Efficacy of Transvaginal Surgery Using an ORIHIME Mesh With Wider Arms and Adjusted Length.

INTRODUCTION: Transvaginal mesh surgery (TVM) is an effective treatment measure for pelvic organ prolapse (POP). However, the ORIHIME mesh (Kono Seisakusho, Japan, Tokyo), which has the disadvantage of poor adherence to tissues, is currently the only product available for this procedure. Our research team has previously developed a modified ORIHIME mesh with wider arms with the aim of minimizing the risk of POP recurrence. Additionally, the length of the mesh behind the anterior vaginal wall has been adjusted to prevent urinary incontinence. The current study aims to examine the efficacy of this modified mesh in minimizing postoperative complications in patients undergoing uphold-type TVM. METHODS: The data of 84 patients who underwent TVM using ORIHIME at our hospital since July 2019 were retrospectively analyzed. The patients were divided into three groups as follows: (a) normal arms (NA; arm width < 6 cm; n = 29 cases); (b) wide arms without length adjustment (WA and LA (-); arm width > 6 cm; n = 27 cases); and (c) wide arms with length adjustment (WA and LA (+); n = 28 cases). Data were collected using various questionnaires, and the residual urine volume was measured before and after surgery. Additionally, the 60-minute pad test was performed where possible, and the recurrence and complication rates were recorded. RESULTS: The incidence of mesh exposure and urinary incontinence in daily life tended to be lower in the WA and LA (+) groups, although this difference was not statistically significant. The one-year postoperative POP recurrence rate, residual urine volume, International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score were significantly lower in the WA and LA (+) groups compared to the other groups. CONCLUSION: Uphold-type TVM using the modified ORIHIME mesh with wider arms and adjusted length was associated with better postoperative treatment outcomes compared to TVM using the traditional ORIHIME mesh.

Relationship between the Tortuosity of the Extracranial Internal Carotid and Vertebral Arteries on Magnetic Resonance Imaging/Angiography and Vascular Risk Factors in a Japanese Population.

Objective We aimed to investigate the relationship between tortuosity of the extracranial internal carotid artery (ICA) or vertebral artery (VA) and vascular risk factors among residents of Asahikawa, northeast Japan. Methods We retrospectively surveyed participants of "brain dock" medical brain checkups, which involved magnetic resonance imaging and angiography. We measured the tortuosity of the ICA and VA, and evaluated vascular risk factors based on medical interviews, questionnaires, and medical records. Results A total of 218 participants were enrolled in the study. ICA tortuosity (right and left) was significantly correlated with age [odds ratio (OR): 2.452, 95% confidence interval (CI): 1.695-3.548, p<0.001]. A more pronounced correlation was observed in females than in males (OR: 1.678, 95% CI: 1.004-2.807, p=0.048). VA tortuosity (right and left) was significantly correlated with age (OR: 1.786, 95% CI: 1.250-2.550, p=0.001) and smoking history (OR: 2.140, 95% CI: 1.235-3.707, p=0.007), and was more pronounced in females than in males (OR: 1.864, 95% CI: 1.107-3.137, p=0.019). Conclusion ICA tortuosity was correlated with age, while VA tortuosity was correlated with age and smoking history. ICA and VA tortuosity were more pronounced in females than in males.

Favorable Postoperative Outcomes After Transvaginal Mesh Surgery Using a Wide-Arm ORIHIME® Mesh.

Introduction Transvaginal mesh surgery (TVM) is an effective treatment option for pelvic organ prolapse (POP). Although ORIHIME®, the only available mesh product, is thin, soft, and easy to handle, it has the disadvantages of sliding off or mildly adhering to the surrounding tissues. The current study compared the efficacy of using wide-arm ORIHIME (Kono Seisakusho, Japan, Tokyo), non-wide arm ORIHIME, Gynemesh PS (Johnson and Johnson, Japan, Tokyo), and Polyform (Boston Scientific Japan, Japan, Tokyo) meshes for TVM. Methods The study included 116 patients who underwent TVM (Prolift with Gynemesh PS (n = 14); Elevate with Polyform (n = 43); Uphold with non-wide-arm ORIHIME (n = 24); Uphold with wide-arm ORIHIME (n = 35)) at our hospital. Pre- and post-surgical changes in symptoms were measured using questionnaires and 60-minute pad weight testing and compared by mesh type and surgical methods used. Results The residual urine volume, 60-minute pad weight testing, international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), and international consultation on incontinence questionnaire-short form score (ICIQ-SF) significantly improved one year postoperatively in the TVM with the wide-arm ORIHIME group. Comparison of pre and one-year postoperative findings by mesh type and surgical methods used showed no significant differences in the 60-minute pad test, IPSS, Quality of Life (QOL), OABSS, and urinary incontinence in daily life scores, and improvement in residual urine volume, ICIQ-SF, and mesh exposure and POP recurrence rates in the TVM with the wide-arm ORIHIME group. Conclusion TVM with wide-arm ORIHIME had better postoperative outcomes compared to TVM with other mesh products.

Optimal extent of lymph node dissection for high-risk gastric cancer stratified by a national clinical database risk calculator.

BACKGROUND: For patients with gastric cancer, a well-balanced treatment that considers both oncological aspects and surgical risk is demanded. This study aimed to explore the optimal extent of lymph node dissection (LND) for patients with gastric cancer according to surgical risk, stratified by the risk calculator system produced by the Japan National Clinical Database (NCD). PATIENTS AND METHODS: We retrospectively evaluated 187 patients who underwent radical gastrectomy for gastric cancer. Using the median predicted anastomotic leak rate obtained by the NCD risk calculator as the cutoff value, we classified 97 and 90 patients as having high and low risks, respectively. RESULTS: In low-risk patients, although limited LND reduced the postoperative intraabdominal infectious complications (IAIC), multivariate analysis revealed standard LND as an independent prognostic factor that improved Relapse-free survival (RFS). In high-risk patients, the rates of postoperative IAIC and RFS were similar between standard and limited LND. Pancreatic fistula was not observed in the limited dissection group. CONCLUSION: Limited LND might be the optimal treatment strategy for patients with gastric cancer with high surgical risk.

A case of a thoracic duct cyst extending from the mediastinum to the cisterna chyli resected using bilateral thoracoscopic surgery in the prone position.

BACKGROUND: Thoracic duct cysts are extremely rare mediastinal tumors. We report a case of a thoracic duct cyst extending from the caudal aspect of the left main bronchus to the left renal artery that was safely and completely resected via bilateral thoracoscopic surgery in the prone position. CASE PRESENTATION: A 77-year-old male was referred to our hospital for follow-up computed tomography (CT) of prostate cancer, which revealed a mediastinal tumor and fatty low-density along the posterior mediastinum of the para-aortic artery with a slightly high-density component. Magnetic resonance imaging revealed a T2-weighted image with high intensity. The preoperative radiological diagnosis was lipoma or well-differentiated liposarcoma. CT in the prone position suggested that the tumor could be resected from the thoracic cavity to the caudal side, and bilateral thoracoscopic surgery was performed in the prone position. Based on the surgical findings, the tumor was diagnosed as a thoracic duct cyst rather than a lipoma. Dissection around the thoracic duct cyst was performed using a vessel-sealing system to prevent leakage of the chyle, and reliable clipping was performed to resect the cisterna chyli. Histopathological examination revealed smooth muscle structures around the cyst, suggestive of a thoracic duct cyst. The diagnosis of a thoracic duct cyst was made based on a high triglyceride level of 1310 mg/dL on examination of the milky-white cyst fluid. The patient's postoperative course was uneventful, and he was discharged 4 days postoperatively. A CT scan performed 13 months after surgery showed no recurrence. CONCLUSIONS: A rare thoracic duct cyst extending from the mediastinum to the cisterna chyli was safely and completely resected using bilateral thoracoscopic surgery, with the patient in the prone position.

[A case of lithium intoxication with reversible parkinsonism].

A 73-year-old man, who had been treated for bipolar disorder since he was 39 years old, was admitted because he had developed difficulty in walking and moving his hands for the past 2 months. He was suspected of having Parkinson's syndrome. On admission, his blood lithium level was at the upper limit of normal (1.34 mEq/l), but his food intake gradually decreased and his communication difficulties worsened. On the sixth day of hospitalization, his blood lithium level was in the toxic range (2.44 mEq/l). His general condition, including motor symptoms, improved after lithium medication was discontinued and infusions (normal saline) were started. On the 24th day of admission, he was transferred to the psychiatry department for a psychotropic medication adjustment. It is important to note that chronic intoxication can occur even at the upper limit of the therapeutic range and that salt reduction at the start of the inpatient diet may be a trigger for intoxication.

Risk factors of "loss of independence" in elderly patients who received gastrectomy for gastric cancer.

OBJECTIVE: The aim of this study was to clarify the risk of loss of independence (LOI) following gastrectomy in elderly patients with gastric cancer (GC). METHODS: In this prospective study, frailty was assessed preoperatively by a frailty index (FI) in 243 patients aged ≥ 65 years who underwent gastrectomy for GC between August 2016 and December 2020. Patients were assigned into two groups (high FI vs. low FI) to investigate frailty and the risk of LOI after gastrectomy for GC. RESULTS: Overall and minor (Clavien-Dindo classification [CD] 1, 2) complication rates were significantly higher in the high FI group, but the two groups had similar rates of major (CD ≥ 3) complications. The frequency of pneumonia was significantly higher in the high FI group. In univariate and multivariate analyses for LOI after surgery, high FI, older age (≥ 75 years), and major (CD ≥ 3) complications were independent risk factors. A risk score assigning 1 point for each of these variables was useful in predicting postoperative LOI (LOI: score 0, 7.4%; score 1, 18.2%; score 2, 43.9%; score 3, 100%; area under the curve [AUC] = 0.765.) CONCLUSIONS: LOI after gastrectomy was independently associated with high FI, older age (≥ 75 years), and major (CD ≥ 3) complications. A simple risk score assigning points for these factors was an accurate predictor of postoperative LOI. We propose that frailty screening should be applied for all elderly GC patients before surgery.

[Surgical Technique for Mesorectal Division in the Robotic Anterior Resection for Rectal Cancer].

Since April 2018, robot-assisted rectal resection has been approved as an insurance medical treatment, and robot- assisted rectal resection is rapidly becoming widespread. Even in robot-assisted laparoscopic surgery, mesorectal division is difficult in a narrow pelvic cavity. At the beginning of the operation, Vessel Sealer ExtendTM(price 89,250 yen)was used, but as the procedure became stable, the mesorectal division was started with bipolar forceps and monopolar scissors. The purpose of this study was to investigate the mesorectal division time and postoperative complications associated with changes in the procedure. 36 patients who underwent robot-assisted anterior resection for rectal cancer by the same surgeon from January 2019 to December 2021. We compared mesorectal division time and postoperative complication. Median operation time were 267 minutes, median console time were 132 minutes. There were no complications such as intestinal obstruction or anastomotic leakage. There was no difference in mesorectal division time time between Vessel Sealer groups and Scissors groups(14 min 55 sec vs 16 min 5 sec). The mesorectal division with bipolar forceps and monopolar scissors could be performed without extending the operation time, and could be performed with cost-benefit and safely.

Establishment of a gastric cancer cell line with high microsatellite instability, OCUM-13, derived from Borrmann type-2 primary tumor.

Gastric cancer (GC) with microsatellite instability (MSI) has been reported to be sensitive to immunotherapy, however some of GC cases with MSI remain resistant to immunotherapy. Cancer cell lines showing MSI might be useful for the analysis of mechanisms of immunotherapy, while only a few GC cell lines with MSI are available so far. In this study, we established a unique GC cell line with MSI, OCUM-13, from a primary GC with abundant tumor-infiltrating lymphocytes. MSI assay indicated that OCUM-13 cells as well as the primary tumor showed a band shift in more than 3 of 5 microsatellite loci, suggesting that OCUM-13 did have high MSI. The subcutaneous inoculation of OCUM-13 cells into mice performed tumor formation. Insulin-like growth factor 1 receptor inhibitor decreased the growth of OCUM-13 cells. The newly established cell line with MSI, OCUM-13, might be useful for the analysis of cancer therapy for GC with MSI.

Comparison of Short-Term Surgical Outcomes of Two Types of Robotic Gastrectomy for Gastric Cancer: Ultrasonic Shears Method Versus the Maryland Bipolar Forceps Method.

BACKGROUND: This study investigated the impact and short-term surgical outcomes of two different main energy devices for robotic gastrectomy for gastric cancer. The outcomes of robotic gastrectomy with ultrasonic shears and those of robotic gastrectomy with conventional forceps were compared. METHODS: We retrospectively evaluated 171 patients who underwent robotic distal gastrectomy or total gastrectomy for gastric cancer. We classified patients into the ultrasonic shears (US) and Maryland bipolar (MB) forceps groups according to the main energy device used for robotic gastrectomy. RESULTS: We extracted 58 patients from the US group and 58 patients from the MB forceps groups using propensity score matching. The total console time (310 min [interquartile range (IQR), 253-369 min] and 332 min, [IQR, 294-429 min]; p = 0.022) and the console time to gastrectomy (222 min [IQR, 177-266 min] and 247 min [IQR, 208-321 min]; p = 0.004) were significantly shorter in the US group than in the MB forceps group. Less blood loss occurred in the US group than in the MB forceps group (20 mL [IQR, 10-40 mL] and 30 mL [IQR, 16-80 mL]; p = 0.014). The postoperative complication rate and postoperative hospital stay length were similar between groups. A multivariate multiple linear regression analysis demonstrated that the use of an ultrasonically activated device was one an independent factor that reduced the operative time of robotic gastrectomy. CONCLUSION: Using ultrasonic shears as the main energy device may contribute to better surgical outcomes after robotic gastrectomy for gastric cancer.

[PENILE STRANGULATION CAUSED BY A METALLIC RING SUCCESSFULLY TREATED BY PENILE PUNCTURE PLUS BLOOD REMOVAL INSTEAD OF DESTROYING THE RING].

A 63-year-old man visited our hospital with a complaint of penile swelling caused by metallic ring entrapment in the penis. He had put the ring around his penis 4 hours prior and was subsequently unable to remove it. We attempted to remove the ring using a ring cutter but that was unsuccessful. We then inserted two 18 G needles into the corpus cavernosum through the glans penis and removed blood by manual compression according to a technique called the "string method." The swelling gradually decreased, and we successfully removed the ring without destroying it. The total duration of strangulation was about 5 hours. The patient was subsequently discharged after ensuring he had no urinary difficulties. No complications were observed during the follow-up period.In almost all penile strangulation cases caused by hard objects, such as metallic rings, reported in Japan, the objects were typically destroyed and penile puncture and blood removal, as was performed in our case, was rare. Although penile puncture and blood removal is not commonly performed in Japan, this technique can be performed quickly and inexpensively in the emergency room and should be considered an initial treatment for penile strangulation caused by hard objects.

Jejunal Mesentery Preservation Reduces Leakage at Esophagojejunostomy After Minimally Invasive Total Gastrectomy for Gastric Cancer: a Propensity Score-Matched Cohort Study.

PURPOSE: The mesentery of the jejunum (MJ) of the Roux limb is conventionally divided when Roux-en-Y reconstruction is performed after total gastrectomy for gastric cancer (GC). However, the impact of dividing or preserving the MJ on anastomotic leakage (AL) at the esophagojejunostomy (EJS) site after minimally invasive total gastrectomy for GC is unclear. METHODS: This retrospective cohort study enrolled 226 patients with GC who underwent EJS after laparoscopic or robotic total gastrectomy, including preservation of the MJ (n = 87) and division of the MJ (n = 137). The prevalence of anastomotic complications at the EJS and short-term outcomes were compared between groups using propensity score (PS) matching. RESULTS: After PS matching, 69 patients were selected for the preserving and dividing MJ groups. There were no significant intergroup differences in patient backgrounds, including oncological stage, body mass index, and gender ratio. After PS matching, overall and severe complications after surgery were compared between the preserving and dividing MJ groups (21.7% vs. 27.5%, p = 0.554 and 8.7% vs. 13.8%, p = 0.137, respectively). However, the rate of AL at the EJS was significantly lower in the preserving than that in the dividing MJ group (1.4% vs. 13.0%, p = 0.017). In addition, the median postoperative hospital stay was significantly shorter in the preserving than that in the dividing MJ group (13.0 days vs. 16.0 days, p = 0.005). CONCLUSIONS: Preserving the MJ significantly reduced AL at the EJS after minimally invasive total gastrectomy for GC.

Candidate Oncogenes, ARHGAP4, NOS3, and OR51B5, for the Development of Scirrhous-type Gastric Cancer.

BACKGROUND/AIM: Scirrhous-type gastric cancer (SGC), one of the most intractable cancer subtypes, is characterized by rapid cancer cell proliferation and infiltration accompanied by extensive stromal fibrosis. One of the reasons for its poor prognosis may be the lack of molecular target drugs for SGC, because of the unknown driver genes. Exploration of somatic mutations in the human samples of SGC using next-generation sequencing (NGS) has been hampered by abundant fibrous tissues in these samples. Therefore, this study aimed to determine a novel oncogene by RNA-sequencing using SGC cell lines, avoiding contamination with fibrosis. MATERIALS AND METHODS: In silico analysis of RNA-sequencing public data of the gastric cancer cell line, and RNA- sequencing using five of our unique SGC cell lines, OCUM1, OCUM2MLN, OCUM8, OCUM12, and OCUM14 were performed. RESULTS: We found three differentially expressed genes, ARHGAP4, NOS3, and OR51B5 that are significantly over-expressed in SGC cells. Immunohistochemical analysis indicated that the protein expression levels of these three genes were significantly higher in SGC than in other types of gastric cancer. The prognosis of patients with positive expression of these three genes was significantly poorer than those with negative expression. In particular, ARHGAP4 expression was an independent predictor of poor prognosis and recurrence. CONCLUSION: ARHGAP4, NOS3, and OR51B5 may be candidate driver genes for SGC. ARHGAP4 may be a promising molecular target for SGC.

Ingenuity and tips for laparoscopic local resection for local recurrence of early gastric cancer after endoscopic submucosal dissection: A case report.

INTRODUCTION AND IMPORTANCE: The presence of severe comorbidities is associated with poor surgical outcomes in patients who undergo curative resection for gastric cancer. Herein, we present a report of laparoscopic local resection (LLR) for the local recurrence of gastric cancer in a patient with severe comorbidities. CASE PRESENTATION: A 73-year-old man underwent endoscopic submucosal dissection (ESD) for an early gastric cancer located at the greater curvature of the gastric antrum. One year after the ESD, follow-up gastroscopy revealed a local recurrence. CLINICAL DISCUSSION: LLR was performed owing to severe comorbidities such as chronic heart failure, severe chronic obstructive pulmonary disease, and diabetes mellitus. We confirmed the location of the tumor with an endoscope, and full-thickness stitches were placed outside the tumor to prevent displacement between the submucosal and serosal muscular layers. Full-thickness resection of the stomach wall was performed along the stitch points using an ultrasonic shear. The edge of the resection line was closed using a laparoscopic stapling system. The patient had an uneventful postoperative course and was discharged 8 days after the operation. The patient had no disease recurrence and late complications such as digestive symptom and weight loss at the 9-month follow-up after the operation. CONCLUSION: LLR might be a suitable treatment option for high-risk patients with gastric cancer. During full-thickness resection of the stomach wall, our method enables the maintenance of a negative margin without the need for ESD.

Lipocalin-2 negatively regulates epithelial-mesenchymal transition through matrix metalloprotease-2 downregulation in gastric cancer.

BACKGROUND: Although the role of Lipocalin-2 (LCN2) in cancer development has been focused on recent studies, the molecular mechanisms and clinical relevance of LCN2 in gastric cancer (GC) still remain unclear. METHODS: Transcriptome analysis of GC samples from public human data was performed according to Lauren's classification and molecular classification. In vitro, Western blotting, RT-PCR, wound healing assay and invasion assay were performed to reveal the function and mechanisms of LCN2 in cell proliferation, migration and invasion using LCN2 knockdown cells. Gene set enrichment analysis (GSEA) of GC samples from public human data was analyzed according to LCN2 expression. The clinical significance of LCN2 expression was investigated in GC patients from public data and our hospital. RESULTS: LCN2 was downregulated in diffuse-type GC, as well as in Epithelial-Mesenchymal Transition (EMT) type GC. LCN2 downregulation significantly promoted proliferation, invasion and migration of GC cells. The molecular mechanisms of LCN2 downregulation contribute to Matrix Metalloproteinases-2 (MMP2) stimulation which enhances EMT signaling in GC cells. GSEA revealed that LCN2 downregulation in human samples was involved in EMT signaling. Low LCN2 protein and mRNA levels were significantly associated with poor prognosis in patients with GC. LCN2 mRNA level was an independent prognostic factor for overall survival in GC patients. CONCLUSIONS: LCN2 has a critical role in EMT signaling via MMP2 activity during GC progression. Thus, LCN2 might be a promising therapeutic target to revert EMT signaling in GC patients with poor outcomes.

[A Case of Massive Prostate Abscess Treated by Transperineal Drainage].

The patient was an 81-year-old man who visited a clinic for fever and lower abdominal pain. He was subsequently diagnosed with prostatitis based on computed tomography (CT) findings that showed swelling of the prostate. Despite treatment with antibacterial therapy, his symptoms did not improve significantly. Since the patient also had myelodysplastic syndrome, he was transferred to our hospital and subsequently diagnosed with prostate abscess based on findings on magnetic resonance imaging (MRI). The abscess had spread widely from the dorsal side of the trigone of the bladder to anterior wall of the rectum. Transperineal drainage was performed to preserve the urethral mucosa of the prostatic urethra. Considering the shape of the abscess cavity, one pigtail catheter was placed in the prostate and another was placed transperineally on the dorsal side of the trigone of the bladder. Cystostomy was performed at the same time. Culture of the abscess revealed the presence of Staphylococcus aureus. As there was little exudate from the abscess 9 days after drainage, the pigtail catheter on the dorsal side of the trigone of the bladder was removed following an injection of minocycline into the abscess. CT showed shrinkage of the abscess 4 days later, and the remaining intraprostatic pigtail catheter was removed after an injection of minocycline. The cystostomy pigtail catheter was subsequently removed since the patient was able to urinate smoothly after clamping. MRI confirmed the disappearance of the abscess cavity 2 months later.

CXCR2 signaling might have a tumor-suppressive role in patients with cholangiocarcinoma.

BACKGROUND: We reported that chemokine C-X-C motif receptor 2 (CXCR2) signaling appears to play an important role in the pathogenic signaling of gastric cancer (GC), and although CXCR2 may have a role in other solid cancers, the significance of CXCR2 in cholangiocarcinoma (CCA) has not been evaluated. Herein, we determined the clinicopathologic significance of CXCL1-CXCR2 signaling in CCA. MATERIALS AND METHODS: Two human CCA cell lines, OCUG-1 and HuCCT1, were used. CXCR2 expression was examined by western blotting. We investigated the effects of CXCL1 on the proliferation (by MTT assay) and migration activity (by a wound-healing assay) of each cell line. Our immunohistochemical study of the cases of 178 CCA patients examined the expression levels of CXCR2 and CXCL1, and we analyzed the relationship between these expression levels and the patients' clinicopathologic features. RESULTS: CXCR2 was expressed on both CCA cell lines. CXCL1 significantly inhibited both the proliferative activity and migratory activity of both cell lines. CXCL1 and CXCR2 were immunohistochemically expressed in 73% and 18% of the CCA cases, respectively. The CXCL1-positive group was significantly associated with negative lymph node metastasis (p = 0.043). The CXCR2-positive group showed significantly better survival (p = 0.042, Kaplan-Meier). A multivariate logistic regression analysis revealed that CXCR2 expression (p = 0.031) and lymph node metastasis (p = 0.004) were significantly correlated with the CCA patients' overall survival. CONCLUSION: CXCR2 signaling might exert a tumor-suppressive effect on CCA cells. CXCR2 might be a useful independent prognostic marker for CCA patients after surgical resection.

A rare genetic variant in the cleavage site of prepro-orexin is associated with idiopathic hypersomnia.

Idiopathic hypersomnia (IH) is a rare, heterogeneous sleep disorder characterized by excessive daytime sleepiness. In contrast to narcolepsy type 1, which is a well-defined type of central disorders of hypersomnolence, the etiology of IH is poorly understood. No susceptibility loci associated with IH have been clearly identified, despite the tendency for familial aggregation of IH. We performed a variation screening of the prepro-orexin/hypocretin and orexin receptors genes and an association study for IH in a Japanese population, with replication (598 patients and 9826 controls). We identified a rare missense variant (g.42184347T>C; p.Lys68Arg; rs537376938) in the cleavage site of prepro-orexin that was associated with IH (minor allele frequency of 1.67% in cases versus 0.32% in controls, P = 2.7 × 10-8, odds ratio = 5.36). Two forms of orexin (orexin-A and -B) are generated from cleavage of one precursor peptide, prepro-orexin. The difference in cleavage efficiency between wild-type (Gly-Lys-Arg; GKR) and mutant (Gly-Arg-Arg; GRR) peptides was examined by assays using proprotein convertase subtilisin/kexin (PCSK) type 1 and PCSK type 2. In both PCSK1 and PCSK2 assays, the cleavage efficiency of the mutant peptide was lower than that of the wild-type peptide. We also confirmed that the prepro-orexin peptides themselves transmitted less signaling through orexin receptors than mature orexin-A and orexin-B peptides. These results indicate that a subgroup of IH is associated with decreased orexin signaling, which is believed to be a hallmark of narcolepsy type 1.

Impact of Early Intervention for Idiopathic Normal Pressure Hydrocephalus on Long-Term Prognosis in Prodromal Phase.

Objectives: Because the progression of idiopathic normal pressure hydrocephalus (iNPH) is partially irreversible, we hypothesized that early intervention would markedly improve its prognosis. To test this hypothesis, we retrospectively investigated the long-term prognosis of patients with early intervention in the prodromal phase of iNPH. Methods: We defined the prodromal phase of iNPH as a 3m Timed Up and Go (TUG) of 13.5 s or less and a Mini-Mental State Examination (MMSE) of 24 or more. Of the 83 iNPH patients who underwent shunt surgery at Osaka Medical and Pharmaceutical University Hospital over 3 years from January 2015, 12 prodromal phase cases (73.3 ± 6.2 years, 10 males and 2 females) were included in the study. The iNPH grading scale (INPHGS), MMSE, Frontal Assessment Battery (FAB), intermittent gait disturbance (IGD), social participation status, and development of comorbidities were evaluated over 4 years. Results: Preoperative MMSE was 27.2 ± 1.5, FAB was 14.1 ± 1.8, TUG was 10.7 ± 1.4 s, and total iNPHGS was 2.8 ± 1.4. At 1, 2, 3, and 4 years postoperatively, total INPHGS improved to 0.8, 0.9, 1.5, and 1.7, respectively, and remained significantly better than preoperatively except at 4 years postoperatively. The MMSE improved slightly to 27.5 after 1 year and then declined by 0.35 per year. After 4 years, the mean MMSE was 26.1, and only one patient had an MMSE below 23. FAB improved to 15.2 after 1 year and then declined slowly at 0.85/year. Ten patients (83%) maintained a high capacity for social participation postoperatively. The preoperative tendency to fall and IGD in 9 (75%) and 8 (67%) patients, respectively, completely disappeared postoperatively, resulting in improved mobility. Shunt malfunction associated with four weight fluctuations and one catheter rupture caused temporary worsening of symptoms, which were recovered by valve re-setting and catheter revision, respectively. Conclusion: Early intervention in the prodromal phase of iNPH patients maintained good cognitive and mobility function and social participation ability in the long term. The maintenance of long-term cognitive function suggests its preventive effect on dementia. To realize early intervention for iNPH, it is desirable to establish an early diagnosis system for iNPH.

Jumping to conclusions correlates with negative symptoms, poor response inhibition, and impaired functioning in individuals diagnosed with schizophrenia.

BACKGROUND: The jumping to conclusions (JTC) bias is the tendency to make immediate decisions based on little information. There are few studies that have investigated the relationship between JTC and frontal lobe function. We examined the association between JTC and the Brief Psychiatric Rating Scale (BPRS), Frontal Assessment Battery (FAB), and Global Assessment of Functioning (GAF) scale in individuals with schizophrenia. METHODS: In total, 50 individuals diagnosed with schizophrenia and 50 healthy control individuals were administered the beads task. Individuals diagnosed with schizophrenia were assessed using the FAB, BPRS, and GAF. RESULTS: There was a significant negative correlation between JTC and the negative symptoms of the BPRS (rs=-.368, p = .008). There was a significant positive correlation between JTC and the Go/No-Go task of the FAB (rs=.319, p = .026), and the GAF (rs=.433, p = .002). CONCLUSION: JTC in individuals with schizophrenia may be categorized according to several causes, including negative symptoms and poor response inhibition.