Cost-efficient PCR based DNA barcoding of marine invertebrate specimens with NovaSeq amplicon sequencing.

BACKGROUND: The marine environment harbors high biodiversity; however, it is poorly understood. Nucleotide sequence data of all marine organisms should be accumulated before natural and/or anthropogenic environmental changes jeopardize the marine environment. In this study, we report a cost-effective and easy DNA barcoding method. This method can be readily adopted without using library preparation kits. It includes multiplex PCR of short targets, indexing PCR, and outsourcing to a sequencing service using the NovaSeq system. METHODS AND RESULTS: We targeted four mitochondrial genes [cytochrome c oxidase subunit I (COI), COIII, 16S rRNA (16S), and 12S rRNA (12S)] and three nuclear genes [18S rRNA (18S), 28S rRNA (28S), internal transcribed spacer 2 (ITS2)] in 95 marine invertebrate specimens, which were primarily annelids. The primers, including adapters and indices for NovaSeq sequencing, were newly designed. Two PCR runs were conducted. The 1st PCR amplified specific loci with universal primers and the 2nd added sequencing adapters and indices to the 1st PCR products. The gene sequences obtained from the FASTQ files were subjected to BLAST search and phylogenetic analyses. One run using 95 specimens yielded sequences averaging 2816 bp per specimen for a total length of six loci. Nuclear genes were more successfully assembled compared with mitochondrial genes. A weak but significantly negative correlation was observed between the average length of each locus and success rate of the assembly. Some of the sequences were almost identical to the sequences obtained from specimens collected far from Japan, indicating the presence of potentially invasive species identified for the first time. CONCLUSIONS: We obtained gene sequences efficiently using next-generation sequencing rather than Sanger sequencing. Although this method requires further optimization to increase the success rate for some loci, it is used as a first step to select specimens for further analyses by determining the specific loci of the targets.

Iliac vein variation in the sacral promontory on three-dimensional computed tomography angiography: a prospective observational study before laparoscopic sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Venous injury may occur during exposure of the anterior longitudinal ligament at the anterior sacral promontory (SP). We aimed to quantitatively measure the extent of the vascular window (VW) in front of the SP in patients with internal iliac vein (IIV) variations using preoperative three-dimensional computed tomography angiography (3DCTA). We hypothesized that patients with IIV variations would have a narrow VW. METHODS: This prospective observational study included patients scheduled for laparoscopic sacrocolpopexy (LSC) between July 2022 and April 2023 who underwent preoperative 3DCTA. The primary endpoint was the VW measurement in the standard and variant IIV groups using 3DCTA before LSC. The secondary endpoint was the difference between the two IIV groups adjusted for age, body mass index, hypertension, and diabetes using an analysis of covariance (ANCOVA) model. Multiple regression analysis was performed to analyze the effect of factors on the distance from the SP to great vascular bifurcations. RESULTS: There were 20 cases of IIV variation (20.2%). VW was 28.8 ± 12.4 mm in the variant group and 39.6 ± 12.6 mm in the standard group (p = 0.001). In the ANCOVA model, IIV variations affected VW (coefficient, -11.8; 95% confidence interval [CI], -18.4 to -5.08, p < 0.001). Multivariate analysis revealed that the aorta-SP distance decreased with age (coefficient, -0.44; 95% CI, -0.77 to -0.11, p = 0.009). CONCLUSIONS: One in five women has a vascular variant at the SP that restricts the "safe" zone of fixation to < 3 cm.

Association between comorbidities and survival in patients with metastatic urothelial carcinoma treated with pembrolizumab.

BACKGROUND: This study aims to investigate the relationship between comorbidities and survival in patients with mUC treated with pembrolizumab as a second-line treatment. METHODS: From February 2018 to October 2021, we analyzed the data of 185 consecutive patients with metastatic UC who received pembrolizumab as second-line therapy at The Jikei University Hospital and five affiliated hospitals. We used the Charlson Comorbidity Index (CCI) to assess the comorbidities. The outcomes of interest were progression-free survival (PFS) and overall survival (OS). To compare the survival differences, inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and the IPTW-adjusted Cox regression hazards model were used. RESULTS: After IPTW adjustment, patient characteristics were well-balanced between patients with high CCI and those with low CCI. The IPTW-adjusted Kaplan-Meier curves of PFS and OS based on CCI revealed that the patients with high CCI (2 or more) had a shorter PFS (median, 1.6 vs. 2.8 months) and a shorter OS (median, 12.4 vs. 18.8 months) (0-1). Similarly, in the IPTW-adjusted Cox regression hazards model, patients with high CCI had significantly shorter PFS [HR, 1.84 (95% CI 1.26-2.68; p = 0.002)] and OS [HR, 1.98 (95% CI 1.20-3.27; p = 0.008)] than those with lower CCI. CONCLUSIONS: High CCI was associated with a higher risk of disease progression as well as overall mortality in mUC patients treated with second-line pembrolizumab.

Effectiveness of pembrolizumab in trial-ineligible patients with metastatic urothelial carcinoma.

BACKGROUND: The KEYNOTE-045 trial showed that pembrolizumab therapy improved the survival of patients with advanced urothelial carcinoma (UC). However, its effectiveness in trial-ineligible patients remains unclear. MATERIALS AND METHODS: We conducted a multicenter retrospective study to evaluate the effectiveness of pembrolizumab in patients with metastatic UC who were trial-ineligible. The data of 164 consecutive patients with platinum-treated metastatic UC who received pembrolizumab as second-line therapy were analyzed. Trial eligibility was assessed using the KEYNOTE-045 criteria. Inverse probability of treatment weighting (IPTW) was used to balance patient characteristics. Overall survival (OS) and progression-free survival (PFS) were examined using the IPTW-adjusted Kaplan-Meier method. IPTW-adjusted restricted mean survival times (RMSTs) were compared between ineligible and eligible patients. RESULTS: Seventy-five patients (45.7%) were classified as ineligible based on the KEYNOTE-045 criteria. Baseline hemoglobin concentration of less than 9.0 g/dL was the most common reason for trial protocol violation (N = 23 [14.0%]). An IPTW-adjusted logistic regression model showed that the trial-eligibility was not significantly associated with objective response (OR: 0.65, 95% CI: 0.32 to 1.29, P = 0.22). Ineligible patients had similar RMST for PFS (difference: 3.8 months, 95% CI: -1.6 to 9.3, P = 0.17) and RMST for OS (difference: 1.4 months, 95% CI: -5.4 to 8.2, P = 0.93) compared with eligible patients. CONCLUSIONS: This study suggests that the effectiveness of pembrolizumab may be retained in ineligible patients with platinum-treated metastatic UC. Expanding trial eligibility criteria for these patients may be beneficial.

Populations of the Intertidal Crab Macrophthalmus banzai are Not Grouped by Latitude: Taiwan Population is Genetically Closer to the Populations in the Japanese Mainland Than the Ryukyu Islands.

Macrophthalmus banzai is an intertidal crab species of Macrophthalmidae inhabiting muddy tidal flats in the northwestern Pacific. A previous study on the population genetic structure of Japanese M. banzai based on the mitochondrial COI gene sequences revealed the presence of two genetically distinguished groups, i.e., the northern group (Honshu, Shikoku, and Kyushu Islands) and the southern group (the Ryukyu Islands). In the present study, we newly determined the COI gene sequences of M. banzai collected from Taiwan and conducted population genetic analyses of these sequences together with Japanese sequences obtained from GenBank to reveal the genetic relationship of this species between Japan and Taiwan. The SAMOVA and pairwise ΦST analysis showed that the Taiwan population is more closely related to the northern group than the southern group. This indicates that the populations of M. banzai are not genetically differentiated by latitude but probably by the pathway of the Kuroshio Current, resulting in the isolation of the population in the Ryukyu Islands. Such a pattern is consistent with the population genetic structure of the fiddler crab Tubuca arcuata shown by a previous study, whereas the pattern differs from those of other intertidal invertebrates. The difference in the larval durations may have influenced the difference in population genetic structures among species. The present study provides a further case of the genetic structure of intertidal species that are not simply regulated by geographic distances.

Sources of Polycyclic Aromatic Hydrocarbons in Fecal Pellets of a Marphysa Species (Annelida: Eunicidae) in the Yoro Tidal Flat, Japan.

The fecal pellets of Marphysa sp. E sensu Abe et al. (2019) (Annelida, Eunicidae) living in the Yoro tidal flat (Ichihara, Chiba, Japan) contain high levels of polycyclic aromatic hydrocarbons (PAHs), and the concentrations rapidly decrease over time. To investigate the origin of the high-concentration PAHs in the fecal pellets and food sources of the worms, the PAH concentrations, carbon and nitrogen stable isotope ratios (δ13C and δ15N), total organic carbon, and total nitrogen for two types of sediment (sands and reduced muds), fecal pellets, and the body of the worms were determined. The PAH concentrations and chemical properties of the fecal pellets were similar to those of the reduced muds (20-30 cm sediment depth). The δ13C, δ15N, and C/N values of reduced muds were the same as the typical values of terrestrial C3 plants, suggesting that reduced muds were derived from terrestrial plants. These data indicated that the worms selectively take up reduced muds containing high levels of PAHs. The δ13C and δ15N values of the worm bodies indicated that the worms did not use the organic carbon derived from terrestrial C3 plants as primary nutrition. Taking into consideration their selective uptake of reduced muds, excretion, and subsequent rapid decrease of PAHs in the fecal pellets, the worms could contribute to the remediation of chemical pollutants in the tidal flat sediments.

Comparison of outcomes of laparoscopic sacrocolpopexy with concomitant supracervical hysterectomy or uterine preservation.

INTRODUCTION AND HYPOTHESIS: Sacrocolpopexy was traditionally performed for post-hysterectomy prolapse or during concurrent hysterectomy. Sacrocolpopexy outcome with uterine preservation is poorly investigated. This study compared outcomes of laparoscopic sacrocolpopexy with concurrent supracervical hysterectomy or uterine preservation. METHODS: This retrospective study compared data of patients with pelvic organ prolapse who underwent laparoscopic sacrocolpopexy with uterine preservation with the data of controls who underwent laparoscopic sacrocolpopexy with supracervical hysterectomy. We analyzed composite failure in uterine preservation versus concurrent supracervical hysterectomy (primary objective) and evaluated factors associated with the primary outcome of composite failure after laparoscopic sacrocolpopexy with preservation or supracervical hysterectomy (secondary objective). Composite failure was defined as subjective bulge symptoms, reoperation, or anatomical prolapse. Cox models indicated time to composite failure as an endpoint. RESULTS: Of 274 patients, 232 underwent laparoscopic sacrocolpopexy with supracervical hysterectomy and 42 underwent laparoscopic uterine preservation. After propensity score matching (ratio: 2, for the laparoscopic sacrocolpopexy with supracervical hysterectomy group), 56 patients (24.1%) were in the supracervical hysterectomy group and 28 (66.7%) in the uterine preservation group. All patients underwent 24 months of follow-up. The composite failure rates were 10.7% for supracervical hysterectomy and 3.6% for preservation (p=0.87). The mean estimated blood loss was 10 ml (preservation, 10.0 ml [5.0-10.0] versus supracervical hysterectomy, 10.0 ml [10.0-15.0]; p=0.007). In the Cox proportional hazards model, higher preoperative body mass index and the point Ba increased composite failure risk. CONCLUSIONS: Although not statistically significant, composite failure in the two techniques is likely clinically meaningful.

Clinical benefit of continuing pembrolizumab treatment beyond progression in patients with metastatic urothelial carcinoma.

BACKGROUND: There has been no clinical evidence to justify continued pembrolizumab therapy beyond progression in patients with metastatic urothelial carcinoma (UC). MATERIALS AND METHODS: We conducted a multicenter retrospective study evaluating the clinical efficacy of continued use of pembrolizumab beyond progression in patients with metastatic UC. Data from 51 patients with metastatic UC, who developed progression during second-line pembrolizumab therapy, were analyzed. Progression was defined based on the Immunotherapy Response Evaluation Criteria in Solid Tumors. The outcome was overall survival (OS). The association between continued treatment, OS, and the risk of all-cause mortality was tested using log-rank test, conventional and time-dependent Cox regression models. RESULTS: No significant difference in patient characteristics was noted between patients continuing pembrolizumab beyond progression (N = 21) and those discontinuing pembrolizumab (N = 30). Median OS was significantly longer in the continuation group (17.8 vs. 8.8 months; P = 0.038). A multivariable conventional Cox regression model identified continued pembrolizumab administration as a significant independent prognostic factor of all-cause mortality (hazard ratio [HR]: 0.21, 95% confidence interval [CI]: 0.05-0.90, P = 0.036), irrespective of the time from treatment initiation to progression and concurrent clinical progression. Further, longer duration of pembrolizumab treatment beyond progression was independently associated with a reduced risk of all-cause mortality in a multivariable time-dependent Cox regression model, when used as a time-dependent variable (HR: 0.07, 95% CI: 0.01-0.45, P = 0.006). CONCLUSIONS: Continued pembrolizumab administration beyond progression might be beneficial in patients with metastatic UC who were clinically stable.

Novel insight into the correlation between hernia orifice of cystocele and lower urinary tract function: a pilot study.

BACKGROUND: It has been hypothesized that women with significant pelvic organ prolapse (POP), particularly of the anterior vaginal wall, may have voiding dysfunction (VD). Although the VD mechanism due to cystocele is not fully understood, different vaginal compartments have rarely been closely examined. This study attempted to further elucidate the correlation between POP and VD through a new subgroup classification using cystoscopy. METHODS: This study reviewed clinical records of 49 women who underwent cystocele repair. All patients were scheduled for laparoscopic sacrocolpopexy, preoperatively underwent uroflowmetry and postvoid residual urine volume (PVR) measurement, and completed pelvic floor function questionnaires. Bladder examination by cystoscopy was additionally performed using the lithotomy position with the Valsalva maneuver. RESULTS: Subjects were divided into four groups according to hernia orifice presence determined by cystoscopy, which included the trigone type, posterior wall type, trigone and urethra type, and trigone and posterior wall type. The posterior wall type had statistically higher PVR values versus the trigone and posterior wall type (P = 0.013). The posterior wall type had statistically lower values for average urine flow rate versus the urethra and trigone type (P = 0.020). There were no significant differences noted in the pelvic floor function questionnaires among the four groups. CONCLUSIONS: A new bladder defect classification based upon hernia orifice location was associated with lower urinary tract function. Posterior wall hernia presence caused significant voiding function deterioration. This new subgroup classification, which can more clearly identify and indicate bladder function, is also comparable among patients.

Medium-term outcomes 2 years after laparoscopic sacrocolpopexy: a retrospective cohort study in Japan.

This study was performed to investigate medium-term outcomes and reoperation rates after laparoscopic sacrocolpopexy (LSC). We examined 119 patients undergoing LSC for symptomatic pelvic organ prolapse (POP). The primary outcomes were subjective failure and anatomical failure at 2 years; a score ≥ 2 on question 3 of the PFDI-20 was considered to indicate subjective failure. POP-Q stage 2 or higher in any compartment was considered to indicate anatomical failure. Secondary outcomes were reoperations for POP recurrence, mesh-related complications, and stress urinary incontinence (SUI). The rates of subjective failure and anatomical failure were 4.2% (n = 5) and 9.2% (n = 11), respectively. Reoperations were needed in 13.4% (n = 16) of patients, including SUI with tape procedure in 7.5% (n = 9), POP recurrence in 4.2% (n = 5), and mesh-related complications in 1.6% (n = 2). The subjective failure rate at 2 years after LSC was acceptably low.Impact StatementWhat is already known on this subject? Laparoscopic sacrocolpopexy (LSC) has clinical efficacy equivalent to open sacrocolpopexy, and there is evidence that LSC involves less blood loss and shorter length of hospital stay. However, there is still insufficient evidence to assess medium-term outcomes after LSC in Japan.What the results of this study revealed? The findings of this study showed excellent medium-term rates of subjective failure (4.2%) and anatomical failure (8.4%) after LSC. We demonstrated that patients with persistent postoperative vaginal bulge (subjective failure) also had no improvement in postoperative urinary and colorectal symptoms. Our cohort had low rates of reoperation (13.4%) after LSC. The most common reoperations were for stress urinary incontinence (SUI) (7.5%), followed by pelvic organ prolapse (POP) recurrence (4.2%) and mesh-related complications (1.6%).What are the implications of these findings in clinical practice and/or further research? This study showed that LSC is a safe and effective treatment for POP. Comparative evaluation of anatomical outcomes and the patient's condition is required to understand the extent to which LSC positively impacts a woman's pelvic floor-related quality of life.

Laparoscopic sacrocolpopexy for pelvic organ prolapse in the elderly: safety and outcomes.

Due to its low postoperative complication rate, vaginal surgery is the preferred intervention for pelvic organ prolapse (POP) in elderly patients. We aimed to assess outcomes and perioperative complication rates associated with laparoscopic sacrocolpopexy (LSC) in elderly women. We retrospectively reviewed the medical records of 74 consecutive patients [52 (70.3%) aged <75 years; 22 (29.7%) aged ≥75 years] with POP who underwent LSC between August 2015 and December 2017. We evaluated preoperative risks using the Charlson Comorbidity Index (CCI) and complications, using the Clavien-Dindo grading (CDG). No between-group differences were observed in CCI. CDG indicated fewer perioperative complications in patients aged >75 years. Anatomical success rates at 15 months were 95.5% and 90.4% in patients aged ≥75 and <75 years, respectively. LSC has a high anatomical correction rate and few perioperative complications regardless of age. Thus, the appropriate surgical intervention method would depend on the patient's health and comorbidities.IMPACT STATEMENTWhat is already known on this subject? Laparoscopic sacrocolpopexy (LSC) is a superior method to vaginal surgery because of its anatomical and functional outcomes, particularly regarding sexual activity.What do the results of this study add? In this single-center study with a 15-month follow-up, we demonstrated that LSC has a high anatomical correction rate and few perioperative complications regardless of age at the time of surgery. Furthermore, there was no significant difference in the rate of complications between the ≥75 and <75 years groups. Thus, LSC may be considered for women aged >75 years. However, in these elderly patients, the surgical method should be determined according to their health status and medical comorbidities.What the implications are of these findings for clinical practice and/or further research? Age should not be the basis for exclusion from laparoscopic procedures. Moreover, LSC is a suitable and valid option for elderly women with POP. As the study population consisted of a homogenous group of Japanese women, it lacks generalisability. Studies evaluating these outcomes are required in other populations.

Comparison of the Immunotherapy Response Evaluation Criteria in Solid Tumours (iRECIST) with RECIST for capturing treatment response of patients with metastatic urothelial carcinoma treated with pembrolizumab.

OBJECTIVE: To evaluate the clinical usefulness of Immunotherapy Response Evaluation Criteria in Solid Tumours (iRECIST) in patients with metastatic urothelial carcinoma (UC) treated with pembrolizumab. The iRECIST is designed to accurately capture the tumour response treated with immunotherapy. PATIENTS AND METHODS: We conducted a multicentre retrospective study evaluating the clinical utility of iRECIST in 91 patients with metastatic UC treated with second-line pembrolizumab. The objective response (OR) and time to progression (TTP) in accordance with both iRECIST and RECIST version 1.1 were compared with overall survival (OS) and risk of all-cause mortality, and analysed using log-rank and multivariable Cox regression models, respectively. Predictive performance of the criteria was studied using Harrell's concordance index (c-index). The clinical usefulness of each criterion was compared using decision curve analysis. RESULTS: Of 57 patients with progressive disease per RECIST, a considerable number of patients were reclassified to immune stable disease (six, 10.5%), immune partial response (two, 3.5%), and immune complete response (two, 3.5%) per iRECIST. Multivariable Cox regression models showed that both OR (hazard ratio [HR] 0.10, 95% confidence interval [CI] 0.03-0.35; P = 0.001) and TTP (HR 0.59, 95% CI 0.46-0.77; P < 0.001) per iRECIST were significantly associated with all-cause mortality. Furthermore, iRECIST had a significant, increased predictability of OS compared with RECIST (OR, c-index: 0.70, increase: 0.04, P = 0.046; TTP, c-index: 0.88, increase: 0.07, P = 0.039). On decision curve analysis, iRECIST presented better net benefit gains than did RECIST. CONCLUSIONS: Compared with RECIST, iRECIST could more accurately predict OS of patients with metastatic UC treated with pembrolizumab. The iRECIST has the potential to be a new standard for tumour response evaluation of these patients.

Modified Glasgow prognostic score is a pre-surgical prognostic marker of disease mortality in upper urinary tract urothelial carcinoma.

BACKGROUND: To investigate the prognostic value of pre-surgical modified Glasgow prognostic score in upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. METHODS: We retrospectively reviewed the clinical records of 273 urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. The modified Glasgow prognostic score was evaluated based on pre-surgical serum C-reactive protein and albumin. Association of modified Glasgow prognostic score with recurrence-free survival, cancer-specific survival and overall survival rates was estimated using Kaplan-Meier method and log-rank test was used to compare survival outcome. Cox regression analyses were performed for the assessment of the modified Glasgow prognostic score with recurrence-free survival, cancer-specific survival and overall survival. RESULTS: Of total 273 patients, the modified Glasgow prognostic score 0, 1 and 2 were assigned in 216 (79%), 45 (17%) and 12 (4%), respectively. The recurrence-free survival, cancer-specific survival and overall survival of urinary tract urothelial carcinoma patients with modified Glasgow prognostic score 2 were significantly worse than those with modified Glasgow prognostic score 0. On univariate analysis, modified Glasgow prognostic score 2 was associated with worse recurrence-free survival, cancer-specific survival and overall survival (all P value <0.01). On multivariate analyses, modified Glasgow prognostic score 2 was independently associated with worse cancer-specific survival and overall survival (hazard ratio: 4.73, 95% confidence interval: 1.31-17.2 and hazard ratio: 3.66, 95% confidence interval: 1.08-12.4, respectively). In the subgroup analyses of advanced urinary tract urothelial carcinoma patients, modified Glasgow prognostic score 2 was independently associated with worse recurrence-free survival (hazard ratio 4.31, 95% confidence interval: 1.69-11.1). CONCLUSIONS: Pre-surgical modified Glasgow prognostic score independently predicts cancer-specific survival and overall survival of urinary tract urothelial carcinoma patients. Assessment of pre-surgical modified Glasgow prognostic score status could help identifying the worse survivor of urinary tract urothelial carcinoma patients.

Prognostic model with alkaline phosphatase, lactate dehydrogenase and presence of Gleason pattern 5 for worse overall survival in low-risk metastatic hormone-sensitive prostate cancer.

BACKGROUND: Randomized trials showed the survival benefits of the combined use of androgen receptor axis-targeted agents with androgen deprivation therapy in metastatic hormone-sensitive prostate cancer (mHSPC), regardless of the risk. However, treating patients with low-risk mHSPC with such intensive treatment is still debatable. METHODS: This retrospective study included 155 low-risk patients among 467 mHSPC patients treated in our affiliated institutions. The association between predictive factors and treatment outcomes was estimated using the Kaplan-Meier method and log-rank test. Predictive factors for castration resistant prostate cancer (CRPC)-free survival were investigated using Cox regression analyses. RESULTS: During the median follow-up of 39 months, 38.7% of patients developed CRPC and 14.2% died. In the multivariate analyses, a presence of Gleason pattern 5 (hazard ratio [HR] 2.04), high alkaline phosphatase (HR 1.007) and high lactate dehydrogenase (HR 1.009) were significant predictive factors for shorter CRPC-free survival. Finally, 155 patients were stratified into favorable- and unfavorable-risk groups based on the numbers of the predictive factors. The overall survival (OS) in the unfavorable-risk group (total scores: 2-3) was significantly worse than that of the favorable-risk group (total score: 0-1) (P = 0.02). This prognostic model was assessed with 50 low-risk mHSPC patients from the external validation dataset and found both the time to CRPC, and the OS in the unfavorable-risk group was significantly worse than that of the favorable-risk group (P < 0.01). CONCLUSIONS: The combination of Gleason pattern 5, high alkaline phosphatase and lactate dehydrogenase can predict those with worse OS in low-risk mHSPC patients.

Complications and clinical outcomes of laparoscopic sacrocolpopexy for pelvic organ prolapse.

Evidence on laparoscopic sacrocolpopexy (LSC) is lacking. Herein, we describe the complications and outcomes of LSC. This single-centre, retrospective cohort study included women with pelvic organ prolapse (POP) who underwent LSC between 2015 and 2017. Preoperative, intraoperative, postoperative, and demographic data were collected. We evaluated patients using the Pelvic Organ Prolapse Quantification system and questionnaires. The primary outcomes were operative characteristics, perioperative complications, early postoperative complications, and anatomical results at 12 months. Forty-six patients (median age: 71 years) underwent LSC. The median follow-up period was 12.0 ± 5.0 (range: 11-26) months. The perioperative complications were bladder perforation and vaginal injury (2.2%). Two (4.3%) patients required reoperation for port-site hernia. One (2.2%) patient developed a retroperitoneal abscess, and one (2.2%) had worsened stress urinary incontinence after LSC. Three (6.5%) patients presented with recurrence of prolapse. LSC is safe and effective for POP.IMPACT STATEMENTWhat is already known on this subject? Laparoscopic sacrocolpopexy (LSC) has become a widely used intervention strategy during the last decade; nevertheless, few studies have reported its outcomes and complications.What do the results of this study add? We demonstrate that LSC for pelvic organ prolapse (POP) has favourable anatomical and voiding functional results, and few perioperative complications. However, it is important to preoperatively inform patients regarding the incidence of mesh-related postoperative complications, although they are not life-threatening, and secure their informed consent.What are the implications of these findings for clinical practice and/or further research? We believe that the LSC procedure, because of its short-term and functional outcomes in the lower urinary tract discussed here, will be more commonly available in clinical practice as a feasible and safe surgical option for POP. However, prospective, large-sample studies should be performed to verify the efficacy of LSC, as further evaluation of the procedure is required.

Cross-Cultural Validation Study of the Japanese Version of the ABILOCO-Kids in Ambulatory Children With Cerebral Palsy Using Rasch Analysis.

Aims: To determine the structural validity, construct validity, cross-cultural validity, internal consistency and test-retest reliability of the Japanese version of the ABILOCO-Kids in children with cerebral palsy. Methods: One-hundred sixteen parents of children with cerebral palsy (Gross Motor Function Classification System level I [n = 66], II [n = 32], and III [n = 18]) reported on walking ability using the Japanese version of the ABILOCO-Kids. For test-retest reliability, 23 participants were evaluated. Results: The mean ABILOCO-Kids logit score was 2.48 (range -7.44 to 5.83). Rasch analysis and principal component analysis were used to determine the structural validity. The construct validity was confirmed on the basis of differences in the ABILOCO-Kids scores among the Gross Motor Function Classification System levels. Cronbach's α and the item-to-total correlation coefficient supported the internal consistency. The intra-class correlation coefficient was 0.96, standard error of measurement 0.56 and minimal detectable change 1.55. The cross-cultural validity analyses showed differential item functioning according to the analyses of the invariance of item difficulty and person's ability estimates. Conclusions: The ABILOCO-Kids is a reliable and valid measure of walking ability in children with cerebral palsy in Japan. The lack of evidence on cross-cultural validity indicates we should interpret results cautiously in cases of international comparison.

First Report of the Morphology and rDNA Sequences of Two Pseudopolydora Species (Annelida: Spionidae) from Japan.

The morphology of two Pseudopolydora species, P. cf. reticulata Radashevsky and Hsieh, 2000 and P. achaeta Radashevsky and Hsieh, 2000 are reported from Japan for the first time. Pseudopolydora cf. reticulata was collected from Japanese tidal flats, and individuals possess the characteristic netlike pigmentation on the dorsum of anterior chaetigers and the longitudinal black band along midline of caruncle. Pseudopolydora achaeta was collected from subtidal bottom mud of Onagawa Bay, and individuals have distinctive characteristics, such as intensive black pigmentation on dorsal and ventral sides of the anterior body and nearly straight vertical rows of major spines on the fifth chaetiger. The morphology of P. cf. reticulata is very similar to that of P. cf. kempi, with which it had been confused in Japan. We analyzed the 18S and 28S rRNA gene sequences of all five Pseudopolydora species recorded from Japan and found strong evidence that they are genetically distinct. Our analysis also suggests that boring polydorids have evolved among non-boring ones; the genus Pseudopolydora, which mostly shows the non-boring form, appears to have remained in a more ancestral condition.

Radiographic Progression at Castration-Resistant Prostate Cancer Diagnosis: A Prognostic Indicator of Metastatic Hormone-Sensitive Prostate Cancer.

BACKGROUND: The critical role of radiographic assessment at the time of castration-resistant prostate cancer (CRPC) diagnosis is underscored by this study. We performed a retrospective analysis of radiographic changes in metastasis from the time of diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) to CRPC diagnosis. We also explored its impact on prognosis post-CRPC. MATERIALS AND METHODS: We retrospectively analyzed 98 men who underwent radiographic examinations (bone scans and computed tomography [CT]) at the time of CRPC diagnosis. When radiographic studies demonstrated progression at CRPC diagnosis, patients were assigned to the radiographic progressive disease (rPD) group. The remaining patients were placed in the "non-rPD" group. The overall survival (OS) post-CRPC was compared between the 2 groups. RESULTS: The median OS post-CRPC was significantly shorter in the rPD group (n = 50) compared to the non-rPD group (n = 48) (32 months vs. not reached, P = .0124). Multivariate analysis showed that radiographic progression and shorter time to CRPC were associated with a shorter OS post-CRPC (hazard ratio [HR] = 3.14; 95% confidence interval [CI], 1.21-8.12, P = .019). CONCLUSION: Radiographic progression at the point of CRPC diagnosis independently predicts a shorter OS post-CRPC in patients with mHSPC. Therefore, assessing radiographic changes at the time of CRPC diagnosis could be instrumental in managing CRPC in patients with mHSPC.

Development of the GABA-ergic signaling system and its role in larval swimming in sea urchin.

The present study aimed to elucidate the development and γ-amino butyric acid (GABA)-ergic regulation of larval swimming in the sea urchin Hemicentrotus pulcherrimus by cloning glutamate decarboxylase (Hp-gad), GABAA receptor (Hp-gabrA) and GABAA receptor-associated protein (Hp-gabarap), and by performing immunohistochemistry. The regulation of larval swimming was increasingly dependent on the GABAergic system, which was active from the 2 days post-fertilization (d.p.f.) pluteus stage onwards. GABA-immunoreactive cells were detected as a subpopulation of secondary mesenchyme cells during gastrulation and eventually constituted the ciliary band and a subpopulation of blastocoelar cells during the pluteus stage. Hp-gad transcription was detected by RT-PCR during the period when Hp-Gad-positive cells were seen as a subpopulation of blastocoelar cells and on the apical side of the ciliary band from the 2 d.p.f. pluteus stage. Consistent with these observations, inhibition of GAD with 3-mercaptopropioninc acid inhibited GABA immunoreactivity and larval swimming dose dependently. Hp-gabrA amplimers were detected weakly in unfertilized eggs and 4 d.p.f. plutei but strongly from fertilized eggs to 2 d.p.f. plutei, and Hp-GabrA, together with GABA, was localized at the ciliary band in association with dopamine receptor D1 from the two-arm pluteus stage. Hp-gabarap transcription and protein expression were detected from the swimming blastula stage. Inhibition of the GABAA receptor by bicuculline inhibited larval swimming dose dependently. Inhibition of larval swimming by either 3-mercaptopropionic acid or bicuculline was more severe in older larvae (17 and 34 d.p.f. plutei) than in younger ones (1 d.p.f. prism larvae).

Medium-Term Risk of Recurrent Pelvic Organ Prolapse within 2-Year Follow-Up after Laparoscopic Sacrocolpopexy.

Objective: The present study was performed to determine the risk of recurrent pelvic organ prolapse (POP) within 2 years after laparoscopic sacrocolpopexy (LSC) in patients with uterovaginal prolapse. Materials and Methods: A retrospective comparative study was performed in a population of 204 patients over a 2-year follow-up period following LSC with concomitant supracervical hysterectomy or uterine preservation at a single urological clinic between 2015 and 2019. The primary outcome was surgical failure following LSC in cases of POP, focusing on failures occurring before the 2ndyear of follow-up. Logistic regression analysis was used to determine the odds ratios (ORs) for surgical failure. Results: The primary outcome, surgical failure in cases of POP, occurred 2 years after the initial surgery in 19 of the 204 patients (9.3%) (95% confidence interval [CI], 5.7% - 14.2%). Surgical failure was most common in the anterior compartment (n = 10, 4.9%), and further surgery was performed in seven of the patients with surgical failure (3.4%). The poor primary outcome was predicted by lysis of adhesions (OR, 7.5, 95% CI, 1.6-33.8, P = 0.008) and preoperative POP stage IV (OR, 3.5; 95% CI, 1.1-10.8, P = 0.03) on multivariable logistic regression analysis. Conclusion: The overall rate of surgical failure following LSC in our cohort was 9.3% over the 2-year follow-up period after surgery, and preoperative prolapse stage IV was associated with a higher risk of recurrence.