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Abstract Background Empirical antibiotic treatment against peritoneal dialysis (PD)-related peritonitis should be immediately initiated before PD effluent culture results are obtained. As culture results guide the choice of antibiotics, culture-negative peritonitis (CNP) is a serious issue. In addition, the identification of the causative organism often indicates a possible source of infection. This study aimed to clarify the predictors of CNP. Methods This single-center, retrospective study was conducted from November 2007–December 2018 in patients undergoing PD with peritonitis at our institution, where 204 peritonitis episodes (57 culture-negative, 147 culture-positive) were investigated based on demographics, and clinical parameters. CNP predictors were investigated using logistic regression. Results CNP rate was significantly higher in female and in patients with higher platelet counts, lower dialysate cell counts at peritonitis diagnosis, and higher serum β2-microglobulin levels. In multivariate logistic regression, female sex (odds ratio [OR] 2.69, 95% confidence interval [CI] 1.31–5.54), dialysate cell count at diagnosis (OR0.99, 95% CI 0.99–0.99), and serum β2-microglobulin level (OR 1.04, 95% CI 1.00–1.07) were significantly associated with CNP. The areas under the receiver operating characteristic curve for female patients, dialysate cell counts at diagnosis of peritonitis, serum β2-microglobulin level, and female patients + dialysate cell counts at diagnosis of peritonitis + serum β2-microglobulin level were 0.604, 0.694, 0.603, and 0.751, respectively. Conclusions Female sex, dialysate cell counts at peritonitis diagnosis, and serum β2-microglobulin levels may be predictors of CNP.

Introduction: It remains controversial whether it is better to continue oral low-dose aspirin (LDA) during the perioperative period in spinal surgery. This study aims to evaluate the safety of continued LDA administration in the perioperative periods of microendoscopic laminectomy (MEL) by assessing perioperative complications and clinical outcomes. Methods: We ultimately included 88 patients (35 males, 53 females) who underwent one level of MEL for lumbar spinal canal stenosis from April 2016 to March 2022. Patients who did not undergo anticoagulation therapy were classified into Group A (65 patients), those who stopped anticoagulation therapy at the perioperative periods were classified into Group B (9 patients), and those who continued oral administration of LDA throughout the perioperative periods were classified into Group C (14 patients). Surgery time, intraoperative estimate blood loss (EBL), differences between hemoglobin (Hb) and platelet (Plt) before and after surgery, perioperative complications, and cross-sectional area of hematoma and dural sac on MRI taken within 1 week and at 6 months or more after surgery were assessed between three groups. The EuroQol-5 dimensions (EQ-5D), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were also evaluated as the clinical outcomes. Results: There was no statistically significant difference between the three groups in operation time, intraoperative EBL, differences between Hb and Plt before and after surgery, and cross-sectional area of hematoma and dural sac on MRI. A case of hematoma removal was confirmed in Group A. There was also no statistically significant difference between the three groups in EQ-5D, ODI, and each domain of JOABPEQ. Conclusions: The continuation of LDA throughout the perioperative periods did not affect perioperative complications and clinical outcomes of one-level MEL. In MEL, it might be possible to continue oral administration of LDA throughout the perioperative periods.

Abstract Background Stenotrophomonas maltophilia (S. maltophilia) is being increasingly recognized as an important cause of nosocomial infections, particularly in immunocompromised patients, such as patients undergoing dialysis. S. maltophilia peritonitis is strongly associated with the loss of peritoneal catheter among patients undergoing peritoneal dialysis (PD) owing to its resistance to different groups of antibiotics. Thus, the aim of this study was to investigate the characteristics of and risk factors for S. maltophilia peritonitis in patients undergoing PD. Methods This single-center, retrospective, case–control study was conducted between April 2013 and October 2022. Patients who were undergoing PD at Kawashima Hospital and were diagnosed with S. maltophilia peritonitis were included in this study. Controls were randomly selected from among patients who were undergoing PD and were diagnosed with peritonitis caused by microorganisms other than S. maltophilia. The demographic data, clinical characteristics, and initial treatment data of the patients were analyzed to determine the risk factors for PD-related S. maltophilia peritonitis. Results Five patients with S. maltophilia peritonitis and 15 controls (three controls to one case) were included in this study. The incidence of S. maltophilia peritonitis was significantly more frequent among patients with diabetes mellitus (80.0% vs. 20.0%; p = 0.031) and among patients with higher white blood cell counts in the dialysate after appropriate antibiotic therapy (2561/µL [349–4654/µL] vs. 20/µL [20–23/µL]; p = 0.0006) than among the control patients. Although all the patients were treated with appropriate antibiotics after the identification of S. maltophilia, they had a significantly higher rate of catheter removal than the controls (80.0% vs. 0.0%; p = 0.001). Conclusions Diabetes mellitus may be an important risk factor for S. maltophilia peritonitis in patients undergoing PD.

Abstract Background Crescentic immunoglobulin A (IgA) nephropathy, defined as > 50% of the glomeruli with crescents, often has a poor renal prognosis. Because of the high prevalence of pre-eclampsia in the second trimester of pregnancy, we often fail to investigate the new onset of glomerulonephritis and the aggravation of subclinical nephropathies. We report a case of nephrotic syndrome suggestive of crescentic IgA nephropathy possibly triggered by pregnancy. Case presentation A 33-year-old multipara was referred for persistent proteinuria, hematuria, and hypoalbuminemia two months postpartum. The patient was diagnosed with proteinuria for the first time at 36 weeks of gestation. The patient was normotensive during pregnancy. Renal biopsy revealed crescentic IgA nephropathy, with cellular crescents in 80% of the glomeruli and no global sclerosis. After treatment with pulse steroids followed by high-dose oral glucocorticoids and tonsillectomy, a gradual improvement was seen in proteinuria, hematuria, and hypoalbuminemia. Conclusion Although the precise mechanism remains unclear, pregnancy possibly triggered the new onset of crescentic IgA nephropathy or the aggravation of subclinical IgA nephropathy.

Abstract Background The impact of intraoperative pulmonary hemodynamics on prognosis after off-pump coronary artery bypass (OPCAB) surgery remains unknown. In this study, we examined the association between intraoperative vital signs and the development of major adverse cardiovascular events (MACE) during hospitalization or within 30 days postoperatively. Methods This retrospective study analyzed data from a university hospital. The study cohort comprised consecutive patients who underwent isolated OPCAB surgery between November 2013 and July 2021. We calculated the mean and coefficient of variation of vital signs obtained from the intra-arterial catheter, pulmonary artery catheter, and pulse oximeter. The optimal cut-off was defined as the receiver operating characteristic curve (ROC) with the largest Youden index (Youden index = sensitivity + specificity – 1). Multivariate logistic regression analysis ROC curves were used to adjust all baseline characteristics that yielded P values of

Abstract Cerebral cavernous malformations (CCMs) are blood vessel malformations, often untreated if asymptomatic. However, upon cardiac surgery with cardiopulmonary bypass, cerebral edema/hemorrhage may occur. We successful performed mitral valve plasty for a case of severe mitral regurgitation with multiple CCMs. Preoperative head magnetic resonance imaging and strict perioperative management are important.

Abstract We successfully performed concomitant septal myectomy and mitral valve repair in a child with Noonan syndrome.

Study Design Case series. Purpose To evaluate the radiographic and clinical results of C1 laminoplasty without fusion. Overview of Literature C1 laminectomy has been the standard procedure for decompression at the C1 level. However, there have been some reports of trouble cases after C1 laminectomy. C1 laminoplasty might be superior to C1 laminectomy with regard to maintaining the original C1 anatomical shape, preventing compression from the posterior soft tissue, and ensuring an adequate bone-grafting site around the C1 posterior part if additional salvage fusion surgery is necessary afterward. Methods Seven patients with spinal cord compression without obvious segmental instability at the C1/2 level treated by C1 laminoplasty were included. The indication of C1 laminoplasty was same as that of C1 laminectomy. C1 laminoplasty was performed in the same way as subaxial double-door laminoplasty. The imaging findings were evaluated using X-ray, computed tomography, and magnetic resonance imaging. The clinical results were evaluated using the Japanese Orthopaedic Association (JOA) Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) and JOA score. Peri- and postoperative complications were also investigated. Results No patient showed increased C1/2 segmental instability after the surgery. The mean pre- and postoperative JOA scores were 8.6 and 11.7, respectively. The mean recovery rate was 40.2%. The effective rate in the JOACMEQ was 50% for the cervical spine function, 33% for the upper extremity function, 50% for the lower extremity function, 17% for the bladder function, and 17% for the quality of life. No major complication that seemed to be unique to C1 laminoplasty was observed over a period of about 4 years follow-up. Conclusions C1 laminoplasty for patients without obvious segmental instability might be a viable alternative procedure to C1 laminectomy.

Abstract Intraoperative evaluation of blood flow using ICG angiography revealed no significant abnormality. However, the anastomotic stenosis was revealed by postoperative CT angiography; more precise intraoperative evaluation methods need to be developed.

Abstract The diversion of the inferior vena cava into the left atrium after surgical atrial septal defect closure is a fatal complication. Cases of atrial septal defect with no inferior rim should be treated with this complication in mind.

Introduction: The prevalence of patients with osteoporosis continues to increase in aging societies, including Japan. The first choice for managing osteoporotic vertebral compression fracture (OVF) is conservative treatment. Failure in conservative treatment for OVF may lead to non-union or vertebral collapse, resulting in neurological deficit and subsequently requiring surgical intervention. This multicenter nationwide study in Japan was conducted to comprehensively understand the outcomes of surgical treatments for OVF non-union. Methods: This multicenter, retrospective study included 403 patients (89 males, 314 females, mean age 73.8 ± 7.8 years, mean follow-up 3.9 ± 1.7 years) with neurological deficit due to vertebral collapse or non-union after OVF at T10-L5 who underwent fusion surgery with a minimum 1-year follow-up. Radiological and clinical outcomes at baseline and at the final follow-up (FU) were evaluated. Results: OVF was present at a thoracolumbar junction such as T12 (124 patients) and L1 (117 patients). A majority of OVF occurred after a minor trauma, such as falling down (55.3%) or lifting objects (8.4%). Short segment fusion, including affected vertebra, was conducted (mean 4.0 ± 2.0 vertebrae) with 256.8 minutes of surgery and 676.1 g of blood loss. A posterior approach was employed in 86.6% of the patients, followed by a combined anterior and posterior (8.7%), and an anterior (4.7%) approach. Perioperative complications and implant failures were observed in 18.1% and 41.2%, respectively. VAS scores of low back pain (74.7 to 30.8 mm) and leg pain (56.8 to 20.7 mm) improved significantly at FU. Preoperatively, 52.6% of the patients were unable to walk and the rate of non-ambulatory patients decreased to 7.5% at FU. Conclusions: This study demonstrated that substantial improvement in activity of daily living (ADL) was achieved by fusion surgery. Although there was a considerable rate of complications, fusion surgery is beneficial for elderly OVF patients with non-union.

Alogliptin is one of the dipeptidyl peptidase-4 inhibitors used to treat patients with type 2 diabetes. Little is known about the nephrotoxicity associated with alogliptin, such as nephrotic syndrome or interstitial nephritis. We report a biopsy-proven rare case of minimal change nephrotic syndrome and interstitial nephritis induced by alogliptin. A 68-year-old man who had been prescribed alogliptin was hospitalized for nephrotic syndrome. On admission, serum creatinine level was elevated with increased urinary β2-microglobulin and N-acetyl-β-d-glucosaminidase excretion. Kidney biopsy revealed minor glomerular abnormalities and interstitial nephritis, and gallium-67 scintigraphy showed uptake in both kidneys. A drug lymphocyte stimulation test for alogliptin was positive. With discontinuation of alogliptin treatment alone, serum creatinine level normalized in parallel with urine β2-microglobulin and N-acetyl-β-d-glucosaminidase levels. In addition, complete remission of nephrotic syndrome was observed. Drug-induced dual pathology has not been previously reported with alogliptin. In summary, clinicians should keep in mind that alogliptin can induce minimal change nephrotic syndrome and interstitial nephritis. Index Words: Alogliptin, minimal change nephrotic syndrome, interstitial nephritis, gallium-67 scintigraphy, drug lymphocyte stimulation test

The use of veno-arterial extracorporeal membrane oxygenation (ECMO) in patients with sepsis-induced cardiogenic shock has been reported, but the clinical implication of the Impella percutaneous axial-flow left ventricular assist device for such patients remains unknown. We had a 37-year-old man with septic shock and severely reduced cardiac function. Veno-arterial ECMO and concomitant Impella CP support ameliorated his end-organ dysfunction and achieved cardiac recovery, whereas severe mitral valve regurgitation due to chordal rupture developed later. Mitral valve replacement concomitant with ECMO removal as well as an Impella upgrade successfully treated the patient. ECMO and Impella support might be an effective therapeutic strategy for the bridge to recovery in patients with sepsis-induced cardiogenic shock; however, paying attention to mitral chordal rupture is highly encouraged.

Mortality and morbidity remain high following transcatheter aortic valve replacement (TAVR) in dialysis patients or those with low left ventricular ejection fraction. Therapeutic strategy for those with these comorbidities remains unestablished. We had a dialysis patient with peripheral artery disease and low left ventricular ejection fraction, who received successfully scheduled trans-apical TAVR following sufficient reverse remodeling by 3-month optimal medical therapy. Our strategy should be validated in a larger robust cohort.

Study Design Prospective cohort study. Purpose The present study aimed to evaluate the difference in the preoperative curve flexibility between the supine and prone positions in patients with adolescent idiopathic scoliosis (AIS). Overview of Literature In AIS, a side-bending view is necessary to differentiate a structural curve from a nonstructural curve using the Lenke classification system. However, there are no published studies about which position, supine or prone, is more effective when evaluating preoperative curve flexibility using side-bending X-ray images in AIS patients. Methods Radiographs were analyzed for 32 AIS patients (26 females, six males) who underwent posterior correction and fusion of their main thoracic (MT) curves. Cobb angles of MT, proximal thoracic (PT), and thoracolumbar/lumbar (TL/L) curves were measured preoperatively using upright, supine (anteroposterior and side-bending), and prone (posteroanterior and side-bending) X-rays. Results The average Cobb angles of PT, MT, and TL/L curves on preoperative upright/supine/prone X-rays were 29.1°/26.7°/26.6°, 60.7°/48.5°/48.2°, and 41.0°/32.6°/33.1°, respectively. The average Cobb angles of PT, MT, and TL/L curves on supine/prone sidebending X-rays were 19.2°/20.3°, 36.3°/36.4°, and 13.9°/15.7°, respectively. The flexibility rates of PT, MT, and TL/L curves in supine/prone positions were 35.3%/32.5%, 40.6%/40.2%, and 71.7%/68.2%, respectively. Comparing flexibility rates in the prone position with those in the supine position in each case, the average ratios of PT, MT, and TL/L curves were found to be 1.0, 1.0, and 0.9, respectively. There were no statistically significant differences between supine and prone side-bending X-ray measurements. However, the Lenke classification in six of 32 patients (18.8%) differed between supine and prone positions because the TL/L curve in the supine position was slightly more flexible than in the prone position. Conclusions Supine side-bending films may be suitable for the evaluation of preoperative curve flexibility in AIS, especially for lumbar modifier C.

Abstract Background Cilostazol is an antiplatelet drug that is widely prescribed for the prevention of secondary stroke. Adverse reactions to cilostazol include headaches, palpitations, and diarrhea. Little is known about the nephrotoxicity of cilostazol, such as acute kidney injury. We report a biopsy-proven case of diffuse tubulointerstitial nephritis induced by cilostazol. Case presentation A 69-year-old woman prescribed cilostazol was hospitalized for acute kidney injury. On admission, her renal function deteriorated, with an increased serum creatinine level. Urinalysis showed hematuria, proteinuria, and hyper-beta2-microglobulinuria. A renal biopsy revealed diffuse tubulointerstitial nephritis associated with IgA nephropathy, and gallium-67 scintigraphy showed uptake in the bilateral kidneys. A drug lymphocyte stimulation test for cilostazol was positive, and the patient was diagnosed with cilostazol-induced acute tubulointerstitial nephritis. Despite discontinuation of cilostazol, her renal function rapidly worsened and steroid pulse therapy was initiated, followed by oral high-dose glucocorticoid therapy. After steroid treatment, her serum creatinine level normalized in parallel with urine beta2-microglobulin. Conclusion Cilostazol can induce acute tubulointerstitial nephritis.

Introduction: The clinical significance of lumbosacral transitional vertebrae (LSTV) has been reported. However, the association between LSTV and lumbosacral pedicle anatomical anomaly has not been investigated. We hypothesized that LSTV might be associated with lumbosacral anatomical anomaly. The purpose of this study was to examine the morphological association between LSTV and lumbosacral pedicle asymmetry (PA) using computed tomography (CT). Methods: A retrospective review of CT images of 347 lumbosacral degenerative disease patients was performed. We divided the subjects into two groups: the normal and LSTV groups. LSTV was classified based on Castellvi's classification. PA was defined as a difference of more than 20° between the right and left angles of the pedicle. Results: Seventy out of 347 lumbosacral degenerative disease patients (20.17%) were diagnosed with LSTV. In the normal group, only a 0.54% incidence of PA was seen; however, with respect to the LSTV group, a 9.29% incidence of PA was seen. A significant difference in PA incidence was observed between the groups (p < 0.001). Type IIIa and Type IV in the LSTV group showed a statistically significant PA incidence rate (p = 0.004 and p = 0.039, respectively). Conclusions: Our study demonstrated that there was a significant difference in the incidence of PA between LSTV subjects and normal subjects. Moreover, the incidence of PA was significantly higher in LSTV subjects with severe anomaly. These results suggested that lumbosacral spine anomaly might have a close relationship with the incidence of PA and lumbosacral nerve root asymmetry. Therefore, morphological evaluation of the pedicle is important for preoperative surgical management, especially in cases using pedicle screws. This information could lower the incidence of pedicle screw malposition when pedicle screws are inserted at the lumbosacral spine.

Abstract Background A lot of risk factors for mortality have been proposed in hemodialysis patients. However, most of the findings were derived from the analyses using all of the hemodialysis patients. What we really want to know is the prognostic factor in stable hemodialysis patients who have good activities of daily living, because it is difficult to estimate their prognosis by physical appearance. Methods This is a 7-year observational study. The study involved registering 631 patients who had undergone hemodialysis for more than 1 year at enrollment and were still alive more than 1 year after it. Demographic and clinical data were collected to analyze the relationship with mortality. Moreover, the patients were age-stratified to investigate age-dependent prognostic factors. Results Low serum sodium concentration is an independent risk factor for all-cause and cardiovascular mortality common to a wide range of ages in stable hemodialysis patients. Causes of hyponatremia included the predialysis blood glucose level as well as the variables related to nutrition, inflammation, and fluid overload. Conclusions Low serum sodium concentration is a significant prognostic factor in stable hemodialysis patients. Low serum sodium concentration can be a clue to finding current poor glucose control in stable hemodialysis patients. Predialysis blood glucose level is one of the representative factors correlated with serum sodium concentration.

Abstract Background Immunoglobulin G4-related kidney disease characterized by immunoglobulin G4-positive plasma cell-rich tubulointerstitial nephritis has distinctive serological and radiological findings. Renal prognosis is good because of a good response to glucocorticoids. Here we report a case of successful treatment of highly advanced immunoglobulin G4-related kidney disease presenting renal mass-like regions with end-stage kidney failure. Case Presentation A 59-year-old Japanese man was referred to our hospital because of uremia with a creatinine level of 12.36 mg/dL. Urinalysis revealed mild proteinuria and hyperβ2microglobulinuria, and blood tests showed hyperglobulinemia with an IgG level of 3243 mg/dL and an IgG4 level of 621 mg/dL. Non-contrast computed tomography revealed renal mass-like regions. Based on the findings, immunoglobulin G4-related kidney disease was suspected, however, further radiological examination showed unexpected results. Ga-67 scintigraphy showed no kidney uptake. T2-weighted magnetic resonance imaging revealed high-intensity signals which corresponded to mass-like regions and multiple patchy low-intensity signals in kidney cortex. Finally, the patient was diagnosed with immunoglobulin G4-related kidney disease by renal pathology of severe immunoglobulin G4-positive plasma cell-rich tubulointerstitial nephritis and characteristic fibrosis. He received 50 mg oral prednisolone, which was tapered with a subsequent decrease of serum creatinine and IgG4 levels. One year after initiation of treatment, he achieved normalization of serum IgG4 level and proteinuria, and remained off dialysis with a creatinine level of 3.50 mg/dL. After treatment with steroids, repeat imaging suggested bilateral severe focal atrophy. However, mass-like regions did not show atrophic change although renal atrophy was evident in patchy low-intensity lesions on T2-weighted magnetic resonance imaging. These findings suggest that multiple patchy low-intensity signals and high-intensity mass-like regions were mildly atrophic lesions of immunoglobulin G4-related kidney disease due to severe fibrosis and normal parts of kidney, respectively. Conclusions In immunoglobulin G4-related kidney disease with severe kidney failure, radiological findings should be carefully examined. In addition, renal prognosis may be good despite highly advanced tubulointerstitial nephritis and fibrosis.

Presepsin, a glycoprotein produced during bacterial phagocytosis, is used as a sepsis marker for bacterial infections. However, presepsin levels are affected by renal function, and the evaluation criteria according to kidney function or in chronic kidney diseases remain controversial. Furthermore, presepsin may be increased by sample stirring, but no studies have evaluated this effect.In this study, we excluded the effect of stirring by standardizing the blood collection conditions, analyzed the influence of kidney function on presepsin concentrations, and recalculated the reference range based on the findings. EDTA-whole blood from 47 healthy subjects and 85 patients with chronic kidney disease was collected to measure presepsin by PATHFAST. Presepsin was found to be significantly correlated with the levels of creatinine (r = 0.834), eGFRcreat (r = 0.837), cystatin-C (r = 0.845), and eGFRcys (r = 0.879). Furthermore, in patients with CKD, presepsin levels stratified by eGFRcys showed a significant increase in the CKD G2 patient group and with advancing glomerular filtration rate stage. The following values were obtained: Normal: 97.6 ± 27.4 pg/mL, CKD G1: 100.2 ± 27.6 pg/mL, CKD G2: 129.7 ± 40.7 pg/mL, CKD G3: 208.1 ± 70.2 pg/mL, CKD G4: 320.2 ± 170.1 pg/mL, CKD G5: 712.8 ± 336.3 pg/mL. The reference range, calculated by a nonparametric method using 67 cases of healthy volunteers and patients with chronic kidney disease G1, was found to be 59-153 pg/mL, which was notably lower than the standard reference range currently used. Presepsin concentrations were positively correlated with a few biomarkers of renal function, indicating the necessity to consider the effect of renal function in patients with renal impairment. Using the recalculated reference range considering kidney function may improve the accuracy of evaluating presepsin for diagnosis of sepsis compared to the standard reference currently in use.

Diabetic nephropathy (DN) is among the most serious complications of diabetes mellitus, and often leads to end-stage renal disease ultimately requiring dialysis or renal transplantation. The loss of podocytes has been reported to have a role in the onset and progression of DN. Here, we addressed the activation mechanism of Smad3 signaling in podocytes. Expression of RII and activation of Smad3 were induced by AGE exposure (P

The Nagoya Daruma pond frog Pelophylax porosus brevipodus is distributed in western Japan and is traditionally divided into two local forms: the Okayama form in the west and the Nagoya form in the east. These two forms are genetically differentiated, but have never been defined taxonomically because their distributions are unclear to date. To complete the distributions and identify the boundary of the two forms, we genetically investigated 16 populations including eight populations located within the unexamined area. We found that the distributional boundary is located within a small area of Hyogo Prefecture where haplotypes of mitochondrial cytochrome b (cytb) and D-loop region corresponding to the two forms co-existed. On the other hand, the polymorphic site of the nuclear gene SOX3 revealed introgression over the boundary into Okayama cytb clade. These results suggest that the two forms were geographically isolated from each other in the past, and secondarily contacted and then accepted one-way introgression. As a next step of the research, taxonomic approach is expected to define the two forms.

The aim of this study was to investigate the clinicopathologic features of lumbar disc herniation (LDH) with endplate degeneration and the association between cartilaginous fragments and inflammatory response to the herniated disc.LDH often involves hyaline cartilage fragments pulled from the vertebral endplates. Modic changes are closely associated with LDH that contains hyaline cartilage, and cartilaginous endplates seem to affect resorption of the herniated disc.A total of 78 patients who underwent microscopic discectomy between 9 and 16 weeks after an occurrence of LDH were reviewed. Modic changes, disc degeneration, high-intensity zone, and vertebral corner defect were evaluated using magnetic resonance imaging (MRI). Histopathological observations of cartilaginous endplates and inflamed granulation tissue in the herniated disc were made. In cases with inflamed granulation tissue, neovascularization and macrophage infiltration were also evaluated using immunohistochemical analysis.Modic changes were observed in approximately one-third of the patients (26 cases: type 1, 7; type 2, 17; and type 3, 2). Cartilaginous endplates were observed in 32 cases (41%) and in the majority of cases with Modic changes compared with cases without Modic changes (65%, p = 0.001). Although inflamed granulation tissue was observed in 60 cases (77%), no significant differences were detected in patient age and the composition of the herniated material. Immunohistochemical analysis showed that fewer CD34-positive capillaries and CD68-positive cells were found in cases with cartilaginous fragments compared with those without cartilaginous fragments (p < 0.001). In addition, a higher immunoreactivity to CD34 and CD68 was found in herniated discs

Urinary type IV collagen (U-Col4) and albumin excretion is evaluated to monitor the development of diabetic kidney disease. However, U-Col4 excretion in the general population without diabetes has not yet been fully elucidated. In this study, 1067 participants without diabetes and with urinary albumin-creatinine ratio

Four patients underwent stabilization surgery using both bilateral C2 pedicle screw (PS) and intralaminar screw (LS). Neural and vascular injury resulting from incorrect screw placement was assessed using computed tomography (CT). The evaluation of bone union was assessed by lateral flexion-extension X-ray films and CT. The symptoms were improved in all patients. There were no intraoperative complications. Furthermore, there were no cases of neurological worsening or vascular injury from incorrect screw placement. Failure of instrumentation or screw loosening during the follow-up period did not occur in any of the patients. All cases had accomplished bone union at the final follow-up. Theoretically, the stabilization technique using both bilateral C2 PS and LS at the same time can provide more stability than any other single technique. Simultaneous use of both bilateral C2 PS and LS is potentially a good choice for surgical repair.

The breakage of an epidural catheter is an extremely rare complication. We describe a unique case where a retained epidural catheter fragment after epidural anesthesia was treated by surgery. The epidural catheter broke during its removal, requiring surgery to remove the retained catheter. Intraoperatively, the removal of the catheter was attempted by simple traction, but was impossible because of the adhesion. The adhesion of the dura mater surface was carefully exfoliated and the successful removal of the catheter was accomplished. Conventionally, it was said that this follow-up was enough for the retained catheter. However, if a catheter is retained within the spinal canal, surgical removal should thus be considered before the adhesion advances.

Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors. First, we focused on mechanical stress and developed a loading device for applying consecutive mechanical flexion-extension stress to the mouse LF. After 12 weeks of mechanical stress loading, we found that the LF thickness in the stress group was significantly increased in comparison to the control group. In addition, there were significant increases in the area of collagen fibers, the number of LF cells, and the gene expression of several fibrosis-related factors. However, in this mecnanical stress model, there was no macrophage infiltration, angiogenesis, or increase in the expression of transforming growth factor-β1 (TGF-β1), which are characteristic features of LF hypertrophy in LSCS patients. We therefore examined the influence of infiltrating macrophages on LF hypertrophy. After inducing macrophage infiltration by micro-injury to the mouse LF, we found excessive collagen synthesis in the injured site with the increased TGF-β1 expression at 2 weeks after injury, and further confirmed LF hypertrophy at 6 weeks after injury. Our findings demonstrate that mechanical stress is a causative factor for LF hypertrophy and strongly suggest the importance of macrophage infiltration in the progression of LF hypertrophy via the stimulation of collagen production.

The posterior epidural migration of lumbar disc fragments is an extremely rare event with an unknown pathogenesis. To the best of our knowledge, there are no previously reported cases of a change of ordinary disc herniation into the posterior epidural migration of lumbar disc fragments as confirmed by magnetic resonance imaging (MRI). A 26-year-old male presented to our department complaining of left buttock and lateral leg pain. An ordinary herniation was shown in the first MRI. The patient's unilateral symptoms changed into bilateral symptoms while awaiting admission to the hospital. Posterior migrated lumbar disc fragments were shown in the second MRI taken at the time of admission. Microendoscopic surgery providing a detailed observation of the region was performed. Our case indicates that an ordinary lumbar disc herniation may lead to the posterior migration of lumbar disc fragments, and that microendoscopic surgery may provide a treatment.

Dysregulation of the cell proliferation has been implicated in the pathophysiology of a number of diseases. Cellular senescence limits proliferation of cancer cells, preventing tumorigenesis and restricting tissue damage. However, the role of cellular senescence in proliferative nephritis has not been determined. The proliferative peak in experimental rat nephritis coincided with a peak in E2A expression in the glomeruli. Meanwhile, E12 (an E2A-encoded transcription factor) did not promote proliferation of Mesangial cells (MCs) by itself. We identified caspase-8-binding protein FLICE-associated huge protein (FLASH) as a novel E2A-binding partner by using a yeast two-hybrid screening. Knockdown of FLASH suppressed proliferation of MCs. This inhibitory effect was partially reversed by the knockdown of E2A. In addition, the knockdown of FLASH induced cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) expression, but did not affect p53 expression. Furthermore, overexpression of E12 and E47 induced p21, but not p53 in MCs, in the absence of FLASH. We also demonstrated that E2A and p21 expression at the peak of proliferation was followed by significant induction of FLASH in mesangial areas in rat proliferative glomerulonephritis. Moreover, we revealed that FLASH negatively regulates cellular senescence via the interaction with E12. We also demonstrated that FLASH is involved in the TNF-α-induced p21 expressions. These results suggest that the functional interaction of E2A and FLASH play an important role in cell proliferation and cellular senescence via regulation of p21 expression in experimental glomerulonephritis.

A 67-year-old man was admitted with severe back pain and bilateral lower limb swelling. Enhanced computed tomography showed an infrarenal abdominal aortic aneurysm (92 × 75 mm 2 ) and a short aortocaval fistula (7 mm). Immediately afterward, circulatory collapse occurred, and the patient was rushed to the operating theater. A much larger aortocaval fistula (22 × 35 mm 2 ) than that demonstrated by preoperative computed tomography was found and was repaired with a Dacron patch while using two balloon-tipped catheters to control bleeding. Then, the abdominal aortic aneurysm was replaced with a bifurcated graft. The patient’s postoperative course was uneventful. In this case, enhanced computed tomography detected the aortocaval fistula, but could not assess its size accurately. Successful surgical repair of an aortocaval fistula depends on early accurate delineation of the fistula and prompt control of bleeding.

CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that promotes hypertrophic differentiation of chondrocytes. Indian hedgehog (Ihh) also stimulates the hypertrophic transition of chondrocytes. Furthermore, runt-related transcription factor-2 (RUNX2) was reported to regulate chondrocyte maturation during skeletal development and to directly regulate transcriptional activity of Ihh. In this study, we investigated whether the interaction of C/EBPβ and RUNX2 regulates the expression of Ihh during chondrocyte differentiation.Immunohistochemistry of embryonic growth plate revealed that both C/EBPβ and Ihh were strongly expressed in pre-hypertrophic and hypertrophic chondrocytes. Overexpression of C/EBPβ by adenovirus vector in ATDC5 cells caused marked stimulation of Ihh and Runx2. Conversely, knockdown of C/EBPβ by lentivirus expressing shRNA significantly repressed Ihh and Runx2 in ATDC5 cells. A reporter assay revealed that C/EBPβ stimulated transcriptional activity of Ihh. Deletion and mutation analysis showed that the C/EBPβ responsive element was located between -214 and -210 bp in the Ihh promoter. An electrophoretic mobility shift assay (EMSA) and a chromatin immunoprecipitation (ChIP) assay also revealed the direct binding of C/EBPβ to this region. Moreover, reporter assays demonstrated that RUNX2 failed to stimulate the transcriptional activity of the Ihh promoter harboring a mutation at the C/EBPβ binding site. EMSA and ChIP assays showed that RUNX2 interacted to this element with C/EBPβ. Immunoprecipitation revealed that RUNX2 and C/EBPβ formed heterodimer complex with each other in the nuclei of chondrocytes. These data suggested that the C/EBPβ binding element is also important for RUNX2 to regulate the expression of Ihh. Ex vivo organ culture of mouse limbs transfected with C/EBPβ showed that the expression of Ihh and RUNX2 was increased upon ectopic C/EBPβ expression.C/EBPβ and RUNX2 cooperatively stimulate expression of Ihh through direct interactions with a C/EBPβ binding element, which further promotes hypertrophic differentiation of chondrocytes during the chondrocyte differentiation process.

BACKGROUND: Gas6 is a growth factor that causes proliferation of mesangial cells in the development of glomerulonephritis. Gas6 can bind to three kinds of receptors; Axl, Dtk, and Mer. However, their expression and functions are not entirely clear in the different glomerular cell types. Meanwhile, representative cell cycle regulatory protein p27 has been reported to be expressed in podocytes in normal glomeruli with decreased expression in proliferating glomeruli, which inversely correlated with mesangial proliferation in human IgA nephropathy (IgAN). METHODS: The aim of this study is to clarify Gas6 involvement in the progression of IgAN. Expression of Gas6/Axl/Dtk was examined in 31 biopsy proven IgAN cases. We compared the expression levels with histological severity or clinical data. Moreover, we investigated the expression of Gas6 and its receptors in cultured podocytes. RESULTS: In 28 of 31 cases, Gas6 was upregulated mainly in podocytes. In the other 3 cases, Gas6 expression was induced in endothelial and mesangial cells, which was similar to animal nephritis models. Among 28 podocyte type cases, the expression level of Gas6 correlated with the mesangial hypercellularity score of IgAN Oxford classification and urine protein excretion. It also inversely correlated with p27 expression in glomeruli. As for the receptors, Axl was mainly expressed in endothelial and mesangial cells, while Dtk was expressed in podocytes. In vitro, Dtk was expressed in cultured murine podocytes, and the expression of p27 was decreased by Gas6 stimulation. CONCLUSIONS: Gas6 was uniquely upregulated in either endothelial/mesangial cells or podocytes in IgAN. The expression pattern can be used as a marker to classify IgAN. Gas6 has a possibility to be involved in not only mesangial proliferation via Axl, but also podocyte injury via Dtk in IgAN.

Phenotypic transformation of mesangial cells (MCs) is implicated in the development of glomerular disease; however, the mechanisms underlying their altered genetic program is still unclear. α-smooth muscle actin (α-SMA) is known to be a crucial marker for phenotypic transformation of MCs. Recently, E-boxes and the class I basic helix-loop-helix proteins, such as E12 have been shown to regulateα-SMA expression. Therefore, we tried to identify a novel E12 binding protein in MCs and to examine its role in glomerulonephritis. We found that PIASy, one of the protein inhibitors of activated STAT family protein, interacted with E12 by yeast two-hybrid screens and coimmunopreciptation assays. Overexpression of E12 significantly enhanced theα-SMA promoter activity, and the increase was blocked by co-transfection of PIASy, but not by a PIASy RING mutant. In vivo sumoylation assays revealed that PIASy was a SUMO E3 ligase for E12. Furthermore, transforming growth factor-β (TGF-β) treatment induced expression of both PIASy and E12, consistent with α-SMA expression. Moreover, reduced expression of PIASy protein by siRNA specific for PIASy resulted in increased TGF-β-mediated α-SMA expression. In vivo, PIASy and E12 were dramatically upregulated along with α-SMA and TGF-β in the proliferative phase of Thy1 glomerulonephritis. Furthermore, an association between PIASy and E12 proteins was observed at day 6 by IP-western blotting, but not at day 0. These results suggest that TGF-β up-regulates PIASy expression in MCs to down-regulateα-SMA gene transcription by the interaction with E12.

Platelet-derived growth factor (PDGF) plays critical roles in mesangial cell (MC) proliferation in mesangial proliferative glomerulonephritis. We showed previously that Smad1 contributes to PDGF-dependent proliferation of MCs, but the mechanism by which Smad1 is activated by PDGF is not precisely known. Here we examined the role of c-Src tyrosine kinase in the proliferative change of MCs. Experimental mesangial proliferative glomerulonephritis (Thy1 GN) was induced by a single intravenous injection of anti-rat Thy-1.1 monoclonal antibody. In Thy1 GN, MC proliferation and type IV collagen (Col4) expression peaked on day 6. Immunohistochemical staining for the expression of phospho-Src (pSrc), phospho-Smad1 (pSmad1), Col4, and smooth muscle α-actin (SMA) revealed that the activation of c-Src and Smad1 signals in glomeruli peaked on day 6, consistent with the peak of mesangial proliferation. When treated with PP2, a Src inhibitor, both mesangial proliferation and sclerosis were significantly reduced. PP2 administration also significantly reduced pSmad1, Col4, and SMA expression. PDGF induced Col4 synthesis in association with increased expression of pSrc and pSmad1 in cultured MCs. In addition, PP2 reduced Col4 synthesis along with decreased pSrc and pSmad1 protein expression in vitro. Moreover, the addition of siRNA against c-Src significantly reduced the phosphorylation of Smad1 and the overproduction of Col4. These results provide new evidence that the activation of Src/Smad1 signaling pathway plays a key role in the development of glomerulosclerosis in experimental glomerulonephritis.

Purpose. To evaluate the outcome of osteoplastic laminotomy after excision of primary tumours of the thoracolumbar and lumbar spine. Methods. Records of 10 male and 11 female consecutive patients aged 15 to 57 (mean, 37) years who underwent osteoplastic laminotomy for excision of spinal cord tumours in the thoracolumbar (n=13) and lumbar (n=8) spine were reviewed. After tumour resection, the removed posterior elements were reattached to the superior and inferior processes using anchoring sutures. Pre- and postoperative functional status was retrospectively graded according to the modified McCormick scale. Spinal deformities were classified as sagittal and coronal malalignment, segmental instability, and spondylolisthesis. Results. The mean follow-up duration was 43 (range, 12–108) months. The mean number of laminae excised was 1.3 (range, 1–4). At the final follow-up, the modified McCormick scale score improved in 16 patients, remained unchanged in 4, and deteriorated in one. No patient developed any severe complication, recurrence, spondylolisthesis, or aseptic necrosis of grafted laminae. In 2 patients their spinal deformities became worse: one had segmental instability of 17° at L3–4 secondary to non-union of the L3 lamina; the other (with type-I neurofibromatosis and dystrophic deformity) underwent fusion for severe low back pain and lumbar kyphosis and progressive rotational dislocation, despite union of the grafted L2 lamina. Conclusions. Osteoplastic laminotomy preserves the structures that could be important for spinal stability and may reduce the risk of deformities. Anterior strut grafting and posterior fusion may be necessary in neurofibromatosis patients with dystrophic deformities.

X-linked Alport syndrome is a hereditary progressive renal disease resulting from the disruption of collagen a 3a 4a 5 (IV) heterotrimerization caused by pathogenic variants in the COL4A5 gene. This study aimed to report a male case of X-linked Alport syndrome with a mild phenotype accompanied by an atypical expression pattern of type IV collagen a 5 [a5 (IV)] chain in glomerulus. A 38-year-old male presented with proteinuria (2.3 g/day) and hematuria. He has been detected urinary protein and occult blood since childhood. A renal biopsy was performed at the age of 29 years; however, a diagnosis of Alport syndrome was not considered. A renal biopsy 9 years later revealed diffuse thinning and lamellation of the glomerular basement membrane. A staining for a5 (IV) revealed a normal expression pattern in the glomerular basement membrane and a complete negative expression in Bowman's capsule and distal tubular basement membrane. Using next-generation sequencing, we detected a COL4A5 missense variant within exon 35 (NM_000495.5: c.3088G>A, p. G1030S). The possibility of X-linked Alport syndrome should be considered when negative expression of a 5 (IV) staining on Bowman's capsule was observed. [ABSTRACT FROM AUTHOR]