathy and macular hole retinal detachment at Tokyo Medical and Dental University between 2012 and 2016 were studied. Fundus photographs and/or optical coherence tomography were examined before and after PPV at every visit. RESULTS: A total of 133 eyes were followed for 39 months with the mean age of 62.8 years and the mean axial length of 30.0 mm. Postoperatively, 14 eyes (10.5%) developed fovea-centered MA, observed initially as a small, isolated, whitish lesion at the center of fovea at 3.5 months after PPV. The appearance of the MA was distinctly different from the choroidal neovascularization-related MA or patchy atrophy-related MA. With time, the lesions enlarged circumferentially. In these 14 eyes, the final best-corrected visual acuity was worse than the baseline, although the difference was not significant. The occurrence of MA was significantly associated with the preoperative foveal status. CONCLUSION: The development of MA can occur in 11% of highly myopic eyes after PPV for myopic traction maculopathy and macular hole retinal detachment. This postoperative MA might be a new complication of pathologic myopia.

Long-term Successful Treatment of Rituximab for Steroid-resistant Minimal Change Nephrotic Syndrome and Idiopathic Thrombocytopenic Purpura.

A 22-year-old woman had been diagnosed with idiopathic thrombocytopenic purpura (ITP) 5 years earlier. After undergoing splenectomy, she relapsed frequently following prednisolone tapering. She was complicated with minimal change nephrotic syndrome (MCNS) while taking 20 mg of prednisolone. Despite treatment with prednisolone, cyclosporin and low-density lipoprotein-apheresis, MCNS and ITP did not improve. We added rituximab in 4 weekly infusions of 375 mg/m2. MCNS and ITP were in complete remission. After administering rituximab once, all medicines were discontinued. No relapse had occurred by 50 months following the first rituximab administration. Rituximab affects steroid-resistant MCNS and ITP for a long time without complications.

A case of fatal osteolytic hypercalcemia complicated with IgG4-related ophthalmic disease leading to renal failure.

A 40-year-old male was hospitalized with renal impairment and severe hypercalcemia. His concentration of serum IgG4 was high, but serum whole PTH, 1-25(OH)2 vitamin D3 and PTHrP were not elevated. Computed tomography showed swelling of the bilateral lacrimal glands and systemic lymphadenopathy. The histological findings of lacrimal gland biopsy fulfilled the diagnostic criteria of IgG4-related ophthalmic disease (IgG4ROD). Bone scintigraphy showed increased ectopic uptake in the stomach, heart, lungs, and kidneys. He died on day 16 of admission, although the therapies for hypercalcemia were continued. Autopsy results showed an increase of osteoclasts in the bone marrow and metastatic calcification in multiple organs, and excluded from the differential diagnosis other disorders which present lymph-node swelling and hypercalcemia such as cancer, lymphoma, Castleman's disease, and sarcoidosis. He was given a diagnosis of IgG4ROD with osteolytic hypercalcemia.

Impaired mental health status in patients with chronic kidney disease is associated with estimated glomerular filtration rate decline.

AIM: Deteriorated health-related quality of life (HRQOL) is associated with increased risk for death in both chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients; however, the impact of HRQOL on CKD progression is not well investigated. METHODS: We aimed to evaluate the association between HRQOL and CKD progression in Japanese patients with CKD. One hundred and three outpatients who visited the department of nephrology at our hospital (mean estimated glomerular filtration rate (eGFR); 32.1 ± 11.2 mL/min per 1.73 m2 ) between April 2007 and March 2012 were enrolled in this study. The primary outcome was 30% decline of eGFR or ESRD. We assessed HRQOL of all participants at baseline, including the physical component summary (PCS), the mental component summary (MCS) and the role/social component summary (RCS), using SF-36. Based on the baseline score of PCS, MCS and RCS, we divided all subjects into two groups by median. RESULTS: We studied 66 men (64.1%) and 37 women aged 61.7 ± 10.0 years old. During approximately 2.5 years of follow-up period, 59 patients (57.3%) reached 30% eGFR decline or ESRD. Cox regression analyses demonstrated that lower MCS score was significantly associated with CKD progression (hazard ratio (HR) = 1.83, 95% CI = 1.04-3.21, P = 0.035), but that lower PCS score and RCS score were not (HR = 0.70, 95% CI = 0.39-1.25, P = 0.223; HR = 0.95, 95% CI = 0.54-1.67, P = 0.854, respectively). CONCLUSION: We found that impaired mental health was associated with CKD progression. The evaluation of the mental health should be performed in the patients with CKD.

Suprachoroidal hemorrhage followed by swept-source optical coherence tomography: a case report.

BACKGROUND: To report a case of Suprachoroidal Hemorrhage followed by Swept-Source Optical Coherence Tomography. CASE PRESENTATION: A 66-year-old woman with a rhegmatogenous retinal detachment in her left eye underwent pars plana vitrectomy. During the intraocular photocoagulation for a retinal tear after fluid-air exchange, a vitreous hemorrhage and suprachoroidal hemorrhage (SCH) developed. The surgical incisions were closed after filling the vitreous cavity with silicone oil. Two weeks later, the hemolyzed hemorrhage was removed, and new silicone oil was injected. After the surgery, a low reflective region was detected near the macula in the swept-source optical coherence tomographic (SS-OCT) images. The low reflective region was caused by the residual hemorrhage. The size of the reflective region gradually decreased and was not present at 3 months. We conclude that SS-OCT can be used to follow the resolution of a suprachoroidal hemorrhage. CONCLUSION: SS-OCT can be used to detect and follow the natural course of a suprachoroidal hemorrhage including the absorptive processes.

The characteristics of patients with hypermagnesemia who underwent emergency hemodialysis.

AIM: This study aimed to clarify the characteristics of patients who presented with severe hypermagnesemia and subsequently underwent emergency hemodialysis. METHODS: We investigated the age, gender, complications, clinical symptoms, causal drugs, electrocardiogram findings, and laboratory data of 15 patients. RESULTS: Magnesium oxide had been administered in all cases and 14 patients were over 65 years old. The male : female ratio was 6:9. Chief complaints included a disturbance of consciousness, hypotension, bradycardia, and respiratory failure. The median serum magnesium value before hemodialysis was 6.0 (3.7-18.6) mg/dL. The daily dosage of magnesium oxide was ≤ 2.0 g in 12 cases. The median serum creatinine value before hemodialysis was 5.39 (0.54-10.29) mg/dL. However, in two cases, the creatinine value was not elevated. Complications of acute kidney injury exacerbated the hypermagnesemia in nine cases. CONCLUSIONS: We recommend that the serum magnesium value should be measured in older patients who are taking magnesium oxide and are showing signs and symptoms of a disturbance of consciousness, hypotension, bradycardia, and respiratory failure of an uncertain etiology, even if the serum creatinine value is not elevated or the dosage of magnesium oxide is within recommended levels.

Arthroscopic Osteosynthesis for the Treatment of Coronoid Process Fractures: A Case Series.

The treatment strategy and surgical indication for coronoid process fractures are not clear. Many methods of surgery have been described. We report on the use of arthroscopic osteosynthesis for this type of fracture. This method is minimally invasive and effective for confirming the reduction, and it is advantageous for postoperative pain and early recovery after surgery.

CCDC102B confers risk of low vision and blindness in high myopia.

The incidence of high myopia is increasing worldwide with myopic maculopathy, a complication of myopia, often progressing to blindness. Our two-stage genome-wide association study of myopic maculopathy identifies a susceptibility locus at rs11873439 in an intron of CCDC102B (P = 1.77 × 10-12 and Pcorr = 1.61 × 10-10). In contrast, this SNP is not significantly associated with myopia itself. The association between rs11873439 and myopic maculopathy is further confirmed in 2317 highly myopic patients (P = 2.40 × 10-6 and Pcorr = 1.72 × 10-4). CCDC102B is strongly expressed in the retinal pigment epithelium and choroids, where atrophic changes initially occur in myopic maculopathy. The development of myopic maculopathy thus likely exhibits a unique background apart from the development of myopia itself; elucidation of the roles of CCDC102B in myopic maculopathy development may thus provide insights into preventive methods for blindness in patients with high myopia.

Ultrawide-Field OCT to Investigate Relationships between Myopic Macular Retinoschisis and Posterior Staphyloma.

PURPOSE: To investigate the relationships between myopic macular retinoschisis (MRS) and posterior staphylomas and to reveal the characteristics of other retinal lesions associated with MRS. DESIGN: Retrospective, observational case series. PARTICIPANTS: Seven hundred twenty-nine eyes of 420 patients with high myopia, which was defined as myopic refractive error of more than -8.0 diopters or an axial length longer than 26.5 mm. METHODS: Highly myopic eyes were examined by ultrawide-field (UWF) swept-source (SS) OCT with scan width of up to 23 mm and scan depth of 5 mm. The OCT features of MRS and posterior staphylomas and their spatial relationship were examined in UWF SS OCT images. MAIN OUTCOME MEASURES: Associations between MRS and staphylomas. RESULTS: In 729 eyes with mean axial length of 30.2±2.1 mm, posterior staphyloma was detected in 482 eyes (66.1%) and MRS was detected in 136 eyes (18.7%). All 136 eyes with an MRS showed outer retinoschisis, and 40 eyes (29.4%) also showed inner retinoschisis. Posterior staphyloma was detected significantly more frequently in eyes with MRS (117/136 [86.0%]) than in eyes without MRS (365/593 [61.6%]; P < 0.001). In all eyes with both staphyloma and outer retinoschisis, the area of the outer retinoschisis was restricted to the area within the staphyloma. In 1 of the 19 eyes with outer retinoschisis but without staphyloma, the outer retinoschisis extended beyond the range of the scanned fundus area. Among the 40 eyes with inner retinoschisis, the inner retinoschisis was located within the region of the outer retinoschisis in 39 eyes (97.5%). In all eyes with inner retinoschisis, retinal lesions causing an inward-directed tractional force were found within the area of the inner retinoschisis. CONCLUSIONS: In highly myopic eyes, the sites of the MRS and staphylomas were spatially related to each other. Posterior-directed force in association with staphylomas, and an inward-directed force resulting from epiretinal membranes or vitreoretinal attachments, may act as causative factors for MRS. However, the exact mechanisms related to the development of an MRS are probably diverse and complex.

TAFRO syndrome successfully treated with tocilizumab: A case report and systematic review.

Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome is considered as a unique clinicopathologic variant of multicentric Castleman's disease and is recently reported in Japan. This entity represents a severe inflammatory state leading to organ failures such as severe liver dysfunction seen in our case, and can be treated by immunosuppressive agents, steroids, and cyclosporine shown in several case reports. A systematic review and our case suggest the potential utility of tocilizumab as a treatment for TAFRO syndrome.

Incidence and risk factors of acute kidney injury in the Japanese trauma population: A prospective cohort study.

INTRODUCTION: Previous studies have reported the prevalence and risk factors of acute kidney injury (AKI) in relatively young trauma patients. The aims of this study were to identify the prevalence and risk factors of AKI among older Japanese trauma patients. METHODS: We conducted a prospective observational study in the 8-bed intensive care unit (ICU) of a Japanese tertiary-care hospital. Participants comprised trauma patients aged 18 years or older admitted to the ICU. Our primary outcome was the incidence of AKI within 10days of admission, according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: Among 333 patients, 66 (19.8%) developed AKI (Stage 1, n=54; Stages 2, n=5; and Stage 3, n=7). Multivariate logistic regression analysis revealed that the incidence of AKI was associated with increased age (odds ratio (OR), 1.38; 95% confidence interval (CI), 1.15-1.65), male sex (OR, 2.06; 95%CI, 1.04-4.07), greater amount of red blood cell transfusions (OR, 1.61; 95%CI, 1.04-1.17), and presence of underlying chronic kidney disease (CKD) (OR, 3.97; 95%CI, 1.78-8.83). Length of stay in the ICU was significantly longer in patients with AKI (6days) than in those without (3days; p<0.001). Patients ≥65 years old were more likely to develop AKI (26.2% vs 11.6%; p<0.001). No significant differences in ICU stay (median, 4 vs 4days; p=0.70), hospital stay (median, 24 vs 21days; p=0.45), or 28-day mortality (2.1% vs 1.4%; p=0.19) were evident between age groups. CONCLUSIONS: Approximately 20% of trauma patients developed AKI, and the elderly were more likely to develop AKI. Older age, male, greater units of red blood cell transfusions, and underlying CKD were associated with incidence of AKI.

Posterior Staphylomas in Pathologic Myopia Imaged by Widefield Optical Coherence Tomography.

Purpose: To examine posterior staphylomas by widefield optical coherence tomography (WF-OCT) and three-dimensional magnetic resonance imaging (3D-MRI). Methods: Highly myopic patients (myopic refractive error >8.0 diopters or axial length >26.5 mm) who had previously undergone orbital 3D-MRI were examined by WF-OCT. Results: The study included 100 eyes of 57 patients with a mean age of 67.9 ± 10.7 years (range, 44-85 years) and mean axial length of 30.0 ± 2.3 mm (range, 25.1-36.5 mm). All staphylomas detected on the 3D-MRI, except for two very large staphylomas, were visualized on the WF-OCT images. Morphologic hallmarks of the staphylomas were smoothly configured staphyloma border with a gradual thinning of the choroid and an inward protrusion of the sclera at the staphyloma edge. Comparing the detectability of the staphylomas on the WF-OCT images versus 3D-MRI revealed no significant difference between both techniques (P = 0.12; χ2 test). Comparing the staphyloma classification between both techniques showed a good concordance with a concordance index kappa of 0.61 (95% confidence interval: 0.50-0.72). A spatial relationship between the staphylomatous areas and the macula and optic nerve head was observed by WF-OCT. Conclusions: WF-OCT can provide tomographic images of posterior staphylomas in a resolution and size unachievable so far, and may replace 3D-MRI in assessing posterior staphylomas. Future studies using WF-OCT may explore the detailed morphologic characteristics of posterior staphylomas and give clues to the etiology of staphylomas.