Serum cytokine profiles in myasthenia gravis with anti-muscle-specific kinase antibodies.

This study measured the serum levels of of 15 cytokines in 15 patients with anti-muscle-specific kinase antibody-positive MG (MuSK-MG) using a multiplex suspension array system. Fifteen patients with non-inflammatory neurological diseases served as controls. Compared with controls, patients with MuSK-MG showed higher levels of Th1- (IFN-γ), Th2- (IL-25, IL-31, and IL-33), Th17- (IL-22), Treg-related cytokines (IL-10), and soluble CD40 ligand (sCD40L). Higher serum Th2-related cytokines (IL-25 and IL-31) levels were correlated with less MG Foundation of America (MGFA) class. These suggest that Th2-related cytokines have protective effects, whereas sCD40L and others may facilitate the disease.

Activation of the classical complement pathway in myasthenia gravis with acetylcholine receptor antibodies.

INTRODUCTION/AIMS: Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction (NMJ) of skeletal muscle. Complement activation is one of the mechanisms by which anti-acetylcholine receptor (anti-AChR) autoantibodies reduce synaptic transmission at the NMJ. In this study, we aimed to examine the activation of the complement pathways, including the classical pathway, as potential contributors to the pathogenesis of MG with anti-AChR antibodies. METHODS: In this single-center, observational study of 45 patients with anti-AChR-antibody-positive generalized MG, serum concentrations of major components of the complement pathways, including C1q, C5, C5a, soluble C5b-9 (sC5b-9), Ba, and complement factor H, were measured using an enzyme-linked immunosorbent assay. A total of 25 patients with a non-inflammatory neurological disorder served as controls. In addition, the relationships of complement activation with clinical characteristics were examined. RESULTS: The patients with MG exhibited lower serum levels of C5 (p = .0001) and higher serum levels of sC5b-9 (p = .004) compared with the control group. At about 6 months (range, 172-209 days) after the start of immunotherapy, serum levels of Ba were significantly higher than baseline levels (p = .002) and were associated with improvement in MG clinical scores. DISCUSSION: Herein, we provide evidence for the activation of the classical complement pathway and its association with disease activity in anti-AChR-antibody-positive generalized MG.

Role of soluble forms of follicular helper T-cell membrane molecules in the pathogenesis of myasthenia gravis.

This study examined the role of Tfh and Treg associated molecules also known as checkpoint molecules, their ligands, and IL-21 in myasthenia gravis (MG) pathogenesis. Serum levels of sPD-1, sPD-L1, sICOS, sICOSLG, sCTLA4, and IL-21 were measured in 39 patients with acetylcholine receptor (AChR) antibody-positive generalized MG and 27 controls. sPD-1 and IL-21 levels were higher in MG patients than in controls. Additionally, sPD-1 levels correlated positively with the levels of IL-21, sICOSLG, sCTLA4, and AChR antibody titers. sICOS are correlated with MGADL and AChR antibody titers. These Tfh associated molecules could be used as biomarkers of MG disease activity.

Serum pentraxin 3 concentration correlates with disease severity in patients with myasthenia gravis.

OBJECTIVE: Myasthenia gravis (MG) is an antibody-mediated inflammatory disease affecting post-synaptic membranes of neuromuscular junctions, and objective biomarkers of MG disease activity are lacking. Pentraxin 3 (PTX3) is an acute-phase inflammatory glycoprotein in the same family as C-reactive protein that is associated with disease activity in several autoimmune disorders. Thus, we investigated whether circulating PTX3 is a useful biomarker of MG activity. METHODS: Serum PTX3 was measured in 40 patients with MG who were positive for anti-acetylcholine receptor antibody, and in 30 healthy and disease controls, using a commercial enzyme-linked immunosorbent assay kit. In patients with MG, the correlation of serum PTX3 levels with disease severity scales at serum sampling, including MG Foundation of America (MGFA) classification, MG activity of daily living (MG-ADL) score, and quantitative MG (QMG) score, were investigated. RESULTS: Although there was no significant difference in serum PTX3 between the MG and control groups (mean, 3346 pg/mL in MG group vs. 2870 pg/mL in control group, P = 0.56), serum PTX3 moderately correlated with all disease severity scores (MGFA classification: Spearman's ρ = 0.53, P = 0.0004; MG-ADL score: Spearman's ρ = 0.45, P = 0.004; QMG score: Spearman's ρ = 0.50, P = 0.004). CONCLUSION: Our results suggest that circulating PTX3 may reflect the extent of neuromuscular junction damage and might be involved in the pathogenesis of MG.

Significance of pelvic lymph node dissection during radical prostatectomy in high-risk prostate cancer patients receiving neoadjuvant chemohormonal therapy.

We aimed to determine the survival and staging benefit of limited pelvic lymph node dissection (PLND) during radical prostatectomy (RP) in high-risk prostate cancer (PC) patients treated with neoadjuvant chemohormonal therapy. We retrospectively analyzed 516 patients with high-risk localized PC (< cT4N0M0) who received neoadjuvant androgen-deprivation therapy plus estramustine phosphate followed by RP between January 2010 and March 2020. Since we stopped limited PLND for such patients in October 2015, we compared the surgical outcomes and biochemical recurrence-free survival (BCR-FS) between the limited-PLND group (before October 2015, n = 283) and the non-PLND group (after November 2015, n = 233). The rate of node metastases in the limited-PLND group were 0.8% (2/283). Operation time was significantly longer (176 vs. 162 min) and the rate of surgical complications were much higher (all grades; 19 vs. 6%, grade ≥ 3; 3 vs. 0%) in the limited-PLND group. The inverse probability of treatment weighting-Cox analysis revealed limited PLND had no significant impact on BCR-FS (hazard ratio, 1.44; P = 0.469). Limited PLND during RP after neoadjuvant chemohormonal therapy showed quite low rate of positive nodes, higher rate of complications, and no significant impact on BCR-FS.

Prognostic impact of eligibility for adjuvant immunotherapy in locally advanced urothelial cancer.

Objective: To evaluate the effect of postoperative pathological findings related to the eligibility of adjuvant immunotherapy on oncologic outcomes in patients with localized and locally advanced muscle-invasive bladder carcinoma (MIBC) and upper tract urothelial carcinoma (UTUC). Patients and methods: We retrospectively evaluated 1082 patients treated with radical cystectomy (n = 597) and nephroureterectomy (n = 485) between January 2000 and April 2021. Patients were divided into two groups: pT3-4 or pN+ without neoadjuvant chemotherapy and ypT2-4 or pN+ treated with neoadjuvant chemotherapy (trial-eligible group) or others (trial-ineligible group). The primary outcome was the effect of trial eligibility for adjuvant immunotherapy on disease-free survival (DFS) and overall survival (OS). Secondary outcomes included the additional effect of lymphovascular invasion (LVI) status to the clinical trial criteria on prognosis and a risk model development. Results: The median ages of the patients were 69 and 72 years in the MIBC and UTUC groups, respectively. Fifty-two percent of patients met the trial inclusion criteria. Trial eligibility was significantly associated with poor DFS and OS among patients with MIBC and UTUC. LVI-positive status was significantly associated with poor prognosis among patients in the trial-eligible group. A very high risk (LVI+ or pN+ among the pT3-4 or ypT2-4) was significantly associated with poor prognosis. Conclusion: A total of 52% of patients were eligible for adjuvant immunotherapy. Trial eligibility was significantly associated with a poor prognosis. LVI+ and pN+ may play a key role in candidate selection for adjuvant immunotherapy.

Immunoadsorption apheresis versus intravenous immunoglobulin therapy for exacerbation of myasthenia gravis.

Immunoadsorption apheresis (IA) or intravenous immunoglobulin (IVIg) is used to treat exacerbation of myasthenia gravis (MG). This study aimed to compare the efficacy and safety between IA and IVIg for MG patients with anti-acetylcholine receptor (AChR) antibodies. We retrospectively studied 19 AChR antibody-positive generalized MG patients who underwent IA (n = 9) or IVIg treatment (n = 10). We reviewed the MG activities of daily living profile (MG-ADL) scores at baseline, 1 and 3 months after the treatment. Adverse events during the treatment period were also reviewed. The MG-ADL scores showed significantly greater improvement from the baseline in the IA group than in the IVIg group (1 month: -7 vs -3, P = .035; 3 months -9 vs -2.5, P = .016). An adverse event that led to the discontinuation of the treatment was observed in only one patient in the IVIg group (anaphylactic reaction). Our data suggest that the IA treatment is safe and more efficacious than the IVIg treatment for aggravation of anti-AChR-positive MG. Larger prospective studies are required to confirm the finding.

High levels of serum interleukin-6 are associated with disease activity in myasthenia gravis.

Myasthenia gravis (MG), a neuromuscular junction disorder, is caused by pathogenic autoantibodies. Interleukin-6 (IL-6) plays important roles in T helper 17 (Th17), T follicular helper (Tfh), and B cell activations as well as in antibody production. This study aimed to evaluate the clinical significance of serum IL-6 level as a biomarker of disease activity in patients with anti-acetylcholine receptor (AChR) antibody-positive MG. In the present study, serum IL-6 levels were measured in 93 treatment-naïve patients with anti-AChR antibody-positive MG and compared with those in 101 controls. Moreover, correlations between serum IL-6 levels and clinical characteristics were analyzed. Serum IL-6 levels were significantly higher in patients with anti-AChR antibody-positive MG than in controls (median [interquartile range], 2.5 [1.5-8.3] pg/mL vs. 1.5 [1.5-3.2] pg/mL, P < 0.001). The serum levels were correlated with the MG Foundation of America clinical classification (Spearman's ρ = 0.27; P < 0.01) and decreased following immunosuppressive treatment in parallel with disease activity (P = 0.01). In conclusion, IL-6 is involved in the pathogenesis of anti-AChR antibody-positive MG and could be a therapeutic target in MG.

Relationship of frailty with treatment modality selection in patients with muscle-invasive bladder cancer (FRART-BC study).

BACKGROUND: We aimed to investigate the association of frailty with treatment selection in patients with muscle-invasive bladder cancer (MIBC) as frailty is one of the key factors for modality selection. METHODS: We retrospectively evaluated frailty in 169 patients with MIBC from January 2014 to September 2020 using the Fried phenotype, modified frailty index, and frailty discriminant score. The primary purpose was comparing the frailty between the patients who underwent radical cystectomy (RC) with those who had trimodal therapy (TMT) for bladder preservation. Secondary purposes were comparing the frailty between the groups and the effect of TMT on overall survival adjusting the frailty by multivariate Cox proportional hazards analysis using inverse probability of treatment weighting (IPTW)-adjusted model. RESULTS: Of 169 patients, 96 and 73 were classified into the RC and the TMT groups, respectively. The median age of the TMT group was significantly higher than that of the RC group (80 vs. 69 years). Frailty levels and prevalence in the Fried phenotype, modified frailty index, and frailty discriminant score were significantly higher in the TMT group than those in the RC group. Logistic regression analysis showed that frailty was significantly associated with the TMT selection. Overall survival was significantly shorter in the TMT group by the IPTW-adjusted Cox regression analysis (hazard ratio 2.48, P=0.043). CONCLUSIONS: Frailty was significantly different between the RC and TMT in patients with MIBC and might be one of the key factors for treatment selection.

Long-term outcomes and prognostic factors in generalized myasthenia gravis.

OBJECTIVE: This study aimed to investigate the timing of meeting the criteria for a status of "minimal manifestation (MM) or better" and the factors that influenced whether "MM or better status" or "MM or better status with an oral prednisolone (PSL) dose of 5 mg/day or less (5-mg MM)" was met in patients with acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (MG). METHODS: We performed a retrospective study in 93 patients with AChR antibody-positive generalized MG who were followed for 3 years after the start of immunotherapy. We reviewed clinical data, such as MG-related symptoms, the MG activities of daily living profile (MGADL) score, immunotherapy including the dose of PSL, and achievement of the status of MM or better at baseline and 3, 6, 12, 24, and 36 months after treatment. RESULTS: An MM or better status was achieved in 60% of the patients 3 months and in 90% of the patients 2 years after initiating immunotherapy. At 2 years, 60% of the patients had achieved the treatment goal, which was an "5-mg MM". More frequent plasmapheresis and higher dose of PSL within 3 months after immunotherapy initiation were associated with difficulty in achieving the 5-mg MM status at 2 years. CONCLUSION: Approximately 60% of the MG patients achieved the treatment goal within 2 years after treatment. PSL dose and the cumulative number of plasmapheresis procedures at 3 months after immunotherapy initiation may help identify treatment-resistant patients with MG.

Rate of change in acetylcholine receptor antibody levels predicts myasthenia gravis outcome.

OBJECTIVE: To investigate the association between changes in anti-acetylcholine receptor antibody (AChR Ab) levels induced by immunosuppressive treatment and myasthenia gravis (MG) prognosis at 1-year post-treatment in patients with MG. METHODS: We included 53 consecutive AChR Ab-positive patients with MG whose AChR Ab levels were remeasured within 100 days of initiating immunosuppressive treatment (median remeasuring time post-treatment: 71 (55-84) days). The AChR Ab level reduction rate (RR-AChRAb, %/day) adjusted for the time between treatment initiation, and AChR Ab level remeasurement was calculated as follows: (pretreatment-post-treatment AChR Ab level)/pretreatment AChR Ab level/days between therapy initiation and AChR Ab level remeasurement ×100. Participants were divided into two groups based on the cut-off value of RR-AChR Ab, determined using receiver operating characteristic analyses for achieving minimal manifestation (MM) or better status at 1-year postimmunosuppressive treatment. The Myasthenia Gravis Foundation of America postintervention status and MG activity of daily living (MG-ADL) score at 1-year post-treatment were compared between the two groups. RESULTS: The RR-AChRAb cut-off value was 0.64%/day. The high RR-AChRAb group had a higher ratio of MM or better status (90% vs 65%, p=0.03) and lower MG-ADL score (median; 1 vs 2, p=0.04) than the low RR-AChRAb group. Kaplan-Meier analyses showed the early MM achievement in the high RR-AChRAb group (p=0.002, log-rank test). CONCLUSIONS: High RR-AChRAb is associated with a favourable outcome at 1-year post-treatment. AChR Ab remeasurement within 100 days of therapy may be useful for predicting AChR Ab-positive MG outcomes at 1-year post-treatment.

Dispersion of mean consecutive differences in single-fiber electromyography increases diagnostic sensitivity for myasthenia gravis.

INTRODUCTION: In this study we aimed to investigate the dispersion of mean consecutive difference (MCD) of concentric needle jitter studies of patients with myasthenia gravis (MG) and its effect on diagnostic sensitivity for MG. METHODS: One hundred fifty-three patients, including 76 patients with MG and 77 controls with possible MG who later received another diagnosis, underwent stimulated concentric needle jitter studies of the frontalis muscle. MCD mean, standard deviation (SD), and coefficient of variation (CV) were calculated. Diagnostic sensitivity and specificity were determined using receiver operating characteristic (ROC) analyses. RESULTS: MG patients showed a significantly greater MCD mean (MG: control, 26.3 µs; 13.5 µs [median]; P < .0001), MCD SD (MG: control, 12.8 µs; 5.1 µs [median]; P < .0001), and MCD CV (MG: control, 46.1; 37.5 [median]; P < .001) than those without MG. An ROC curve of SD showed a large area under the curve (0.88), and a cut-off value of 7.2 µs, which was calculated by maximum Youden index, exhibited high diagnostic sensitivity (86%) for MG. Combined MCD mean, outliers, and SD criteria showed higher sensitivity (88%) than conventional criteria alone (82%), at the expense of lower specificity. Five MG patients with normal MCD mean and abnormal MCD SD had only ocular symptoms. DISCUSSION: The dispersion of MCD as measured by MCD SD greater than 7.2 µs is significantly increased in patients with MG and may be a useful measure of abnormal jitter in the diagnosis of MG, especially for identifying patients with mild disease.

The effect of frailty on the quality of life and lower urinary symptoms following robot-assisted radical prostatectomy: A longitudinal analysis (FRARP-QL Study).

OBJECTIVES: We aimed to evaluate the effect of frailty on health-related quality-of-life (HRQOL) and lower urinary symptoms (LUTS) following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (CaP). MATERIALS AND METHODS: We longitudinally evaluated geriatric 8 (G8), HRQOL, and LUTS for 12 months in 118 patients with RARP from January 2017 to April 2020. Patients were divided into frail (G8 ≤14) and nonfrail (G8 >14) groups. We compared the effect of frailty on HRQOL and LUTS between the frail and nonfrail groups before and 12 months after RARP. RESULTS: The median age of patients was 68 years. The number of patients in the frail and nonfrail groups were 41 and 77, respectively. No significant difference in patients' background was observed between the groups, except for the presence of cardiovascular disease (22% vs. 7.8%, P = 0.041). There was no significant difference in HRQOLs and LUTS between the groups at baseline. Similarly, HRQOLs, LUTS, and pad-free continence rates were not significantly different between the groups at 12 months after RARP. In the nonfrail group, LUTS at 12 months following RARP significantly improved compared to those at the baseline, but it did not significantly improve in the frail group. Multivariable logistic regression analysis demonstrated that frailty was not significantly associated with LUTS worsening. CONCLUSIONS: Frailty was not significantly associated with the worsening of HRQOL, LUTS, and pad-free continence rates in patients treated with RARP.

Effect of frailty and comorbidity on surgical contraindication in patients with localized prostate cancer (FRART-PC Study).

OBJECTIVES: To determine how frailty and comorbidities affect surgical contraindication in patients with localized prostate cancer (CaP). MATERIALS AND METHODS: We evaluated the effects of frailty in 479 patients with localized CaP who were treated with robot-assisted radical prostatectomy (RARP), or radiotherapy (RT) eligible for surgery (RT-nonfrail), or those with RT ineligible for surgery due to frailty or comorbidity (RT-frail) from February 2017 to April 2020. We retrospectively compared the geriatric 8 screening (G8) scores between patients with surgical indications (RARP and RT-nonfrail groups) and those with surgical contraindications (RT-frail group). The effect of G8 score in the RT-frail groups was investigated using multivariate logistic regression analysis. We developed and validated a nomogram for surgical contraindication in patients with localized CaP. RESULTS: The median age of patients was 70 years. There were 256, 60, and 163 patients in the RARP, RT-nonfrail, and RT-frail, respectively. The G8 score in the RARP and RT-nonfrail groups was significantly higher than in the RT-frail group (15 vs. 14, respectively, P < 0.001). Age, comorbidities (cerebrocardiovascular disease or chronic respiratory disease), and G8 score were significantly associated with the RT-frail group. The nomogram showed that the area under the curve was 0.872 and 0.923 in the training and validation sets, respectively. The cutoff for surgical contraindication was >39.5%. CONCLUSIONS: The G8 score and comorbidities have a significant effect on surgical contraindication in patients with localized CaP.

Association between the baseline frailty and quality of life in patients with prostate cancer (FRAQ-PC study).

BACKGROUND: The association between baseline frailty and health-related quality of life (HRQOL) in patients with prostate cancer (PC) remains unknown. METHODS: We retrospectively evaluated the association of pretreatment frailty with HRQOL in 409 patients with PC from February 2017 to April 2020. Frailty and HRQOL were evaluated using the geriatric 8 (G8) screening tool and QLQ-C30 questionnaire, respectively. The primary objective was comparison of G8 and QOL scores between the localized diseases (M0 group) and metastatic castration-sensitive PC (mCSPC group). Secondary objectives were to study the association of G8 and QOL scores in each group and effect of frailty (G8 ≤ 14) on worse QOL. RESULTS: The median age of patients was 70 years. There were 369 (surgery: 196, radiotherapy: 156, androgen deprivation therapy alone: 17) patients in the M0 and 40 patients in the mCSPC groups. There was a significant difference between the M0 and mCSPC groups in the G8 score (14.5 vs. 12.5), functioning QOL (94 vs. 87), global QOL (75 vs. 58), and 100-symptom QOL (94 vs. 85) scores. G8 scores were significantly associated with functioning, global, and 100-symptom QOL scores in both M0 and mCSPC groups. The multivariable logistic regression analyses showed that frailty (G8 ≤ 14) was significantly associated with worse global QOL, functioning QOL, and 100-symptom QOL scores. CONCLUSION: The baseline frailty and HRQOL were significantly different between the localized and metastatic disease. The baseline frailty was significantly associated with worse HRQOL in patients with PC.

Oncologic and patient-reported outcomes after robot-assisted radical prostatectomy in men aged ≥75 years.

OBJECTIVE: The present study aimed to evaluate oncologic outcomes, patient-reported outcomes (PROs), and frailty in older adult patients aged ≥75 years who underwent robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: This retrospective study reviewed the medical records of 752 patients who underwent RARP from July 2011 to May 2020. The PROs were evaluated by Expanded Prostate Cancer Index Composite questionnaire at baseline and 1 year after RARP. Patients were divided into 3 groups according to age at RARP: <70, 70-74, and ≥75 years. Oncologic outcomes and PROs were compared between the ≥75 and 70-74 years groups and between the ≥75 and <70 years groups. RESULTS: Median follow up was 47 months. Of the 752 patients, 469, 216, and 74 were classified into the <70, 70-74, and ≥75 years groups, respectively. No significant differences were observed in the biochemical recurrence-free survival, cancer-specific survival, and overall survival among the groups. No significant differences were observed in the PROs and pad-free rates at baseline and 1 year after RARP among the groups. The full satisfaction (Expanded Prostate Cancer Index Composite score = 100) at 12 months after RARP was significantly higher in the ≥75 years group (27%) than in the <70 years group (15%, P = 0.045). CONCLUSION: The oncologic outcomes and PROs in select patients with prostate cancer aged ≥75 years were feasible and acceptable with RARP.

[Recurrent cerebral embolism due to the disseminated carcinomatosis of bone marrow with early gastric cancer].

A 67-year-old woman who had undergone laparoscopic proximal gastrectomy for early gastric cancer 10 months previously was admitted to our hospital due to dysarthria. Brain MRI demonstrated acute multiple small infarcts in the right middle cerebral artery (MCA) and the right posterior inferior cerebellar artery (PICA) territory, and she was diagnosed as embolic stroke. Anticoagulant therapy did not prevent further ischemic stroke. No embolic sources were detected by MR angiography, carotid duplex sonography, transthoracic and transesophageal echocardiography, and Holter electrocardiography. We also performed upper gastrointestinal endoscopy and contrast-enhanced CT of the thoracoabdominal area, but there was no evidence of local recurrence or lymph node metastases of gastric cancer. As the ALP and D-dimer levels were gradually increasing, we performed PET/CT, which revealed fluorodeoxyglucose (FDG) uptake in the vertebra bone, and disseminated carcinomatosis of bone marrow with early gastric cancer was diagnosed after bone marrow biopsy on Day 41. After undergoing chemotherapy, she had no further stroke and died on Day 207.

Increased serum acetylcholine receptor α1 subunit protein in anti-acetylcholine receptor antibody-positive myasthenia gravis.

Complement-dependent disruption of motor endplate is detected in anti-acetylcholine receptor (AChR) antibody-positive myasthenia gravis (MG). We measured serum AChR α1 subunit protein levels, which may be associated with neuromuscular damage, in 55 patients with MG (47 were seropositive and 8 were negative) and in 20 controls. Serum AChR α1 subunit protein concentrations were higher in patients with anti-AChR antibody-positive MG than those in controls (P = .04), were negatively correlated with MG activities of daily living score (P = .01), and tended to be higher in ocular MG than in generalized MG. AChR α1 subunit protein elevation may be related to seropositive MG pathogenesis, especially in the ocular type.

Aberrant N-Glycosylation Profile of Serum Immunoglobulins is a Diagnostic Biomarker of Urothelial Carcinomas.

The aim of this study to determine whether the aberrant N-glycosylated serum immunoglobulins (Igs) can be applied as a diagnostic marker of urothelial carcinoma (UC). Between 2009 and 2016, we randomly obtained serum available from 237 UC and also 96 prostate cancer as other cancer controls from our serum bank and also obtained-from 339 healthy volunteers (HV)-controls obtained from community-dwelling volunteers in Iwaki Health Promotion Project. A total of 32 types of N-glycan levels on Igs were determined by high-throughput N-glycomics and analyzed by multivariable discriminant analysis. We found five UC-associated aberrant N-glycans changes on Igs and also found that asialo-bisecting GlcNAc type N-glycan on Igs were significantly accumulated in UC patients. The diagnostic N-glycan Score (dNGScore) established by combination of five N-glycans on Igs discriminated UC patients from HV and prostate cancer (PC) patients with 92.8% sensitivity and 97.2% specificity. The area under the curve (AUC) for of the dNGScore was 0.969 for UC detection that was much superior to that of urine cytology (AUC, 0.707) and hematuria (AUC, 0.892). Furthermore, dNGScore can detect hematuria and urine cytology negative patients. The dNGscore based on aberrant N-glycosylation signatures of Igs were found to be promising diagnostic biomarkers of UCs.

Characteristic Posterior-dominant Lower Limb Muscle Involvement in Limb-girdle Muscular Dystrophy due to a DNAJB6 Phe93Leu Mutation.

A 41-year-old man presented with gradually progressing proximal-dominant lower limb atrophy and weakness. His brother, mother and maternal aunt had the same symptoms. A physical examination and muscle imaging (CT and ultrasound) showed selective muscle involvement of the bilateral paraspinal, gluteus and posterior groups of lower limb muscles. Based on the characteristic muscle involvement pattern, the clinical findings and the muscle biopsy results, we made a straightforward diagnosis of limb-girdle muscular dystrophy (LGMD) due to a DNAJB6 Phe93Leu mutation based on a targeted gene analysis. In the differential diagnosis of adult-onset LGMD syndromes, in addition to investigating the family history, it is important to perform an extensive physical examination to determine the pattern of muscle involvement, and to perform a muscle biopsy. Our case suggests that posterior-dominant lower limb muscle impairment with gluteus and truncal muscle involvement and the detection of rimmed vacuoles on a muscle biopsy could be clues for the diagnosis of LGMD due to DNAJB6 mutations.