Appendectomy and Long-term Colorectal Cancer Incidence, Overall and by Tumor Fusobacterium nucleatum Status.

OBJECTIVE: To test hypotheses that appendectomy history might lower long-term colorectal cancer risk and that the risk reduction might be strong for tumors enriched with Fusobacterium nucleatum, bacterial species implicated in colorectal carcinogenesis. BACKGROUND: The absence of the appendix, an immune system organ and a possible reservoir of certain pathogenic microbes, may affect the intestinal microbiome, thereby altering long-term colorectal cancer risk. METHODS: Utilizing databases of prospective cohort studies, namely the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association of appendectomy history with colorectal cancer incidence overall and subclassified by the amount of tumor tissue Fusobacterium nucleatum​​ (Fusobacterium animalis). We used an inverse probability weighted multivariable-adjusted duplication-method Cox proportional hazards regression model. RESULTS: During the follow-up of 139,406 participants (2,894,060 person-years), we documented 2811 incident colorectal cancer cases, of which 1065 cases provided tissue F. nucleatum analysis data. The multivariable-adjusted hazard ratio of appendectomy for overall colorectal cancer incidence was 0.92 (95% CI, 0.84-1.01). Appendectomy was associated with lower F. nucleatum-positive cancer incidence (multivariable-adjusted hazard ratio, 0.53; 95% CI, 0.33-0.85; P=0.0079), but not F. nucleatum-negative cancer incidence (multivariable-adjusted hazard ratio, 0.98; 95% CI, 0.83-1.14), suggesting a differential association by F. nucleatum status (Pheterogeneity=0.015). This differential association appeared to persist in various participant/patient strata including tumor location and microsatellite instability status. CONCLUSIONS: Appendectomy likely lowers the future long-term incidence of F. nucleatum-positive (but not F. nucleatum-negative) colorectal cancer. Our findings do not support the existing hypothesis that appendectomy may increase colorectal cancer risk.

Foxp and Skor family proteins control differentiation of Purkinje cells from Ptf1a- and Neurog1-expressing progenitors in zebrafish.

Cerebellar neurons, such as GABAergic Purkinje cells (PCs), interneurons (INs) and glutamatergic granule cells (GCs) are differentiated from neural progenitors expressing proneural genes, including ptf1a, neurog1 and atoh1a/b/c. Studies in mammals previously suggested that these genes determine cerebellar neuron cell fate. However, our studies on ptf1a;neurog1 zebrafish mutants and lineage tracing of ptf1a-expressing progenitors have revealed that the ptf1a/neurog1-expressing progenitors can generate diverse cerebellar neurons, including PCs, INs and a subset of GCs in zebrafish. The precise mechanisms of how each cerebellar neuron type is specified remains elusive. We found that genes encoding the transcriptional regulators Foxp1b, Foxp4, Skor1b and Skor2, which are reportedly expressed in PCs, were absent in ptf1a;neurog1 mutants. foxp1b;foxp4 mutants showed a strong reduction in PCs, whereas skor1b;skor2 mutants completely lacked PCs, and displayed an increase in immature GCs. Misexpression of skor2 in GC progenitors expressing atoh1c suppressed GC fate. These data indicate that Foxp1b/4 and Skor1b/2 function as key transcriptional regulators in the initial step of PC differentiation from ptf1a/neurog1-expressing neural progenitors, and that Skor1b and Skor2 control PC differentiation by suppressing their differentiation into GCs.

Effects of single and repeated bouts of flywheel exercise on jump performance and muscle damage in athletes and non athletes.

BACKGROUND: Although recent studies have investigated the effects of flywheel (FW) training on muscle function, the effects of transient FW exercise on jump performance in athletes are unknown. This study examined the effects of single and repeated bouts of FW squat exercises on jump performance and muscle damage in male collegiate basketball players. METHODS: The participants were 10 healthy college-age men (nonathletes) and 11 male basketball players (athletes). The intervention involved 100 squat exercises (10 repetitions × 10 sets) using an FW device. To examine the repeated-bout effects, the protocol was conducted again after a 2-week interval. Squat jumps, countermovement jumps, drop jumps, and rebound jumps were evaluated as jump performance, while isometric maximal voluntary contraction (MVC) torque in knee extension, muscle soreness, range of motion, thigh circumference, muscle thickness, and echo intensity were evaluated as markers of muscle damage. Measurements were taken at baseline, immediately after exercise, 24 h later, and 72 h later. RESULTS: The jump performance of nonathletes decreased after exercise (p < 0.05), while that of the athletes did not. The results were similar for muscle soreness. MVC torque decreased significantly after the first exercise in both groups (p < 0.05) and was significantly lower in the nonathletes versus athletes. Significant repeated-bout effects were found for muscle soreness in nonathletes but not athletes. CONCLUSIONS: These results suggest that a single bout of FW exercise reduces jump performance in male nonathletes but not basketball players.

Non-classical Monocytes Enhance the Efficacy of Immune Checkpoint Inhibitors on Colon Cancer in a Syngeneic Mouse Model.

BACKGROUND/AIM: The response rate to immune checkpoint inhibitors (ICIs) is approximately 10%-30% and only in a few cancer types. In the present study, we determined whether non-classical monocytes (NCMs) could enhance ICI efficacy in colon cancer using a syngeneic mouse model. MATERIALS AND METHODS: The MC38 C57BL/6 mouse colon cancer model was used. Cells collected from the bone marrow of C57BL/6 mice were cultured, and NCMs were fractionated by cell sorting and administered via the tail veins to the mice implanted with MC38 cells. The anti-mouse PD-L1 antibody was administered three times, and tumor volume and overall survival were observed. RESULTS: More tumors were eradicated and more complete response occurred, after cotreatment with ICIs and NCMs than after treatment with ICIs alone. Moreover, no efficacy was observed when NCMs were administered alone. CONCLUSION: NCMs enhance ICI efficacy. The underlying mechanisms and clinical applications will be studied in the future.

Soluble PD-L1 changes in advanced non-small cell lung cancer patients treated with PD-1 inhibitors: an individual patient data meta-analysis.

Introduction: Currently, first-line immune checkpoint inhibitors (ICIs), including programmed cell death protein-1 (PD-1) inhibitors, are utilized as monotherapy in advanced non-small cell lung cancer (NSCLC) patients with high programmed death ligand-1 (PD-L1) expression (≧50%). Pre-treatment or post-treatment serum soluble PD-L1 (sPD-L1) has been identified as a potential biomarker for assessing ICI efficacy through fixed-point observations. However, existing studies on sPD-L1 changes have produced inconsistent results or have had sample sizes too small to detect clinically meaningful effect sizes. To elucidate the role of sPD-L1, we conducted a collaborative individual patient data meta-analysis of PD-1 inhibitor treatments. Methods: We conducted a thorough search of articles in PubMed via Medline, Embase, Scopus, and Cochrane databases from inception to October 20, 2023. Trials were deemed eligible if they contained individual datasets for advanced NSCLC patients, including data on overall survival (OS)/progression-free survival (PFS), as well as pre- and post-treatment sPD-L1 levels after 3-4 cycles of PD-1 inhibitor treatments. Our analysis focused on patients who completed 3-4 cycles of PD-1 inhibitor treatments. The primary outcome measure was OS/PFS, and we assessed changes in sPD-L1 concentration pre- and post-treatment through ELISA analyses. Results: From our search, we identified a potential seven trials, encompassing 256 patients. Among these, two trials with 26 patients met the criteria for inclusion in our primary analyses. Over a median follow-up period of 10 months, pooled univariate analysis revealed that increases in sPD-L1 levels during PD-1 inhibitor treatment were not associated with OS (HR = 1.25; CI: 0.52-3.02)/PFS (HR = 1.42; CI: 0.61-3.30) when compared to cases with sPD-L1 decreases. Subgroup analyses indicated that the impact of sPD-L1 changes on overall mortality/progression-related mortality remained consistent regardless of gender, age, or the type of treatment (nivolumab or pembrolizumab). Conclusion: Our findings suggest that changes in sPD-L1 levels during PD-1 inhibitor treatment do not significantly influence the prognosis of advanced NSCLC patients, regardless of gender, age, or treatment type. Continuous monitoring of sPD-L1 may not offer significant advantages compared to fixed-point observations.

Corrigendum: Soluble PD-L1 changes in advanced non-small cell lung cancer patients treated with PD-1 inhibitors: an individual patient data meta-analysis.

[This corrects the article DOI: 10.3389/fimmu.2023.1308381.].

Novel quantitative immunohistochemical analysis for evaluating PD-L1 expression with phosphor-integrated dots for predicting the efficacy of patients with cancer treated with immune checkpoint inhibitors.

Introduction: Programmed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method. Methods: In total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression. Results: PD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group. Conclusion: Quantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method.

A gene regulatory network combining Pax3/7, Sox10 and Mitf generates diverse pigment cell types in medaka and zebrafish.

Neural crest cells generate numerous derivatives, including pigment cells, and are a model for studying how fate specification from multipotent progenitors is controlled. In mammals, the core gene regulatory network for melanocytes (their only pigment cell type) contains three transcription factors, Sox10, Pax3 and Mitf, with the latter considered a master regulator of melanocyte development. In teleosts, which have three to four pigment cell types (melanophores, iridophores and xanthophores, plus leucophores e.g. in medaka), gene regulatory networks governing fate specification are poorly understood, although Mitf function is considered conserved. Here, we show that the regulatory relationships between Sox10, Pax3 and Mitf are conserved in zebrafish, but the role for Mitf is more complex than previously emphasized, affecting xanthophore development too. Similarly, medaka Mitf is necessary for melanophore, xanthophore and leucophore formation. Furthermore, expression patterns and mutant phenotypes of pax3 and pax7 suggest that Pax3 and Pax7 act sequentially, activating mitf expression. Pax7 modulates Mitf function, driving co-expressing cells to differentiate as xanthophores and leucophores rather than melanophores. We propose that pigment cell fate specification should be considered to result from the combinatorial activity of Mitf with other transcription factors.

Optogenetic manipulation of Gq- and Gi/o-coupled receptor signaling in neurons and heart muscle cells.

G-protein-coupled receptors (GPCRs) transmit signals into cells depending on the G protein type. To analyze the functions of GPCR signaling, we assessed the effectiveness of animal G-protein-coupled bistable rhodopsins that can be controlled into active and inactive states by light application using zebrafish. We expressed Gq- and Gi/o-coupled bistable rhodopsins in hindbrain reticulospinal V2a neurons, which are involved in locomotion, or in cardiomyocytes. Light stimulation of the reticulospinal V2a neurons expressing Gq-coupled spider Rh1 resulted in an increase in the intracellular Ca2+ level and evoked swimming behavior. Light stimulation of cardiomyocytes expressing the Gi/o-coupled mosquito Opn3, pufferfish TMT opsin, or lamprey parapinopsin induced cardiac arrest, and the effect was suppressed by treatment with pertussis toxin or barium, suggesting that Gi/o-dependent regulation of inward-rectifier K+ channels controls cardiac function. These data indicate that these rhodopsins are useful for optogenetic control of GPCR-mediated signaling in zebrafish neurons and cardiomyocytes.

Optogenetic manipulation of neuronal and cardiomyocyte functions in zebrafish using microbial rhodopsins and adenylyl cyclases.

Even though microbial photosensitive proteins have been used for optogenetics, their use should be optimized to precisely control cell and tissue functions in vivo. We exploited GtCCR4 and KnChR, cation channelrhodopsins from algae, BeGC1, a guanylyl cyclase rhodopsin from a fungus, and photoactivated adenylyl cyclases (PACs) from cyanobacteria (OaPAC) or bacteria (bPAC), to control cell functions in zebrafish. Optical activation of GtCCR4 and KnChR in the hindbrain reticulospinal V2a neurons, which are involved in locomotion, induced swimming behavior at relatively short latencies, whereas activation of BeGC1 or PACs achieved it at long latencies. Activation of GtCCR4 and KnChR in cardiomyocytes induced cardiac arrest, whereas activation of bPAC gradually induced bradycardia. KnChR activation led to an increase in intracellular Ca2+ in the heart, suggesting that depolarization caused cardiac arrest. These data suggest that these optogenetic tools can be used to reveal the function and regulation of zebrafish neurons and cardiomyocytes.

First navigation with wireless muometric navigation system (MuWNS) in indoor and underground environments.

Navigation in indoor and underground environments has been extensively studied to realize automation of home, hospital, office, factory and mining services, and various techniques have been proposed for its implementation. By utilizing the relativistic and penetrative nature of cosmic-ray muons, a completely new wireless navigation technique called wireless muometric navigation system (MuWNS) was developed. This paper shows the results of the world's first physical demonstration of MuWNS used on the basement floor inside a building to navigate (a person) in an area where global navigation satellite system (GNSS)/ global positioning system (GPS) signals cannot reach. The resultant navigation accuracy was comparable or better than the positioning accuracy attainable with single-point GNSS/GPS positioning in urban areas. With further improvements in stability of local clocks used for timing, it is anticipated that MuWNS can be adapted to improve autonomous mobile robot navigation and positioning as well as other underground and underwater practical applications.

Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD-L1) expression in colorectal carcinoma.

Objectives: The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of Fusobacterium nucleatum. We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of F. nucleatum in colorectal carcinoma. Methods: We assessed tumor CD274 expression by immunohistochemistry and F. nucleatum DNA within tumor tissue by quantitative PCR in 812 cases among 4465 incident rectal and colon cancer cases that had occurred in two prospective cohort studies. Multivariable logistic regression analyses with inverse probability weighting were used to adjust for selection bias because of tissue data availability and potential confounders including microsatellite instability status, CpG island methylator phenotype, LINE-1 methylation level and KRAS, BRAF and PIK3CA mutations. Results: Fusobacterium nucleatum DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue (P = 0.0077). For one category-unit increase in three ordinal F. nucleatum categories (negative vs. low vs. high), multivariable-adjusted odds ratios (with 95% confidence interval) of the low, intermediate and high CD274 categories (vs. negative) were 0.78 (0.41-1.51), 0.64 (0.32-1.28) and 0.50 (0.25-0.99), respectively (P trend = 0.032). Conclusions: Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor F. nucleatum enrichment) tend to be used by different tumor subgroups.

The Application of Sulfur Influences Microbiome of Soybean Rhizosphere and Nutrient-Mobilizing Bacteria in Andosol.

This study aimed to determine the effect of sulfur (S) application on a root-associated microbial community resulting in a rhizosphere microbiome with better nutrient mobilizing capacity. Soybean plants were cultivated with or without S application, the organic acids secreted from the roots were compared. High-throughput sequencing of 16S rRNA was used to analyze the effect of S on microbial community structure of the soybean rhizosphere. Several plant growth-promoting bacteria (PGPB) isolated from the rhizosphere were identified that can be harnessed for crop productivity. The amount of malic acid secreted from the soybean roots was significantly induced by S application. According to the microbiota analysis, the relative abundance of Polaromonas, identified to have positive association with malic acid, and arylsulfatase-producing Pseudomonas, were increased in S-applied soil. Burkholderia sp. JSA5, obtained from S-applied soil, showed multiple nutrient-mobilizing traits among the isolates. In this study, S application affected the soybean rhizosphere bacterial community structure, suggesting the contribution of changing plant conditions such as in the increase in organic acid secretion. Not only the shift of the microbiota but also isolated strains from S-fertilized soil showed PGPB activity, as well as isolated bacteria that have the potential to be harnessed for crop productivity.

LPS Administration during Fertilization Affects Epigenetic Inheritance during Embryonic Development.

Intrauterine inflammation can cause infertility by disrupting reproductive function. The pathogenesis underlying this process may primarily involve endotoxins from lipopolysaccharides (LPS), which are produced by Gram-negative bacteria. However, the long-term effects of endotoxins in mammalian pregnancy following LPS exposure during fertilization have not been clarified. In this study, we performed experiments to analyze the influence of LPS on early embryonic development and fetal development in mice. Mice uteruses were examined for the expression of genes related to the inflammatory response. The expression of Il-1ß and Il-6 increased following the administration of 200 and 1000 µg/kg LPS. Exposure to LPS using in vitro fertilization (IVF) significantly decreased the embryonic developmental rate. A concentration of 100 µg/kg LPS significantly increased the placental weight and fetal crown -rump length (CRL), whereas a concentration of 200 µg/kg LPS significantly decreased the placenta weight and fetal weight in vivo. These findings indicate that maternal LPS during fertilization affects fetal development until the late stage of pregnancy. Thus, maternal endotoxins may affect epigenetic inheritance during embryonic development from the early to late stages of pregnancy.

Direct activation of microglia by ß-glucosylceramide causes phagocytosis of neurons that exacerbates Gaucher disease.

Gaucher disease (GD) is the most common lysosomal storage disease caused by recessive mutations in the degrading enzyme of ß-glucosylceramide (ß-GlcCer). However, it remains unclear how ß-GlcCer causes severe neuronopathic symptoms, which are not fully treated by current therapies. We herein found that ß-GlcCer accumulating in GD activated microglia through macrophage-inducible C-type lectin (Mincle) to induce phagocytosis of living neurons, which exacerbated Gaucher symptoms. This process was augmented by tumor necrosis factor (TNF) secreted from activated microglia that sensitized neurons for phagocytosis. This characteristic pathology was also observed in human neuronopathic GD. Blockade of these pathways in mice with a combination of FDA-approved drugs, minocycline (microglia activation inhibitor) and etanercept (TNF blocker), effectively protected neurons and ameliorated neuronopathic symptoms. In this study, we propose that limiting unrestrained microglia activation using drug repurposing provides a quickly applicable therapeutic option for fatal neuronopathic GD.

The association between gingivitis and oral spirochetes in young cats and dogs.

Although gingivitis frequently occurs in young cats, spirochetes are often found in the early stages of periodontal disease. This study was conducted to determine the association between gingivitis and oral spirochetes in young cats and dogs. The degree of gingivitis was evaluated in a total of 68 cats and 31 dogs under one year of age, and plaques were collected from each carnassial. To detect spirochetes or Porphyromonas gulae in plaque samples, 16S rRNA gene was amplified by polymerase chain reaction (PCR) using specific primers. All data were analyzed using Fisher's exact probability test and odds ratio (OR) with a 95% confidence interval (95% CI). The prevalence of gingivitis was significantly higher in young cats (92.6%) than in young dogs (45.2%). The positive rate of spirochetes by PCR in gingivitis cases was 85.4% in young cats and 15.4% in young dogs, and the positive rate of P. gulae was 66.7% in young cats and 15.4% in young dogs. Both results were significantly higher in young cats than in young dogs. In young cats, spirochetes were significantly associated with gingivitis (OR = 7.95; 95% CI = 1.17, 53.83; P < 0.05), but P. gulae was not (OR = 2.44; 95% CI = 0.38, 15.66; P = 0.23). These results suggest that spirochetes may be associated with the early stages of periodontal disease in cats.

Clinicopathological variables and risk factors for lung recurrence after resection of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate even after curative resection. Lung recurrence may have better outcomes than other recurrences. However, its detailed clinicopathological features are unclear. We investigated the clinicopathological features and risk factors for lung recurrence after pancreatectomy for PDAC. METHODS: The study included 161 patients with potentially and borderline resectable PDAC who had undergone R0 or R1 pancreatectomy between January 2008 and December 2016. We retrospectively examined the prognosis and predictors for lung recurrence after curative resection. RESULTS: Seventeen patients (10.6%) had isolated lung recurrence. The median overall and recurrence-free survivals were 38.0 and 16.1 months, respectively. In multivariate analysis, para-aortic lymph node (PALN) metastasis (p = 0.006) and female sex (p = 0.027) were independent factors for lung recurrence. CONCLUSION: Lung recurrence had a better prognosis than other recurrences. PALN metastasis and female sex are independent risk factors for lung recurrence after curative resection for PDAC.

Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2.

C-type lectin receptors (CLRs) elicit immune responses upon recognition of glycoconjugates present on pathogens and self-components. While Dectin-1 is the best-characterized CLR recognizing ß-glucan on pathogens, the endogenous targets of Dectin-1 are not fully understood. Herein, we report that human Dectin-1 is a ligand for CLEC-2, another CLR expressed on platelets. Biochemical analyses revealed that Dectin-1 is a mucin-like protein as its stalk region is highly O-glycosylated. A sialylated core 1 glycan attached to the EDxxT motif of human Dectin-1, which is absent in mouse Dectin-1, provides a ligand moiety for CLEC-2. Strikingly, the expression of human Dectin-1 in mice rescued the lethality and lymphatic defect resulting from a deficiency of Podoplanin, a known CLEC-2 ligand. This finding is the first example of an innate immune receptor also functioning as a physiological ligand to regulate ontogeny upon glycosylation.

Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b.

MHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant T (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted T cell subsets is largely unknown. Here, we report that mice in which a T cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated in immature thymocytes (Bcl11b∆iThy mice) develop chronic inflammation. Bcl11b∆iThy mice lack conventional T cells and MAIT cells, whereas CD4+IL-18R+ αß T cells expressing skewed Traj33 (Jα33)+ T cell receptors (TCR) accumulate in the periphery, which are necessary and sufficient for the pathogenesis. The disorders observed in Bcl11b∆iThy mice are ameliorated by MR1-deficiency, transfer of conventional T cells, or germ-free conditions. We further show the crystal structure of the TCR expressed by Traj33+ T cells expanded in Bcl11b∆iThy mice. Overall, we establish that MR1-reactive T cells have pathogenic potential.

Efficacy and safety of desmopressin orally disintegrating tablets 25 and 50 µg in male patients with nocturia: A Japanese real-world multicenter clinical study.

OBJECTIVES: To clarify Japanese real-world clinical data on the use of desmopressin 25 and 50 µg orally disintegrating tablets (ODT) for male patients with nocturia and evaluate the predictive factors to improve nighttime frequency. METHODS: We retrospectively accumulated real-world clinical data from 27 institutions in Japan. Male patients with two or more episodes of nocturia who received desmopressin ODT for nocturnal polyuria (NP) from 2019 through 2021 were included. The primary endpoint was the change of nighttime frequency until 3 months after desmopressin administration. The secondary endpoints were to clarify the persistence rate, adverse events, and predictive factors of decreasing nighttime frequency. RESULTS: A total of 118 patients were eligible to participate in this study. The persistence rate of desmopressin on the Kaplan-Meier curve at week 12 was 51.3. The reason for discontinuation was mainly the occurrence of adverse events in 67 patients (56.8%), particularly hyponatremia in 7 patients (5.9%). Nighttime frequencies at baseline, - 1 month and 1 - 3 months after desmopressin administration were 4.1 ± 1.3, 2.9 ± 1.4 (P < .01), and 2.6 ± 1.3 (P < .01), respectively. The mean nighttime urine volume voided at baseline was significantly larger in patients whose nighttime frequency decreased by two or more times than in those with a decrease of less than two times. CONCLUSIONS: Desmopressin 25 and 50 µg ODT treatments are feasible for male patients with NP in Japanese real-world clinical practice. Patients with higher voided volumes, particularly in the nighttime, may have great benefit from desmopressin.