A case of non-traumatic rectus sheath hematoma in a post-kidney transplant patient undergoing catheter embolization during anticoagulation treatment for atrial fibrillation.

A 65-year-old man, a post living donor kidney transplant patient, was admitted to the intensive care unit (ICU) with a severe bacterial infection. He also tested positive for coronavirus disease and had a cough. On admission, heparin was administered for atrial fibrillation. On the third day of hospitalization, his general condition had recovered, and he was discharged from the ICU to the general ward. On the fourth day of hospitalization, he experienced abdominal pain, and a hard mass was palpated in the left lower abdomen. On the fifth day of hospitalization, contrast-enhanced computed tomography showed an extensive rectus sheath hematoma (RSH) extending from the left lower abdominal wall to the left side of the bladder, with extravasation from a small branch of the left inferior epigastric artery. Heparin was discontinued, and transcatheter arterial embolization was performed to control the bleeding. RSH is a rare disease, and cases of extensive hematoma in post-kidney transplant patients occur even less frequently. Patients taking anticoagulants and those with chronic kidney disease are at high risk for RSH, so physicians should be cognizant of this disease when these patients develop abdominal pain.

The incidence and influencing factors of in-hospital frailty progression following transcatheter aortic valve implantation.

Objective Patients undergoing transcatheter aortic valve implantation (TAVI) are generally older and frailty is therefore an important clinical issue. The baseline degree of frailty is associated with the prognosis in patients undergoing TAVI; however, the incidence of in-hospital frailty progression and its influencing factors have not yet been elucidated. Methods This observational, single-center study retrospectively evaluated 281 patients who underwent TAVI. The degree of frailty at baseline and discharge was evaluated using the Clinical Frailty Scale (CFS). In-hospital frailty progression was defined as an increase of at least one level in the CFS score at discharge from baseline, and predictors of frailty progression were assessed. Results The median baseline CFS score was 4.0 (interquartile range: 3.0-4.0). In-hospital frailty progression was observed in 49 patients (17.4%). No significant differences were observed in age, sex, comorbidities, or surgical risk scores between patients with and without frailty progression. Patients with frailty progression experienced stroke more frequently during hospitalization than those without (12.2% vs. 1.3%, p = 0.001). A multivariable logistic analysis showed that in-hospital stroke was a significant predictor of frailty progression (odds ratio, 10.7; 95% confidence interval: 2.34-49.2, p = 0.002). Patients with frailty progression had a longer hospital stay than those without frailty progression [7.0 (4.0-17.0) vs. 4.0 (4.0-8.0) days, p = 0.001]. Conclusions In-hospital frailty progression was not uncommon in patients undergoing TAVI. Stroke incidence was a significant influencing factor in frailty progression, whereas baseline comorbidities and surgical risks were not.

Feasibility and efficacy of real-time ultrasound-guided venous closure with suture-mediated vascular closure device.

BACKGROUND: Venous vascular access complications are usually nonfatal but are the most common complications after transvenous catheter intervention. Vascular closure devices (VCDs) have recently become available for venous closure. OBJECTIVE: This study aimed to evaluate the feasibility and efficacy of real-time ultrasound-guided venous closure with suture-mediated VCDs in patients who underwent catheter ablation. METHODS: This single-center observational study enrolled 226 consecutive patients who underwent elective catheter ablation with femoral venipuncture. For hemostasis, vessel closure by VCD was performed with real-time ultrasound guidance after 2022 (n = 123) and without ultrasound guidance in 2021 (n = 103). The occurrence of venous access site-related complications (major, minor, or other) was compared. RESULTS: The rate of device failure was significantly lower in patients with ultrasound guidance than in those without (1.6% vs 6.3%; P = .048). The occurrence of all venous access site-related complications was significantly lower in patients with ultrasound guidance than in those without (4.9% vs 18.4%; P = .001). Time to ambulation was shorter in patients with ultrasound guidance than in those without (2.0 ± 0.1 hours vs 2.2 ± 0.6 hours; P < .001). CONCLUSION: Real-time ultrasound guidance can reduce device failure, access site-related complications, and time to ambulation in performing venous closure with a VCD.

Predictability of noninvasive liver fibrosis score for cardiac events in patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. However, although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events. METHODS AND RESULTS: We evaluated 4071 patients with NAFLD diagnosed using ultrasonography. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index and NAFLD fibrosis score (NFS). The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease. The median age of the evaluated patients was 61 (52-69) years, and 2201 (54.1%) were male. During the median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan-Meier survival analysis demonstrated that MACE increased progressively with the FIB4 index (log-rank, p < 0.001) and NFS (log-rank, p < 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (low group as reference vs. intermediate group, hazard ratio [HR]: 1.860 [95% confidence interval (CI), 1.326-2.610; p < 0.001]; vs. high group, HR:3.325 [95% CI, 2.017-5.479; p < 0.001]), as well as NFS (low NFS group as reference vs. intermediate group, HR: 1.938 [95% CI, 1.391-2.699; p < 0.001]; vs. high group, HR: 3.492 [95% CI, 1.997-6.105; p < 0.001]). CONCLUSIONS: The FIB4 index and NFS are associated with the probability of MACE in patients with NAFLD. CLINICAL TRIALS: The study design was approved by the ethics review board of Ogaki Municipal Hospital (approval number: 20221124-12, registration date: November 28th, 2022). https://www.ogaki-mh.jp/chiken/kenkyu.html.

Trends of Early Helicobacter pylori-Uninfected Gastric Cancer in an Aging Regional Area.

Background/Objectives: We aimed to determine the trends over time and current status of early Helicobacter pylori-uninfected gastric cancer (HpUIGC) treatment in a region with an aging population. Methods: This retrospective, multi-center observational study was conducted at seven major general hospitals in Kagoshima Prefecture. From January 2009 to July 2022, 2091 patients who received endoscopic resection (ER) for early gastric cancer (EGC) were retrospectively enrolled, of which 35 were identified as early HpUIGC cases. Results: The number of ERs for EGC demonstrated a significant increasing trend from 2010 to 2021 (p = 0.01 for trend). Furthermore, the 12-year period from 2010 to 2021 was divided into an early and late phase every 6 years. In the early phase, there were 5 cases (0.7%) of early HpUIGC, while in the late phase, there were 25 cases (2.1%), indicating a significant increase in the proportion of ERs for early HpUIGC cases in the late phase (p = 0.02). Conclusions: The proportion of ERs for early HpUIGC, which are more common in relatively young patients, may be increasing as a proportion of all ERs for GC, even in areas of Japan with an aging population.

Detecting and exploring kidney-derived extracellular vesicles in plasma.

BACKGROUND: Extracellular vesicles (EVs) have received considerable attention as ideal biomarkers for kidney diseases. Most reports have focused on urinary EVs, that are mainly derived from the cells in the urinary tract. However, the detection and the application of kidney-derived EVs in plasma remains uncertain. METHODS: We examined the kidney-derived small EVs (sEVs) in plasma that were supposedly released from renal mesangial and glomerular endothelial cells, using clinical samples from healthy controls and patients with kidney transplants. Plasma from healthy controls underwent ultracentrifugation, followed by on-bead flow cytometry, targeting α8 integrin, an antigen-specific to mesangial cells. To confirm the presence of kidney-derived sEVs in peripheral blood, plasma from ABO-incompatible kidney transplant recipients was ultracentrifuged, followed by western blotting for donor blood type antigens. RESULTS: Immunohistochemistry and immunoelectron microscopy confirmed α8 integrin expression in kidney mesangial cells and their sEVs. The CD9-α8 integrin double-positive sEVs were successfully detected using on-bead flow cytometry. Western blot analysis further revealed transplanted kidney-derived sEVs containing blood type B antigens in non-blood type B recipients, who had received kidneys from blood type B donors. Notably, a patient experiencing graft kidney loss exhibited diminished signals of sEVs containing donor blood type antigens. CONCLUSION: Our findings demonstrate the potential usefulness of kidney-derived sEVs in plasma in future research for kidney diseases.

Clinical Impacts of Urinary Neutrophil Gelatinase-Associated Lipocalin in Patients With Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Chronic kidney disease (CKD) is associated with poor prognosis in patients undergoing percutaneous coronary intervention (PCI). Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker for renal injury. However, the association between urinary NGAL concentrations and renal and cardiovascular events in patients with CKD undergoing PCI has not been elucidated. This study investigated the clinical impact of urinary NGAL concentrations on renal and cardiovascular outcomes in patients with non-dialysis CKD undergoing PCI.Methods and Results: We enrolled 124 patients with non-dialysis CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) undergoing elective PCI. Patients were divided into low and high NGAL groups based on the median urinary NGAL concentration measured the day before PCI. Patients were monitored for renal and cardiovascular events during the 2-year follow-up period. Kaplan-Meier analyses showed that the incidence of renal and cardiovascular events was higher in the high than low NGAL group (log-rank P<0.001 and P=0.032, respectively). Multivariate Cox proportional hazards analyses revealed that urinary NGAL was an independent risk factor for renal (hazard ratio [HR] 4.790; 95% confidence interval [CI] 1.537-14.924; P=0.007) and cardiovascular (HR 2.938; 95% CI 1.034-8.347; P=0.043) events. CONCLUSIONS: Urinary NGAL could be a novel and informative biomarker for predicting subsequent renal and cardiovascular events in patients with CKD undergoing elective PCI.

Mortality and hyperkalaemia-associated hospitalisation in patients with chronic kidney disease: comparison of sodium zirconium cyclosilicate and sodium/calcium polystyrene sulfonate.

Background: Sodium zirconium cyclosilicate (SZC), a novel drug used for treating hyperkalaemia, is effective in reducing serum potassium levels. The effects of potassium adsorbents on the mortality and hyperkalaemia-associated hospitalisation rates remain unclear. We aimed to examine how mortality and hyperkalaemia-associated hospitalisation rates vary with usage of various potassium adsorbents. Methods: This retrospective study used patients' data between April 2008 and August 2021 obtained from a large-scale Japanese medical claims database. Consecutive patients with chronic kidney disease (CKD) prescribed potassium adsorbents were enrolled and divided into three groups according to the adsorbent type [SZC, calcium polystyrene sulfonate (CPS), and sodium polystyrene sulfonate (SPS)] and were observed for 1 year. The primary outcome was a composite of mortality and hyperkalaemia-associated hospitalisation. Results: In total, 234, 54 183, and 18 692 patients were prescribed SZC, CPS, and SPS, respectively. The SZC group showed a higher event-free survival rate than the other two groups. The hazard ratio for the primary outcome in the CPS and SPS groups was similar in the analyses of the subgroups of patients who did not receive renal replacement therapy and those who received haemodialysis. The SZC group had a higher renin-angiotensin-aldosterone system inhibitors (RAASi) continuation rate compared to CPS and SPS groups, the difference being especially significant for SPS. Conclusions: This real-world study demonstrated the therapeutic effect of SZC in reducing mortality and hyperkalaemia-associated hospitalisations. The high RAASi continuation rate in the SZC group might be a contributing factor for improvement of the primary outcome.

Clinical features, future cardiac events, and prognostic factors following percutaneous coronary intervention in young female patients.

BACKGROUND: The proportion of young females among the patients who undergo percutaneous coronary intervention (PCI) is relatively small, and information on their clinical characteristics is limited. This study investigated the clinical characteristics and prognostic factors for future cardiac events in young females who underwent PCI. METHODS: This multicenter observational study included 187 consecutive female patients aged < 60 years who underwent PCI in seven hospitals. The primary composite endpoint was the incidence of cardiac death, nonfatal myocardial infarction, and target vessel revascularization. RESULTS: The mean patient age was 52.1 ± 6.1 years and 89 (47.6%) had diabetes, and renal dysfunction (an estimated glomerular filtration rate < 60 mL/min/1.73 m2) was observed in 38 (20.3%). During a median follow-up of 3.3 years, the primary endpoint occurred in 28 patients. The Cox proportional hazards models showed that renal dysfunction was an independent predictor for the primary endpoint (hazard ratio 3.04, 95% confidence interval 1.25-7.40, p = 0.01), as well as multivessel disease (hazard ratio 2.79, 95% confidence interval 1.12-6.93, p = 0.03). Patients with renal dysfunction had a significantly higher risk for the primary endpoint than those without renal dysfunction. CONCLUSIONS: Renal dysfunction was strongly associated with future cardiac events in young females who underwent PCI.

Changes in antibody titer after four and five doses of the SARS-CoV-2 vaccine in Japanese post-kidney transplant patients.

INTRODUCTION: Immunosuppressed patients exhibit low antibody acquisition rates following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Kidney transplant recipients previously exhibited low antibody acquisition rates after two vaccine doses, which increased after the third dose. We evaluated antibody titers of Japanese post-kidney transplant patients after the fourth and fifth vaccinations. METHODS: Antibody titers for SARS-CoV-2 spike protein were measured between 3 weeks and 3 months after the fourth or fifth vaccination. RESULTS: Increased antibody acquisition rates were observed after the fourth (75.0% antibody-positive) and fifth (81.5% antibody-positive) vaccinations. The antibody-acquired group after the fourth vaccination exhibited a higher body mass index and estimated glomerular filtration rate (eGFR) than the non-acquired group. A higher eGFR was associated with antibody acquisition after the fifth vaccination. CONCLUSION: In Japanese post-kidney transplant patients, the antibody acquisition rate increased with each vaccine additional dose. Additional vaccinations are recommended to protect against SARS-CoV-2 infection.

A case of late-onset organizing pneumonia following COVID-19 infection in a post-kidney transplant patient.

A 50-year-old man who had undergone a living-donor kidney transplant 12 years prior for chronic renal failure due to autosomal dominant polycystic kidney disease contracted coronavirus disease 19 (COVID-19). He had a positive antigen test, mild symptoms, sore throat, and fever of 37.9 â„ƒ. The patient was treated with molnupiravir for 5 days, and the symptoms disappeared 5 days after onset. However, 10 days after onset, he developed a fever of approximately 37 â„ƒ and a non-productive cough; 27 days after onset, the patient was hospitalized for anorexia and a worsening respiratory condition. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test results on admission were negative, and no antiviral medications were administered against SARS-CoV-2. Computed tomography revealed extensive ground-glass opacities in both lung fields. The patient was treated with steroid pulse therapy, ceftriaxone, atovaquone, azithromycin, and respiratory management using a high-flow nasal cannula. The combined therapies were successful, and the patient was managed with a nasal oxygen cannula after 3 days. Oxygen administration was discontinued after 6 days of hospitalization, and the patient was discharged after 14 days. Based on the laboratory findings, bacterial, interstitial, and Pneumocystis pneumonia were unlikely. The success of the steroid pulse therapy suggested that respiratory failure was caused by pneumonia due to the immune response after COVID-19 infection.

Establishment of an adverse effect prevention protocol on plasma exchange using fresh frozen plasma prior to ABO-incompatible living donor kidney transplantation at our hospital.

INTRODUCTION: Simple plasma exchange (PE) with fresh-frozen plasma replacement allows antibody removal for ABO-incompatible living donor kidney transplantation, but is associated with a high incidence of allergic reactions. We developed, implemented, and evaluated a protocol for safe preoperative PE. METHODS: The protocol comprised pretreatment (125 mg methylprednisolone infusion, 400 mg acetaminophen and 30 mg diphenhydramine orally) with a replacement fluid rate < 20 mL/min. Allergic reaction incidence was investigated in controls who underwent ABO-incompatible living donor kidney transplantation between 2016 and March 2020 (group C) and patients who underwent the protocol and procedure between April 2020 and February 2023 (group N). RESULTS: Ten (group C) and 19 (group N) patients performed 11 and 30 sessions of PE, respectively. Allergic reactions occurred in 81.8% and 36.7% (p = 0.014), respectively, with an odds ratio of the protocol was 0.056 (95% CI 0.0059-0.5380, P = 0.013). CONCLUSION: Our protocol resulted in a significantly lower incidence of allergic reactions.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits and atypical pathological findings treated with corticosteroid and rituximab.

A 16-year-old girl with fever that appeared after taking the second COVID-19 vaccine presented to the clinic with a serum creatinine of 0.89 mg/dL and C-reactive protein of 6.9 mg/dL. She had proteinuria and microscopic hematuria, with slowly worsening kidney function. Her kidney biopsy showed fibrocellular crescents in seven of nine glomeruli that were observed under light microscopy. Another glomerulus showed endocapillary hypercellularity and mesangial cell proliferation. Electron-dense deposits were significant in the mesangial area, with monoclonal IgG1-κ and C3 deposition by immunofluorescence. The patient was diagnosed with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and atypical pathological finding of diffuse crescent formation. The treatment regimen for PGNMID has not yet been established, and the appropriate duration of treatment is unknown. In our case, considering that rituximab acts by binding to CD20 on the surface of B cells through its crystallizable fragment, it was administered in addition to prednisolone, which successfully decreased the proteinuria over time.

Case Report: The leopard sign as a potential characteristic of chronic granulomatous disease-associated colitis, unrelated to colitis severity.

Background: Chronic granulomatous disease (CGD) is an inborn immune disorder in which the phagocytic system cannot eradicate pathogens, and autoinflammation occurs. Approximately half of the patients have associated gastrointestinal symptoms. Although most cases with CGD-associated colitis present nonspecific histology, colonoscopy in some cases shows brownish dots over a yellowish oedematous mucosa, which is termed a "leopard sign". However, the significance of these signs remains unclear. Methods: We collected data from patients with CGD whose colonoscopic findings showed the leopard sign. Results: Three patients with CGD and leopard signs were enrolled in this study. One patient underwent colonoscopy for frequent diarrhoea and weight gain failure, and another for anal fistula. The third patient was without gastrointestinal symptoms and underwent colonoscopy as a screening test before allogeneic haematopoietic cell transplantation (HCT). Endoscopic findings showed a mild leopard sign in the first case; however, non-contiguous and diffuse aphthae were observed throughout the colon. The other two cases were unremarkable except for the leopard sign. All the patients achieved remission with oral prednisolone or HCT. One patient underwent colonoscopy after HCT; results revealed improvements in endoscopy (including the leopard sign) and histological findings. However, another patient underwent colonoscopy after prednisolone treatment; this revealed no change in the leopard sign. Conclusion: The leopard sign in the colon may be a characteristic endoscopic finding of CGD, even in patients who do not develop severe gastrointestinal symptoms; however, it does not reflect the severity of CGD-associated colitis.

＜Editors' Choice＞ Mesenchymal stem/stromal cells generated from induced pluripotent stem cells are highly resistant to senescence.

The use of mesenchymal stem/stromal cells (MSCs) has attracted attention in the field of regenerative medicine based on their anti-inflammatory and tissue repair-promoting effects. Bone marrow is widely used as a source of MSCs; however, the performance of bone marrow (BM)-MSCs deteriorates as the cells age along with cell passaging. Recently, it has been reported that MSCs can be generated from induced pluripotent stem cells (iPSCs), which is expected to represent a new source of MSCs. However, few studies have investigated aging in iPSC-derived MSCs (iMSCs) and their functions. In this study, we investigated whether iMSCs overcome cellular senescence compared to that in BM-MSCs. Cellular senescence was quantitatively evaluated by staining iMSCs and BM-MSCs with fluorescein di-ß-D-galactopyranoside (FDG) and following flow cytometer analysis. The hepatocyte growth factor (HGF) concentration in the culture supernatant was also measured as a factor in the therapeutic efficacy of nephritis. The iMSCs did not reach their proliferation limit and their morphology did not change even after 10 passages. The FDG positivity of BM-MSCs increased with passaging, whereas that in iMSCs did not increase. The HGF concentration increased with passaging in iMSCs. In conclusion, our results suggest that iMSCs may be less susceptible to senescence than BM-MSCs and may be used in clinical applications.

Impact of proteinuria on long-term prognosis in patients with coronary artery disease.

BACKGROUND: This study aimed to investigate the association between proteinuria and long-term prognosis in patients with coronary artery disease. METHODS: This was a single-center observational study. A total of 1351 patients were identified who underwent percutaneous coronary intervention, and whose urine data were available. Patients were divided into two groups according to the presence (n = 245) or absence (n = 1106) of proteinuria. All-cause and cardiovascular deaths were primarily evaluated. RESULTS: The prevalence rates of hypertension and diabetes were significantly higher, and the baseline estimated glomerular filtration rate (eGFR) was lower in patients with proteinuria than in those without proteinuria. During the median follow-up of 4.1 years (interquartile range, 1.7-6.8 years), the occurrences of all-cause and cardiovascular deaths were significantly higher in patients with proteinuria. Multivariable Cox regression analysis indicated that the presence of proteinuria was a significant predictor of cardiovascular death as well as age, BMI, reduced eGFR, and left ventricular ejection fraction. When stratified into four groups based on eGFR category (eGFR <60 or ≥60 ml/min/1.73 m2) and absence or presence of proteinuria, the incidence rates of all-cause and cardiovascular deaths were highest in patients with proteinuria and eGFR less than 60 ml/min/1.73 m2. Furthermore, the incidence rates of all-cause and cardiovascular deaths were significantly higher in patients with proteinuria among both diabetic and nondiabetic patients. CONCLUSION: Proteinuria is associated with the long-term prognosis, and all-cause and cardiovascular deaths in patients with coronary artery disease, regardless of eGFR and the presence or absence of diabetes mellitus.

A successful case of an endoscopic submucosal dissection using a combination of the pocket-creation method and traction with a spring-and-loop with clip for early gastric cancer with severe ulcer scarring.

Video 1ESD for gastric cancer with severe scarring using PCM and S-O clip.

Effects of iron-based phosphate binders on mortality and cardiovascular events in patients receiving maintenance dialysis.

Phosphate binders are the main treatment for hyperphosphatemia in patients with chronic kidney disease, and iron-based phosphate binders have been used with increasing frequency in recent years. This study examined the association of the use of iron-based, rather than non-iron-based, phosphate binders with the incidence of cardiovascular events, in a real-world setting. We used data from a cohort comprising representative adult patients on maintenance hemodialysis in Japan. The exposure of interest was the time-varying use of phosphate binders, classified into "iron-based", "only non-iron-based", and "no use". The primary outcome was a composite of cardiovascular events and all-cause deaths. A marginal structural Cox regression model was used to deal with possible time-dependent confounding. Of the 2247 patients from 58 hemodialysis facilities, iron-based and only non-iron-based phosphate binders were used in 328 (15%) and 1360 (61%), respectively, at baseline. Hazard ratios (95% confidence intervals) for iron-based and non-iron-based phosphate binders versus no use of phosphate binders were 0.35 (0.24, 0.52) and 0.44 (0.33, 0.58), respectively. The hazard ratio for iron-based relative to non-iron-based phosphate binders was 0.81 (0.58, 1.13), which was not statistically significant. Further studies are warranted to elucidate whether the use of iron-based phosphate binders reduces the event rate.