Outcomes of active surveillance for Japanese patients with prostate cancer (PRIAS-JAPAN).

OBJECTIVE: To report the outcomes of repeat biopsies, metastasis and survival in the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study, a prospective observational study for Japanese patients, initiated in 2010. PATIENTS AND METHODS: At the beginning, inclusion criteria were initially low-risk patients, prostate-specific antigen (PSA) density (PSAD) <0.2, and ≤2 positive biopsy cores. As from 2014, GS3+4 has also been allowed for patients aged 70 years and over. Since January 2021, the age limit for Gleason score (GS) 3 + 4 cases was removed, and eligibility criteria were expanded to PSA ≤20 ng/mL, PSAD <0.25 nd/mL/cc, unlimited number of positive GS 3 + 3 cores, and positive results for fewer than half of the total number of cores for GS 3 + 4 cases if magnetic resonance imaging fusion biopsy was performed at study enrolment or subsequent follow-up. For patients eligible for active surveillance, PSA tests were performed every 3 months, rectal examination every 6 months, and biopsies at 1, 4, 7 and 10 years, followed by every 5 years thereafter. Patients with confirmed pathological reclassification were recommended for secondary treatments. RESULTS: As of February 2024, 1302 patients were enrolled in AS; 1274 (98%) met the eligibility criteria. The median (interquartile range) age, PSA level, PSAD, and number of positive cores were 69 (64-73) years, 5.3 (4.5-6.6) ng/mL, 0.15 (0.12-0.17) ng/mL, and 1 (1-2), respectively. The clinical stage was T1c in 1089 patients (86%) and T2 in 185 (15%). The rates of acceptance by patients for the first, second, third and fourth re-biopsies were 83%, 64%, 41% and 22%, respectively. The pathological reclassification rates for the first, second, third and fourth re-biopsies were 29%, 30%, 35% and 25%, respectively. The 1-, 5- and 10-year persistence rates were 77%, 45% and 23%, respectively. Six patients developed metastasis, and one patient died from prostate cancer. CONCLUSION: Pathological reclassification was observed in approximately 30% of the patients during biopsy; however, biopsy acceptance rates decreased over time. Although metastasis occurred in six patients, only one death from prostate cancer was recorded.

Double somatic mutations in CTNNB1 and GNA11 in an aldosterone-producing adenoma.

Double somatic mutations in CTNNB1 and GNA11/Q have recently been identified in a small subset of aldosterone-producing adenomas (APAs). As a possible pathogenesis of APA due to these mutations, an association with pregnancy, menopause, or puberty has been proposed. However, because of its rarity, characteristics of APA with these mutations have not been well characterized. A 46-year-old Japanese woman presented with hypertension and hypokalemia. She had two pregnancies in the past but had no history of pregnancy-induced hypertension. She had regular menstrual cycle at presentation and was diagnosed as having primary aldosteronism after endocrinologic examinations. Computed tomography revealed a 2 cm right adrenal mass. Adrenal venous sampling demonstrated excess aldosterone production from the right adrenal gland. She underwent right laparoscopic adrenalectomy. The resected right adrenal tumor was histologically diagnosed as adrenocortical adenoma and subsequent immunohistochemistry (IHC) revealed diffuse immunoreactivity of aldosterone synthase (CYP11B2) and visinin like 1, a marker of the zona glomerulosa (ZG), whereas 11ß-hydroxylase, a steroidogenic enzyme for cortisol biosynthesis, was mostly negative. CYP11B2 IHC-guided targeted next-generation sequencing identified somatic CTNNB1 (p.D32Y) and GNA11 (p.Q209H) mutations. Immunofluorescence staining of the tumor also revealed the presence of activated ß-catenin, consistent with features of the normal ZG. The expression patterns of steroidogenic enzymes and related proteins indicated ZG features of the tumor cells. PA was clinically and biochemically cured after surgery. In conclusion, our study indicated that CTNNB1 and GNA11-mutated APA has characteristics of the ZG. The disease could occur in adults with no clear association with pregnancy or menopause.

Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

The effect of tenotomy, neurotomy, and dual injury on mouse rotator cuff muscles: Consequences for the mouse as a preclinical model.

A common animal model of muscle pathology following rotator cuff tear (RCT) is a tenotomy of the supraspinatus and infraspinatus, often combined with neurotomy of the suprascapular nerve, which induces a more robust atrophy response than tenotomy alone. However, the utility of this model depends on its similarity to human muscle pathology post-RCT, both in terms of the disease phenotype and mechanisms of muscle atrophy and fatty infiltration. Given the clinical prevalence of nerve injury is low and the muscular response to denervation is distinct from mechanical unloading in other models, an understanding of the biological influence of the nerve injury is critical for interpreting data from this RCT model. We evaluated the individual and combined effect of tenotomy and neurotomy across multiple biological scales, in a robust time-series in the mouse supraspinatus. Muscle composition, histological, and gene expression data related to muscle atrophy, degeneration-regeneration, fatty infiltration, and fibrosis were evaluated. Broadly, we found tenotomy alone caused small, transient changes in these pathological features, which resolved over the course of the study, while neurotomy alone caused a significant fatty atrophy phenotype. The dual injury group had a similar fatty atrophy phenotype to the neurotomy group, though the addition of tenotomy did marginally enhance the fat and connective tissue. Overall, these results suggest the most clinically relevant injury model, tenotomy alone, does not produce a clinically relevant phenotype. The dual injury model partially recapitulates the human condition, but it does so through a nerve injury, which is not well justified clinically.

Assessment of clinical and radiological characteristics of Japanese patients with SAPHO syndrome.

OBJECTIVE: This study aimed to analyse the radiological characteristics and clinical diversity of Japanese patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a heterogeneous disorder. METHODS: Radiographs and clinical information from 115 Japanese patients (female/male: 81/34, mean age at onset: 48.7 years) diagnosed with SAPHO syndrome between January 2007 and December 2020 were retrospectively reviewed. Additionally, the treatment for SAPHO syndrome was explored. RESULTS: Among the 115 patients, 70 patients had complications, including palmoplantar pustulosis, acne, or psoriasis. Imaging studies included bone scintigraphy, magnetic resonance imaging, computed tomography, and positron emission tomography in 71, 58, 70, and 23 patients, respectively. The most frequent lesions were arthritis and hyperostosis of the sternoclavicular joints in 96 patients; spinal lesions, including sacroiliac arthritis were observed in 85 patients. Peripheral aseptic osteitis was observed in 22 patients, and the tibia was involved in 12. The treatments consisted of analgesics, bisphosphonates, conventional synthetic disease-modifying anti-rheumatic drugs, and biologics (tumour necrosis factor inhibitors and interleukin-23p19 inhibitors) in 85, 15, 23, and 10 patients (8 and 2 patients), respectively. CONCLUSION: Sternoclavicular hyperostosis and pustulosis are frequently observed in patients with SAPHO syndrome. Biological agents were more frequently used in patients with peripheral osteitis and arthritis.

Effectiveness and Safety of a Mixture of Nobiletin and Tangeretin in Nocturia Patients: A Randomized, Placebo-Controlled, Double-Blind, Crossover Study.

Nobiletin and tangeretin (NoT) are flavonoids derived from the peel of Citrus depressa, and they have been found to modulate circadian rhythms. Because nocturia can be considered a circadian rhythm disorder, we investigated the efficacy of NoT for treating nocturia. A randomized, placebo-controlled, double-blind, crossover study was conducted. The trial was registered with the Japan Registry of Clinical Trials (jRCTs051180071). Nocturia patients aged ≥50 years who presented nocturia more than 2 times on a frequency-volume chart were recruited. Participants received NoT or a placebo (50 mg once daily for 6 weeks), followed by a washout period of ≥2 weeks. The placebo and NoT conditions were then switched. Changes in nocturnal bladder capacity (NBC) were the primary endpoint, and changes in nighttime frequency and nocturnal polyuria index (NPi) were secondary endpoints. Forty patients (13 women) with an average age of 73.5 years were recruited for the study. Thirty-six completed the study, while four withdrew. No adverse events directly related to NoT were observed. NoT had little effect on NBC compared with the placebo. In contrast, NoT significantly changed nighttime frequency by -0.5 voids compared with the placebo (p = 0.040). The change in NPi from baseline to the end of NoT was significant (-2.8%, p = 0.048). In conclusion, NoT showed little change in NBC but resulted in decreased nighttime frequency with a tendency toward reduced NPi.

Monitoring the courtship flight trajectory of Latham's snipe (Gallinago hardwickii) using microphone arrays.

This study is the first to quantitatively measure the courtship display flights of Latham's snipe (Gallinago hardwickii), which is a "near threatened" species as of 2022 (IUCN red list of threatened species). By using a 16-channel microphone array and 8-channel microphone arrays, we localized the fine-scale movements of courtship flights of one male performing at high altitude and high speed, and we estimated the direction from which each sound arrived using robot audition. Preliminary analyses of the azimuthal and elevation angles of the courtship flights partially revealed a fine-scale flight trajectory. First, a male Latham's snipe gradually gained altitude while vocalizing sharp and harsh repeating calls, until it reached the flight peak altitude, then dove down while producing winnowing sound to the ground along the wetland zones without tall vegetation. This observation method is methodologically useful to establish a better understanding of Latham's snipe courtship flight site selection. Furthermore, this method can be extended to investigate other rare nocturnal or crepuscular birds that are too timid to risk ringing or tagging.

Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study.

OBJECTIVES: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients. METHODS: Patients with RA were administered TCZ, with or without MTX, for 3 years; those who received TCZ+MTX combination therapy were selected. After remission was achieved, MTX was discontinued without flare development in one group (discontinued [DISC] group, n = 33) and continued without flare development in another group (maintain [MAIN] group, n = 37). The clinical efficacy of TCZ+MTX therapy, patient background characteristics, and adverse events were compared between groups. RESULTS: The disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 3, 6, and 9 months was significantly lower in the DISC group (P < .05, P < .01, and P < .01, respectively). Further, the DAS28-ESR remission rate at 6 and 9 months and Boolean remission rate at 6 months were significantly higher in the DISC group (P < .01 for all). Disease duration was significantly longer in the DISC group (P < .05). Furthermore, the number of patients with stage 4 RA was significantly higher in the DISC group (P < .01). CONCLUSIONS: Once remission was achieved, MTX was discontinued in patients who responded favorably to TCZ+MTX therapy, despite the prolonged disease duration and stage progression.

[Evaluation of Patients with Localized Prostate Cancer in whom Long-Term Successful Androgen Deprivation Therapy was Ceased].

We evaluated the clinical course of patients with localized prostate cancer in whom long-term successful androgen deprivation therapy (ADT) was ceased. Study subjects were 24 patients with stage B prostate cancer who were initially treated with ADT for a median duration of 93 months. The median age at the cessation of ADT was 84 years. The median nadir serum prostate specific antigen (PSA) level was 0.022 ng/ml. The median duration of follow-up from the cessation of ADT was 31 months. During follow-up, five patients showed PSA elevation of ≥2 ng/ml from the nadir. Serum testosterone level was tested in 20 patients, and five showed testosterone recovery ≥0.5 ng/ml. Seven patients died from diseases other than prostate cancer, but there were no deaths caused by prostate cancer. This study demonstrated that long-term successful ADT for localized prostate cancer could be ceased with adequate follow-up evaluation.

Simultaneous Reverse Shoulder Arthroplasty and Open Reduction With Internal Fixation for Bilateral Proximal Humerus Fractures in the Elderly: A Report of Two Cases.

Simultaneous bilateral proximal humerus fractures (PHFs) caused by a single trauma are considered rare. We herein report two patients with bilateral PHFs treated based on our treatment strategy: reverse shoulder arthroplasty (RSA) to obtain rigid stability for one shoulder and open reduction with internal fixation (ORIF) to regain the mobility of external and internal rotation for the other. By using Neer's four-segment fracture classification, patients underwent RSA for one shoulder with the more advanced fracture type and ORIF for the other. In Case 1, a 74-year-old female presented with bilaterally comminuted PHFs and underwent surgical treatment with RSA and ORIF. In Case 2, a 78-year-old female with the comorbidity of rheumatoid arthritis and a history of total elbow arthroplasty for both elbows had bilateral PHFs and underwent surgical treatment with RSA and ORIF. Postoperatively, both patients were instructed to perform exercises including passive range of motion (ROM) for a week, active ROM exercises for two weeks, and muscle strengthening for six weeks after the surgery. At the follow-up, both patients were satisfied with the pain relief and functional recovery. Especially, increased ROM for external and internal rotation was obtained in shoulders with ORIF. These case reports describe a viable treatment option comprising simultaneous RSA and ORIF, and this surgical approach may restore shoulder functions in cases of bilateral PHFs.

Comparison of the medical costs between active surveillance and other treatments for early prostate cancer in Japan using data from the PRIAS-JAPAN study.

OBJECTIVES: To compare the medical costs of active surveillance with those of robot-assisted laparoscopic prostatectomy, brachytherapy, intensity-modulated radiation therapy, and hormone therapy for low-risk prostate cancer. METHODS: The costs of protocol biopsies performed in the first year of surveillance (between January 2010 and June 2020) and those of brachytherapy and radiation therapy performed between May 2019 and June 2020 at the Kagawa University Hospital were analyzed. Hormone therapy costs were assumed to be the costs of luteinizing hormone-releasing hormone analogs for over 5 years. Active surveillance-eligible patients were defined based on the following: age <74 years, ≤T2, Gleason score ≤6, prostate-specific antigen level ≤10 ng/ml, and 1-2 positive cores. We estimated the total number of active surveillance-eligible patients in Japan based on the Japan Study Group of Prostate Cancer (J-CAP) study and the 2017 cancer statistical data. We then calculated the 5-year treatment costs of active surveillance-eligible patients using the J-CAP and PRIAS-JAPAN study data. RESULTS: In 2017, number of active surveillance-eligible patients in Japan was estimated to be 2808. The 5-year total costs of surveillance, prostatectomy, brachytherapy, radiation therapy, and hormone therapy were 1.65, 14.0, 4.61, 4.04, and 5.87 million United States dollar (USD), respectively. If 50% and 100% of the patients in each treatment group had opted for active surveillance as the initial treatment, the total treatment cost would have been reduced by USD 6.89 million (JPY 889 million) and USD 13.8 million (JPY 1.78 billion), respectively. CONCLUSION: Expanding active surveillance to eligible patients with prostate cancer helps save medical costs.

Auditory Survey of Endangered Eurasian Bittern Using Microphone Arrays and Robot Audition.

Bioacoustics monitoring has become increasingly popular for studying the behavior and ecology of vocalizing birds. This study aims to verify the practical effectiveness of localization technology for auditory monitoring of endangered Eurasian bittern (Botaurus stellaris) which inhabits wetlands in remote areas with thick vegetation. Their crepuscular and highly secretive nature, except during the breeding season when they vocalize advertisement calls, make them difficult to monitor. Because of the increasing rates of habitat loss, surveying accurate numbers and their habitat needs are both important conservation tasks. We investigated the feasibility of localizing their booming calls, at a low frequency range between 100-200 Hz, using microphone arrays and robot audition HARK (Honda Research Institute, Audition for Robots with Kyoto University). We first simulated sound source localization of actual bittern calls for microphone arrays of radii 10 cm, 50 cm, 1 m, and 10 m, under different noise levels. Second, we monitored bitterns in an actual field environment using small microphone arrays (height = 12 cm; width = 8 cm), in the Sarobetsu Mire, Hokkaido Island, Japan. The simulation results showed that the spectral detectability was higher for larger microphone arrays, whereas the temporal detectability was higher for smaller microphone arrays. We identified that false detection in smaller microphone arrays, which was coincidentally generated in the calculation proximate to the transfer function for the opposite side. Despite technical limitations, we successfully localized booming calls of at least two males in a reverberant wetland, surrounded by thick vegetation and riparian trees. This study is the first case of localizing such rare birds using small-sized microphone arrays in the field, thereby presenting how this technology could contribute to auditory surveys of population numbers, behaviors, and microhabitat selection, all of which are difficult to investigate using other observation methods. This methodology is not only useful for the better understanding of bitterns, but it can also be extended to investigate other rare nocturnal birds with low-frequency vocalizations, without direct ringing or tagging. Our results also suggest a future necessity for a robust localization system to avoid reverberation and echoing in the field, resulting in the false detection of the target birds.

ACTH-independent production of 11-oxygenated androgens and glucocorticoids in an adrenocortical adenoma.

SIGNIFICANCE STATEMENT: Due to its rarity, biochemical and histologic characteristics of androgen and glucocorticoid co-secreting adrenocortical adenomas are largely unknown. Herein, we report a case of adrenocortical adenoma that caused marked hyperandrogenemia and mild autonomous cortisol secretion. In this study, we investigated serum steroid profiles using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and histologic characteristics of the resected tumor. LC-MS/MS revealed highly elevated levels of 11-oxygenated androgens which have not been well studied in adrenal tumors. The expression patterns of steroidogenic enzymes determined by immunohistochemistry supported the results of steroid profiling and suggested the capacity of the tumor cells to produce 11-oxygenated androgens. Measurement of 11-oxygenated steroids should facilitate a better understanding of androgen-producing adrenocortical neoplasms.

Clinical Impact of Detecting Low-Frequency Variants in Cell-Free DNA on Treatment of Castration-Resistant Prostate Cancer.

PURPOSE: Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA (ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from patients with CRPC and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%. EXPERIMENTAL DESIGN: This prospective, multicenter cohort study enrolled patients with CRPC eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pretreatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF ≥0.1% were detected using an in-house pipeline. We investigated progression-free survival (PFS) and overall survival (OS) after different ctDNA fraction cutoffs were applied. RESULTS: One hundred patients were analyzed (median follow-up 10.7 months). We detected deleterious ATM, BRCA2, and TP53 variants even in samples with ctDNA fraction below 2%. When the ctDNA fraction cutoff value of 0.4% was applied, significant differences in PFS and OS were found between patients with and without defects in ATM or BRCA2 [HR, 2.52; 95% confidence interval (CI), 1.24-5.11; P = 0.0091] and TP53 (HR, 3.74; 95% CI, 1.60-8.71; P = 0.0014). However, these differences were no longer observed when the ctDNA fraction cutoff value of 2% was applied, and approximately 50% of the samples were classified as ctDNA unquantifiable. CONCLUSIONS: Detecting low-frequency ctDNA variants with a VAF <1% is important to identify clinically informative genomic alterations in CRPC.

[Two Cases of Renal Pelvic Rupture Due to Trauma in a Patient with Ureteropelvic Junction Stenosis].

A pathologic kidney with hydronephrosis is prone to rupture after minor trauma to the renal pelvis ; however, it is controversial whether drainage, such as nephrostomy and ureteral stenting, should be performed in this setting. Herein we report traumatic rupture of the renal pelvis in 2 patients with ureteropelvic junction stenosis at two centers. Case 1 : A 15-year-old boy sustained a blunt injury on his left back while playing football. His family physician referred the patient to our hospital for suspected left renal injury. Contrast-enhanced abdominal computed tomography showed left hydronephrosis and fluid accumulation in the left retroperitoneal space, which led to a diagnosis of rupture of the left renal pelvis. The patient was treated conservatively ; however, fluid accumulation around the kidney worsened. A ureteral stent was placed, and the patient's renal colic and imaging findings improved. Case 2 : A 13-yearold boy fell and bruised his abdomen while playing soccer. He was unable to walk because of pain, and was brought to our hospital by ambulance. Contrast-enhanced abdominal computed tomography showed left hydronephrosis and fluid accumulation in the left retroperitoneal space, which led to a diagnosis of rupture of the left renal pelvis. A ureteral stent was placed on the same day, and the patient's renal colic improved.

Clinical Features of Ulnar Tunnel Syndrome and the Diagnostic Value of Nerve Conduction Measurements.

OBJECTIVES: The purposes of this study were to assess the clinical features of ulnar tunnel syndrome (UTS) and to investigate the diagnostic value of nerve conduction measurements for UTS. METHODS: Eighteen patients with UTS were reviewed retrospectively. Fifteen patients had intrinsic muscle atrophy and motor weakness, and 15 had numbness with hypesthesia. The compound muscle action potentials (CMAPs) from the first dorsal interosseous (FDI) muscle and the abductor digiti minimi (ADM) muscle and the sensory nerve action potential (SNAP) from the little finger were recorded and analyzed. All patients underwent ulnar tunnel release surgery and neurolysis. Static two-point discrimination test results and pinch strengths were assessed before and after surgery. RESULTS: Before surgery, FDI-CMAP was recorded in 17 patients, and ADM-CMAP in 16, and all showed delayed latency and/or low amplitude. SNAP was recorded in eight patients and two showed delayed latency. The causes of ulnar nerve lesions were ganglion in five patients, traumatic adhesion in four, ulnar artery aberrancy in four, pisohamate arch in three, anomalous muscle in one, and ulnar vein varix in one. The sites of the lesions were in zone 1 of the ulnar tunnel anatomy in 12 patients, in zone 2 in 2, and in zones 1 and 2 in 4. After surgery, all patients obtained recovery of motor function and sensation; however, postoperative FDI-CMAP and ADM-CMAP did not improve to the normal range. CONCLUSIONS: The causes of UTS were ganglion, traumatic adhesion, ulnar artery aberrancy, and pisohamate arch. Both FDI-CMAP and ADM-CMAP were valuable for electrophysiological diagnosis of UTS.

Visualization of a chorus structure in multiple frog species by a sound discrimination device.

We developed a sound discrimination device to identify and localize the species of nocturnal animals in their natural habitat. The sound discrimination device is equipped with a microphone, a light-emitting diode, and a band-pass filter. By tuning the center frequency of the filter to include a dominant frequency of the calls of a focal species, we enable the device to be illuminated only when detecting the calls of the focal species. In experiments in a laboratory room, we tuned the sound discrimination devices to detect the calls of Hyla japonica or Rhacophorus schlegelii and broadcast the frog calls from loudspeakers. By analyzing the illumination pattern of the devices, we successfully identified and localized the two kinds of sound sources. Next, we placed the sound discrimination devices in a field site where actual male frogs (H. japonica and R. schlegelii) produced sounds. The analysis of the illumination pattern demonstrates the efficacy of the developed devices in a natural environment and also enables us to extract pairs of male frogs that significantly overlapped or alternated their calls.

[A Case of Emphysematous Pyelonephritis Complicated by Bacterial Endophthalmitis in which Multidisciplinary Therapy Led to Preservation of the Kidney].

A 49-year-old male with untreated diabetes mellitus type 2 experienced eyesight deterioration and general malaise, and was treated for uveitis and orbital cellulitis. Later, he was taken to a local hospital via ambulance for a consciousness disorder and was diagnosed with bilateral infectious endophthalmitis, a right ureteral stone, and emphysematous pyelonephritis. He was then referred to our hospital for further examination and treatment. We immediately initiated intravenous antibiotic therapy with meropenem and glycemic control with continuous subcutaneous insulin infusion, and placed a ureteral and percutaneous drain tube into the right ureter and the emphysema, respectively. We performed a diagnostic and therapeutic vitrectomy on the patient's left eye. Urinary, blood, and vitreous cultures were positive for Klebsiella aerogenes. Abdominal contrast-enhanced computed tomography showed bilaterally comparable renal contrast enhancement. On the 60th hospital day, we performed endoscopic combined intrarenal surgery (ECIRS) and completely removed the urinary stone. Although he lost light sensitivity in his right eye, his left eyesight improved, and his blood glucose level was adequately managed by oral medication. Three months after the surgery, he was discharged from our hospital and he showed no sign of recurrence of the infection at ten months after surgery.

Rheumatoid arthritis patients with low baseline Health Assessment Questionnaire scores have a risk of functional disability progression: a post hoc analysis of a nationwide longitudinal cohort in Japan.

OBJECTIVES: To determine prognostic factors for the Health Assessment Questionnaire-Disability Index (HAQ-DI) progression in patients with rheumatoid arthritis (RA) in clinical practice. METHODS: We evaluated 388 biological disease-modifying anti-rheumatic drug (bDMARD)-naïve Japanese patients with RA with moderate to high disease activity at study entry after being treated with conventional synthetic DMARDs. These patients were treated according to a treat-to-target (T2T) strategy for one year. The Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the HAQ-DI were assessed every three months. We also evaluated joint destruction using a modified total Sharp score at baseline and at one year. HAQ-DI progression was defined as the yearly progression of HAQ-DI >0.1. We performed a multiple logistic regression analysis to explore the factors predicting HAQ-DI progression at one year. RESULTS: HAQ-DI progression was observed in 18% of the patients. The multiple logistic regression analysis revealed the independent variables associated with HAQ-DI progression were: DAS28-ESR >5.1 at baseline (odds ratio [OR] 0.31, 95% con dence interval [CI] 0.13-0.74, p=0.0083); HAQ-DI score at baseline <0.5 (OR 2.27, 95% CI 1.22-4.26, p=0.0102); and achievement of low disease activity at 12 weeks (OR 0.42, 95% CI 0.21-0.82, p=0.0112). CONCLUSIONS: Our data suggest that maintaining clinical improvement according to T2T and initiating the treatment at an early stage are important for functional improvement after one year and that patients with low baseline HAQ scores have a higher risk of HAQ disability progression.

Bach1 promotes muscle regeneration through repressing Smad-mediated inhibition of myoblast differentiation.

It has been reported that Bach1-deficient mice show reduced tissue injuries in diverse disease models due to increased expression of heme oxygenase-1 (HO-1)that possesses an antioxidant function. In contrast, we found that Bach1 deficiency in mice exacerbated skeletal muscle injury induced by cardiotoxin. Inhibition of Bach1 expression in C2C12 myoblast cells using RNA interference resulted in reduced proliferation, myotube formation, and myogenin expression compared with control cells. While the expression of HO-1 was increased by Bach1 silencing in C2C12 cells, the reduced myotube formation was not rescued by HO-1 inhibition. Up-regulations of Smad2, Smad3 and FoxO1, known inhibitors of muscle cell differentiation, were observed in Bach1-deficient mice and Bach1-silenced C2C12 cells. Therefore, Bach1 may promote regeneration of muscle by increasing proliferation and differentiation of myoblasts.