Treatment trends in patients with de novo metastatic prostate cancer in the era of upfront combination therapy.

OBJECTIVES: The objective of this study is to assess the trends in treatment selection for patients with de novo metastatic castration-sensitive prostate cancer in the era of upfront combination therapy. METHODS: This multicenter retrospective study included 595 patients treated with either upfront combination therapy (upfront novel hormonal therapies and taxane-based chemotherapy) or vintage therapy (androgen deprivation therapy with or without bicalutamide) between 2016 and 2021. High tumor burden metastatic disease was defined when a patient met the CHAARTED or LATITUDE criteria. We evaluated trends in treatment selection and reasons for selecting vintage therapy. RESULTS: Of the 595, 123 and 472 patients were classified as having low and high tumor-burden disease, respectively. The Use of upfront combination therapy was found to be rapidly increasing with utilization rates of 72% and 54% in 2021 for high and low tumor-burden disease, respectively. Multivariable logistic regression analysis found older age, poor performance status, and nonacademic center were significantly associated with the selection of vintage therapy. Of the 163 patients who received vintage hormone therapy after approval of upfront therapy, 74.2% had a specific reason for avoiding upfront therapy. The reasons for selecting vintage therapy included refusal (39.8%), older age (67.6%), frailty (56.3%), and comorbidity (40.8%). Furthermore, 16.9% of patients declined upfront combination therapy due to cost concerns. CONCLUSION: Upfront combination therapy use has 72% and 54% prevalence among patients with high and low tumor burden diseases, respectively, in this current practice. Older age, poor performance status, and facility bias were negatively associated with the use of upfront combination therapy.

Real-world effects of novel androgen receptor axis-targeted agents on oncological outcomes in non-metastatic castration-resistant prostate cancer: A multi-institutional retrospective study.

Background: The benefits of novel androgen receptor axis-targeted agents (ARATs) on oncological outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in real-world settings are unclear. Methods: This multi-institutional retrospective study included 178 patients with nmCRPC treated between September 2003 and August 2022. Patients were divided into two groups: those who were treated with any novel ARATs, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate, during any line of nmCRPC treatment (novel ARATs group) and those who were not (control group). Multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of novel ARATs on metastasis-free survival (MFS) and overall survival (OS). Results: The median age and follow-up period after nmCRPC diagnosis were 76 years and 37 months, respectively. Of the 178 patients, 122 (69%) were treated with novel ARATs after nmCRPC diagnosis. The MFS and OS in the novel ARATs group were significantly longer than those in the control group (P < 0.001 and P = 0.020, respectively). In multivariable analyses, a prostate-specific antigen doubling time (PSADT) of <3 months and novel ARATs were independently and significantly associated with MFS and OS. The effects of novel ARATs on MFS were consistently observed across subgroups stratified by age (<75 years or ≥75 years), history of radical treatment (no or yes), biopsy Gleason score (<9 or ≥9), clinical stage (≤cT3 and cN0, or cT4 or cN1), and PSADT (≥3 months or <3 months). Conclusion: Novel ARATs were significantly associated with improved oncological outcomes in patients with nmCRPC in a real-world setting, regardless of tumor aggressiveness.

Clinical Characteristics of Cryopyrin-Associated Periodic Syndrome and Long-Term Real-World Efficacy and Tolerability of Canakinumab in Japan: Results of a Nationwide Survey.

OBJECTIVE: We assess the clinical characteristics of patients with cryopyrin-associated periodic syndrome (CAPS) in Japan and evaluate the real-world efficacy and safety of interleukin-1 (IL-1) inhibitors, primarily canakinumab. METHODS: Clinical information was collected retrospectively, and serum concentrations of canakinumab and cytokines were analyzed. RESULTS: A total of 101 patients were included, with 86 and 15 carrying heterozygous germline and somatic mosaic mutations, respectively. We identified 39 mutation types, and the common CAPS-associated symptoms corresponded with those in previous reports. Six patients (5.9% of all patients) died, with four of the deaths caused by CAPS-associated symptoms. Notably, 73.7% of patients (100%, 79.6%, and 44.4% of familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous articular syndrome/neonatal onset multisystem inflammatory disease, respectively) achieved complete remission with canakinumab, and early therapeutic intervention was associated with better auditory outcomes. In some patients, canakinumab treatment stabilized the progression of epiphysial overgrowth and improved height gain, visual acuity, and renal function. However, 23.7% of patients did not achieve inflammatory remission with crucial deterioration of organ damage, with two dying while receiving high-dose canakinumab treatment. Serological analysis of canakinumab and cytokine concentrations revealed that the poor response was not related to canakinumab shortage. Four inflammatory nonremitters developed inflammatory bowel disease (IBD)-unclassified during canakinumab treatment. Dual biologic therapy with canakinumab and anti-tumor necrosis factor-α agents was effective for IBD- and CAPS-associated symptoms not resolved by canakinumab monotherapy. CONCLUSION: This study provides one of the largest epidemiologic data sets for CAPS. Although early initiation of anti-IL-1 treatment with canakinumab is beneficial for improving disease prognosis, some patients do not achieve remission despite a high serum concentration of canakinumab. Moreover, IBD may develop in CAPS after canakinumab treatment.

Primary resistance to nivolumab plus ipilimumab therapy in patients with metastatic renal cell carcinoma.

BACKGROUND: Nivolumab plus ipilimumab (NIVO+IPI) is the first-line treatment for patients with metastatic renal cell carcinoma (mRCC). Approximately 40% of patients achieve a durable response; however, 20% develop primary resistant disease (PRD) to NIVO+IPI, about which little is known in patients with mRCC. Therefore, this investigation aimed to evaluate the clinical implication of PRD in patients with mRCC to select better candidates in whom NIVO+IPI can be initiated as first-line therapy. METHODS: This multi-institutional retrospective cohort study used data collected between August 2015 and January 2023. In total, 120 patients with mRCC treated with NIVO+IPI were eligible. Associations between immune-related adverse events and progression-free survival, overall survival (OS), and objective response rate were analyzed. The relationship between other clinical factors and outcomes was also evaluated. RESULTS: The median observation period was 16 months (interquartile range, 5-27). The median age at NIVO+IPI initiation was 68 years in the male-dominant population (n = 86, 71.7%), and most patients had clear cell histology (n = 104, 86.7%). PRD was recorded in 26 (23.4%) of 111 investigated patients during NIVO+IPI therapy. Patients who experienced PRD showed worse OS (hazard ratio: 4.525, 95% confidence interval [CI]: 2.315-8.850, p < 0.001). Multivariable analysis showed that lymph node metastasis (LNM) (odds ratio: 4.274, 95% CI: 1.075-16.949, p = 0.039) was an independent risk factor for PRD. CONCLUSIONS: PRD was strongly correlated with worse survival rates. LNM was independently associated with PRD in patients with mRCC receiving NIVO+IPI as first-line therapy and might indicate that a candidate will not benefit from NIVO+IPI.

Development of a Cell-Based Assay Using a Split-Luciferase Reporter for Compound Screening.

Recently, the finding of recurrent mutations in the spliceosome components in cancer has indicated that the spliceosome is a potential target for cancer therapy. However, the number of small molecules known to affect the cellular spliceosome is currently limited probably because of the lack of a robust cell-based approach to identify small molecules that target the spliceosome. We have previously reported the development of a genetic reporter to detect the cellular levels of small nuclear ribonucleoproteins (snRNPs), which are subunits of the spliceosome, using a split luciferase. However, the original protocol was designed for small scale experiments and was not suitable for compound screening. Here, we found that the use of cell lysis buffer used in blue native polyacrylamide gel electrophoresis (BN-PAGE) dramatically improved the sensitivity and the robustness of the assay. Improved assay conditions were used to discover a small molecule that altered the reporter activity. Our method may be used with other cellular macromolecular complexes and may assist in the discovery of small bioactive molecules.

Impact of nephroureterectomy on postoperative renal function in upper tract urothelial carcinoma: A multicenter retrospective study.

OBJECTIVE: To assess the impact of radical nephroureterectomy on postoperative renal function in patients with upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively evaluated 645 patients with UTUC treated with radical nephroureterectomy between January 2000 and May 2022. The primary outcome was the rate of postoperative estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 . Secondary outcomes included the rate of eGFR decline, identification of factors related to eGFR decline, and the impact of comorbidities (diabetes or cardiovascular disease) on postoperative eGFR at 1 year. RESULTS: The median preoperative and postoperative eGFR levels were 55.6 and 43.3 mL/min/1.73 m2 , respectively. The rate of patients with preoperative and postoperative eGFR ≥60 mL/min/1.73 m2 was 40.9% and 9.0%, respectively. The median decline in eGFR after surgery was 25.1%. The presence of preoperative unilateral hydronephrosis and eGFR <60 mL/min/1.73 m2 was significantly associated with a low decline of postoperative eGFR and poor survival. The impact of the presence of comorbidities on postoperative eGFR at 1 year was significant (p < 0.001). CONCLUSION: Impaired renal function is prevalent in patients with UTUC. The rate of patients with postoperative eGFR ≥60 mL/min/1.73 m2 was 9.0%. The presence of preoperative renal impairment was significantly related to a low decline in postoperative eGFR and poor survival. The presence of comorbidities had a significant effect on eGFR decline 1 year after radical nephroureterectomy.

Comparison of neoadjuvant chemohormonal therapy vs. extended pelvic lymph-node dissection in high-risk prostate cancer treated with robot-assisted radical prostatectomy.

We compared the impact of treatment strategies on postoperative complications and prognosis between robot-assisted radical prostatectomy (RARP) plus extended pelvic lymph-node dissection (ePLND) and RARP plus neoadjuvant chemohormonal therapy (NCHT) without ePLND. We retrospectively evaluated 452 patients with high-risk prostate cancer (defined as any one of prostate-specific antigen ≥ 20 ng/mL, Gleason score 8-10, or cT2c-3) who were treated with RARP between January 2012 and February 2021. The patients were divided into two groups: RARP with ePLND (ePLND group) and NCHT plus RARP without ePLND (NCHT group). We compared the complication rate (Clavien-Dindo classification), biochemical recurrence-free survival, and castration-resistant prostate cancer (CRPC)-free survival between the groups. We performed multivariable Cox regression analysis using inverse probability weighting (IPTW) methods to assess the impact of the different treatments on prognosis. There were 150 and 302 patients in the ePLND and NCHT groups, respectively. The postoperative complication rate was significantly higher in the ePLND group than in the NCHT group (P < 0.001). IPTW-adjusted biochemical recurrence-free survival and CRPC-free survival were significantly higher in the NCHT group than in the ePLND group (hazard ratio [HR] 0.29, P < 0.001, and HR 0.29, P = 0.010, respectively). NCHT plus RARP without ePLND may reduce the risk of postoperative complications compared with ePLND during RARP. The impact of treatment strategies on oncological outcomes needs further studies.

Effects of apalutamide dose reduction on skin-related adverse events in patients with advanced prostate cancer: A multicenter retrospective study.

BACKGROUND: We aimed to evaluate the effects of apalutamide dose reduction on skin-related adverse events (AEs) and castration-resistant prostate cancer (CRPC)-free survival in patients with advanced prostate cancer (PC). METHODS: We retrospectively evaluated 35 patients with nonmetastatic CRPC and 72 patients with treatment-naïve metastatic castration-sensitive PC (mCSPC) who were treated with apalutamide. The primary outcome was the effect of apalutamide dose reduction on skin-related AEs. The secondary outcomes were the effect of apalutamide dose reduction on skin-related AEs in patients with small body size, postskin AE apalutamide discontinuation rate, and CRPC-free survival in patients with mCSPC treated with upfront apalutamide plus androgen deprivation therapy. RESULTS: Of the 107 patients, 65 (60.7%) and 42 (39.3%) were treated with full and reduced doses of apalutamide, respectively. The skin-related AE rate was not significantly different between the groups (55% vs. 43%, p = 0.761). In the group receiving reduced apalutamide dose, the incidence of skin-related AEs was significantly lower in patients with small body sizes (body weight <67 kg and body mass index <24 kg/m2 ) than in those with other body sizes. The postskin AE apalutamide discontinuation rate was significantly differed between patients receiving the full (50%) and reduced (16.7%) doses. In the 72 patients with mCSPC, CRPC-free survival was not significantly different between the full and reduced dose groups. CONCLUSION: Apalutamide dose reduction was not significantly associated with the incidence of skin-related AEs. However, dose reduction in patients with small body sizes may alleviate skin-related AEs without sacrificing oncological outcomes.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome: Clinical characteristics and treatment outcomes - a single center study in Japan.

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease occurring in children. Although PFAPA is the most common periodic fever syndrome found in children, there are only a few studies defining the clinical characteristics and the efficacy of treatment strategies among Japanese children. This study aimed to clarify the demographic characteristics and clinical features of patients with PFAPA syndrome and to evaluate treatment efficacy. METHODS: We retrospectively reviewed the clinical features of children with PFAPA who visited Saitama Children's Medical Center between January and December 2019. We also evaluated treatment strategies and their efficacy; abortive treatment with corticosteroids, prophylaxis with cimetidine or colchicine, and surgical management with tonsillectomy. RESULTS: A total of 100 Japanese children (61% male) with PFAPA were included. Median age of onset was 3 years, median duration of fever episodes was 5 days, and median interval between episodes was 4 weeks. The symptoms (frequencies) were pharyngitis (89%), exudate on tonsils (71%), cervical adenitis (50%), and aphthous stomatitis (49%). Approximately 37% of patients took prednisolone for aborting fever attacks, showing a 100% response; 93% were treated with cimetidine, showing an 79.6% response, and 18% were treated with colchicine, showing a 66.7% response. Only one patient underwent tonsillectomy. CONCLUSIONS: Among Japanese children with PFAPA, 28% of them were ≥5 years with a male predominance. Pharyngitis is the most frequent symptom associated with fever. Cimetidine is suitable for initial therapy because of its safety and efficacy.

Actinomycosis of the Middle Ear in Children: Case Report and Literature Review.

Actinomycosis of the middle ear is a rare infectious disease, characterized by a slowly progressive clinical course. We report the case of a 9-year-old girl with recurrent otitis media, who presented with clinical signs of a cholesteatoma. She underwent tympanoplasty and ossiculoplasty. After surgery, actinomycosis was diagnosed histologically. We also provide a review of 16 published pediatric cases.

Anesthetic management of tracheal stent extraction using a double gum elastic bougie technique.

BACKGROUND: Tracheal stenosis is a life-threatening condition, and management of a patient with a risk of tracheal stenosis is challenging for anesthesiologists. In this report, we describe a method for airway management using two gum elastic bougie method when removing a tracheal stent via a tracheostomy orifice with a risk of airway restenosis. CASE PRESENTATION: A 71-year-old man had an enlarged squamous cell carcinoma of the lung invading the upper mediastinum that had caused severe stenosis of the trachea. Two months after diagnosis, a tracheal stent had been placed to maintain tracheal patency. One month after stent placement, acute respiratory failure was induced by upper airway obstruction caused by subglottic airway edema due to mechanical stimulation of the cranial end of the stent, and the patient was rescued by oral tracheal intubation. Tracheal stent extraction was scheduled to relieve the laryngeal edema. Since there was a risk of tracheal restenosis because of the possibility of accidental evulsion of the orally tracheal tube which intubated to secure an emergency airway and tracheal stent extraction, two gum elastic bougies were inserted through the oral tracheal tube and tracheostomy orifice to facilitate re-intubation. After extraction of the tracheal stent, airway openness was maintained and tracheostomy was completed without any complication. CONCLUSION: Successful management of tracheal stent extraction was performed using a double gum elastic bougie technique.

Ultrasound evaluation of inflammation in patients with chronic recurrent multifocal osteomyelitis involving the mandible: report of three cases.

Chronic recurrent multifocal osteomyelitis (CRMO) is aseptic and can be diagnosed by excluding other diseases, such as bacterial osteomyelitis, scurvy, metabolic disorders, and malignant diseases; therefore, bone biopsy is usually performed to confirm the diagnosis. To prevent misdiagnosis, the appropriate timing and location for biopsy should be determined from an active phase of inflammation. We presented 3 cases of CRMO involving the mandible: Case 1: A 2-year-old girl diagnosed with CRMO in the chronic phase. A sonogram showed a slightly low echoic area adjacent to the bone cortex. Pathological examination revealed a slight accumulation of leukocytes and plasma cells, as well as predominant fibrous stroma. Case 2: A 9-year-old girl diagnosed with CRMO with massive new osteoid formation. A sonogram showed a massive inhomogeneous low echoic area adjacent to the bone cortex. Pathological examination revealed massive osteoid formation and scattered inflammatory cells infiltration. Case 3: A 3-year-old girl diagnosed with CRMO in the active phase. A sonogram showed a massive hypoechoic area adjacent to the bone cortex and hyperechogenicity associated with a muscular and subcutaneous edema. Pathological examination revealed massive bone destruction and neutrophils infiltration within damaged osteoid. Ultrasound was able to visualize the degree of inflammation in the mandible corresponding to that of the surrounding soft tissue in all 3 cases. Therefore, ultrasound would be useful in determining the appropriate timing and location for bone biopsy.

Effect of desflurane on changes in regional cerebral oxygenation in patients undergoing one-lung ventilation is equivalent to the effect of propofol.

OBJECTIVES: Desaturation is an important clinical problem during one-lung ventilation (OLV) since it may induce cerebral hypoxia. Measurement of cerebral oxygenation has been shown to provide accurate information about episodes of cerebral hypoxemia. The purpose of this study was to compare the effect of desflurane on changes in cerebral oxygenation during OLV with the effect of propofol. METHODS: A randomized, single-blinded, prospective study was conducted. Fifty adult patients who were scheduled to undergo thoracic surgery were randomly assigned to anesthetic management using desflurane with remifentanil (Group D: n = 25) or using propofol and remifentanil (Group P: n = 25). RESULTS: The characteristics of the patients were very similar. Intergroup analysis of changes in cerebral oxygenation showed no significant difference on the operative side (two-way ANOVA, F (7, 368) = 0.425, p = 0.887) or the non-operative side (two-way ANOVA, F (7, 367) = 1.342, p = 0.229). Intragroup analysis of changes in cerebral oxygenation using one-way ANOVA showed no significant difference on the operative side (Group P; p = 0.585, Group D; p = 0.928) or the non-operative side in both groups (Group P; p = 0.657, Group D; p = 0.602). CONCLUSIONS: The effects of desflurane and propofol on changes in cerebral oxygenation in patients undergoing OLV were equivalent. Our results indicated that desflurane might be an appropriate anesthetic during OLV for maintaining cerebral oxygenation with an effective equivalent to that of propofol.

Infected simple renal cyst due to Streptococcus pneumoniae rapidly diagnosed by the melting temperature mapping method: a case report.

BACKGROUND: Spontaneous infection of preexisting solitary renal cysts has been documented in adults but is extremely rare in children. To date, no cases of simple renal cysts infected with Streptococcus pneumoniae have been described. Recently, reports have described the diagnosis of bacterial infection using the 16 S rRNA gene as well as the accompanying antimicrobial stewardship for microorganisms that are difficult to culture and for culture-negative cases after preceding antibacterial administration. CASE PRESENTATION: A four-year-old Japanese girl who had a pleuroperitoneal shunt inserted to drain a right pleural effusion due to occlusion of the hepatic portion of the inferior vena cava at three years old visited our hospital due to fever and respiratory discomfort. She was incidentally found to have a right simple renal cyst 10 months before admission. The patient was suspected to have pneumonitis or catheter-related blood stream infection on chest X-ray, which showed right-side pleural effusion. She was diagnosed with invasive pneumococcal infection, as Streptococcus pneumoniae was detected from blood culture on admission. Transient improvements in her symptoms and decreases in the white blood cell count and C-reactive protein level were observed after effective antibiotic administration, but her respiratory condition deteriorated. Enhanced CT showed right renal cyst enlargement and enhancement and thickening of the surrounding wall. Using the melting temperature (Tm) mapping method, S. pneumoniae was rapidly detected directly from pus 4.5 hours after drainage. The specimen culture was negative, but the extracted 16 S rDNA sequence revealed 100 % identity for S. pneumoniae from the same specimen the subsequent day. We successfully performed optimal treatment and reduced medical cost based on the positive Tm mapping method result. CONCLUSIONS: We report the first case of a S. pneumoniae-infected simple renal cyst. The drainage culture was negative, but the Tm mapping method rapidly detected S. pneumoniae directly from the drainage. The Tm mapping method may have great impacts on rapid diagnosis and effective antimicrobial stewardship.

Clinical impact of myositis-specific autoantibodies on long-term prognosis of juvenile idiopathic inflammatory myopathies: multicentre study.

OBJECTIVES: This study aimed to investigate the clinical characteristics, treatment and prognosis of juvenile idiopathic inflammatory myopathies (JIIM) in Japan for each myositis-specific autoantibody (MSA) profile. METHODS: A multicentre, retrospective study was conducted using data of patients with JIIM at nine paediatric rheumatology centres in Japan. Patients with MSA profiles, determined by immunoprecipitation using stored serum from the active stage, were included. RESULTS: MSA were detected in 85 of 96 cases eligible for the analyses. Over 90% of the patients in this study had one of the following three MSA types: anti-melanoma differentiation-associated protein 5 (MDA5) (n = 31), anti-transcriptional intermediary factor 1 alpha and/or gamma subunits (TIF1γ) (n = 25) and anti-nuclear matrix protein 2 (NXP2) (n = 25) antibodies. Gottron papules and periungual capillary abnormalities were the most common signs of every MSA group in the initial phase. The presence of interstitial lung disease (ILD) was the highest risk factor for patients with anti-MDA5 antibodies. Most patients were administered multiple drug therapies: glucocorticoids and MTX were administered to patients with anti-TIF1γ or anti-NXP2 antibodies. Half of the patients with anti-MDA5 antibodies received more than three medications including i.v. CYC, especially patients with ILD. Patients with anti-MDA5 antibodies were more likely to achieve drug-free remission (29 vs 21%) and less likely to relapse (26 vs 44%) than others. CONCLUSION: Anti-MDA5 antibodies are the most common MSA type in Japan, and patients with this antibody are characterized by ILD at onset, multiple medications including i.v. CYC, drug-free remission, and a lower frequency of relapse. New therapeutic strategies are required for other MSA types.

Careful medical interview and ultrasonography enabled detection of acute kidney injury and hematoma after lumbar trigger point injection-a case report.

BACKGROUND: Trigger point blocks are now widely practiced, especially in pain treatment. Among the complications of lumbar trigger point injection, reports of medically induced kidney injury are very rare, and diagnosis during emergency treatment is rare. CASE PRESENTATION: A 78-year-old woman on antiplatelet medication following a stroke was diagnosed with treatable type A aortic dissection at another hospital after undergoing lumbar trigger point injection. On arrival at our hospital, there were no signs of hemodynamic deterioration. Additional careful medical re-interview and ultrasonography by anesthesiologists enabled a definitive diagnosis of acute kidney damage and hematoma caused by lumbar trigger point injection, and aortic dissection surgery was abandoned. CONCLUSION: This clinical case demonstrates the importance of awareness of potential kidney injury and hematoma during lumbar trigger point injection.

Effective Endoscopic Closure of Cholecysto-duodenal and Transverse Colon Fistulas Due to Squamous Cell Carcinoma of the Gallbladder Using Polyglycolic Acid Sheets and a Covered Metal Stent.

An 81-year-old woman presented with abdominal distension and right hypochondrial pain. Abdominal contrast computed tomography and magnetic resonance imaging revealed an 11-cm gallbladder tumor. The patient was diagnosed with squamous cell carcinoma of the gallbladder by endoscopic ultrasound-guided fine-needle aspiration from the gastric antrum. Thereafter, the gallbladder tumor enlarged, and cholecysto-duodenal and transverse colon fistulas were formed. A covered metal stent was placed on the transverse colon, and polyglycolic acid sheets were injected into the duodenum to close the fistulas endoscopically. Endoscopic closure is less invasive than surgery and considered effective for patients with poor general health conditions.

External validation of the EULAR/ACR idiopathic inflammatory myopathies classification criteria with a Japanese paediatric cohort.

OBJECTIVES: To assess the performance of the EULAR/ACR idiopathic inflammatory myopathies (IIMs) classification criteria to classify juvenile IIMs (JIIMs) in an Asian paediatric population. METHODS: Sixty-eight JIIM patients and 49 non-JIIM patients diagnosed at seven major paediatric rheumatology centres in Japan between 2008 and 2015 were enrolled. Retrospective data were collected, and each patient's data form was submitted. The expert group reviewed the forms and re-examined the diagnoses. The EULAR/ACR criteria were then applied and the probability of having JIIM was determined for each case. The sensitivity and specificity of the EULAR/ACR criteria were compared with those of other existing criteria. RESULTS: The sensitivity/specificity of the EULAR/ACR classification criteria were 92.1/100% with muscle biopsy data (n = 38); 86.7/100% without muscle biopsy data (n = 30) and 89.7/100% in our total cohort (n = 68). The sensitivity of Bohan and Peter's criteria and Tanimoto's criteria were 80.9 and 64.7% in our total cohort, respectively. Among 68 physician-diagnosed JIIM patients, seven cases (three JDM and four overlap myositis) were not classified as JIIM because the probability did not reach the cut-off point (55%). The three JDM patients all presented with only one of the three skin manifestations that are listed in the criteria: Gottron's sign. CONCLUSION: Our validation study with Japanese JIIM cases indicates that the EULAR/ACR classification criteria for IIM generally perform better than existing diagnostic criteria for myositis.

A case of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) strain meningitis and ventriculitis following BCG vaccination.

The Bacillus Calmette-Guérin (BCG) vaccine is widely used worldwide. Intracranial manifestation as an adverse event of BCG is extremely rare. A previously healthy 16-month-old boy was referred to our hospital for eye contact difficulties and progressive gait disturbance lasting two months. He was inoculated with BCG at seven months of age. Brain magnetic resonance imaging (MRI) revealed hydrocephalus with widespread and disseminated enhancement lesions with thickening of the third ventricle floor, and brain tissue pathologically showed non-caseous granulomatous inflammation. Immunosuppressive therapies were initiated because of a provisional diagnosis of neurosarcoidosis. Three months later, a positive polymerase chain reaction (PCR) result for the Mycobacterium tuberculosis complex was obtained. Eventually, M. bovis (BCG Tokyo 172 strain) was identified in the cerebrospinal fluid (CSF) and shunt tube culture. The prolonged use of antituberculosis drugs and multiple shunt replacement surgeries were needed for recovery. There was no evidence of immunodeficiency. Unfortunately, he had severe neurological sequelae of bilateral blindness and neurodevelopmental delay. Our purpose in this report was to highlight the potential for intracranial manifestations of adverse reactions related to BCG vaccination. We propose that the CSF PCR assay of Mycobacterium tuberculosis (MTB) complex should be applied repeatedly in children suspected of intractable neurosarcoidosis, with a history of BCG vaccination.