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Introduction: In this study, we aimed to identify biomarkers for predicting treatment outcomes and efficacy of chemotherapy plus nivolumab, as well as predict immune-related adverse events (irAEs) characteristics of immune checkpoint inhibitors., Methods: This multicenter study included 104 patients who received chemotherapy plus nivolumab as the primary treatment for unresectable advanced recurrent gastric cancer. Blood test results were collected before the start and after two courses of treatment. The neutrophil-lymphocyte ratio, prognostic nutritional index (PNI), and lactate dehydrogenase/albumin ratio (LAR) were examined after treatment in each case to determine changes compared to values before the start of treatment., Results: A total of 57 (54.8%) patients experienced a complete or partial response. The LAR of the stable disease (SD)/progressive disease (PD) group significantly increased (p=0.018). An examination of the presence of grade ≥3 irAEs and changes in related factors showed that the LAR of all patients increased., Conclusion: The LAR was correlated with the best therapeutic response; therefore, it may be a potential biomarker of treatment outcomes and efficacy., (S. Karger AG, Basel.)

Background: There are few reports on conversion surgery (CS) after chemotherapy plus nivolumab as a first-line treatment in patients with unresectable advanced or recurrent gastric cancer (GC). This multicenter study was conducted to analyze real-world data on CS after chemotherapy plus nivolumab as a first-line treatment and to identify predictive biomarkers., Methods: This multicenter study included 104 patients who received chemotherapy plus nivolumab as primary treatment for unresectable advanced recurrent GC from 12 institutes. We investigated and analyzed patient characteristics and blood test data in the presence or absence of CS, the relationship between the Gustave Roussy Immune Score (GRIm-s) and CS, and the characteristics of CS cases., Results: CS was performed in 12 patients (11.5%). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was significantly better in patients who underwent CS (p < 0.0001). There were no CS cases with high-risk GRIm-s (0%), however there were 22 non-CS cases (23.9%). No high-risk GRIm-s cases were converted to CS. Minimally invasive surgery was performed in 50.0% of the cases, with R0 resection in all cases and only one case of urinary retention (Grade II) as a postoperative complication, indicating a good postoperative short-term outcome. There were two cases of postoperative recurrence (16.7%), both of which were grade 1b., Conclusions: The short-term postoperative results of CS after chemotherapy plus nivolumab as the first-line treatment for GC were acceptable in this study. There were no high-risk GRIm-s cases among those who underwent CS, suggesting that the GRIm-s may be a predictor of CS., (© 2024. Society of Surgical Oncology.)

There have been predictions that the use of the macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) in zirconium-89 ( 89 Zr) immuno-positron emission tomography ( 89 Zr-immunoPET) could enhance the in vivo stability of 89 Zr radioimmunoconjugates. However, conjugating [ 89 Zr]Zr-DOTA to a monoclonal antibody (mAb) remains a challenge as the heat treatment required for [ 89 Zr]Zr-DOTA chelation can lead to thermal denaturation of the mAb moieties. We developed a method for synthesizing [ 89 Zr]Zr-DOTA-mAb based on a tetrazine (Tz)-conjugated bifunctional DOTA derivative 2,2',2″-(10-(1-(4-(1,2,4,5-tetrazin-3-yl)phenyl)-3,21,26-trioxo-6,9,12,15,18-pentaoxa-29-carboxy-2,22,25-triazanonacosane-29-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (DOTAGA-Tz) and the inverse electron-demand Diels-Alder (IEDDA) click chemistry reaction where trans -cyclooctene-modified mAbs are conjugated to [ 89 Zr]Zr-DOTAGA without being exposed to heat. The stability of IEDDA-derived [ 89 Zr]Zr-DOTAGA-trastuzumab was confirmed by in vitro, ex vivo, and in vivo testing and comparative analysis against the conventional deferoxamine (DFO) counterpart [ 89 Zr]Zr-DFO-trastuzumab. The in vivo immunoPET imaging using [ 89 Zr]Zr-DOTAGA-trastuzumab clearly visualized human epidermal growth factor receptor 2-positive malignancies in murine xenograft models. Greater tumor contrast was observed from [ 89 Zr]Zr-DOTAGA-trastuzumab at a 72-h delayed scan compared with [ 89 Zr]Zr-DFO-trastuzumab. These findings suggest that our IEDDA ligation approach can be an effective means of synthesizing [ 89 Zr]Zr-DOTA-mAb and can enhance the theranostic potential of 89 Zr-immunoPET in DOTA-mediated radioimmunotherapy.

Introduction: Individuals involved with the criminal justice system face challenges in receiving and maintaining substance use disorder (SUD) treatment and support. Although telephone monitoring (TM) could reduce these barriers, data on TM for community-dwelling individuals involved with the criminal justice system and research on individuals who drop out of TM are scarce. We examined the factors associated with dropping out early from the Voice Bridges Project, which provides TM for individuals on probation for drug-related convictions through community mental health centers in Japan., Methods: Participants (n = 546) were individuals aged ≥20 years with methamphetamine-related convictions who were on probation. Univariate analyses examine the associations between one-year follow-up status and baseline variables, and multivariate Cox proportional hazards regression analyses identify the risk and protective factors associated with dropping out. Stratified analyses report results based on sex and halfway-house residency., Results: The one-year dropout rate was 43.6 % (n = 238). Multivariate analysis identified two risk factors for dropping out-halfway-house residency and suicide attempts in the past year, and two protective factors-higher education and the current use of SUD services. Sex-stratified analyses showed that halfway-house residency was a risk factor for both men and women. Attempted suicide was a risk factor for women. Conversely, higher education and current use of SUD services were protective factors for men., Conclusions: Our results identify unique risk factors for women, such as a recent history of suicide attempts, and distinctive protective factors for men, including higher education and current use of SUD services, emphasizing the importance of sex-specific approaches. Furthermore, the study reveals that irrespective of sex, vulnerable individuals, such as halfway-house residents, are at a higher risk of dropping out from TM., Competing Interests: Declaration of competing interest Toshihiko Matsumoto received financial support for this research from the Ministry of Health, Labour and Welfare, Japan. Shiori Tsutsumi received financial support for this research from the Japan Science and Technology Agency and Keio University. The authors declare that although they received funding as mentioned above, this financial support did not influence the outcomes, interpretation, or presentation of the research findings. The research was conducted independently, and the views expressed in this paper are those of the authors and not necessarily those of the funding agencies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The stereoselective 5- endo -trig oxygenative cyclization of α,β-unsaturated oximes was achieved using molecular oxygen (O 2 ) and a manganese catalyst. Several 4-hydroxy-4,5-dihydroisoxazoles were obtained in high yields by directly incorporating O 2 from the atmosphere (eliminating the necessity for a pure oxygen environment) and using an unprecedentedly low loading of Mn(acac) 3 (as little as 0.020 mol %) without additional additives. Because of its desirable features, such as operational simplicity, inexpensive catalyst, mild reaction conditions (open flask conditions at room temperature), and broad substrate compatibility, this novel reaction provides an attractive synthetic approach to producing 4-hydroxy-4,5-dihydroisoxazoles.

Radiotherapy combined with temozolomide (TMZ+RT) is the primary treatment for high-grade glioma. TMZ is classified as a moderate emetic risk agent and, thus, supportive care for nausea and vomiting is important. In Nagoya University Hospital, all patients are treated with a 5-hydroxy-tryptamine 3 receptor antagonist (5-HT 3 RA) for the first 3 days. The daily administration of 5-HT 3 RA is resumed after the 4th day based on the condition of patients during TMZ+RT. Therefore, the present study investigated risk factors for nausea and vomiting in patients requiring the daily administration of 5-HT 3 RA. Patients with high-grade glioma who received TMZ+RT between January 2014 and December 2019 at our hospital were included. Patients were divided into two groups: a control group (patients who did not resume 5-HT 3 RA) and resuming 5-HT 3 RA group (patients who resumed 5-HT 3 RA after the 4th day), and both groups were compared to identify risk factors for nausea and vomiting during TMZ+RT. There were 78 patients in the control group (68%) and 36 in the resuming 5-HT 3 RA group (32%). A multivariate analysis of patient backgrounds in the two groups identified age <18 years, PS 2 or more, and occipital lobe tumors as risk factors for nausea and vomiting. Nausea and vomiting were attenuated in 30 patients (83%) in the resuming 5-HT 3 RA group following the resumption of 5-HT 3 RA. The results obtained highlight the importance of extracting patients with these risk factors before the initiation of therapy and the early resumption or daily administration of 5-HT 3 RA according to the condition of each patient., Competing Interests: The authors declare no conflict of interest.

Background: Olaparib and niraparib (poly adenosine diphosphate [ADP]-ribose polymerase [PARP] inhibitors) have significant antitumor action in patients with ovarian cancer. However, the incidence of nausea and vomiting among patients on these drugs in clinical trials is rather high. There are no guidelines on antiemetic treatment for nausea caused by oral anticancer agents. This study aimed to investigate the incidence of nausea and vomiting caused by PARP inhibitors and the actual situation of antiemetic therapy in patients with gynecologic cancer. Methods: Patients with gynecologic cancer who were scheduled to receive PARP inhibitors were enrolled. Data on PARP inhibitor-induced nausea and vomiting were collected from patient diaries for 21 days. The primary endpoint was the incidence of vomiting during the 21 days after starting olaparib and niraparib. Results: Overall, between January 2020 and March 2023, 134 patients were enrolled. Of the 129 patients who were evaluated, 28 (21.7%) received prophylactic antiemetics for 21 days, and 101 (78.3%) did not. The overall incidence of PARP inhibitor-induced vomiting was 16.3%. The incidence of vomiting in the group that did not receive antiemetic prophylaxis was 13.9%. On dividing the group that did not receive antiemetic prophylaxis into the olaparib and niraparib subgroups, the incidence of vomiting was found to be 18.6% for the olaparib group and 10.3% for the niraparib group. Conclusion: The incidence of emesis without antiemetic prophylaxis among patients on olaparib and niraparib ranged from 10% to 30%. Therefore, olaparib and niraparib can be classified in the low emetogenic risk and prophylactic antiemetic therapy at the time of treatment initiation may be unnecessary., Competing Interests: Competing Interests: Ms. Yamamoto received personal fees from Chugai outside of the submitted work. Dr. Tsuchiya received personal fees from Chugai, Taiho, Ono, Sun Pharma, Kyowa-Kirin, Pfizer, Eizai, and Daiichi Sankyo outside the submitted work. Dr. Iihara received personal fees from Taiho, Chugai, Yakult, Astellas, Eli Lilly, Daiichi Sankyo, AstraZeneca, Nippon Kayaku, Ono, and Nippon Boehringer Ingelheim and consulting fees for their institution from Taiho and Eisai outside the submitted work. Dr. Suzuki received personal fees from Takeda and AstraZeneca outside of the submitted work. Mr. Watanabe received personal fees from Chugai outside of the submitted work. Dr. Suzuki A received personal fees from Toa Eiyo, Asahi Kasei, Daiichi Sankyo, Pfizer, Eisai, Nippon Shinyaku, Celltrion Healthcare Japan, Otsuka, Sandoz, Tsumura, Nipro, Taiho, Kyowa-Kirin, Nippon Chemiphar, Japan Blood Products Organization, Takeda, and Nippon Boehringer Ingelheim and grants for their institution from Nippon Kayaku, Asahi Kasei, Chugai, Taiho, Daiichi Sankyo, Japan Blood Products Organization, Mochida, and Sun Pharma outside the submitted work. Dr. Abe received personal fees from Taiho, Chugai, AstraZeneca, and Takeda outside the submitted work., (© The author(s).)

Purpose: We conducted muscle synergy and gait analyses in a monoplegic patient whose gait function improved through training, to explore the possibility of using these parameters as indicators of training., Case Presentation: A 49-year-old male had monoplegia of the right lower limb caused by infarction of the left paracentral lobule. After 2 months of training, he was able to walk and returned to work., Methods: Consecutive analyses were done after admission. Muscle synergy analysis: during walking, surface electromyograms of gluteus maximus, quadriceps femoris, adductor femoris, hamstrings, tibialis anterior, medial/lateral gastrocnemius, and soleus on both sides were recorded and processed for non-negative matrix factorization (NNMF) analysis. Gait analysis: markers were placed at foot, and walking movements were video recorded as changes in position of the markers., Results: Compared with three muscle synergies detected on the non-paretic side, two muscle synergies were extracted on the paretic side at admission, and the number increased to three and then four with progress in rehabilitation training. Changes in weighting and activity of the muscle synergies were greater on the non-paretic side than on the paretic side. With training, the knee joint flexor and the ankle dorsiflexor activities on the paretic side and the gluteus maximus activity on the non-paretic side increased during swing phase as shown by weight changes of muscle synergies, and gait analysis showed increased knee joint flexion and ankle joint dorsiflexion during swing phase in the paretic limb. On the non-paretic side, however, variability of muscle activity was observed, and three or four muscle synergies were extracted depending on the number of strides analyzed., Conclusion: The number of muscle synergies is considered to contribute to motor control. Rehabilitation training improves gait by increasing the number of muscle synergies on the paretic side and changing the weights of the muscles constituting the muscle synergies. From the changes on the non-paretic side, we propose the existence of compensatory mechanisms also on the non-paretic side. In muscle synergy analysis, in addition to the filters, the number of strides used in each analysis set has to be examined. This report highlights the issues of NNMF as analytical methods in gait training for stroke patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ebihara, Hirota, Kumakura and Nagaoka.)

By nature, humans are " tojisha (participating subjects/player-witnesses)" who encounter an unpredictable real world. An important characteristic of the relationship between the individual brain and the world is that it creates a loop of interaction and mutual formation. However, cognitive sciences have traditionally been based on a model that treats the world as a given constant. We propose incorporating the interaction loop into this model to create "world-informed neuroscience (WIN)". Based on co-productive research with people with minority characteristics that do not match the world, we hypothesize that the tojisha and the world interact in a two-dimensional way of rule-based and story-based. By defining the cognitive process of becoming tojisha in this way, it is possible to contribute to the various issues of the real world and diversity and inclusion through the integration of the humanities and sciences. The critical role of the brain dopamine system as a basis for brain-world interaction and the importance of research on urbanicity and adolescent development as examples of the application of WIN were discussed. The promotion of these studies will require bidirectional translation between human population science and animal cognitive neuroscience. We propose that the social model of disability should be incorporated into cognitive sciences, and that disability-informed innovation is needed to identify how social factors are involved in mismatches that are difficult to visualize. To promote WIN to ultimately contribute to a diverse and inclusive society, co-production of research from the initial stage of research design should be a baseline requirement., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rationale: Gorham-Stout disease (GSD) is a rare disease that causes massive osteolysis and proliferation of abnormal lymphangiomatous tissues. Patients with GSD often experience pain associated with bone fractures and chylothorax. However, bleeding caused by abnormal lymphangiomatous tissue or hematological dysfunction rarely occurs., Patient Concerns: A 22-year-old female patient with GSD presented with severe left hip and lower limb pain. The GSD had disappeared her right pelvic bone and femur, but no abnormalities were found in the bones at the site of the pain., Diagnoses: The patient presented with a chylothorax and cerebrospinal fluid leakage. She was treated with sirolimus and an epidural blood patch, and her symptoms resolved. Computed tomography and magnetic resonance imaging revealed an epidural hematoma extending from L3 to the caudal region, and blood results revealed a consumption coagulopathy., Interventions: We presumed that the hematoma caused pain and prescribed pregabalin and morphine. The pain gradually subsided., Outcomes: An unexpected liver subcapsular hemorrhage occurred 4 months later, and the patient went into hemorrhagic shock. Transcatheter arterial embolization was promptly performed, and the patient recovered., Lessons: GSD infrequently causes bleeding related to abnormal lymphangiomatous tissues and coagulopathy, yet it can lead to serious events if it occurs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The 22q11.2 deletion syndrome (22q11DS) is characterised by a changing pattern of overlapping intellectual, physical, and mental disabilities along the course of one's life. However, the impact of overlapping disorders (multimorbidity) on educational challenges remains unclear., Method: A survey was conducted with 88 caregivers of individuals with 22q11DS. A quantitative analysis of educational challenges and support needs divided into age groups (7-12, 13-15, 16-18, and 19 years and over) and a qualitative analysis of the free-text items in the questionnaire was conducted., Results: Caregivers were more interested in comprehensive developmental support when their children were younger, and the emphasis shifted to concerns regarding environments that matched individual characteristics at older ages. Furthermore, when there are multiple disabilities or disorders, support is concentrated on the more obvious disabilities, and the lack of support for the less superficially obvious disabilities associated with multiple difficulties, including mental health problems, can be a challenge for people with 22q11DS and their families., Conclusions: This study suggests a need for increased focus on multimorbidity and associated disabilities in school education that are difficult to observe because of their mildness or borderline levels if present alone., (© 2023 The Authors. Journal of Applied Research in Intellectual Disabilities published by John Wiley & Sons Ltd.)

Aim: The 22q11.2 deletion syndrome (22q11DS) is associated with a high prevalence of mental health comorbidities. However, not enough attention has been paid to the elevated prevalence of high trait anxiety that begins early in life and may be enduring. We sought to identify specific medical, welfare, or educational difficulties associated with high trait anxiety in 22q11DS., Methods: A questionnaire-based survey was conducted for the parents of 22q11DS individuals ( N  = 125). First, a multiple regression analysis was conducted to confirm the hypothesis that high trait anxiety in individuals with 22q11DS would be associated with parents' psychological distress. This was based on 19 questionnaire options regarding what difficulties the parents currently face about their child's disease, characteristics, and traits. Next, we explored what challenges faced in medical, welfare, and educational services would be associated with the trait anxiety in their child., Results: The multiple regression analysis confirmed that the high trait anxiety was significantly associated with parental psychological distress ( β  = 0.265, p  = 0.018) among the 19 clinical/personal characteristics of 22q11DS. Furthermore, this characteristic was associated with various difficulties faced in the medical care, welfare, and education services, and the parent-child relationship., Conclusion: To our knowledge, this is the first study to clarify quantitatively how the characteristic of high anxiety level in 22q11DS individuals is related to the caregivers' perceived difficulties in medical, welfare, and educational services. These results suggest the necessity of designing service structures informed of the fact that high trait anxiety is an important clinical feature of the syndrome., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Background: Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method., Patients and Methods: We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities., Results: In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%., Conclusion: Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Aim: Young carers (YCs) refer to children under the age of 18 who assume responsibilities that would normally be assumed by adults, such as caring for family members in need of care. In recent years, the concept of YCs has been expanding in Japan, and the government has been rapidly implementing strategies to support them. There is a need for a survey scale for YCs that uses standardized methods that can be compared internationally., Method: The BBC/University of Nottingham Survey for estimating the prevalence of YCs and caring activities of United Kingdom adolescents was translated into Japanese, and its reliability and validity were tested with 313 adolescents. Moreover, the prevalence of YCs was estimated in a school-based survey among 5000 adolescents., Results: The Young Carers Scale Japanese version (YCS-J) was acceptably reliable and valid. The original six-factor model for caring activity in the Multidimensional Assessment of Caring Activities Checklist for Young Carers (MACA-YC18) was supported by confirmatory factor analysis. The prevalence of YCs among 5000 adolescents in the Tokyo metropolitan area was estimated to be 7.4%, comparable to that reported in Western countries and in recent surveys in Japan using nonstandardized methods. YCs exhibited significantly higher scores for prosocial behavior and emotional symptoms than non-YCs., Conclusions: The YCS-J, as an internationally comparable instrument, will be useful for understanding the actual situation of YCs in Japan, and to disseminate and implement support through cooperation among education, welfare, and healthcare sectors., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Contrast-enhanced computed tomography (CT) scan (portal phase) at the onset. Emphysema is detected in the ileal wall (b, c: Arrows) and free air is detected in the abdominal cavity (a: Arrowhead). CT scan imaging settings: (a-c) window level (WL) 60 and window width (WW) 300. (d-f) WL 0 and WW 433. By changing the imaging settings, intestinal emphysema and free air can be more easily identified., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Production of 99 Mo/ 99m Tc using an electron linear accelerator (linac) and activated carbon (AC)-based 99m Tc generator (linac-AC) is an alternative approach to the conventional fission production of 99 Mo/ 99m Tc. As a preliminary investigation of the clinical applicability of a linac-AC-derived 99m Tc radiopharmaceutical, the biodistribution of linac-AC-derived [ 99m Tc]sodium pertechnetate ([ 99m Tc]NaTcO 4 ) was measured and compared against fission-derived [ 99m Tc]NaTcO 4 at one time point., Methods: 99 Mo was produced by irradiating nonenriched MoO 3 targets with bremsstrahlung photons generated from 55.5-MeV linac electron beams. 99m Tc was then separated and purified from the 99 Mo using an AC-based 99m Tc generator. Subsequently, biodistribution of the linac-AC-derived [ 99m Tc]NaTcO 4 in healthy female Slc:ICR mice (n = 6) was measured by dissection and compared with that of fission-derived [ 99m Tc]NaTcO 4 (n = 4) at 30 min after injection., Results: The two types of [ 99m Tc]NaTcO 4 exhibited similar biodistribution in all the organs and tissues examined: the uptakes of [ 99m Tc]NaTcO 4 prepared from the linac-AC method and those prepared from the fission method were 138.9 ± 69.9%ID/g and 160.6 ± 49.2%ID/g in the thyroids, respectively, 33.4 ± 5.5%ID/g and 29.4 ± 9.1%ID/g in the salivary glands, respectively, and less than 10%ID/g in blood and all the other organs. No adverse effects were observed in the mice administered with either [ 99m Tc]NaTcO 4 ., Conclusion: The clinical applicability of linac-AC-derived [ 99m Tc]NaTcO 4 was suggested by its similar biodistribution with fission-derived [ 99m Tc]NaTcO 4 at one time point. Further biodistribution studies at multiple time points are encouraged to demonstrate the bioequivalence between linac-AC- and fission-derived [ 99m Tc]NaTcO 4 ., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Behavioral neuroscience has dealt with short-term decision making but has not defined either daily or longer-term life actions. The individual brain interacts with the society/world, but where that point of action is and how it interacts has never been an explicit scientific question. Here, we redefine value as an intrapersonal driver of medium- and long-term life actions. Value has the following three aspects. The first is value as a driving force of action, a factor that commits people to take default-mode or intrinsic actions daily and longer term. It consists of value memories based on past experiences, and a sense of values, the source of choosing actions under uncertain circumstances. It is also a multilayered structure of unconscious/automatic and conscious/self-controlled. The second is personalized value, which focuses not only on the value of human beings in general, but on the aspect that is individualized and personalized, which is the foundation of diversity in society. Third, the value is developed through the life course. It is necessary to clarify how values are personalized through the internalization of parent-child, peer, and social experiences through adolescence, a life stage almost neglected in neuroscience. This viewpoint describes the brain and the behavioral basis of adolescence in which the value and its personalization occur, and the importance of this personalized value as a point of interaction between the individual brain and the world. Then the significance of personalized values in psychiatry is discussed, and the concept of values-informed psychiatry is proposed., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Objective: To examine the role of primary motor cortex in gait through exploring the dissociation of impaired voluntary leg muscle contraction and preserved rhythmic activities during gait in a patient who had a stroke., Subject and Methods: A 49-year-old man with an infarct in the primary motor cortex exhibited automatic-voluntary dissociation in the paretic leg. Functional studies were conducted using surface electromyography (EMG) and near-infrared spectroscopy (NIRS)., Results: The patient was incapable of voluntary contraction of individual leg muscles on the paretic right side but was able to walk automatically while contracting those muscles rhythmically. Surface EMG confirmed the earlier findings objectively. The preserved automatic activities helped recovery of gait capability, but NIRS showed no functional recovery in the corresponding motor cortex during treadmill gait. We considered that the loss of voluntary leg muscle contraction and the preserved gait capacity in this patient represented a form of automatic-voluntary dissociation., Conclusions: The preserved gait capability suggests that the leg representation of the primary motor cortex may not play a major functional role in gait, but other components of the nervous system, including the spinal central pattern generator, would serve important functions to maintain gait capability., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Disturbances in presynaptic dopamine activity and levels of GABA (gamma-aminobutyric acid) and glutamate plus glutamine collectively may have a role in the pathophysiology of psychosis, although separately they are poor diagnostic markers. We tested whether these neurotransmitters in combination improve the distinction of antipsychotic-naïve patients with first-episode psychosis from healthy control subjects., Methods: We included 23 patients (mean age 22.3 years, 9 male) and 20 control subjects (mean age 22.4 years, 8 male). We determined dopamine metabolism in the nucleus accumbens and striatum from 18 F-fluorodopa ( 18 F-FDOPA) positron emission tomography. We measured GABA levels in the anterior cingulate cortex (ACC) and glutamate plus glutamine levels in the ACC and left thalamus with 3T proton magnetic resonance spectroscopy. We used binominal logistic regression for unimodal prediction when we modeled neurotransmitters individually and for multimodal prediction when we combined the 3 neurotransmitters. We selected the best combination based on Akaike information criterion., Results: Individual neurotransmitters failed to predict group. Three triple neurotransmitter combinations significantly predicted group after Benjamini-Hochberg correction. The best model (Akaike information criterion 48.5) carried 93.5% of the cumulative model weight. It reached a classification accuracy of 83.7% ( p  = .003) and included dopamine synthesis capacity (K i 4p ) in the nucleus accumbens ( p  = .664), GABA levels in the ACC ( p  = .019), glutamate plus glutamine levels in the thalamus ( p  = .678), and the interaction term K i 4p  × GABA ( p  = .016)., Conclusions: Our multimodal approach proved superior classification accuracy, implying that the pathophysiology of patients represents a combination of neurotransmitter disturbances rather than aberrations in a single neurotransmitter. Particularly aberrant interrelations between K i 4p in the nucleus accumbens and GABA values in the ACC appeared to contribute diagnostic information., (© 2022 The Authors.)

Background: Postsecondary student suicide is one of Japan's most severe public health problems. Gatekeeper training (GKT) programs are a generally recommended suicide prevention intervention in Japan. For suicide countermeasures, an online program tailored to students may enhance self-efficacy as a gatekeeper., Objective: This study aims to describe a research protocol to investigate the effect of a newly developed internet-delivered online peer GKT program to improve postsecondary student self-efficacy as gatekeepers for suicide countermeasures in Japan., Methods: This study is a 2-arm, parallel, randomized controlled trial with a 1:1 (intervention: waiting list) allocation. Participants (n=320) will be recruited, and those who meet the inclusion criteria will be randomly allocated to the intervention or waiting list control group. An approximately 85-minute, 6-section, internet-based gatekeeper program for postsecondary students has been developed that includes videos to help participants acquire skills as gatekeepers. The intervention group will complete the program within 10 days. The primary outcome, self-efficacy as a gatekeeper, is measured using the Gatekeeper Self-Efficacy Scale at baseline, immediately after taking the program, and 2 months after the survey after completing the program follow-up. To compare the primary outcomes, a t test, where the significance level is 5% (2-sided), will be used to test the intervention effect on an intention-to-treat basis., Results: The study was at the stage of data collection at the time of submission. We recruited participants for this study during August and September 2021, and data collection will continue until December 2021. The data analysis related to the primary outcome will start in December 2021, and we hope to publish the results in 2022 or 2023., Conclusions: This is the first study to investigate the effectiveness of an online GKT program for postsecondary students to improve self-efficacy as a gatekeeper using a randomized controlled trial design. The study will explore the potential of an online peer gatekeeper program for postsecondary students that can be disseminated online to a large number of students with minimal cost., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000045325; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000051685., International Registered Report Identifier (irrid): DERR1-10.2196/34832., (©Kyosuke Nozawa, Ayaka Ishii, Hiroki Asaoka, Mai Iwanaga, Yousuke Kumakura, Yuri Oyabu, Tomohiro Shinozaki, Kotaro Imamura, Norito Kawakami, Yuki Miyamoto. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.04.2022.)

Local anesthetics with long-lasting effects and selectivity for nociceptors have been sought over the past decades. In this study, we investigated whether amiodarone, a multiple channel blocker, provides long-lasting local anesthesia and whether adding a TRPV1 channel activator selectively prolongs sensory anesthetic effects without prolonging motor blockade. Additionally, we examined whether amiodarone provides long-lasting analgesic effects against inflammatory pain without TRPV1 channel activator co-administration. In the sciatic nerve block model, 32 adult C57BL/6J mice received either bupivacaine, amiodarone with or without capsaicin (a TRPV1 agonist), or vehicle via peri-sciatic nerve injection. Sensory and motor blockade were assessed either by pinprick and toe spread tests, respectively. In another set of 16 mice, inflammatory pain was induced in the hind paw by zymosan injection, followed by administration of either amiodarone or vehicle. Mechanical and thermal sensitivity and paw thickness were assessed using the von Frey and Hargreaves tests, respectively. The possible cardiovascular and neurological side effects of local amiodarone injection were assessed in another set of 12 mice. In the sciatic nerve block model, amiodarone produced robust anesthesia, and the co-administration of TRPV1 agonist capsaicin prolonged the duration of sensory blockade, but not that of motor blockade [complete sensory block duration: 195.0 ± 9.8 min vs. 28.8 ± 1.3 min, F (2, 21) = 317.6, p < 0.01, complete motor block duration: 27.5 ± 1.6 min vs. 21.3 ± 2.3 min, F (2, 22) = 11.1, p = 0.0695]. In the zymosan-induced inflammatory pain model, low-dose amiodarone was effective in reversing the mechanical and thermal hypersensitivity not requiring capsaicin co-administration [50% withdrawal threshold at 8 h (g): 0.85 ± 0.09 vs. 0.25 ± 0.08, p < 0.01, withdrawal latency at 4 h (s) 8.5 ± 0.5 vs. 5.7 ± 1.4, p < 0.05]. Low-dose amiodarone did not affect zymosan-induced paw inflammation. Local amiodarone did not cause cardiovascular or central nervous system side effects. Amiodarone may have the potential to be a long-acting and nociceptor-selective local anesthetic and analgesic method acting over open-state large-pore channels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kotoda, Matsuoka, Wada, Jayakar, Ino, Kawago and Kumakura.)

Introduction: Novel diagnostic and therapeutic options are urgently needed for patients with metastatic castration-resistant prostate cancer (CRPC). PSMA-617 is one of the most promising ligands that bind to prostate specific membrane antigen (PSMA), the cell surface biomarker of CRPC. Of the radiolabeled PSMA ligands developed to date, [ 68 Ga]Ga-PSMA-617 is most commonly used for PSMA positron emission tomography (PET) prior to radioligand therapy (RLT) with [ 177 Lu]Lu-PSMA-617. However, the presence of 68 Ga radioactivity (half-life 68 m) in urine at the early PET imaging time point complicates optimization of the therapeutic dose of PSMA-617 labeled with 177 Lu (half-life 6.7 d). Thus, PET imaging with the long-lived positron emitter 89 Zr (half-life 3.3 d) would be better suited in order to optimize the dose of [ 177 Lu]Lu-PSMA-617 as 89 Zr PET allows scans after excretion of the radioactive urine. Until now, PSMA-617 could not be radiolabeled with 89 Zr with high radiochemical yield due to poor incorporation of 89 Zr into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Here we report a novel method for radiolabeling PSMA-617 with 89 Zr and the preliminary results of small-animal PET with [ 89 Zr]Zr-PSMA-617., Methods: We labeled PSMA-617 with 89 Zr in a 1:1 mixture of DMSO and HEPES buffer at 90 °C for 30 min, followed by quality control analysis by HPLC. We then determined the dissociation constant (K d ) and logD values of [ 89 Zr]Zr-PSMA-617. We obtained PET images of [ 89 Zr]Zr-PSMA-617 at 24 h in mice bearing both LNCaP (PSMA-positive) and PC-3 (PSMA-negative) tumors (N = 5). The ex vivo [ 89 Zr]Zr-PSMA-617 biodistribution was then examined separately using tissue samples of LNCaP-bearing mice at 2 h (N = 4) and 24 h (N = 4)., Results: [ 89 Zr]Zr-PSMA-617 was prepared with a radiochemical yield of 70 ± 9%. The K d value was 6.8 ± 3.5 nM. The logD value was -4.05 ± 0.20. PET images showed the highest uptake in LNCaP tumors (maximum standardized uptake value, SUV max  = 0.98 ± 0.32) and low uptake in kidneys (SUV max  = 0.18 ± 0.7) due to the absence of urine radioactivity., Conclusion: [ 89 Zr]Zr-PSMA-617 was successfully prepared using DMSO and HEPES buffer. [ 89 Zr]Zr-PSMA-617 visualized PSMA-positive LNCaP tumors in the absence of radioactive urine 24 h p.i., Advances in Knowledge and Implications for Patient Care: This method of radiolabeling PSMA-617 with 89 Zr using DMSO would be suitable for future clinical trials. Prediction of radiation dose by using [ 89 Zr]Zr-PSMA-617 leads to the safe and effective RLT with [ 177 Lu]Lu-PSMA-617., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ryota Imura and Hiroyuki Ida are employees of JFE Engineering Corporation. This research was partially conducted with research funds of the JFE Engineering Corporation. No other potential conflicts of interest relevant to this article exist., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The conceptualization of personal recovery began in Europe and North America and has spread worldwide. However, the concept of personal recovery in addition to recovery-promoting factors may be influenced by culture. We explored how users of mental health services in Japan perceive their own personal recovery and the factors that promote it., Methods: We conducted semi-structured interviews and focus group interviews with individuals using mental health services. The interview data were analysed using thematic analysis with a grouped framework analysis approach. We used a coding framework based on the existing CHIME framework (connectedness, hope and optimism about the future, identity, meaning in life, and empowerment)., Results: Data were obtained from 30 users of mental health services (mean age: 40.4 years; 46.7% women; 50.0% with schizophrenia). "Compassion for others" was newly extracted in "Connectedness", and "Rebuilding/redefining identity not being as shaped by social norms" was newly extracted in "Identity" as personal recovery. "Positive experiences in childhood" (including positive parenting support from neighbours) was newly extracted as a recovery-promoting factor., Conclusions: Our unique findings on the rebuilding identity/defining identity free from conformity to social norms due to interactions with familiar people, including peers, may be culture dependent. This study raises overarching questions regarding how socio-cultural values influence the development of identity and personal values and how they are in turn reflected in personal recovery., (© 2022. The Author(s).)

We asked if sensation-seeking is linked to premorbid personality characteristics in patients with addictive disorders, or the characteristics follow the sensation-seeking activity. We interpreted the former as a state associated with normal rates of dopamine synthesis, and the latter as a trait of individuals with abnormally high rates of synthesis. We previously determined dopaminergic receptor density in striatum, and we now tested the hypothesis that an elevated dopaminergic condition with increased extracellular dopamine and receptor density follows increased dopamine synthesis capacity in highly sensation-seeking individuals, as measured by positron emission tomography of 18 men with tracer fluorodopa (FDOPA). We detected a site in left caudate nucleus where the volume of distribution of FDOPA-derived metabolites correlated negatively with FDOPA metabolite turnover, consistent with decreased metabolite breakdown in highly sensation-seeking subjects. High rates of sensation-seeking attenuated the dopamine turnover in association with a low rate of dopamine recycling, low dopamine oxidation, and elevated extracellular dopamine and receptors in caudate nucleus. In contrast, low rates of sensation-seeking were associated with rapid dopamine recycling, rapid dopamine oxidation, low extracellular dopamine, and low receptor density. We conclude that the modulation of dopaminergic neurotransmission associated with sensation-seeking is a state of sensation-seeking, rather than a trait of personality following abnormal regulation of dopaminergic neurotransmission., (© 2021. The Author(s).)

Background: Dopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate of 18 F-DOPA to 18 F-dopamine (k 3 ) and the effect of treatment on psychotic symptoms in antipsychotic-naïve patients with first-episode psychosis. We further explored the effect of treatment with a partial dopamine D 2 receptor agonist (aripiprazole) on k 3 and dopamine synthesis capacity (DSC) determined by the four-parameter model and by the conventional tissue reference method., Methods: Sixty-two individuals (31 patients and 31 control subjects) underwent 18 F-DOPA positron emission tomography at baseline, and 15 patients were re-examined after 6 weeks. Clinical re-examinations were completed after 6 weeks (n = 28) and 6 months (n = 15). Symptoms were evaluated with the Positive and Negative Syndrome Scale., Results: High baseline decarboxylation rates (k 3 ) were associated with more positive symptoms at baseline (p < .001) and with symptom improvement after 6 weeks (p = .006). Subregion analyses showed that baseline k 3 for the putamen (p = .003) and nucleus accumbens (p = .013) and DSC values for the nucleus accumbens (p = .003) were associated with psychotic symptoms. The tissue reference method yielded no associations between DSC and symptoms or symptom improvement. Neither method revealed any effects of group or treatment on average magnitudes of k 3 or DSC, whereas changes in dopamine synthesis were correlated with higher baseline values, implying a potential effect of treatment., Conclusions: Striatal decarboxylation rate at baseline was associated with psychotic symptoms and treatment response. The strong association between k 3 and treatment effect potentially implicate on new treatment strategies., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Parents of children with 22q11.2 deletion syndrome (22q11DS) experience distress not only due to multimorbidity in the patients, but also due to professionals' lack of understanding about 22q11DS and insufficient support systems. This study investigated relationships between medical, welfare, and educational challenges and parental psychological distress. A cross-sectional survey was conducted on primary caregivers of children with 22q11DS. Participants included 125 parents (114 mothers, 91.2%; average age = 44.3 years) who reported their challenges, psychological distress, and child's comorbidities of 22q11DS. Results showed that the difficulty in going to multiple medical institutions (β = 0.181, p < 0.05) and lack of understanding by welfare staff and insufficient welfare support systems for 22q11DS (β = 0.220-0.316, all p < 0.05) were associated with parental psychological distress, even after adjusting for child's comorbidities. In the subsample of parents whose child attended an educational institution, inadequate management in classroom and mismatch between service and users in educational settings were associated with psychological distress (β = 0.222-0.296, all p < 0.05). This study reveals the importance of assessing not only severity of comorbidities in 22q11DS, but also the medical, welfare, and educational challenges for parental mental health., (© 2021 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Long-term alteration of dopaminergic neurotransmission is known to modulate the D 2 /D 3 receptor expression in the brain. The modulation can occur as a response to pathological processes or pharmacological intervention. The receptor density can be monitored by in vivo positron emission tomography (PET) of [ 11 C] raclopride. To obtain accurate measurements of receptor-ligand interaction, it is essential to estimate binding parameters at true (if transient) equilibrium of bound and unbound ligand quantities. We designed this study as a comparison of two quantitative approaches to transient equilibrium, the TRansient EquilibriuM BoLus Estimation (TREMBLE) method and the Transient Equilibrium Model (TEM) method, to determine binding parameters at transient equilibrium with bolus injection of the radioligand. The data demonstrates that TREMBLE unlike TEM identified the time at which equilibrium existed. TREMBLE revealed that equilibrium prevailed at one or more times after bolus injection and identified differences of receptor density among regions such as putamen and caudate nucleus. We demonstrated that TREMBLE is a quantitative approach suitable for the study of pathophysiological conditions of certain types of neurotransmission the brain., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Using two static scans for 123 I-meta-iodobenzyl-guanidine ( 123 I-MIBG) myocardial scintigraphy ignores the dynamic response from vesicular trapping in nerve terminals. Moreover, the long pause between scans is impractical for patients with Lewy body diseases (LBDs). Here, we optimized indices that capture norepinephrine kinetics, tested their diagnostic performance, and determined the differences in 123 I-MIBG performance among disease groups., Methods: We developed a new 30-min protocol for 123 I-MIBG dynamic planar imaging for suspected LBD patients. Pharmacokinetic modelling of time-activity curves (TACs) was used to calculate three new indices: unidirectional uptake of 123 I-MIBG to vesicular trapping (iUp), rate of myocardial 123 I-MIBG loss (iLoss), and non-specific fractional distribution of 123 I-MIBG in the interstitial space. We compared the performance of the new and existing indices with regard to discrimination of patients with or without LBDs. Subgroup analysis was performed to examine differences in 123 I-MIBG turnover between patients in a dementia with Lewy bodies (DLB) group and two Parkinson's disease (PD) groups, one with and the other without REM sleep behaviour disorder (RBD)., Results: iLoss was highly discriminative, particularly for patients with low myocardial 123 I-MIBG trapping, and the new indices outperformed existing ones. ROC analysis revealed that the AUC of iLoss (0.903) was significantly higher than that of early HMR (0.863), while comparable to that of delayed HMR (0.892). The RBD-positive PD group and the DLB group had higher turnover rates than the RBD-negative PD group, indicating a potential association between prognosis and iLoss., Conclusion: 123 I-MIBG turnover can be quantified in 30 min using a three-parameter model based on 123 I-MIBG TACs. The discriminatory performance of the new model-based indices might help explain the neurotoxicity or neurodegeneration that occurs in LBD patients., (© 2021. The Author(s).)

Introduction: Tapentadol has analgesic effects comparable to those of conventional opioids and is associated with fewer side effects, including gastrointestinal symptoms, drowsiness, and dizziness, than other opioids. However, the safety of tapentadol in the Japanese population remains unclear; the present multicentre study aimed to examine the safety of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events., Methods: The safety of tapentadol was assessed retrospectively in patients with any type of cancer treated between August 18, 2014 and October 31, 2019 across nine institutions in Japan. Patients were examined at baseline and at the time of opioid discontinuation. Multivariate analysis was performed to identify factors associated with tapentadol discontinuation owing to adverse events., Results: A total of 906 patients were included in this study, and 685 (75.6%) cases were followed up until tapentadol cessation for any reason. Among patients who discontinued treatment, 119 (17.4%) did so because of adverse events. Among adverse events associated with difficulty in taking medication, nausea was the most common cause of treatment discontinuation (4.7%), followed by drowsiness (1.8%). Multivariate analysis showed that those who were prescribed tapentadol by a palliative care physician (odds ratio [OR] 2.60, 95% confidence interval [CI] 1.36-4.99, p = 0.004), patients switching to tapentadol due to side effects from previous opioids (OR 2.19, 95% CI 1.05-4.56, p = 0.037), and patients who did not use naldemedine (OR 5.06, 95% CI 2.47-10.37, p < 0.0001) had an increased risk of treatment discontinuation owing to adverse events., Conclusions: This study presents the safety profile of tapentadol and the characteristics of patients likely to discontinue this treatment owing to adverse events in the Japanese population. Prospective controlled trials are required to evaluate the safety of tapentadol and validate the present findings., Trial Registration Number: UMIN 000044282 (University Hospital Medical Information Network)., (© 2021. The Author(s).)

Aim: Psychiatric disturbances are the major adverse effects of corticosteroids. There are no consistent conclusions regarding changes in steroid dosage and the incidence of psychiatric conditions, due in part to the lack of consistent evaluation criteria. The purpose of this research was to determine the incidence and dose-dependency of psychiatric conditions as assessed by trained psychiatrists., Methods: A retrospective chart review was conducted at a university hospital in Japan. We identified inpatients receiving oral prednisolone treatment, who were referred to the consultation-liaison psychiatry team from April 2015 to March 2018. Patients were divided into high-dose (≥0.5 mg/kg/day) and low-dose (<0.5 mg/kg/day) groups. We investigated the associations between steroid dosage and incidence of psychiatric conditions., Results: A total of 93 patients (35 in the high-dose group, 58 in the low-dose group) were included. Various psychiatric conditions, such as insomnia, delirium, depression, and psychosis, occurred during steroid therapy. The most common condition was insomnia (72%). We observed no significant differences in the patient background characteristics and the incidence of most psychiatric conditions between the high-dose and low-dose groups. However, there were more patients with delirium in the low-dose group than in the high-dose group., Conclusions: Based on the accurate assessment of psychiatric conditions by psychiatrists, our analysis suggests that, among inpatients referred to a consultation-liaison psychiatry team, the incidence of psychiatric conditions, with the exception of delirium, is independent of the dose of oral prednisolone., (© 2021 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Background and Aim: Long-term cumulative incidence of and risk factors for metachronous advanced colorectal neoplasia, including both advanced colorectal adenoma (≥10 mm, or with villous or high-grade dysplasia) and colorectal cancer, are critical for surveillance strategies. The aim of this study was to determine the cumulative incidence of metachronous advanced colorectal neoplasia and its risk factors., Methods: A retrospective cohort study was conducted on 6720 consecutive individuals who underwent general health check-ups and colonoscopy. Colorectal adenomas at initial colonoscopy were categorized as low-risk (1-2 small [<10 mm] tubular adenomas) or high-risk adenoma (≥3 tubular adenomas of any size; at least one adenoma ≥10 mm; or villous adenoma or adenoma with high-grade dysplasia). Kaplan-Meier estimates and hazard ratio by Cox-proportional hazard regression were calculated., Results: The cumulative incidence (95% confidence interval [CI]) of metachronous advanced colorectal neoplasia at 5 and 10 years was 5.7% [4.6-7.1], and 11% [8.9-14] in the low-risk adenoma group, and 10% [8.6-13], and 17% [14-21] in high-risk adenoma group, respectively. Adjusted hazard ratio [95% CI] of low-risk adenoma (vs. no colorectal adenoma), high-risk adenoma (vs. no colorectal adenoma), current smoking and positive fecal immunochemical test were 1.34 [1.04-1.74], 1.94 [1.48-2.55], 1.55 [1.2-2.02] and 1.69 [1.35-2.1], respectively. Adjusted hazard ratio [95% CI] of positive fecal immunochemical test was 1.88 [1.29-2.74] in those with normal colonoscopy., Conclusions: Both low-risk and high-risk adenomas confer substantial risk for metachronous advanced colorectal neoplasia at 10 years. Positive fecal immunochemical test was a significant risk factor for metachronous advanced colorectal neoplasia despite normal colonoscopy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Vertebral compression fractures can cause severe back pain. Although many types of analgesics and interventional treatments are available, they are sometimes ineffective in mitigating the pain. We encountered a case where clonazepam was effective for the management of severe low back pain caused by lumbar vertebral compression fractures., Case Presentation: A 44-year-old male was diagnosed with multiple myeloma and had vertebral compression fractures of the first and second lumbar vertebrae. He had been suffering from severe low back pain on movement with muscle spasm and pain-associated anxiety. We considered this breakthrough low back pain to be caused by facet joint pain; thus, we prescribed clonazepam as a muscle relaxant and anxiolytic. Following this treatment, the intractable breakthrough pain was dramatically relieved., Conclusion: Clonazepam, which has both muscle relaxant and anxiolytic effects, might be helpful in mitigating pain, associated anxiety, and muscle spasms due to vertebral compression fractures., (© 2021. The Author(s).)