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The hot cross bun (HCB) sign encompasses a cross-shaped hyperintensity area in the pons on axial T2-weighted magnetic resonance imaging (MRI). The HCB sign is characteristic of multiple system atrophy (MSA) and has occasionally been observed in other neurological disorders. Here, we report an autopsied case of corticobasal degeneration (CBD) that showed the HCB sign. A female patient presented with progressive gait disturbance and cognitive impairment at the age of 60 years. A neurological examination revealed dysarthria, muscle rigidity of the limbs, akinesia, truncal ataxia, urinary incontinence, and dementia. The HCB sign was observed on a brain MRI at the age of 65 years, and a clinical diagnosis of possible MSA was made. She died of pneumonia at the age of 67 years. A postmortem observation, provided neuropathological findings characteristic of CBD, including the presence of astrocytic plaques, pretangles, neuropil threads, and ballooned neurons in association with four-repeat-tau aggregation. Interestingly, the pons displayed severe neuronal loss and astrogliosis that were prominent in the pontine and raphe nuclei. Myelin sheath depletion was prominent in the transverse fibers of the pontine base and the myelinated fibers of the pontine tegmentum in contrast to relative sparing of the pontine corticospinal tract and medial lemniscus. The cerebellar dentate nucleus exhibited neuronal loss and grumose degeneration. Western blot analysis of sarkosyl-insoluble fractions from brain tissue lysates using an anti-phosphorylated tau antibody identified immunoreactive signal bands in approximately 37-40, 43, 64, and 68 kDa, consistent with CBD. Genetic analysis did not reveal any known pathogenic mutations in the microtubule-associated protein tau gene (MAPT). Our case was characterized by the HCB sign and concordant neuropathological changes in the pons. CBD should be considered an underlying pathology of the HCB sign, even though the pontocerebellar changes would be unusual in CBD cases.

Background Rituximab is conditionally approved in Japan for use in patients with refractory nephrotic syndrome. To meet the conditions of approval, an all-case post-marketing surveillance study was conducted to confirm the real-world safety and efficacy of rituximab in patients of all ages with refractory nephrotic syndrome. Methods All patients scheduled to receive rituximab treatment for refractory nephrotic syndrome were eligible to register (registration: August 29, 2014 through April 15, 2016); the planned observation period was 2 years from the initiation of rituximab treatment (intravenous infusion, 375 mg/m2 once weekly for four doses). The study was conducted at 227 hospitals throughout Japan. Adverse drug reactions (ADRs) were collected for safety outcomes. The efficacy outcomes were relapse-free period and the degree of growth in pediatric ( Results In total, 997 (447 pediatric) patients were registered; 981 (445) were included in the safety analysis set; 852 (402) completed the 2-year observation period; and 810 (429) were included in the efficacy analysis set. Refractory nephrotic syndrome had developed in childhood for 85.0% of patients, and 54.6% were aged ≥15 years. ADRs were observed in 527 (53.7%) patients, treatment-related infection/infestation in 235 (24.0%) patients, and infusion reactions in 313 (31.9%) patients. The relapse-free period was 580 days (95% confidence interval, 511–664). There was a significant change in height standard deviation score (pediatric patients; mean change, 0.093; standard deviation, 0.637; P = 0.009). Conclusion The safety and efficacy of rituximab treatment in patients with refractory nephrotic syndrome were confirmed in the real-world setting. Clinical trial registration UMIN000014997.

The propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of α‐synuclein into filaments is believed to underlie the prion‐like spreading of protein inclusions in a number of human neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We previously determined the atomic structures of α‐synuclein filaments from the putamen of five individuals with MSA. Here, we used filament preparations from three of these brains for the in vitro seeded assembly of recombinant human α‐synuclein. We find that the structures of the seeded assemblies differ from those of the seeds, suggesting that additional, as yet unknown, factors play a role in the propagation of the seeds. Identification of these factors will be essential for understanding the prion‐like spreading of α‐synuclein proteinopathies., The assembly of certain proteins into amyloids underlies multiple neurodegenerative diseases. The spreading of these assemblies through the brain is thought to occur through a prion‐like mechanism. We used filaments extracted from multiple system atrophy brains to seed recombinant α‐synuclein. The resulting structures differ from those of the seeds, indicating that seeded assembly does not necessarily replicate the seed structures.

Background Previous studies suggested that direct-acting antivirals (DAAs) against hepatitis C increased the blood coagulability of patients on warfarin. This study aims to descriptively investigate the effects of DAAs on the blood coagulability and liver function of patients on warfarin in Japan. Methods The Medical Information Database Network (MID-NET®) was used as data source. Fluctuations of blood coagulability and liver function were examined before and after DAA treatment in patients who were prescribed both DAAs and warfarin at least once during the study period from January 1, 2010, to December 31, 2017. Results For the 16 eligible patients, the mean values of both PT-INR and WSI (warfarin sensitivity index) defined as the value obtained by dividing the PT-INR by the warfarin daily dose slightly decreased at the date of completion of the DAA treatment in comparison with those at the date of initiation and subsequently increased at 12 weeks after treatment completion. In contrast, the warfarin daily dose increased at the date of completion of the DAA treatment, followed by a decrease at 12 weeks after its completion. Several laboratory tests related to the liver function also revealed a similar decrease at the end of the DAA treatment. Conclusion The analysis of MID-NET® data provides useful information on drug safety assessment of real-world patients. The results of this study imply that fluctuation of the liver function test results may relate to the fluctuation of blood coagulability in patients on both DAA and warfarin. This study contributes to a deeper understanding of the usefulness and limitations of real-world data in MID-NET® for regulatory purposes.

Background Immunization with various vaccines is considered desirable for children with idiopathic nephrotic syndrome (NS) because of their high risk of severe infections. Vaccinations may precipitate relapses of NS, but there is no available data regarding inactivated influenza (flu) virus vaccines. Methods We retrospectively reviewed the medical records of children with NS who had received flu vaccines between 2002 and 2015. The day of flu vaccination was defined as day 0, and the period between the pre-vaccination and the post-vaccination days was defined as − X to + Y. The risk ratios and their 95% confidence intervals for NS relapse rate were estimated by generalized estimating equation (GEE) Poisson regression. Results A total of 104 pediatric patients received 208 flu vaccines. The mean age at onset of NS was at 4.85 ± 3.87 years old. There were 261 NS relapses between days − 180 and + 180. Compared with the relapse rate in the − 180 to 0 interval (1.19 times/person-year), those in 0 to + 30 (1.23), + 31 to + 60 (1.58), + 61 to + 90 (1.41), + 91 to + 120 (1.41), and + 121 to + 180 (1.32) days groups were slightly increased, but without significance. Multivariate analysis using GEE Poisson regression also showed no significant increase in relapse rate in each day group compared with days − 180 to 0. Risk ratios for NS relapse were significantly higher in children who were treated with steroids at the first vaccination. Conclusions Our results suggest that flu vaccines should not be avoided in children with NS based on the potential for NS relapses. Electronic supplementary material The online version of this article (10.1007/s10157-020-01930-8) contains supplementary material, which is available to authorized users.

The overall prognosis of patients with sarcoma-based cancers has changed little in the last 20 years. There is an urgent need to investigate the metastatic potential of these tumors and to develop anti-metastatic drugs. It is becoming increasingly clear that platelets play an important role in the establishment of metastasis of carcinoma cells and could be a useful therapeutic target for patients with carcinoma. However, little is known about the role of platelets in sarcoma progression. Here, we investigated how osteosarcoma progression relates to platelet function to explore the possibility of anti-platelet therapy. We found that, similar to carcinoma cells, podoplanin (also known as Aggrus)-positive osteosarcoma cells induce platelet aggregation and activation. Administration of anti-glycoprotein Ibα (GPIbα, also known as CD42b) antibody reduced the lung metastasis of osteosarcoma. The supernatant from platelets cocultured with osteosarcoma cells contained several growth factors and promoted proliferation, invasiveness, and sphere formation of osteosarcoma cells in vitro. In addition, the development of lung metastasis was highly dependent on direct interaction between osteosarcoma cells and platelets. To explore the therapeutic target, we focused on the interactions between podoplanin on osteosarcoma and C-type lectin-like receptor (CLEC)-2 on platelets. The administration of a depleting antibody against CLEC-2 efficiently suppressed osteosarcoma metastasis into the lung. We also analyzed clinical data from patient samples at primary and metastatic sites. Although GPIbα expression was similar between the two sites, there was a significant increase in podoplanin at the metastatic site compared to that in the primary site, and the level of podoplanin expression in the primary site correlated with patient prognosis. These findings suggest that blockade of interactions between platelets CLEC-2 and osteosarcoma podoplanin represent the most promising therapeutic strategy for preventing the lung metastasis of osteosarcoma. © 2020 American Society for Bone and Mineral Research.

Although vaccination may precipitate relapses of nephrotic syndrome (NS) in children with idiopathic NS, no data are available regarding NS activity regarding influenza (flu) virus infections and NS relapses after receiving inactivated flu vaccines. We conducted a nationwide study of children aged 6 months to 15 years with idiopathic NS to assess the relationship between NS relapse, flu vaccination, and flu infections. We used a multivariate Poisson regression model (MPRM) to calculate the risk ratio (RR) for flu infection and for NS relapse in children with and without flu vaccination. Data of 306 children were assessed. The MPRM in all 306 children showed a significantly lower RR for flu infection (RR: 0.21, 95% confidence interval [CI]: 0.11–0.38) and for NS relapse (RR: 0.22, 95% CI: 0.14–0.35) in children receiving flu vaccination compared with unvaccinated children. In an additional MPRM only among 102 children receiving flu vaccination, they had a significantly lower risk for NS relapse during the post-vaccination period (RR: 0.31. 95% CI: 017–0.56) compared with the pre-vaccination period. Although our study was observational, based on the favorable results of flu vaccinations regarding flu infections and NS relapse, the vaccine may be recommended for children with NS.

Although vaccination may precipitate relapses of nephrotic syndrome (NS) in children with idiopathic NS, no data are available regarding NS activity regarding influenza (flu) virus infections and NS relapses after receiving inactivated flu vaccines. We conducted a nationwide study of children aged 6 months to 15 years with idiopathic NS to assess the relationship between NS relapse, flu vaccination, and flu infections. We used a multivariate Poisson regression model (MPRM) to calculate the risk ratio (RR) for flu infection and for NS relapse in children with and without flu vaccination. Data of 306 children were assessed. The MPRM in all 306 children showed a significantly lower RR for flu infection (RR: 0.21, 95% confidence interval CI 0.11–0.38) and for NS relapse (RR: 0.22, 95% CI 0.14–0.35) in children receiving flu vaccination compared with unvaccinated children. In an additional MPRM only among 102 children receiving flu vaccination, they had a significantly lower risk for NS relapse during the post-vaccination period (RR: 0.31. 95% CI 017–0.56) compared with the pre-vaccination period. Although our study was observational, based on the favorable results of flu vaccinations regarding flu infections and NS relapse, the vaccine may be recommended for children with NS.

Non-thermal atmospheric pressure plasma (NTAPP)-activated liquids have emerged as new promising anticancer agents because they preferentially injure malignant cells. Here, we report plasma-activated infusion (PAI) as a novel NTAPP-based anti-neoplastic agent. PAI was prepared by irradiating helium NTAP to form a clinically approved infusion fluid. PAI dose-dependently killed malignant melanoma and osteosarcoma cell lines while showing much lower cytotoxic effects on dermal and lung fibroblasts. We found that PAI and salinomycin (Sal), an emerging anticancer stem cell agent, mutually operated as adjuvants. The combined administration of PAI and Sal was much more effective than single-agent application in reducing the growth and lung metastasis of osteosarcoma allografts with minimal adverse effects. Mechanistically, PAI explicitly induced necroptosis and increased the phosphorylation of receptor-interacting protein 1/3 rapidly and transiently. PAI also suppressed the ambient autophagic flux by activating the mammalian target of the rapamycin pathway. PAI increased the phosphorylation of Raptor, Rictor, and p70-S6 kinase, along with decreased LC3-I/II expression. In contrast, Sal promoted autophagy. Moreover, Sal exacerbated the mitochondrial network collapse caused by PAI, resulting in aberrant clustering of fragmented mitochondrial in a tumor-specific manner. Our findings suggest that combined administration of PAI and Sal is a promising approach for treating these apoptosis-resistant cancers.

The propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of α-synuclein into filaments is believed to underlie the prion-like spreading of protein inclusions in a number of human neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We previously determined the atomic structures of α-synuclein filaments from the putamen of five individuals with MSA. Here, we used filament preparations from three of these brains for the in vitro seeded assembly of recombinant human α-synuclein. We find that the structures of the seeded assemblies differ from those of the seeds, suggesting that additional, as yet unknown, factors play a role in the propagation of pathology. Identification of these factors will be essential for understanding the prion-like spreading of α-synuclein proteinopathies.

Non-thermal atmospheric plasma (NTAP)-activated liquids have emerged as new promising anticancer agents because they preferentially injure malignant cells. Here, we report plasma-activated infusion (PAI) as a novel NTAP-based anti-neoplastic agent. PAI was prepared by irradiating helium NTAP to form a clinically approved infusion fluid. PAI dose-dependently killed malignant melanoma and osteosarcoma cell lines showed much lower cytotoxic effects on dermal and lung fibroblasts. We found that PAI and salinomycin (Sal), an emerging anti-cancer stem cell agent, mutually operated as adjuvants. Combined administration of PAI and Sal was much more effective than single agent application in reducing the growth and lung metastasis of osteosarcoma allografts with minimal adverse effects. Mechanistically, PAI explicitly induced necroptosis and increased the phosphorylation of receptor-interacting protein 1/3 in a rapid and transient manner. PAI also suppressed the ambient autophagic flux by activating the mammalian target of rapamycin pathway. PAI increased the phosphorylation of Raptor, Rictor, and p70-S6 kinase, along with decreased LC3-I/II expression. In contrast, Sal promoted autophagy. Moreover, Sal exacerbated the mitochondrial network collapse caused by PAI, resulting in aberrant clustering of fragmented mitochondrial in a tumor-specific manner. Our findings suggest that combined administration of PAI and Sal is a promising approach for treating these apoptosis-resistant cancers.

Simple Summary Osteosarcoma is the most common solid cancer of the bone. Unfortunately, the expected outcome for patients with this and similar types of cancers has changed little over the last 20 years. One important need is to develop new therapies that overcome the development of drug resistance in osteosarcoma cells. The drug gemcitabine (Gem) can kill osteosarcoma cells and prevent them from growing and spreading. Another drug, rapamycin (Rapa), can also kill osteosarcoma cells, but does so in a different way. Here, we investigated whether a combination of Rapa and Gem would exhibit better osteosarcoma treatment efficiency than Rapa and Gem monotherapies. We found that this drug combination was very effective at killing osteosarcoma cells, both in cell cultures and in mice, and the combinatorial treatment was better than treatment with a single agent. Therefore, combinatorial therapy with Gem and Rapa may be an effective approach for treating drug resistant osteosarcoma cells. Abstract The overall prognosis for sarcoma-based cancer patients has remained largely unchanged over the past 10 years. Because there is no effective anticancer drug for patients with chemoresistant osteosarcoma (OS), novel approaches are needed to improve the prognosis. Here, we investigated whether rapamycin (Rapa) could enhance the anti-tumor effects of gemcitabine (Gem) in OS. Gem dose-dependently killed the OS cells, but exhibited much lower cytotoxicity on osteoblasts. Treatment with a combination Gem and Rapa was much more effective than that of either single agent with respect to reducing cell viability, cell invasion, cell migration, and vascular endothelial growth factor production in vitro. Moreover, the combination of these agents suppressed tumor growth, angiogenesis, and lung metastasis in allograft and xenograft murine models of OS with minimal adverse effects. Overall, the combination therapy prolonged the overall survival of tumor-bearing mice. Mechanistically, Gem induced apoptosis and increased the levels of cleaved caspases, while Rapa induced autophagy and microtubule-associated protein light chain 3 (LC3)-I/LC3-II expression both in vitro and in vivo. Our findings suggest that chemotherapy using Gem combined with Rapa may be a novel and promising therapeutic approach for the treatment of OS.

Pancreatic metastasis from prostate cancer (PC) is quite rare. Herein, we report the case of a 67-year-old man with pancreatic metastasis from a neuroendocrine differentiated PC (NEDPC), a local recurrence after radical prostatectomy and androgen deprivation therapy for 6 years. Chemoradiotherapy was initiated for the locally recurrent NEDPC, and it had almost disappeared after the therapy. However, rapidly enlarged pancreatic metastasis from the NEDPC was detected 6 months after therapy. There is no standard treatment available for pancreatic metastasis from NEDPC owing to its rarity; hence, further knowledge and clinical experience regarding it are crucial.

Synucleinopathies, which include multiple system atrophy (MSA), Parkinson’s disease, Parkinson’s disease with dementia and dementia with Lewy bodies (DLB), are human neurodegenerative diseases1. Existing treatments are at best symptomatic. These diseases are characterized by the presence of, and believed to be caused by the formation of, filamentous inclusions of α-synuclein in brain cells2,3. However, the structures of α-synuclein filaments from the human brain are unknown. Here, using cryo-electron microscopy, we show that α-synuclein inclusions from the brains of individuals with MSA are made of two types of filament, each of which consists of two different protofilaments. In each type of filament, non-proteinaceous molecules are present at the interface of the two protofilaments. Using two-dimensional class averaging, we show that α-synuclein filaments from the brains of individuals with MSA differ from those of individuals with DLB, which suggests that distinct conformers or strains characterize specific synucleinopathies. As is the case with tau assemblies4–9, the structures of α-synuclein filaments extracted from the brains of individuals with MSA differ from those formed in vitro using recombinant proteins, which has implications for understanding the mechanisms of aggregate propagation and neurodegeneration in the human brain. These findings have diagnostic and potential therapeutic relevance, especially because of the unmet clinical need to be able to image filamentous α-synuclein inclusions in the human brain. Cryo-electron microscopy reveals the structures of α-synuclein filaments from the brains of individuals with multiple system atrophy.

Mutations in the valosin-containing protein (VCP) gene are known to cause various neurodegenerative disorders. Here, we report 8 Japanese patients [6 men, 2 women; median age at onset: 49.5 (range, 35–58) years] from 5 unrelated families with VCP missense mutations. Although 7 of 8 patients were diagnosed with either inclusion body myopathy or amyotrophic lateral sclerosis, 1 patient showed demyelinating polyneuropathy, which was confirmed by longitudinal nerve conduction studies. Sural nerve biopsy of the patient revealed intranuclear ubiquitin staining in Schwann cells. Three known pathogenic VCP mutations (p.Arg191Gln, p.Arg155Cys, and p.Ile126Phe) were detected. A novel mutation, c.293 A>T (p.Asp98Val), was also identified in a patient with amyotrophic lateral sclerosis and frontotemporal dementia. This mutation was predicted to be “deleterious” or “disease causing” using in silico mutation analyses. In conclusion, demyelinating polyneuropathy may be a novel phenotype caused by VCP mutations. The p.Asp98Val mutation was found to be a novel pathogenic mutation of VCP proteinopathy. We believe our cases represent a wide clinical spectrum of VCP mutations.

We herein report an autopsy case of a 69-year-old man with pseudopseudohypoparathyroidism. The patient suffered from mental retardation and spastic tetraparesis and had all the features of Albright's hereditary osteodystrophy with a normal response to parathyroid hormone in the Ellsworth-Howard test. Computed tomography demonstrated symmetrical massive brain calcification involving the bilateral basal ganglia, thalami, dentate nuclei and cerebral gray/white matter junctions, which was consistent with Fahr's syndrome. Magnetic resonance imaging revealed extensive white matter changes sparing the corpus callosum. Severe ossification of the posterior longitudinal ligament of the cervical spine was also demonstrated. A neuropathological examination revealed massive intracranial calcification within the walls of the blood vessels and capillaries with numerous calcium deposits. The calcium deposits aligned along the capillaries, and deposits in the vessel wall at the initial stage were confined to the border between the tunica media and adventitia. The vascular calcification in the basal ganglia continuously spread over the surrounding white matter into the cortex. The area of vascular calcification in the white matter was very well correlated with the area of the attenuated myelin staining. Axonal loss, myelin sheath loss and gliosis were observed in the white matter with severe vascular calcification. We should recognize the continuous area of vascular calcification and its correlation with extensive white matter changes as possible causes of neuropsychiatric symptoms in pseudopseudohypoparathyroidism with Fahr's syndrome.

Introduction A part of hypercalcemia is a paraneoplastic syndrome. Its association with lymph node metastasis of bladder cancer has been infrequently reported in the literature. Case presentation A 75-year-old male presented with gross hematuria and was diagnosed with bladder cancer without metastasis. Following neoadjuvant chemotherapy, radical cystectomy was performed. The surgical margin was negative. The bladder cancer was classified as pT3bN0 and mainly constituted squamous differentiated urothelial carcinoma and sarcomatoid variant. His perioperative serum calcium levels were normal. At 6 months of surgery, computed tomography revealed lymph node enlargement, and additional 2 weeks later, he developed epileptic seizures with a serum corrected calcium level of 18.7 mg/dL. He was diagnosed with hypercalcemia caused by the lymph node metastasis of bladder cancer. Despite receiving several supportive therapies for 22 days, he died. Conclusion Hypercalcemia associated with bladder cancer is highly resistant to existing therapy, particularly when caused by cancer metastasis.

Introduction Liposarcoma is a malignant neoplasm of the adipose tissue, and dedifferentiated liposarcoma is a relatively rare subtype. Liposarcomas are typically located in the lower extremities or retroperitoneum, but dedifferentiated liposarcoma of the spermatic cord is rare and no case of it with macroscopic ossification has been reported in the literature. Case presentation A male presented to our hospital with a painful, palpable, and hard left suprapubic mass, formed over 3 months. The mass was diagnosed as a spermatic cord tumor and was resected using high orchiectomy. Due to the histological diagnosis of dedifferentiated spermatic cord liposarcoma with ossification and positive margins, a second extended resection and adjuvant radiotherapy were performed. Conclusion To differentiate spermatic cord liposarcoma preoperatively is difficult. There is no gold standard treatment for it, although surgical complete resection with clear microscopic margins would be the most effective treatment.

Over the last three decades, the prognosis of osteosarcoma has remained unchanged; the prognosis for patients with lung metastasis is still poor, and the development of new treatments is urgently required. We previously showed that aggressive osteosarcoma cells express more tissue factor (TF) and demonstrate enhanced extrinsic pathway capacity. Furthermore, tumor growth can be suppressed with the anticoagulant low molecular weight heparin. However, the molecular mechanisms underlying TF regulation are still unclear. Here, we report that transforming growth factor-β (TGF-β) upregulates TF, which can occur via activated platelets. TF was found to be expressed on osteosarcoma cell surfaces, which mediated the production of Xa and thrombin. TF induction by TGF-β was observed in several osteosarcoma cells, and especially in MG 63 cells. Both TF expression by TGF-β and extrinsic pathway activity through TF were rapidly increased. This reaction was inhibited by a TGF-β type I receptor inhibitor and TGF-β neutralizing antibody. Although TGF-β was found to phosphorylate both Smad2 and Smad3, their roles were markedly disparate. Surprisingly, Smad2 knockdown resulted in no inhibitory effect, whereas Smad3 knockdown completely suppressed TGF-β-induced TF expression. Next, data suggested that platelets were the source of TGF-β. We confirmed that thrombin-activated platelets and osteosarcoma cells could release TGF-β, and that platelet-derived TGF-β could induce TF expression. These processes were also inhibited by a TGF-β type I receptor inhibitor and Smad3 knockdown. Moreover, CD42b, TF, TGF-β, Smad2/3, and p-Smad2/3 were also detected in a biopsy sample from an osteosarcoma patient. Collectively, these finding suggested that the interaction between osteosarcoma cells and platelets, via thrombin and TGF-β, results in a continuous cycle, and that anti-platelet or anti-TGF-β therapy could be a promising tool for disease treatment. © 2018 American Society for Bone and Mineral Research.

Primary leiomyosarcoma of the left common iliac artery with development of an arteriovenous fistula is extremely rare. Here we report the case of a 78-year-old woman with primary vascular leiomyosarcoma that presented as acute heart failure involving an arteriovenous fistula. She underwent surgery; however, after the diagnosis of leiomyosarcoma, she did not seek active treatment. She died 8 months after the surgery. This case report supports the need to document and follow-up a primary leiomyosarcoma of the iliac artery, especially when a case includes the presentation of an arteriovenous fistula (AVF). Vascular leiomyosarcoma should be included in the differential diagnosis of an AVF.

A 64-year-old man was admitted with acute onset disturbed consciousness. Cerebrospinal fluid analysis revealed pleocytosis and elevated protein, with negative cultures and PCR. Serum antibodies for autoimmune encephalitis were also negative. Brain magnetic resonance imaging (MRI) was unremarkable, but whole-body CT scan showed a tumor in the left lower lung lobe. Bronchial brush cytology demonstrated clusters of malignant cells, and 18 F-fluorodeoxyglucose positron emission tomography showed multiple lesions and increased uptake in the lung tumor. Clinically the patient had a stage IV lung carcinoma, graded as T3N3M1b (OSS). Steroid therapy had limited efficacy, but chemotherapy dramatically improved his neurological symptoms. Therefore, he was diagnosed with paraneoplastic autoimmune encephalitis based on the diagnostic criteria for paraneoplastic neurological syndromes. He died due to disease progression 14 months later. Subsequent postmortem examination revealed white ill-defined nodules in the left lung, with similar nodules in other organs. The brain weighed 1500 g before fixation, and a nodule was observed in the right precentral gyrus. Microscopically, the lung tumor was a pleomorphic carcinoma with an adenocarcinoma component. Multiple areas of micro-softening (≤500 μm) were identified in the cerebral cortex, gray-white matter junction and basal ganglia, and were distributed diffusely in both the limbic and non-limbic systems. Mild lymphocytic infiltrates were observed involving few intraparenchymal vessels. Few tumor metastases were observed in the right precentral gyrus. The multiple micro-softenings may reflect a chronic neuropathologic change of paraneoplastic autoimmune encephalitis. They were too small to be detected by brain MRI. However, these lesions may have the potential to cause the neurological symptoms in the acute phase because they were observed in many anatomical regions. We should pay attention to subtle findings such as micro-softenings when estimating the neuropathology of autoimmune encephalitis. Further investigations are needed to understand the characteristic neuropathology of this condition.

The (pro)renin receptor is important in the regulation of the tissue renin-angiotensin-aldosterone system. The benefits and safety of single-aliskiren treatment without other renin-angiotensin-aldosterone system inhibitors remain unclear. The serum level of the soluble form of the (pro)renin receptor is thought to be a biomarker reflecting the activity of the tissue renin-angiotensin-aldosterone system. We investigated the effects of single renin-angiotensin-aldosterone system blockade with aliskiren on renal and vascular functions and determined if serum level of the soluble (pro)renin receptor was a predictor of aliskiren efficacy in hypertensive patients with chronic kidney disease. Thirty-nine essential hypertensive patients with chronic kidney disease in our outpatient clinic were randomly assigned to receive either aliskiren or amlodipine. The parameters associated with renal and vascular functions and indices of renin-angiotensin-aldosterone system components, including serum levels of the soluble form, were evaluated before and after 12-week and 24-week treatment. Blood pressure was not significantly different between the groups. No significant changes in serum levels were observed in the soluble (pro)renin receptor in either group. Urinary albumin, protein excretion, and cardio-ankle vascular index significantly decreased in the aliskiren group. In the aliskiren group, there was a significant negative correlation between the basal level of the soluble (pro)renin receptor and the change in plasma aldosterone concentration. Single renin-angiotensin-aldosterone system blockade with aliskiren showed renal and vascular protective effects independent of blood pressure reduction. Serum levels of the soluble (pro)renin receptor may indicate aldosterone production via the (pro)renin receptor in the adrenal gland.

Endoscopic submucosal dissection (ESD) is recognized as an important technique in the nonsurgical management of early gastrointestinal carcinoma and it is continuously undergoing evolution in terms of technique and equipment. The pocket-creation method was recently developed for overcoming various difficulties such as large tumor size and severe fibrosis in ESD. Circumferential ESDs are rare and pose technical difficulties. We present a case of a circumferential rectal ESD using a pocket-creation method with two pockets. The associated planning, strategies, and outcome of the procedure are discussed.

A 41-year-old woman presented with recurrent dizziness. After an attack of dizziness, she felt edematous sensations in her hands. However, according to photographs taken during the attack, the edema on the back of the patient’s hands and fingers appeared mild. Laboratory examinations revealed a low C4 and C1 inhibitor (INH) activity. A direct sequencing analysis of C1INH revealed a pathogenic gene mutation. Based on these results, she was diagnosed with hereditary angioedema (HAE) type 1. These findings indicate that HAE can cause recurrent dizziness, and it should therefore be included in the differential diagnosis in patients with recurrent neurologic symptoms, even in the absence of severe edema.

BACKGROUND Clarifying the mechanisms underlying prostate cancer (PC) progression and resistance to androgen deprivation therapy (ADT) is an urgent clinical issue. ADT influences steroidal metabolism in patients with PC and promotes the accumulation of carbon 21 steroids (C21s), such as progestin. Because the enzymes responsible for C21s metabolism are similar to those for androgen metabolism, PC cells may be able to metabolize C21s intracellularly. Therefore, there is a possibility that intracrine C21s are implicated in PC progression and resistance to ADT, and the influence of C21s on PC cells is yet to be elucidated. In the present study, we focused on 20β-hydroxy-5α-dihydroprogesterone (20β-OHDHP), a C21s metabolized from progestin, and showed that 20β-OHDHP is synthesized in PC cells and is able to directly stimulate the androgen receptor (AR). METHODS LNCaP, VCaP, and DU145 cells, which express a mutant AR (mAR), wild-type AR (wAR), and glucocorticoid receptor (GR), respectively, were incubated in the presence of several agents. After incubation, cell growth was determined by the MTS assay. PSA levels were determined by an enzyme immunoassay, and C21s and androgen levels were measured using liquid chromatography-mass spectrometry. Gene expression was analyzed by quantitative real-time polymerase chain reaction, and steroidal-receptor-related signaling was determined by a reporter assay. RESULTS We affirmed that 20β-OHDHP was synthesized from pregnenolone intracellularly in LNCaP and VCaP cells, and 20β-OHDHP significantly promoted the growth of both cell lines without androgen conversion. 20β-OHDHP directly stimulated both mAR and wAR. The presence of 20β-OHDHP was sufficient for the proliferation and survival of LNCaP or VCaP cells, and 20β-OHDHP promoted cell growth even in the presence of abiraterone. Using DU145 cells, we affirmed that 20β-OHDHP did not stimulate GR, which has a potential to bypass AR signaling in PC cells promote PC cell growth. CONCLUSIONS Under ADT, 20β-OHDHP synthesized intracellularly from accumulated progestin in PC cells may accelerate cell growth via stimulation of both wAR and mAR. This pathway may represent an interesting candidate for targeted therapy.

Although asthma attacks are known adverse events associated with nonsteroidal anti-inflammatory drug (NSAID) use, few studies have quantified these risks. The objectives of this study were to utilize an epidemiological approach to quantitatively evaluate the risk of acute asthma attacks associated with NSAID prescription in Japan and to compare the risks among NSAIDs according to their cyclooxygenase (COX)-2 selectivity.We conducted a self-controlled case series study using Japanese health insurance claims data. Exposed cases were identified as those who had experienced both NSAID prescription and acute asthma attack, which was defined as the combination of an inhalation procedure and the prescription of any inhaled βWe identified 9769 subjects, more than 95% of whom were younger than 60 years. There was a significantly higher risk of acute asthma attacks during the NSAID prescription period when compared with the baseline period. The quantified IRRs were, in descending order, 93.94 (95% CI, 90.10-97.95) for the prescription start date, 3.96 (95% CI, 3.63-4.33) for 1 to 9 days after the prescription start date, 3.01 (95% CI, 2.78-3.25) for 7 days after the prescription end date, 2.19 (95% CI, 1.82-2.65) for9 days after the prescription start date, and 1.44 (95% CI, 1.29 -1.61) for 7 days before the prescription start date. There were lower asthmatic risks for COX-2 selective NSAIDs compared with nonselective NSAIDs.The use of NSAIDs in Japan was associated with an increased risk of acute asthma attacks. However, this risk was lower in COX-2 selective NSAIDs.

Steroid-sparing drugs, such as cyclosporine, are recommended as treatment for children with frequently relapsing nephrotic syndrome (FRNS) and steroid-related toxicities. We recently reported a high rate of relapsing nephrotic syndrome 2 years after discontinuation of cyclosporine treatment, suggesting that long-term treatment is necessary. Cyclosporine-associated nephrotoxicity (CAN) is a potential side effect of long-term cyclosporine treatment. We retrospectively reviewed pediatric patients with FRNS treated with cyclosporine for ≥3 years at a single center between 1999 and 2012. The cyclosporine dose was adjusted to maintain the whole-blood cyclosporine trough level at 80–100 ng/ml for 6 months, at 60–80 ng/ml for 18 months, and then at around 50–60 ng/ml thereafter. Maintenance dose of prednisolone was not prescribed. CAN was graded in terms of arteriolar hyalinosis and the degree of interstitial fibrosis. Thirty-six children (28 males) were enrolled in the study. The median age at the start of long-term cyclosporine treatment was 9.4 years. The median duration of the longest period of cyclosporine treatment was 4.5 years. Most CAN cases were characterized by arteriolar hyalinosis. The frequency of CAN was positively correlated with the duration of cyclosporine treatment, with an odds ratio (95% confidence interval) for CAN of 3.84 (0.79–18.74) after 2–5 years and 6.60 (1.18–36.94) after >5 years of cyclosporine treatment (vs. 0–2 years). Although the frequency of CAN was correlated with the duration of cyclosporine treatment in our pediatric patient population, most cases of CAN involved arteriolar hyalinosis. We conclude that long-term cyclosporine treatment is useful for treating FRNS in children, providing its dose is controlled and kidney biopsies are regularly performed.

Objective The management of blood pressure (BP) in hypertensive patients is the key to preventing a progression of organ damage. The brachial BP (bBP) has been used as the representative method for measuring the BP. The central BP (cBP), which is, different from the bBP due to the propagation and the reflection of the pulse wave in the arterial system, has recently received attention because it can now be estimated non-invasively. We examined the relationships between the difference in the central systolic BP (csBP) and the brachial systolic BP (bsBP) (Δ) and other factors in hypertensive patients. Methods The bsBP and csBP were measured in patients with essential hypertension and the relationships between the bsBP, csBP, or Δ and background factors including age, the brain natriuretic peptide (BNP) level, the estimated glomerular filtration rate (eGFR), flow-mediated vasodilation (an index of vascular endothelial function), the cardio-ankle vascular index (CAVI, an index of arteriosclerosis), and the carotid intima-media thickness (an index of atherosis) were investigated. Results The data of 191 patients were analyzed. Although there was no significant correlation between the CAVI and the bsBP; positive correlations were observed between the CAVI and the csBP (r=0.249, p=0.001). The Δ value showed significant positive correlations with age, and the BNP, eGFR, and CAVI values. Conclusion The csBP is more strongly associated with arteriosclerosis than the bsBP. Moreover, the Δ value is more strongly associated with cardiac function, renal function, and arteriosclerosis than the bsBP or csBP. These data suggested that the Δ value may have a greater prognostic value than the bsBP or csBP and may be worth calculating in the clinical setting.

A 77-year-old woman with Parkinson's disease presented with left chest pain. Physical examination revealed tenderness at her second left sternocostal joint. There was no skin rash. Chest CT revealed hyperostosis of the sternocostal joint, and cervical MRI showed vertebral osteosclerosis and osteolysis. 99mTc-MDP bone scintigraphy showed an increased activity in the sternocostal joint and vertebral column. The patient was diagnosed with SAHPO syndrome according to the diagnostic criteria. Her chest pain was relieved after oral administration of nonsteroidal anti-inflammatory drugs. Although pain is a common non-motor symptom of Parkinson's disease, chest pain is relatively rare, according to a previous reports. When patients with Parkinson's disease complain of chest pain, physicians should make an appropriate differential diagnosis after excluding emergent cardiovascular disease. To the best of our knowledge, this is the first report of Parkinson's disease associated with SAPHO syndrome. The relationship between the two diseases is unclear. However, peripheral inflammation is known to exacerbate ongoing neuronal damage in neurodegenerative diseases, such as Parkinson's disease. Therefore, systemic inflammation of SAPHO syndrome may affect the disease course of Parkinson's disease.

International audience; Granulovacuolar degeneration (GVD) is usually found in Alzheimer's disease (AD) cases or in elderly individuals. Its severity correlates positively with the density of neurofibrillary tangles (NFTs). Mechanisms underlying GVD formation are unknown. We assessed the prevalence and distribution of GVD in cases with TDP-43-related frontotemporal lobar degeneration (FTLD-TDP) and amyotrophic lateral sclerosis (ALS-TDP). Consecutively autopsied cases with FTLD/ALS-TDP and C9orf72 mutations (FTLD/ALS-C9; N = 29), cases with FTLD/ALS-TDP without C9orf72 mutations (FTLD/ALS-nonC9; N = 46), and age-matched healthy controls (N = 40) were studied. The prevalence of GVD was significantly higher in the FTLD/ALS-C9 cases (26/29 cases) than in the FTLD/ALS-nonC9 cases (15/46 cases; Fisher exact test; p

Duodenal and rectal obstructions due to urological malignancies are relatively uncommon. We report an autopsy case of an 83-year-old man with a history of renal pelvic cancer who presented these obstructions. Autopsy revealed that urothelial cancer infiltrated the bladder wall, duodenal wall, rectal wall, and prostate and widely spread in the retroperitoneal lymphatic vessel. We concluded that renal pelvic cancer recurred in the bladder wall and then infiltrated into each organ because of lymphatic dissemination. The gastrointestinal obstructions due to urinary tract cancer were lethal. Further knowledge and clinical experience regarding these types of obstructions are crucial. Keywords: Duodenal obstruction, Lymphatic dissemination, Rectal obstruction, Urothelial carcinoma

Cerebral infarction in patients with cancer is often called Trousseau's syndrome, which is a cancer-associated hypercoagulative state that causes thrombosis; however, the syndrome is rarely caused by bladder cancer. We report a case of Trousseau's syndrome manifesting as multiple cerebral infarctions caused by advanced bladder cancer in a 46-year-old male patient. The patient died due to the infarctions in the hospital. The prognosis of patients with Trousseau's syndrome caused by advanced cancer is poor. According to changing urological clinical settings, considering the risk of Trousseau's syndrome has become crucial for urologists treating patients with advanced cancer. Keywords: Bladder cancer, Cerebral infarction, Trousseau's syndrome, Urothelial cancer

To study discoid meniscus in children who underwent arthroscopic surgery at our center.Thirty-four patients (39 knees) younger than 15 years with discoid lateral meniscus (mean age, 12.9 years; 13 males, 21 females) who underwent arthroscopic surgeries since 2007 were studied. The surgical procedure consisted of, in principle, saucerization with additional suture repair in the case of meniscal instability at the peripheral rim of the residual meniscus. The mechanisms of symptom onset, symptoms, complications and postoperative outcome in these cases were examined. In addition, Lysholm scores were obtained before surgery and at the last postoperative follow-up in all patients.Symptom onset was associated with sports in 18 knees, fall in 3 knees, and no definitive trigger in the remaining knees. The presenting symptoms were pain in 32 knees, catching in 11 knees, and locking in 6 knees. According to Watanabe classification, 26 knees were complete type and 13 knees were incomplete type. The modes of tear included horizontal tear in 10 knees and longitudinal tear in 10 knees, while no definitive tear was present on the knee joint surface. The surgical procedures included saucerization only in 22 knees, partial meniscectomy in 10 knees, and saucerization with suture repair in 5 knees. The mean Lysholm score was 63.9 before surgery, and improved significantly to 92.3 at the last follow-up. Only two knees developed osteochondritis dissecans after surgery. Two knees required reoperation; one knee underwent subtotal meniscectomy and one knee had partial meniscectomy with suturing.Although the short-term outcome after saucerization with or without suture repair for discoid meniscus is favorable, degenerative change or change of lower limb alignment may occur in the long term. Further long-term study is required.

Little is known regarding the epidemiology of idiopathic nephrotic syndrome (INS) in East Asia. Previous studies have suggested higher incidence of INS in Asian children, though decreasing trend of its incidence has also been shown. We conducted a nationwide study of Japanese children aged 6 months to 15 years with INS. Children who were newly diagnosed with INS between 1 January 2010 and 31 December 2012 were eligible. Children with congenital nephrotic syndrome or nephrotic syndrome secondary to nephritis were excluded. A total of 2099 children were initially diagnosed with INS and were followed for up to 4 years. The estimated incidence of INS was 6.49 cases/100,000 children per year, without clear correlation with geographical region. The male:female ratio was 1.9 and approximately 50 % of children were

A 37-year-old man was hospitalized for an evaluation of acute bilateral multiple subcortical infarcts. There were no specific signal abnormalities in the temporal pole or external capsule. An abdominal skin biopsy showed granular, electron-dense, osmiophilic material (GOM) in the smooth muscle cells on electron microscopy. A direct sequencing analysis of NOTCH3 revealed a heterozygous c.986G>A substitution in exon 6, resulting in a Cys329Tyr amino acid replacement. According to these findings, the patient was diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencehalopathy (CADASIL). Thus, early phases of CADASIL can present as acute bilateral multiple subcortical infarcts without a characteristic temporal pole or any external capsule lesions.

BackgroundInformation on the epidemiology of idiopathic nephrotic syndrome (INS) in children, complications of INS and the side effects of steroid therapy is scarce.MethodsThe Japanese Pediatric Survey Holding Information of Nephrotic Syndrome, a nationwide cohort study, was conducted by the Japanese Study Group of Renal Disease in Children and enrolled 2099 children with newly diagnosed INS between 1 January 2010 and 31 December 2012. We conducted a follow-up study of the complications during the first onset and the patients’ prognosis in this cohort.ResultsWe obtained follow-up data on 999 children (672 males) with a median age at onset of 4.5 years [interquartile range (IQR) 2.8–9.4] and a median follow-up period of 4.1 years (IQR 2.5–5.1). At the first onset, 24% of patients experienced severe acute kidney injury (AKI), defined as a serum creatinine increase to a level two or more times the baseline. On logistic regression analysis, age, hematuria, severe hypoalbuminemia (serum albumin ConclusionBased on the results of a multicenter questionnaire survey, the overall survival and renal survival rates were found to be excellent. However, proper management of complications, particularly in AKI and ocular hypertension, is mandatory.

Background The objective of this randomized phase II trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, as the current standard sequence for metastatic colorectal cancer patients. Patients and methods Patients with KRAS exon 2 wild-type metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab ± irinotecan (R-C arm), or the reverse sequence [cetuximab ± irinotecan followed by regorafenib (C-R arm)]. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life. Exploratory end points included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA or multiple serum or plasma proteins. Results One-hundred one patients were randomized and eligible for efficacy analysis. Sequential treatment was successful in 86% patients in both arms. Median OS for R-C and C-R was 17.4 and 11.6 months, respectively (P = 0.0293), with a hazard ratio (HR) of 0.61 for OS [95% confidence interval (CI) 0.39–0.96]. The HR for PFS1 (regorafenib in R-C versus cetuximab in C-R) was 0.97 (95% CI 0.61–1.54), and PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI 0.17–0.50). No unexpected safety signals were observed. The quality of life scores during the entire treatment period was not significantly different between the two arms. Circulating biomarker analyses showed emerging oncogenic alterations in RAS, BRAF, EGFR, HER2, and MET, which were more commonly detected after cetuximab than after regorafenib. Conclusions The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence.

Background In Japan, several large healthcare databases have become available for research since the early 2000’s. However, validation studies to examine the accuracy of these databases remain scarce. We conducted a validation study in order to estimate the positive predictive value (PPV) of local or ICD-10 codes for acute myocardial infarction (AMI) in Japanese claims. In particular, we examined whether the PPV differs between claims in the Diagnosis Procedure Combination case mix scheme (DPC claims) and in non-DPC claims. Methods We selected a random sample of 200 patients from all patients hospitalized at a large tertiary-care university hospital between January 1, 2009 and December 31, 2011 who had an inpatient claim assigned a local or ICD-10 code for AMI. We used a standardized data abstraction form to collect the relevant information from an electronic medical records system. Abstracted information was then categorized by a single cardiologist as being either definite or not having AMI. Results In a random sample of 200 patients, the average age was 67.7 years and the proportion of males was 78.0%. The PPV of the local or ICD-10 code for AMI was 82.5% in this sample of 200 patients. Further, of 178 patients who had an ICD-10 code for AMI based on any of the 7 types of condition codes in the DPC claims, the PPV was 89.3%, whereas of the 161 patients who had an ICD-10 code for AMI based on any of 3 major types of condition codes in the DPC claims, the PPV was 93.8%. Conclusion The PPV of the local or ICD-10 code for AMI was high for inpatient claims in Japan. The PPV was even higher for the ICD-10 code for AMI for those patients who received AMI care through the DPC case mix scheme. The current study was conducted in a single center, suggesting that a multi-center study involving different types of hospitals is needed in the future. The accuracy of condition codes for DPC claims in Japan may also be worth examining for conditions other than AMI such as stroke.

Context Cyclic Cushing syndrome is a rare variant of Cushing syndrome that demonstrates periodic cortisol excess. It has been thought that inhibition of a glucocorticoid positive-feedback loop is associated with remission of hypercortisolism in ACTH-dependent cyclic Cushing syndrome. However, the underlying mechanism that triggers the development of the hypercortisolism is still unknown. We observed a case of ACTH-dependent cyclic Cushing syndrome that was developed by exogenous glucocorticoids, possibly through a glucocorticoid positive-feedback loop. Case Description A 75-year-old woman had experienced cyclic ACTH and cortisol elevations six times in the previous 4 years. Her diagnosis was cyclic Cushing syndrome. During the hypercortisolemic phase, neither low-dose nor high-dose dexamethasone suppressed her plasma ACTH and cortisol levels. Daily metyrapone therapy decreased her plasma cortisol and ACTH levels during every hypercortisolemic phase. After the sixth remission of a hypercortisolemic phase, she took 25 mg of hydrocortisone for 4 weeks and developed ACTH-dependent hypercortisolemia. Treatment with 1 mg of dexamethasone gradually increased both plasma ACTH and cortisol levels over 2 weeks, resulting in the eighth hypercortisolemic phase. Treatment using a combination of dexamethasone and metyrapone did not increase plasma ACTH or cortisol level and successfully prevented development of ACTH-dependent hypercortisolism. Conclusion We present an interesting case of cyclic Cushing syndrome in which ACTH-dependent hypercortisolemic phases relapsed during exogenous glucocorticoid treatment. A glucocorticoid positive-feedback loop and endogenous glucocorticoid synthesis may play key roles in the periodicity of hypercortisolism in cyclic Cushing syndrome.

Background Clostridium ramosum is a generally non-pathogenic enteric anaerobe, and Fournier’s gangrene is a rare necrotizing soft tissue infection with male predisposition affecting the perineum and the genital area. We report, to our knowledge, the first case of Fournier’s gangrene caused by C. ramosum in a female patient with multiple underlying conditions. Case presentation A 44-year-old woman with a 6-year history of insulin-dependent diabetes mellitus after total pancreatectomy and an 11-year history of central diabetes insipidus developed a pain in the genital area after a month of urinary catheter use. The lower abdominal pain worsened gradually over 2 weeks, and the pain, general fatigue, and loss of appetite prompted the patient’s hospital admission. As she had severe edema in her pelvic and bilateral femoral areas, ceftriaxone was started empirically after collecting two sets of blood cultures. On hospital day 2, CT examination revealed the presence of necrotizing faciitis in the genital and pelvic areas, and the antibiotics were changed to a combination of meropenem, vancomycin, and clindamycin. Gram-positive cocci and gram-positive rods were isolated from blood cultures, which were finally identified as Streptococcus constellatus and C. ramosum using superoxide dismutase and 16S rDNA sequencing. An emergent surgery was performed on hospital day 2 to remove the affected tissue. Despite undergoing debridement and receiving combined antimicrobial chemotherapies, the patient’s clinical improvement remained limited. The patient’s condition continued to deteriorate, and she eventually died on hospital day 8. In the present case, the underlying diabetes mellitus, urinary incontinence due to central diabetes insipidus, undernutrition, and edema served as the predisposing conditions. Conclusions C. ramosum is a potentially opportunistic pathogen among immunosuppressed persons and a rare cause of necrotizing fasciitis.