Investigation of the Effect of Therapeutic Plasma Exchange for TAFRO Syndrome: A Pilot Study.

TAFRO syndrome is a rare systemic inflammatory disorder with a fatal course. Nevertheless, a definitive treatment strategy has not yet been established. Anti-inflammatory therapies, including glucocorticoid treatment and immunosuppressants, have not been satisfactory. Therefore, new treatment options are needed for patients with TAFRO syndrome. The effectiveness of therapeutic plasma exchange (TPE) has mainly been reported in several case reports. In this case series study, we investigated the effect of TPE on TAFRO syndrome. We reviewed six consecutive cases with TAFRO syndrome treated at Shinshu University Hospital. All of them underwent TPE. A significant improvement in mean blood pressure, albumin, total bilirubin, and C-reactive protein was observed after TPE. Furthermore, early TPE treatment was suggested to have an impact on the prognosis. More intensive studies are needed to emphasize the overall conclusion obtained that TPE can be an effective/acceptable treatment option for TAFRO syndrome.

Outcomes of critically ill patients with liver failure who require mechanical ventilation: A retrospective, single-center study.

Background and Aims: Critically ill patients with liver failure have high mortality. Besides the management of organ-specific complications, liver transplantation constitutes a definitive treatment. However, clinicians may hesitate to introduce mechanical ventilation for patients on liver transplantation waitlists because of poor prognosis. This study investigated the outcomes of intensive care and ventilation support therapy effects in patients with liver failure. Methods: This single-center study retrospectively enrolled 32 consecutive patients with liver failure who were admitted to the intensive care unit from January 2014 to December 2020. The medical records were reviewed and analyzed retrospectively for Acute Physiologic and Chronic Health Evaluation (APACHE)-II. The model for end-stage liver disease scores, 90-day mortality, and survival was assessed using the Kaplan-Meier method. Results: The average patient age was 45.5 ± 20.1 years, and 53% of patients were women. On intensive care unit admission, APACHE-II and model for end-stage liver disease scores were 20 and 28, respectively. Among 13 patients considered for liver transplantation, 4 received transplants. Thirteen patients (40.6%) were intubated and mechanically ventilated in the intensive care unit. The 90-day mortality rate of patients with and without mechanical ventilation in the intensive care unit (13, 61.5% vs. 19, 47.4%, p = 0.4905) was similar. APACHE-II score >21 was an independent predictor of mechanical ventilation requirement in patients with liver failure during intensive care unit stay. Conclusion: Although critically ill patients with liver failure are at risk of multiorgan failure with poor outcomes, mechanical ventilation did not negatively affect the 90-day mortality or performance rates of liver transplantation. Clinicians should consider mechanical ventilation-based life support in critically ill patients with liver failure who are awaiting liver transplantation.

Anti-SARS-CoV-2 IgG antibody titer after BNT162b2 mRNA COVID-19 vaccination in Japanese patients who underwent renal replacement therapy, hemodialysis, peritoneal dialysis, and kidney transplantation.

BACKGROUND: Coronavirus disease (COVID-19) vaccination is recommended for patients undergoing renal replacement therapy (RRT), including hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KT). However, the difference in the immune response between RRT patients and healthy individuals after mRNA vaccines remains uncertain. METHODS: This retrospective observational study evaluated the anti-severe-acute-respiratory-syndrome-coronavirus-2 (anti-SARS-CoV-2) IgG antibody acquisition, titers and their changes, normal response rate (reaching titers of healthy individuals), factors associated with a normal response, and effectiveness of booster vaccination in Japanese RRT patients. RESULTS: Most HD and PD patients acquired anti-SARS-CoV-2 IgG antibodies after the second vaccination; however, their antibody titers and normal response rates (62-75%) were low compared with those of healthy subjects. Approximately 62% of KT recipients acquired antibodies, but the normal response rate was low (23%). Anti-SARS-CoV-2 IgG antibody waning occurred in the control, HD, and PD groups, while negative or very low titers remained in KT recipients. Third booster vaccination was effective in most HD and PD patients. However, the effect was mild in KT recipients - only 58% reached a normal response level. Multivariate logistic regression analyses demonstrated that younger age, higher serum albumin level, and RRT other than KT were significantly associated with a normal response after the second vaccination. CONCLUSIONS: RRT patients, particularly KT recipients, exhibited poor vaccine responses. Booster vaccination would be beneficial for HD and PD patients; however, its effect in KT recipients was mild. Further COVID-19 vaccinations using the latest vaccine or alternative procedures should be considered in RRT patients.

Predictive Factors of Cytomegalovirus Viremia during the Clinical Course of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: A Single Center Observational Study.

We aim to elucidate factors to aid in the prediction of cytomegalovirus viremia during the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We conducted a single-center, retrospective, observational study of 35 patients with newly diagnosed AAV. Factors associated with the development of CMV viremia were investigated via a logistic regression analysis. The CMV antigenemia test was performed in 25 patients (71%), of whom 15 (60%) were diagnosed with CMV viremia. Of these 15 patients, 5 developed a CMV infection. The total protein, hemoglobin, platelet count and lymphocyte counts at the time of the CMV antigenemia test were significantly lower in patients who developed CMV viremia. In addition, total protein, hemoglobin, platelet count and lymphocyte count also presented significantly decreasing trends in the following order: patients who did not develop CMV viremia, patients who developed CMV viremia without any symptoms, and patients who developed CMV infection. All patients with CMV recovered. In conclusion, the total protein, hemoglobin, platelet count and lymphocyte count may be useful markers for the prediction of CMV viremia and infection after the start of induction of immunosuppressive therapy for patients with AAV.

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Developing Pancreatic Lesion and Diabetes Mellitus: A Case Report and Review of the Literature.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) affects small blood vessels and causes severe systemic organ injury commonly affecting the lungs and kidney. However, gastrointestinal, especially pancreatic, lesions are rare. We report the case of a 67-year-old Japanese man diagnosed with myeloperoxidase (MPO) AAV who developed pancreatic lesions and diabetes mellitus. The patient was admitted to our hospital due to fever, cough, and weight loss. He developed progressive glomerulonephritis, lung nodules, and pancreatic swelling and mass. Additionally, laboratory examination revealed positive MPO-ANCA and elevated glycated hemoglobin A1c, which were suggestive of diabetes mellitus. Renal biopsy revealed necrotizing crescentic glomerulonephritis and vasculitis in the small arteries. Endoscopic ultrasound-guided fine needle aspiration of the pancreas was performed, and histological findings suggested the possibility of pancreatic vasculitis and parenchymal injury. The patient was diagnosed with AAV, which was managed with glucocorticoids. This improved the renal function and pancreatic lesions. Furthermore, blood glucose levels improved despite treatment with glucocorticoids. These findings suggest that AAV-related pancreatic lesions worsened glycemic control. However, glucocorticoid therapy improved vasculitis and pancreatic lesions, which resulted in improved glycemic control.

Relationship between glomerular number in fresh kidney biopsy samples and light microscopy samples.

BACKGROUND: On-site evaluation of fresh kidney biopsy (FKB) samples at the time of biopsy is useful to verify that adequate specimens are acquired. However, some cases present poor correlation between glomerular number in FKB samples and light microscopy (LM) samples. We examined the usefulness of such on-site evaluation. METHODS: We conducted a retrospective cross-sectional observational study (n = 129) to assess the correlation between glomerular number in FKB samples and LM samples and the associated factors hindering the evaluation. RESULTS: There was a significant positive correlation between glomerular number in FKB samples and LM samples. The median ratio of glomerular number (LM samples/FKB samples) was 0.74. According to this ratio, cases were divided into three groups: reasonable estimation (65 cases), underestimation (32 cases), and overestimation (32 cases). Comparing the reasonable and underestimation groups, significant differences were detected in the extent of interstitial fibrosis and tubular atrophy (IFTA) and interstitial inflammation. Logistic regression analysis demonstrated that IFTA and interstitial inflammation were significantly associated with the underestimation. Moreover, the cortex length of FKB samples correlated with glomerular number in LM samples regardless of tubulointerstitial lesions. CONCLUSIONS: Glomerular number determined during on-site evaluation can be a reference for the actual number of glomeruli in LM samples. Since tubulointerstitial lesions make it difficult to recognize glomeruli in FKB samples, the possibility of underestimation for cases with possibly severe tubulointerstitial lesions should be considered. In such cases, evaluation of cortex length of FKB samples may substitute for evaluating glomeruli on-site.

Serum Sulfatide Levels as a Biomarker of Active Glomerular Lesion in Patients with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single Center Pilot Study.

Sulfatides are glycosphingolipids that are associated with coagulation and platelet aggregation. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) activates platelet function and often leads to thrombotic complications. These facts suggest an association between serum sulfatides and AAV. We aimed to clarify the significance of serum sulfatide levels in patients with AAV. We conducted a retrospective, single-center, observational pilot study that included 35 patients who developed AAV and 10 control patients who were candidates for living-donor kidney transplantation. We compared serum sulfatide levels between the control and AAV patients. We analyzed the differences in serum sulfatide levels among four classes (focal, crescentic, mixed, and sclerotic class) of glomerular lesions that were categorized by histopathologic classification of ANCA-associated glomerulonephritis. Serum sulfatide levels in patients with AAV were significantly lower than those in the controls. Serum sulfatide levels were significantly different between the four classes. Additionally, serum sulfatide levels in the crescentic class were significantly lower than those in the other classes. Serum sulfatide levels were significantly correlated with albumin, cholesterol, C-reactive protein, and pentraxin 3. In conclusion, serum sulfatide levels are significantly correlated with inflammation, reflecting crescentic glomerulonephritis, which is an active glomerular lesion in AAV patients.

Comparison of the factors associated with the short-term prognosis between elderly and non-elderly patients with anti-neutrophil cytoplasmic antibody-associated vasculitis: a retrospective observational study.

OBJECTIVES: The difference in factors associated with the prognosis between elderly and non-elderly patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is uncertain. We aimed to elucidate the clinical factors associated with the short-term prognosis (within 6 months from the start of the treatment) and investigate the differences in the associated factors between elderly and non-elderly individuals. METHODS: We performed a dual centre retrospective observational study of patients newly treated with AAV (eosinophilic granulomatous with polyangiitis was excluded). The primary outcome was all-cause death, and the secondary outcome was end-stage renal disease (ESRD) and infectious complications within 6 months after the start of treatment. We analysed factors associated with these outcomes using logistic regression analyses. RESULTS: Of the 79 patients, patients aged ≥75 years were defined as elderly (n=41), whereas those aged <75 years were de¬fined as non-elderly (n=38). In elderly patients, age was significantly associated with all-cause mortality. In the non-elderly patients, the geriatric nutritional risk index was significantly associated with all-cause death. The estimated glomerular filtration rate (eGFR) before the start of treatment was significantly associated with ESRD in elderly and non-elderly patients. In elderly patients, the Birmingham vasculitis score 3, eGFR, methylprednisolone pulse use, and cyclophosphamide use were significantly associated with infectious complications. Factors other than the serum albumin level were not significantly associated with infectious complications in the non-elderly population. CONCLUSIONS: The factors associated with all-cause death and infectious complications differed between elderly and non-elderly patients. Awareness of these differences may contribute to better management of AAV.

A Case of Acute Kidney Injury in a Patient with Renal Hypouricemia without Intense Exercise.

Exercise-induced acute kidney injury (EIAKI) frequently develops in patients with renal hypouricemia (RHUC). However, several cases of RHUC with acute kidney injury (AKI) but without intense exercise have been reported. We encountered a 15-year-old male with RHUC who experienced AKI. He reported no episodes of intense exercise and displayed no other representative risk factors of EIAKI, although a vasopressor had been administered for orthostatic dysregulation before AKI onset. His kidney dysfunction improved with discontinuation of the vasopressor and conservative treatment. Thus, AKI can develop in patients with RHUC in the absence of intense exercise, for which vasopressors may be a risk factor.

Thrombotic Thrombocytopenic Purpura Treated with Rituximab Associated with Primary Sjögren's Syndrome and Primary Hypothyroidism.

A 47-year-old man was admitted to our hospital because of thrombocytopenia and consciousness disturbance. As his laboratory data showed undetectable activity of a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) and the presence of ADAMTS13 inhibitor, he was diagnosed with acquired thrombotic thrombocytopenic purpura (TTP). Asymptomatic primary Sjögren's syndrome (SS) and primary hypothyroidism were incidentally diagnosed on screening. After initial plasma exchange therapy and pulse corticosteroid therapy, the patient received rituximab therapy for refractory TTP with "inhibitor boosting" and recovered. TTP secondary to primary SS is rare but can trigger refractory TTP. Treatment with rituximab, which is considered "inhibitor boosting," should be considered when re-exacerbation occurs.

Verification of serum albumin elevating effect of cell-free and concentrated ascites reinfusion therapy for ascites patients: a retrospective controlled cohort study.

Cell-free and concentrated ascites reinfusion therapy (CART) is frequently used to treat refractory ascites in Japan. However, its efficacy remains unclear. This controlled cohort study verified the serum albumin elevating effect of CART by comparisons with simple paracentesis. Ascites patients receiving CART (N = 88) or paracentesis (N = 108) at our hospital were assessed for the primary outcome of change in serum albumin level within 3 days before and after treatment. A significantly larger volume of ascites was drained in the CART group. The change in serum albumin level was +0.08 ± 0.25 g/dL in the CART group and -0.10 ± 0.30 g/dL in the paracentesis group (P < 0.001). The CART - paracentesis difference was +0.26 g/dL (95%CI +0.18 to +0.33, P < 0.001) after adjusting for potential confounders by multivariate analysis. The adjusted difference increased with drainage volume. In the CART group, serum total protein, dietary intake, and urine volume were significantly increased, while hemoglobin and body weight was significantly decreased, versus paracentesis. More frequent adverse events, particularly fever, were recorded for CART, although the period until re-drainage was significantly longer. This study is the first demonstrating that CART can significantly increase serum albumin level as compared with simple paracentesis. CART represents a useful strategy to manage patients requiring ascites drainage.

Influence of arteriovenous fistula on daily living behaviors involving the upper limbs in hemodialysis patients: a cross-sectional questionnaire study.

BACKGROUND: Arteriovenous fistulae can restrict daily living behaviors involving the upper limbs in hemodialysis patients, but no studies have investigated the detailed effects of an arteriovenous fistula on routine life activities. Accordingly, many medical caregivers are unable to explain the effects of an arteriovenous fistula on daily life, particularly during non-dialysis periods, because they cannot observe them directly. METHODS: Thirty outpatients undergoing hemodialysis at 2 facilities scored the difficulty due to an arteriovenous fistula in performing 48 living behaviors during non-dialysis and 10 behaviors during dialysis into 5 grades in a comprehensive questionnaire survey. These behaviors were selected based on an open-answer pre-questionnaire administered to the 30 patients beforehand. The scores were also compared between dominant arm and non-dominant arm arteriovenous fistula groups. RESULTS: During non-dialysis, the difficulty scores of behaviors restricted out of concern for arteriovenous fistula obstruction (wear a wristwatch, hang a bag on the arm, carry a baby or a dog in the arms, wear a short-sleeved shirt, etc.) increased. The difficulties of "wear a wristwatch" and "hang a bag on the arm" were significantly higher in the non-dominant arm arteriovenous fistula group (both P < 0.05). In contrast, scores related to motor function (write, eat or drink, scratch an itch, etc.) increased remarkably during dialysis because of connection of the arteriovenous fistula to the dialysis machine. The difficulties of "write" and "eat or drink" were significantly higher in the dominant arm arteriovenous fistula group (both P < 0.05). CONCLUSIONS: Several key daily living behaviors restricted by an arteriovenous fistula were identified in this questionnaire survey. These results will be useful for pre-operative explanation of arteriovenous fistula surgery and arm selection in end-stage renal disease patients.

Protein Concentration of Refractory Ascites in Cancer Patients is Reflected by the Presence and Severity of Peritoneal and Liver Metastasis.

Ascites total protein concentration (A-TP) affects the performance of cell-free and concentrated ascites reinfusion therapy (CART). As the factors determining A-TP remain unclear, we examined peritoneal and liver metastasis. Among 98 patients who received CART, 68 with cancer, ascites from no other apparent cause, and complete CT and A-TP data were recruited. Sixty-six patients (97%) with peritoneal and/or liver metastasis on CT were divided into the peritoneal metastasis group (PM group), peritoneal and liver metastasis group (PM + LM group), and liver metastasis group (LM group). A-TP was highest in the PM group (3.9 g/dL [3.4-4.4]), lowest in the LM group (1.0 g/dL [0.9-2.0]), and broadly dispersed in the PM + LM group (3.3 g/dL [2.0-3.8]). All differences were statistically significant. The percentage of metastasis volume occupying the liver was negatively and significantly related to A-TP in the PM + LM group. Taken together, the presence and severity of peritoneal and liver metastasis may influence A-TP.