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Amyotrophic lateral sclerosis (ALS) is an incurable neurological disease, and patients diagnosed with ALS have a survival time of 2–5 years without life-sustaining therapy. Decision-making processes for the acceptance or decline of percutaneous endoscopic gastrostomy (PEG) and tracheostomy with invasive ventilation (TIV) therapy are complex and multifaceted. In this study, we examined whether participation or no participation in clinical trials of ALS had an influence on the decision-making processes of ALS patients. Fifty-seven consecutive ALS participants were recruited. Two participants did not wish to participate in any clinical trials, and Twenty-two participants were enrolled in clinical trials. Twenty-three participants wished to participate but could not be enrolled in any of the clinical trials because they exceeded the number of participants in these trials or they met the exclusion criteria. At baseline, there was no significant difference in the preference rates for PEG and TIV between the participant and non-participant groups, but after the double-blind period/6 months, both preference rates were significantly higher in the non-participant group than in the participant group. Notably, the rate of preferred TIV in the participant group drastically decreased after the double-blind period. A single regression analysis revealed that participation in clinical trials had a strong influence on the change of TIV preference for 6 months. Participation in a clinical trial decreases the willingness to prolong life after the clinical trial. The present results are meaningful when designing clinical trials and discussing life-sustaining treatments with ALS patients.

INTRODUCTION To compare the efficacy and tolerability of dapagliflozin with those of sitagliptin and metformin in patients with type 2 diabetes who have never received glucose-lowering agents. METHODS In this randomized, 12-week, open-label, active-controlled trial, 32 patients were randomly assigned to receive dapagliflozin 5 mg, sitagliptin 50 mg, or metformin 1000 mg per day for 12 weeks. At baseline and at week 12, the patients underwent a meal tolerance test (MTT). RESULTS After 12 weeks of treatment, the changes in fasting and postprandial plasma glucose and plasma glucose area under the curve (AUC)0-120 min levels during the MTT from baseline were significantly improved in the three study groups, and there were no significant differences among the three study groups (P

Background Suture granuloma with hydronephrosis after abdominal surgery is extremely rare. We herein report a successfully treated case of suture granuloma with hydronephrosis caused by ileostomy closure after rectal cancer surgery. Case presentation A 63-year-old male underwent laparoscopic low anterior resection with covering ileostomy. Two months after primary operation, ileostomy closure was performed with two layered hand-sewn suture (Albert–Lembert method) using absorbable suture. In that operation, marginal blood vessels in the mesentery were ligated with silk suture. The patient had remained in remission with no evidence of tumor recurrence, however, 2 years and 5 months after primary surgery, a contrast-enhanced computed tomography (CT) scan showed a mass-forming lesion on the right external iliac artery (43 × 26 mm) and hydronephrosis. Positron emission tomography/computed tomography (PET/CT) showed a mass-forming lesion without high accumulation, which obstructed the right ureter. Recurrence could not be ruled out due to the rapid appearance of tumor and hydronephrosis in the short-term period. Thus, the patient underwent laparotomy. The tumor located in the mesentery near the anastomosis of ileostomy closure and it was strongly adherent to the retroperitoneum, which obstructed the right ureter. The adhesion between the tumor and ureter was carefully dissected and tumor resection with partial small bowel resection was then performed with preservation of the ureter using ureteral stents. Pathological examination of the tumor revealed fibrous proliferation of foreign body granuloma. In the resected tumor, sutures with foreign giant cells were found. Therefore, we diagnosed the tumor as silk suture granuloma, which was caused by the silk suture used to ligate blood vessels of the mesentery at the ileostomy closure. The patient remained well with no evidence of tumor recurrence as 5 years after the primary operation of rectal cancer. Conclusions Suture granuloma is a rare surgery-related complication in the postoperative surveillance of patients with colorectal cancer. If suture granuloma mimicking local recurrence is a differential diagnosis, it would be important to consider to avoid unnecessary extended resection.

Stroke is a disease that easily impairs skeletal muscle characteristics, resulting in low quantity, low quality, and poor strength. However, the recovery process of skeletal muscles in patients with stroke is not well established.We aimed to determine the longitudinal changes in skeletal muscle characteristics in patients with stroke during intensive rehabilitation and examine their relationship with functional recovery.Eighty-five patients with stroke were prospectively recruited. We defined muscle quantity and quality as ultrasonographic muscle thickness and echo intensity, respectively, and muscle strength as knee extension strength. These skeletal muscle characteristics were compared at four time points: on admission, after 2 weeks, after 4 weeks, and at discharge. We also explored the relationship between changes in skeletal muscle characteristics and functional recovery.Non-paretic knee extension torque (F = 5.838,The present study revealed that knee extension muscle strength on the non-paretic side and quadriceps and tibialis anterior thickness on the paretic side significantly improved over time and that changes in the paretic side quadriceps thickness were associated with the recovery of balance ability.

A rapid and simple cancer detection method independent of cancer type is an important technology for cancer diagnosis. Although the expression profiles of biological molecules contained in cancer cell-derived extracellular vesicles (EVs) are considered candidates for discrimination indexes to identify any cancerous cells in the body, it takes a certain amount of time to examine these expression profiles. Here, we report the shape distributions of EVs suspended in a solution and the potential of these distributions as a discrimination index to discriminate cancer cells. Distribution analysis is achieved by low-aspect-ratio nanopore devices that enable us to rapidly analyze EV shapes individually in solution, and the present results reveal a dependence of EV shape distribution on the type of cells (cultured liver, breast, and colorectal cancer cells and cultured normal breast cells) secreting EVs. The findings in this study provide realizability and experimental basis for a simple method to discriminate several types of cancerous cells based on rapid analyses of EV shape distributions.

Alpha‐synuclein is a major component of Lewy bodies, which are a histological hallmark of Parkinson's disease (PD). In this study, we investigated the dynamics of α‐synuclein during the early stage of immature dopaminergic neurons differentiated from human‐induced pluripotent stem cells derived from either a PD patient with SNCA triplication or a healthy donor., Parkinson's disease (PD) is a neurodegenerative disorder caused by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Lewy bodies (LBs), another histological hallmark of PD, are observed in patients with familial or sporadic PD. The therapeutic potential of reducing the accumulation of α‐synuclein, a major LB component, has been investigated, but it remains unknown whether the formation of LBs results in the loss of DA neurons. PARK4 patients exhibit multiplication of the α‐synuclein gene (SNCA) without any pathological mutations, but their symptoms develop relatively early. Therefore, study of PARK4 might help elucidate the mechanism of α‐synuclein aggregation. In this study, we investigated the dynamics of α‐synuclein during the early stage of immature DA neurons, which were differentiated from human‐induced pluripotent stem cells (hiPSCs) derived from either a PARK4 patient with SNCA triplication or a healthy donor. We observed increased α‐synuclein accumulation in PARK4 hiPSC‐derived DA neurons relative to those derived from healthy donor hiPSCs. Interestingly, α‐synuclein accumulation disappeared over time in the PARK4 patient‐derived DA neurons. Moreover, an SNCA‐specific antisense oligonucleotide could reduce α‐synuclein levels during the accumulation stage. These observations may help reveal the mechanisms that regulate α‐synuclein levels, which may consequently be useful in the development of new therapies for patients with sporadic or familial PD.

Several recent reports have shown that a stentless interventional procedure using rotational atherectomy followed by drug-coated balloon (DCB) treatment (RA/DCB) is a potent revascularization therapy for calcified de novo lesions even in the new-generation drug-eluting stent era; however, the role of the RA/DCB procedure for noncalcified de novo lesions remains unclear.A total of 47 consecutive patients (53 lesions) who underwent RA/DCB for coronary de novo lesions were enrolled. According to the presence or absence of severe calcification at target lesions on fluoroscopy, the 47 patients were divided into the noncalcified cases (n = 12) and the calcified cases (n = 35), and the 53 lesions were divided into the noncalcified lesions (n = 14) and the calcified lesions (n = 39).The noncalcified cases tended to have a higher frequency of bleeding risk and had a significantly lower prevalence of dual antiplatelet therapy compared with the calcified cases. The main lesion-specific factors for the RA/DCB procedure among the noncalcified lesions were presence of left circumflex coronary artery ostial lesion. The final burr size, DCB diameter used, and angiographic success rate did not significantly differ between the 2 groups. The noncalcified lesions had a larger reference diameter and a shorter lesion length than the calcified lesions, whereas acute gain and late lumen loss did not differ between the 2 groups. Nine-month clinical outcomes were comparable between the 2 groups.Under drug-eluting stent-unsuitable clinical or lesion conditions, acute and midterm outcomes of RA/DCB for noncalcified de novo lesions might be comparable with those for calcified de novo lesions.Plusieurs rapports récents ont montré qu’une revascularisation sans endoprothèse effectuée par athérectomie rotationnelle (AR) suivie d’un traitement par ballonnet médicamenté (BM) constitue une méthode efficace pour traiter les nouvelles lésions calcifiées, même à l’ère des endoprothèses médicamentées de nouvelle génération; on ne connaît toutefois pas bien l’utilité de l’intervention par AR et BM en cas de nouvelles lésions non calcifiées.Au total, 47 patients consécutifs (53 lésions) ayant subi une intervention par AR et BM pour traiter de nouvelles lésions coronariennes ont été admis dans l’étude. Ces 47 patients ont été répartis en deux groupes, en fonction de l'absence (n = 12) ou de la présence (n = 35) de lésions . cibles sévèrement calcifiées observées à la fluoroscopie. Les 53 lésions ont aussi été réparties en deux groupes : lésions non calcifiées (n = 14) et lésions calcifiées (n = 39).Les patients n’ayant pas de lésion calcifiée étaient généralement plus susceptibles de présenter des saignements et significativement moins nombreux à être sous bithérapie antiplaquettaire, comparativement aux patients ayant des lésions calcifiées. Dans le cas des lésions non calcifiées, la principale caractéristique justifiant une AR et un traitement par BM était la présence d’une lésion ostiale du rameau circonflexe de l’artère coronaire gauche. La taille de la dernière fraise utilisée, le diamètre du BM utilisé et le taux de réussite objectivée par angiographie étaient comparables dans les deux groupes. Les lésions non calcifiées avaient un diamètre de référence plus grand et étaient plus courtes que les lésions calcifiées, tandis que le gain aigu et la perte luminale tardive étaient similaires dans les deux groupes. Les résultats cliniques à neuf mois étaient aussi similaires dans les deux groupes.Lorsque les conditions cliniques ou les lésions ne se prêtent pas à l’utilisation d'une endoprothèse médicamentée, le traitement des nouvelles lésions non calcifiées par AR et BM pourrait donner des résultats immédiats et à moyen terme comparables à ceux du traitement des nouvelles lésions calcifiées.

A biomembrane's role is to be a barrier for interior cytosol from an exterior environment to execute the cell's normal biological functions. However, a water-soluble peptide called cell-penetrating peptide (CPP) has been known for its ability to directly penetrate through the biomembranes into cells (cytolysis) without perturbating cell viability and expected to be a promising drug delivery vector. Examples of CPP include peptides with multiple arginine units with strong cationic properties, which is the key to cytolysis. Here we show the conclusive evidence to support the mechanism of CPP’s cytolysis and way to control it. The mechanism we proposed is attributed to biomembrane’s physicochemical nature as lamellar liquid crystal (Lα). Cytolysis occurs as the temporal and local dynamic phase transitions from Lα to an undulated lamellar with pores called Mesh1. We have shown this phase transfer of Lα composed of dioleoyl-phosphatidylcholine (DOPC) with water by adding oligo-arginine (Rx) as CPP at the equilibrium. Using giant unilamellar vesicle composed of DOPC as a single cell model, we could control the level of cytolysis of CPP (FITC-R8) by changing the curvature of the membrane through osmotic pressure modulation. The cytolysis of CPP utilizes biomembrane's inherent topological and functional flexibility corresponding to the stimuli.

A 3‐month‐old male cross‐breed dog presented with signs of progressive diffuse brain disease. Noncommunicating congenital hydrocephalus concurrent with cervical syringomyelia was diagnosed on magnetic resonance images. On time‐spatial labeling inversion pulse (Time‐SLIP) images CSF flow through the mesencephalic aqueduct was poorly defined and there was flow into the syrinx across the craniocervical junction. After percutaneous ventricular drainage and ventriculoperitoneal shunting, CSF flow through the aqueduct was clearly detected and flow into the syrinx disappeared. In addition, CSF flow in the subarachnoid space at the pons and ventral aspect of the cervical subarachnoid space was restored. Signs of neurological dysfunction improved after ventriculoperitoneal shunting and the cerebral parenchyma was increased in thickness on 2‐year follow‐up computed tomography images. Patterns of CSF flow on Time‐SLIP images before and after CSF drainage or ventriculoperitoneal shunting aid in clarifying disease pathogenesis and confirm effects of CSF drainage.

The ideal treatment for intracranial histiocytic sarcoma (HS) remains unclear. Herein, we report a case of intracranial HS that was successfully treated using prednisolone and radiation therapy. The patient was a 9-year-old spayed female Pembroke Welsh Corgi that presented with epileptic seizures. Magnetic resonance imaging revealed a contrast-enhancing mass adjacent to the right piriform lobe. Prednisolone administration (1 mg/kg/day) decreased the lesion size. Additional palliative radiation therapy (total dose, 37 Gy) resulted in complete disappearance of the lesion. However, on day 164, the dog’s neurological signs deteriorated, and she was euthanized. Necropsy revealed an intracranial metastasis of HS via the cerebrospinal fluid without any extracranial metastasis. Nonetheless, combined prednisolone and radiation therapy might be effective in treating intracranial HS.

OBJECTIVES To investigate the effect of motivation on improvements in the Functional Independence Measure (FIM) scores in subacute stroke patients with cognitive impairment. METHODS This retrospective cohort study included 358 consecutive subacute stroke patients with first-ever stroke and Mini-Mental State Examination score ≤23 at admission. We determined motivation and rehabilitation outcome using the vitality index and FIM-motor gain, respectively. Stepwise multiple regression analysis was performed to identify the factors at admission related to FIM-motor gain. RESULTS Of 80 participants enrolled in this study (mean age: 74.2 ± 11.3 years). The median (interquartile range) vitality index at admission and FIM-motor gain were 7 (4) and 23 (22) points, respectively. Stepwise multiple regression analysis revealed that age (B, -0.43; 95% confidence interval [CI], -0.65-(-0.21); β, -0.31; P

The purpose of this study is to examine the rotational mechanisms of a helmeted head and the effects of whole-body kinematic behavior of a cyclist and head-helmet interaction on head rotation and b...

Systemic inflammatory response has been reported to be associated with prognosis in cancer patients. The aim of this study is to investigate the association between Systemic Immune-Inflammation Index (SII), a novel inflammation-based prognostic score and long-term outcomes among patients with colorectal cancer (CRC) after resection.We retrospectively investigated 733 patients who underwent resection for CRC between January 2010 and December 2014 at the Jikei University Hospital and explored the relationship between SII, calculated by multiplying the peripheral platelet count by neutrophil count and divided by lymphocyte count, and overall survival. In survival analyses, we conducted Cox proportional hazards models, adjusting potential confounders including TNM stage, serum CEA, serum CA 19-9, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and platelet count.In multivariate analysis, age ≥ 65 years (p = 0.003), tumor location (p = 0.043), advanced TNM stage (p 0.001), serum CA 19-9 37 mU/ml (p 0.001), and SII (P for trend = 0.017) were independent and significant predictors of poor patient survival. Compared to patients with low SII, those with high and intermediate SII patients had poorer survival (Hazard ratio 2.48; 95% CI 1.31-4.69, Hazard ratio 1.65; 95% CI 0.83-3.27, respectively).The Systemic Immune-Inflammation Index might be an independent and significant indicator of poor long-term outcomes in patients with CRC after resection.

Objective To report recovery of ambulation of dogs treated with extended thoracolumbar durotomy for severe spinal cord injury caused by intervertebral disc herniation. Study design Descriptive cohort. Animals Twenty-six consecutive paraplegic dogs presented with loss of deep pain sensation after acute thoracolumbar intervertebral disc herniation. Methods Each dog underwent routine diagnostic assessment and surgery for removal of extradural herniated intervertebral disc, followed by a four-vertebral body length durotomy centered on the herniated disc. Each dog was followed up until it was able to walk 10 steps without assistance or until 6 months after surgery. Results Sixteen of 26 dogs recovered to walk unaided (all but one also recovered fecal and urinary continence), and six dogs did not; four dogs were lost to follow-up. One dog was euthanized because of signs consistent with progressive myelomalacia. There was no evidence of detrimental effects of durotomy within the period of study. Using Bayesian analysis, we found a point estimate of successful outcome of 71% with 95% credible interval from 52% to 87%. Conclusion Extended durotomy seemed to improve the outcome of dogs in our case series without increase in morbidity. Clinical significance Extended durotomy appears safe and may improve the outcome of dogs with severe thoracolumbar mixed contusion and compressive injuries associated with acute intervertebral disc extrusion.

In rectal cancer surgery, an insufficient distal margin (DM) is associated with a high risk of local recurrence, whereas an excessive DM will cause low anterior resection syndrome, impairing quality of life. This study aimed to identify the factors that affect the distance between the colorectal resection site and the tumor to optimize achieving the correct DM. The subjects of this study were 219 patients who underwent resection for primary rectal cancer in our department between January 2006 and July 2014. According to Japanese guidelines, DM (rDM) was based on the tumor location, but the pathological DM (pDM) was measured from surgical specimens. The patients were divided into two groups: the pDM-less-than-rDM group (pDM

A 30-month-old Maine Coon presented with progressive proprioceptive ataxia, paraparesis, thoracolumbar pain, and decreased appetite. An extradural mass was detected within the left side of the 13th thoracic vertebral canal that compressed the spinal cord on magnetic resonance (MR) and was considered to be mineralized on computed tomography (CT) images. The resected mass was diagnosed as a vertebral vascular hamartoma. Clinical signs improved, but recurrence was diagnosed by MR and CT imaging at 7 months after surgery. Repeated excisional surgery yielded the same diagnosis and the clinical signs abated. Fifteen months after the second surgery, there was apparent vertebral deformation, but there was no further change on CT images by 29 months.

Background Trichinellosis is a serious zoonosis with a worldwide distribution. Fecund adult worms in the intestine release newborn larvae (NBL) that enter the general circulation from 4 days post infection (dpi). Alternatively activated macrophages in the peritoneal cavities and the diaphragms in Trichinella spiralis infected mice have been reported. However, a role of newborn larvae is poorly understood. Methods The total numbers of peritoneal macrophages in mice infected with 500 muscle-stage larvae were counted during early infection and then total RNA was extracted. Peritoneal macrophages from uninfected C57BL/6 mice were incubated with IL-4 or LPS as a control, or co-cultured with live NBL, and peritoneal macrophages were obtained from mice injected with live or frozen dead NBL into peritoneal cavity. Total RNA was extracted from these macrophages. Two types of gene expression, classical and alternative activation, were examined in the macrophages and diaphragms of the infected mice using semi-quantitative reverse transcription-PCR. Results The number of peritoneal macrophages in T. spiralis infected mice increased significantly. mRNA peak expression of alternative activation markers, Ym1 and arginase-1 (Arg1), was confirmed in the peritoneal macrophages and in diaphragm of mice around 15 dpi, while mRNA expression of classical activation markers, TNFα, IP-10, and iNOS was not detected. Injection of live NBL into the peritoneal cavities induced mRNA expression of Ym1 and Arg1 in the peritoneal macrophages of mice 9 dpi. However, dead NBL did not induce such gene expression. Alternative activation was not detected in the peritoneal macrophages co-cultured with NBL in vitro. Conclusion Gene expression of alternative activation makers, Ym1 and Arg1, was confirmed in the peritoneal macrophages and diaphragms of mice infected with T. spiralis. However, gene expression of classical activation markers was not detected. Live NBL induced an alternative activation of peritoneal macrophages in vivo, but not in vitro.

Corpus callosotomy (CC) is an established palliative surgery for human patients with drug-resistant epilepsy (DRE), especially those with generalized seizures and multiple or unknown epileptogenic focus. However, there are no reports to describe CC in canine patients with epilepsy. Three client-owned Cavalier King Charles Spaniels with DRE are included in this case series. In presurgical evaluations, an apparent epileptogenic zone was not detected in each dog and CC was conducted. Total CC was performed in one dog, whereas the other two received partial CC. One dog recovered from surgery without any complications, but died suddenly by an unknown cause at 10 h after surgery. For the other two dogs, postoperative evaluations including seizure outcomes, complications, and quality of life of the dogs and owners were assessed for at least 12 months. Both dogs showed a remarkable decrease in seizure frequency (averaged 80.3% reduction) and severity after surgery. The antiseizure medications were maintained, and not only the mentation and activity of the dogs, but also the quality of life of dogs and owners were improved postoperatively. Although technical improvement and more large-scale studies are needed, CC is a treatment option for dogs with DRE in veterinary medicine.

Nucleic acid therapeutics have been attracting attention as novel drug discovery modalities for intractable diseases including amyotrophic lateral sclerosis. This review provides an overview of the current status and prospects of antisense oligonucleotide treatment for amyotrophic lateral sclerosis. Recently, the results of a phase I/II study using the antisense oligonucleotides Tofersen to treat familial amyotrophic lateral sclerosis with superoxide dismutase 1 mutation have been reported. Intrathecal Tofersen administration resulted in a 36% reduction in superoxide dismutase 1 level in the cerebrospinal fluid. Another report described two patients with mutant superoxide dismutase 1 treated with an adeno-associated virus encoding a microRNA targeting superoxide dismutase 1. The first patient, who possessed the fast progressive mutant A5V, received a single intrathecal infusion. Although the patient died of respiratory arrest 16 months after treatment, autopsy findings showed a reduction of >90% in superoxide dismutase 1 level in the spinal cord. Clinical trials on antisense oligonucleotide therapies targeting other major amyotrophic lateral sclerosis-causative genes, Fused in sarcoma and chromosome 9 open reading frame 72, are ongoing. To attenuate the pathology of TDP-43, strategies targeting regulators of TDP-43 (ataxin 2) and proteins downstream of TDP-43 (stathmin 2) by antisense oligonucleotides are being developed. The advent of nucleic acid therapeutics has enabled to specifically attack the molecules in the amyotrophic lateral sclerosis pathological cascade, expanding the options for therapeutic targets. This article is protected by copyright. All rights reserved.

Highlights • Cognition at admission may predict daily step count. • Cognitive impairment may increase risk of poor ambulation after subacute stroke. • Ambulation poststroke is influenced by both physical and cognitive factors., Objectives To investigate the physical, cognitive, and psychological factors related to daily step count in patients with subacute stroke. Design Prospective cohort study. Setting A subacute rehabilitation ward with 160 beds. Participants Patients with subacute stroke who could walk independently (N=101). Among the 101 participants enrolled in this study (mean age, 64.5±13.5y), 64.4% (n=65) were men and 69.3% (n=70) were patients with cerebral infarction. Interventions We assessed ambulatory activity using a pedometer placed in the pants pocket on the nonparalyzed side continuously for 7 consecutive days. We also obtained demographic and clinical information and recorded the following measurement scores: Stroke Impairment Assessment Set, FIM, Mini-Mental State Examination (MMSE), Self-Rating Depression Scale, and Apathy Scale. All measurements were collected at admission and discharge. Main Outcome Measures The outcomes assessed were ambulatory activity, motor and sensory functions, functional disability, cognitive function, depressive symptoms, and motivation. Results The median daily steps ambulated at admission and discharge were 5584 steps (interquartile range, 3763-7096 steps) and 5991 steps (interquartile range, 4329-8204 steps), respectively. In the univariate regression analysis, age, sex, serum albumin level, affected side of the brain, and MMSE score at admission were significantly associated with the daily step count at discharge. Multiple regression analysis using these 5 items as independent variables revealed that the MMSE score at admission (reference, 28-30 points; B, −2.07; 95% confidence interval, −3.89 to −0.35; β, −0.22; P=.027) was significantly associated with the daily step count at discharge. Conclusions Cognitive function at admission had a significant association with the daily step count at discharge in patients with subacute stroke who could walk independently.

ObjectiveTo investigate the association between serum asymmetric dimethylarginine (ADMA) levels and the progression and prognosis of amyotrophic lateral sclerosis (ALS), and to compare cerebrospinal fluid (CSF) and serum ADMA levels with other biomarkers of ALS.MethodsSerum ADMA levels of patients with sporadic ALS (n = 68) and disease control patients (n = 54) were measured using liquid chromatography-tandem mass spectrometry. Serum samples were obtained at the time of patient registration for diagnosis. Correlations of ADMA level and other markers (nitric oxide [NO] and neurofilament light chain [NFL] levels) were analyzed. Changes in the ALS Functional Rating Scale–Revised (ALSFRS-R) score from the onset of disease (ALSFRS-R preslope) was used to assess disease progression. Survival was evaluated using the Cox proportional hazards model and Kaplan–Meier analysis.ResultsThe concentration of ADMA in CSF was substantially higher in patients with ALS than in disease controls. Serum ADMA level correlated with CSF ADMA level (r = 0.591, p < 0.0001), and was independently associated with the ALSFRS-R preslope (r = 0.505. p < 0.0001). Patients with higher serum ADMA levels had less favorable prognoses. CSF ADMA level significantly correlated with CSF NfL level (r = 0.456, p = 0.0002) but not with NO level (r = 0.194, p = 0.219).ConclusionADMA level is an independent biomarker of ALS disease progression and prognosis, and reflects the degree of motor neuron degeneration. The increased ADMA level in ALS patients was not associated with the inhibition of NO production.

Blunt traumatic popliteal artery occlusion is a condition on the verge of amputation ([1][1]). Open surgical repair is the first-line treatment ([1][1]), but endovascular treatment (EVT) can be successfully performed as an alternative on the basis of the clinical course. A 23-year-old man was

Background Even in the drug-eluting stent era, ostial lesion of the right coronary artery (RCA) still remains therapeutic challenge for interventional cardiologists. Case Series Case 1 (76 y.o. male) with angina on effort underwent transradial stent-less percutaneous coronary intervention (PCI) using rotational atherectomy (RA) followed by drug-coated balloon (DCB) dilation alone (RA/DCB) against a calcified de novo RCA ostial lesion. Case 2 (86 y.o. female) with recurrent unstable angina and hemodialysis underwent transfemoral RA/DCB against a severe repeat in-stent restenosis probably due to calcified nodule in the RCA ostium. In the both patients, PCI was successfully completed under intravascular ultrasound imaging (IVUS) guidance without complications. Follow-up CAG performed 4–5 months after the procedure revealed no significant lumen narrowing in the both RCA ostial lesions. Conclusions The both cases suggest that stent-less PCI using RA/DCB under IVUS might be an alternative revascularization therapy of choice for calcified RCA ostial lesions.

Spinal and bulbar muscular atrophy (SBMA) is a progressive hereditary neuromuscular disease caused by the testosterone-dependent accumulation of pathogenic polyglutamine-expanded androgen receptor protein. A 41-year-old man with SBMA received the androgen deprivation agent leuprorelin acetate for 7 years in clinical trials and underwent castration following the trial. Suppression of testosterone levels for 14 years resulted in a slower disease progression, as measured prospectively with quantitative measurements, than the historical control data reported in previous studies. This suggests that long-term androgen deprivation delays disease progression in SBMA.