Preliminary Investigation of the Efficacy and Indications of Proton Beam Therapy for Stage IV Pancreatic Adenocarcinoma.

BACKGROUND: The present study aimed to evaluate proton beam therapy (PBT) for stage IV pancreatic adenocarcinoma and its metastases and define the criteria for eligibility. Materials and methods: We retrospectively evaluated the patients who had a histopathological diagnosis of pancreatic adenocarcinoma, had progressed to stage IV, and underwent PBT for both the primary and some metastatic lesions between 2017 and 2022. PBT was performed using the passive scattering technique. RESULTS: Sixteen patients (median age, 72 years; range, 55-85 years) were enrolled. All patients had stage IV pancreatic cancer at the initiation of PBT. The median duration from the date of stage IV diagnosis to the initiation of PBT was 5.8 (range, 0.4-13.5) months. Three patients had been diagnosed as having recurrent stage IV cancer at other institutions before their referral to our hospital because they had local recurrence and distant metastases after the resection of the primary tumor. Chemotherapy was as follows: pre-PBT, 0, 1, 2, and 3 lines in 4, 7, 4, and 1 patients, respectively; concurrent with PBT, 0 and 1 line in 11 and 5 patients, respectively; post-PBT, 0 and 1 line in 5 and 5 patients, respectively; and unknown, 6 patients. The median survival times (MSTs) from the date of stage IV diagnosis for the with or without non-irradiated active metastatic tumor were 11.4 and 20.1 months, respectively. Univariate analysis revealed that the performance status (PS) levels (p < 0.01), the carbohydrate antigen (CA) 19-9 tumor marker levels (p < 0.01), active tumors not treated with irradiation (p = 0.02), and with or without post-PBT chemotherapy (p < 0.01) were statistically significant factors. Multivariate analysis revealed that the CA 19-9 tumor marker levels (p= 0.04), the number of metastatic lesions (p = 0.049), and with or without non-irradiated active metastatic tumors (p = 0.02) were significant factors. CONCLUSION: PBT is indicated when the number of metastases is limited to ≤ 4 lesions and all tumors can be irradiated within the smallest possible number of irradiation fields that can be performed within the patient's tolerable time, which is a subjective duration that depends on the patient's reaction during each session. It may be a viable treatment option for patients with oligometastatic pancreatic cancer.

Anesthetic management with remimazolam for a patient with hereditary angioedema:a case report.

BACKGROUND: Hereditary angioedema (HAE), a genetic disorder caused by C1-inhibitor deficiency or dysfunction, may cause mucosal edema in the upper airway during tracheal intubation and extubation. CASE REPORT: A 57-year-old man with HAE and a history of laryngeal edema, scheduled to undergo cervical laminoplasty under general anesthesia. General anesthesia was induced by continuous injection of remimazolam and remifentanil, during which manual mask ventilation and intubation were performed without difficulty. The patient was extubated under deep anesthesia. After emergence from general anesthesia, he had no significant upper airway edema and was treated with a C1-inhibitor seven hours post-surgery because of slight tongue swelling. No additional airway edema was observed, and the patient was discharged from the intensive care unit the following day. CONCLUSIONS: Deep anesthesia tracheal extubation with remimazolam may be effective in preventing upper airway edema during anesthetic management in patients with HAE. J. Med. Invest. 71 : 184-186, February, 2024.

Predominant affective temperaments in depressive patients with severe social withdrawal.

BACKGROUND: Hikikomori (HK) is characterized by self-isolation and social refusal, being more likely also associated with affective disorders, including depression. This case-control study primarily aimed at identifying (if any) predominant affective temperaments are associated with HK in depressed versus not-depressed individuals. Secondary objectives comprise assessing which other psychopathological dimensions (e.g., boredom, anxiety) are associated with the HK specifier in depressed individuals. METHODS: From the larger SWATCH study, 687 Italian young people were screened for depression, as measured by 9 items-Patient Health Questionnaire (PHQ-9) and HK-like social withdrawal, through the Hikikomori Questionnaire-25 (HQ-25). All subjects were administered a brief-Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-M), the 7 items-Generalized Anxiety Disorder (GAD-7) and the Multidimensional State Boredom Scale (MSBS). RESULTS: Males reported significantly higher scores at HQ-25 total score than females (p = 0.026). In the total sample, HK social withdrawal is positively predicted by MSBS low arousal, disengagement, depressive levels, depressive and irritable affective temperaments, while negatively by anxiety (F(6, 680) = 82.336, p < 0.001, R2 = 0.421). By selecting only depressed sample, HQ-25 is positively predicted by MSBS total score, low arousal and depressive affective temperament, while negatively by MSBS high arousal (F(4, 383) = 48.544, p < 0.001, R2 = 0.336). The logistic regression model found that the likelihood of developing depression with the HK specifier is significantly predicted by depressive and cyclothymic affective temperaments. CONCLUSIONS: These preliminary findings could help in clinically characterizing the relationship between specific affective temperamental profiles among individuals with depression with/without HK specifier, in order to provide a more tailored and personalized therapeutic approach. Our Italian study should be extensively replicated in larger, longitudinal and multicentric pan-European studies, by specifically assessing the impact of these findings on depression clinical course, prognosis and treatment outcomes.

The Serotonin-Mediated Anti-Allodynic Effect of Yokukansan on Paclitaxel-Induced Neuropathic Pain.

Refractory peripheral neuropathy can occur as a side effect in 60-70% of patients receiving Paclitaxel (PTX). Yokukansan (YKS) is a Japanese herbal medicine reported to have analgesic properties for entrapment nerve injuries. Therefore, we investigated the anti-allodynic effect of Yokukansan on Paclitaxel-induced neuropathic pain. All experiments used 6-week-old male Sprague Dawley rats. Mechanical allodynia was evaluated using a dynamic plantar aesthesiometer. A mobile touch-stimulator unit applied progressively increasing force to the mid-plantar region of the hind paw in a vertical direction until the animal withdrew its paw. This was carried out before the Paclitaxel administration and during the first, second, third, and fourth weeks. Using a rat model of PTX-induced neuropathic pain (PTX rat), we injected PTX (intraperitoneally, 2 mg/kg) five times every 2 days. Using the dynamic plantar test, we evaluated the anti-allodynic effect of YKS (orally administered, 1 g/kg). YKS administration on a daily basis significantly enhanced the withdrawal threshold in PTX rats and reduced the expression level of activated microglia immunostaining with Iba1, a specific marker for microglia. The intrathecal administration of WAY-100635 (5-hydroxytryptamine [5-HT]1A receptor antagonist) and Ketanserin (5-HT2A/2C receptor antagonist) inhibited the protective effects of YKS. YKS exhibited an anti-allodynic effect in a rodent model of PTX-induced neuropathic pain by reducing the sensitivity to pain stimuli. These results suggest that Yokukansan may activate 5-HT receptors in the spinal cord, mediating Paclitaxel-induced neuropathic pain.

Elastic Banding Compression as a Novel Treatment to Maintain Hemodynamics in a Patient With Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome (KTS) is also associated with venous thrombosis originating from varicose veins in the lower extremities, pulmonary embolism, and pulmonary hypertension. This study describes the anesthetic management of laparoscopic cholecystectomy in a 54-year-old male KTS patient with orthostatic hypotension due to massive varicose veins in the lower extremities and pulmonary thromboembolism. Compressing the varicosities with an elastic bandage can maintain stable circulatory dynamics even under general anesthesia management to prevent position and insufflation-induced changes that can occur spontaneously.

Comparing interplay effects in scanned proton therapy of lung cancer: Free breathing with various layer and volume rescanning versus respiratory gating with different gate widths.

PURPOSE: We investigated interplay effects and treatment time (TT) in scanned proton therapy for lung cancer patients. We compared free-breathing (FB) approaches with multiple rescanning strategies and respiratory-gating (RG) methods with various gating widths to identify the superior irradiation technique. METHODS: Plans were created with 4/1, 2/2, and 1/4 layered/volume rescans of FB (L4V1, L2V2, and L1V4), and 50%, 30%, and 10% gating widths of the total respiratory curves (G50, G30, and G10) of the RG plans with L4V1. We calculated 4-dimensional dynamic doses assuming a constant sinusoidal curve for six irradiation methods. The reconstructed doses per fraction were compared with planned doses in terms of dose differences in 99% clinical-target-volume (CTV) (ΔD99%), near-maximum dose differences (ΔD2%) at organs-at-risk (OARs), and TT. RESULTS: The mean/minimum CTV ΔD99% values for FB were -1.0%/-4.9%, -0.8%/-4.3%, and -0.1%/-1.0% for L4V1, L2V2, and L1V4, respectively. Those for RG were -0.3%/-1.7%, -0.1%/-1.0%, and 0.0%/-0.5% for G50, G30, and G10, respectively. The CTV ΔD99% of the RGs with less than 50% gate width and the FBs of L1V4 were within the desired tolerance (±3.0%), and the OARs ΔD2% for RG were lower than those for FB. The mean TTs were 90, 326, 824, 158, 203, and 422 s for L4V1, L2V2, L1V4, G50, G30, and G10, respectively. CONCLUSIONS: FB (L4V1) is the most efficient treatment, but not necessarily the optimal choice due to interplay effects. To satisfy both TT extensions and interplay, RG with a gate width as large as possible within safety limits is desirable.

Analysis of respiratory-induced motion trajectories of individual liver segments in patients with hepatocellular carcinoma.

PURPOSE: To analyze the respiratory-induced motion trajectories of each liver segment for hepatocellular carcinoma (HCC) to derive a more accurate internal margin and optimize treatment protocol selection. MATERIALS AND METHODS: Ten-phase-gated four-dimensional computed tomography (4DCT) scans of 14 patients with HCC were analyzed. For each patient, eight representative regions of interest (ROI) were delineated on each liver segment in all 10 phases. The coordinates of the center of gravity of each ROI were obtained for each phase, and then the respiratory motion in the left-right (LR), anteroposterior (AP), and craniocaudal (CC) directions was analyzed. Two sets of motion in each direction were also compared in terms of only two extreme phases and all 10 phases. RESULTS: Motion of less than 5 mm was detected in 12 (86%) and 10 patients (71%) in the LR and AP directions, respectively, while none in the CC direction. Motion was largest in the CC direction with a maximal value of 19.5 mm, with significant differences between liver segment 7 (S7) and other segments: S1 (p < 0.036), S2 (p < 0.041), S3 (p < 0.016), S4 (p < 0.041), and S5 (p < 0.027). Of the 112 segments, hysteresis >1 mm was observed in 4 (4%), 2 (2%), and 15 (13%) in the LR, AP, and CC directions, respectively, with a maximal value of 5.0 mm in the CC direction. CONCLUSION: A significant amount of respiratory motion was detected in the CC direction, especially in S7, and S8. Despite the small effect of hysteresis, it can be observed specifically in the right lobe. Therefore, caution is required when using 4DCT to determine IM using only end-inspiration and end-expiration. Understanding the respiratory motion in individual liver segments can be helpful when selecting an appropriate treatment protocol.

Shifting the paradigm of social withdrawal: a new era of coexisting pathological and non-pathological hikikomori.

PURPOSE OF REVIEW: Social withdrawal syndrome, known as "hikikomori," has been highlighted since the late 1990 s in Japan. Hikikomori is more common in urban areas, and often comorbid with mental disorders, and now spreading throughout the world. In the post-COVID-19 era, not outing is no longer considered pathological in itself as the "new normal," and a novel concept of hikikomori is needed. This review summarizes the concept of hikikomori, and presents the latest methods for identification of hikikomori. RECENT FINDINGS: The novel definition can distinguish between pathological and non-pathological hikikomori using the scale of "Hikikomori Diagnostic Evaluation (HiDE)," which has been developed in the hikikomori research lab at Kyushu University. An online survey among non-working adults has revealed that persons who have become pathological hikikomori for less than three months showed a particularly strong tendency toward gaming disorder and depression. SUMMARY: Now, physical isolation itself is not pathological, but when dysfunction and distress are present, rapid mental health support should be provided. In the novel urban society, the establishment of a checkup system to assess whether persons who stay home are happy or suffering is important for prevention against mental disorders triggered by social isolation.

Pharmacoepidemiology and Clinical Correlates of Lithium Treatment for Bipolar Disorder in Asia.

BACKGROUND: As clinical practices with lithium salts for patients diagnosed with bipolar disorder (BD) are poorly documented in Asia, we studied the prevalence and clinical correlates of lithium use there to support international comparisons. METHODS: We conducted a cross-sectional study of use and dosing of lithium salts for BD patients across 13 Asian sites and evaluated bivariate relationships of lithium treatment with clinical correlates followed by multivariate logistic regression modeling. RESULTS: In a total of 2139 BD participants (52.3% women) of mean age 42.4 years, lithium salts were prescribed in 27.3% of cases overall, varying among regions from 3.20% to 59.5%. Associated with lithium treatment were male sex, presence of euthymia or mild depression, and a history of seasonal mood change. Other mood stabilizers usually were given with lithium, often at relatively high doses. Lithium use was associated with newly emerging and dose-dependent risk of tremors as well as risk of hypothyroidism. We found no significant differences in rates of clinical remission or of suicidal behavior if treatment included lithium or not. CONCLUSIONS: Study findings clarify current prevalence, dosing, and clinical correlates of lithium treatment for BD in Asia. This information should support clinical decision-making regarding treatment of BD patients and international comparisons of therapeutic practices.

Could the Construct of Modern-Type Depression Predict Internet Gaming Disorder in Italian Video Gamers? A Case-Control Study.

A new postmodern depression type, named "Modern-Type Depression" (MTD), is emerging in Western countries. MTD is often underdiagnosed, mainly due to potentially higher comorbidity with technology-based addictions, including Internet Gaming Disorder (IGD). However, the definition of the relationship between MTD and IGD is still controversial, as few data have been published thus far. In particular, there are no data specifically investigating the prevalence of MTD within Italian young subjects with IGD, as well as their mutual association. Hence, within the SWATCH (Social Withdrawal and TeCno-mediated mental Health issues) project, our study aimed to identify the prevalence of MTD in a sample of Italian young adults who play video games by providing a clinical characterization of MTD within a group of IGD individuals (IGD+) versus a group without IGD (IGD-) who play video games. Our cross-sectional case-control study recruited a sample of 543 Italian young video-gaming players (aged 18-35) from the larger SWATCH database, stratified as IGD+ versus IGD-. Subjects were administered the 22-item Tarumi's Modern-Type Depression Trait Scale (TACS-22), the Motives for Online Gaming Questionnaire (MOGQ), and the Internet Gaming Disorder Scale-Short Form (IGDS9-SF). Around 21.7% of the total sample was represented by MTD individuals, while within the IGD sample, around 34% of subjects had MTD. Within the MTD group, significantly higher scores at IGDS-9SF (p < 0.001), MOGQ "Escape from reality" (p < 0.001), "Fantasy" (p < 0.001), and MOGQ total score (p = 0.003) were found compared to MTD-. According to the multivariate regression model, controlled for sex and age, higher scores in the TACS-22 were positively predicted by the total score of IGDS9-SF (p = 0.003), the MOGQ "Escape from Reality" subscale (p = 0.014), and MOGQ "Fantasy" (p = 0.011), and negatively predicted by the MOGQ "Competition" subscale (p = 0.035) [F (4538) = 17.265; p < 0.001]. Our findings suggested that MTD displays a strong association with IGD. Video-gaming players who do not have IGD appear to be less prone to MTD; this suggests that further studies could be carried out to specifically investigate whether pathological use of video games could also be determined by the presence of MTD.

Dose-volume comparisons of proton therapy for pencil beam scanning with and without multi-leaf collimator and passive scattering in patients with lung cancer.

This study evaluated the dose distributions of proton pencil beam scanning (PBS) with/without a multileaf collimator (MLC) compared to passive scattering (PS) for stage I/II lung cancers. Collimated/uncollimated (PBS+/PBS-) and PS plans were created for 20 patients. Internal-clinical-target-volumes (ICTVs) and planning-target-volumes (PTVs) with a 5 mm margin were defined on the gated CTs. Organs-at-risk (OARs) are defined as the normal lungs, spinal cord, esophagus, and heart. The prescribed dose was 66 Gy relative-biological-effectiveness (RBE) in 10 fractions at the isocenter and 50% volume of the ICTVs for the PS and PBS, respectively. We compared the target and OAR dose statistics from the dose volume histograms. The PBS+ group had a significantly better mean PTV conformity index than the PBS- and PS groups. The mean dose sparing for PBS+ was better than those for PBS- and PS. Only the normal lung doses of PBS- were worse than those of PS. The overall performance of the OAR sparing was in the order of PBS+, PBS-, and PS. The PBS+ plan showed significantly better target homogeneity and OAR sparing than the PBS- and PS plans. PBS requires collimating systems to treat lung cancers with the most OAR sparing while maintaining the target coverage.

Experimental validation of a 4D dynamic dose calculation model for proton pencil beam scanning without spot time stamp considering free-breathing motion.

PURPOSE: We developed a 4-dimensional dynamic dose (4DDD) calculation model for proton pencil beam scanning (PBS). This model incorporates the spill start time for all energies and uses the remaining irradiated spot time model instead of irradiated spot time logs. This study aimed to validate the calculation accuracy of a log file-based 4DDD model by comparing it with dose measurements performed under free-breathing conditions, thereby serving as an alternative approach to the conventional log file-based system. METHODS: Three cubic verification plans were created using a heterogeneous block phantom; these plans were created using 10 phase 4D-CT datasets of the phantom. The CIRS dynamic platform was used to simulate motion with amplitudes of 2.5, 3.75, and 5.0 mm. These plans consisted of eight- and two-layered rescanning techniques. The lateral profiles were measured using a 2D ionization chamber array (2D-array) and EBT3 Gafchromic films at four starting phases, including three sinusoidal curves (periods of 3, 4, and 6 s) and a representative patient curve during actual treatment. 4DDDs were calculated using in-house scripting that assigned a time stamp to each spot and performed dose accumulation using deformable image registration. Furthermore, to evaluate the impact of parameter selection on our 4DDD model calculations, simulations were performed assuming a ±10% change in irradiation time stamp (0.8 ± 0.08 s) and spot scan speed. We evaluated the 2D gamma index and the absolute point doses between the calculated values and the measurements. RESULTS: The 2D-array measurements revealed that the gamma scores for the static plans (no motion) and 4DDD plans exceeded 97.5% and 93.9% at 3%/3 mm, respectively. The average gamma score of the 4DDD plans was at least 96.1%. When using EBT3 films, the gamma scores of the 4DDD model exceeded 92.4% and 98.7% at 2%/2 mm and 3%/3 mm, respectively. Regarding the 4DDD point dose differences, more than 95% of the dose regions exhibited discrepancies within ±5.0% for 97.7% of the total points across all plans. The spot time assignment accuracy of our 4DDD model was acceptable even with ±10% sensitivity. However, the accuracy of the scan speed, when varied within ±10% sensitivity, was not acceptable (minimum gamma scores of 82.6% and maximum dose difference of 12.9%). CONCLUSIONS: Our 4DDD calculations under free-breathing conditions using amplitudes of less than 5.0 mm were in good agreement with the measurements regardless of the starting phases, breathing curve patterns (between 3 and 6 s periods), and varying numbers of layered rescanning. The proposed system allows us to evaluate actual irradiated doses in various breathing periods, amplitudes, and starting phases, even on PBS machines without the ability to record spot logs.

Radioactivation effects of titanium caused by clinical proton beam: a simulation study.

Objective. In proton beam therapy (PBT), metals in the patient body perturb the dose distribution, and their radioactivation may affect the dose distribution around the metal; however, the radioactivation effect has been not clarified with PBT. In this study, we aimed to evaluate the radioactivation effect of metal depending on proton energies and secondary neutrons with a clinical proton beam using a Monte Carlo (MC) simulation.Approach.The radionuclides produced from a titanium alloy (Ti-6Al-4V) and their radioactivity were calculated using a 210-MeV passive scattering proton beam with a 60-mm Spread-out Bragg Peak, and the deposited doses caused by the radioactivation were computed using the MC simulation. The position of metal was changed according to the proton mean energy in water. To assess neutron effects on the radioactivation, we calculated the radioactivation in following three situations: (i) full MC simulation with neutrons, (ii) simulation without secondary neutrons generated from the beamline components, and (iii) simulation without any secondary neutrons.Main results.Immediately after the irradiation, the radionuclide with the largest activity was Sc-45 m (half-life of 318 ms) regardless of the proton energy and the presence of neutrons. Total radioactivity tended to increase according to the proton energy. The accumulated dose for 24 h caused by the metal activation showed an increasing trend with the proton energy, with a maximum increase rate of 0.045% to the prescribed dose. The accumulated dose at a distance of 10 mm from the metal was lower than 1/10 of that at a distance of 1 mm.Significance.The radioactivation effect of the titanium was comprehensively evaluated in the clinical passive scattering proton beam. We expect that radioactivation effects on the clinical dose distribution would be small. We consider that these results will help the clinical handling of high-Z metals in PBT.

Development of depression assessment tools using humanoid robots -Can tele-operated robots talk with depressive persons like humans?

BACKGROUND: Depression is a common mental disorder and causes significant social loss. Early intervention for depression is important. Nonetheless, depressed patients tend to conceal their symptoms from others based on shame and stigma, thus hesitate to visit psychiatrists especially during early phase. We hypothesize that application of humanoid robots would be a novel solution. Depressed patients may feel more comfortable talking with such robots than humans. METHODS: We recruited 13 patients with major depressive disorder (MDD) and 27 healthy volunteers as controls. Participants took both tele-operated humanoid robot and human interviews to evaluate severity of depression using the Hamilton Depression Rating Scale (HDRS). In addition, participants completed a self-administered questionnaire asking about their impressions of the robot interview. RESULTS: Confidence interval and t-test analysis have revealed that the HDRS scores are equally reliable between robot and human interviews. No significant differences were observed between the two interviews regarding "nervousness about the interview" and "hesitancy to talk about depressed moods and suicidal ideation." Compared to human interviews, robot interviews yielded significantly lower scores on shame-related factors especially among patients with MDD. LIMITATION: Small sample size, and the evaluator is male only. CONCLUSIONS: This is the first report to show the reliability of tele-operated humanoid robot interviews for assessment of depression. Robot interviews are potentially equally reliable as human interviews. Robot interviews are suggested to be more appropriate in assessing shame-related suppressed emotions and hidden thoughts of depressed patients in clinical practice, which may reduce the stigma associated with depression.

TRPV4-mediated Ca2+ deregulation causes mitochondrial dysfunction via the AKT/α-synuclein pathway in dopaminergic neurons.

Mutations in the gene encoding the transient receptor potential vanilloid member 4 (TRPV4), a Ca2+ permeable nonselective cation channel, cause TRPV4-related disorders. TRPV4 is widely expressed in the brain; however, the pathogenesis underlying TRPV4-mediated Ca2+ deregulation in neurodevelopment remains unresolved and an effective therapeutic strategy remains to be established. These issues were addressed by isolating mutant dental pulp stem cells from a tooth donated by a child diagnosed with metatropic dysplasia with neurodevelopmental comorbidities caused by a gain-of-function TRPV4 mutation, c.1855C > T (p.L619F). The mutation was repaired using CRISPR/Cas9 to generate corrected isogenic stem cells. These stem cells were differentiated into dopaminergic neurons and the pharmacological effects of folic acid were examined. In mutant neurons, constitutively elevated cytosolic Ca2+ augmented AKT-mediated α-synuclein (α-syn) induction, resulting in mitochondrial Ca2+ accumulation and dysfunction. The TRPV4 antagonist, AKT inhibitor, or α-syn knockdown, normalizes the mitochondrial Ca2+ levels in mutant neurons, suggesting the importance of mutant TRPV4/Ca2+/AKT-induced α-syn in mitochondrial Ca2+ accumulation. Folic acid was effective in normalizing mitochondrial Ca2+ levels via the transcriptional repression of α-syn and improving mitochondrial reactive oxygen species levels, adenosine triphosphate synthesis, and neurite outgrowth of mutant neurons. This study provides new insights into the neuropathological mechanisms underlying TRPV4-related disorders and related therapeutic strategies.

Optimal Bladder Volume for Hypofractionated Proton Therapy in Each Localized Prostate Cancer Risk Group.

Background This study aimed to determine the optimal bladder volume (BV) for hypofractionated proton therapy in prostate cancer (PC). Materials and methods Two hundred patients with PC were enrolled in this study and classified into low-, intermediate-, and high-risk groups. Treatment planning was performed by assuming a hypofractionated schedule of 63 Gy (relative biological effectiveness) in 21 fractions. The dose indices of the bladder (V60 and V50) were calculated and classified into four groups according to the BV. A cutoff value with a 95% confidence interval was calculated on the basis of the mean and standard deviation of the dose indices. These values were compared with the dose constraints (V60 < 15 % and V50 < 30 %). Results The dose indices were higher in the high-risk group than in the other risk groups. The cutoff value exceeded dose constraints in the low- and intermediate-risk groups with a BV of â‰¦ 149 cc. Additionally, the cutoff value exceeded the dose constraint in the high-risk group with a BV of ≦ 199 cc. In all the cases, the group with a BV of â‰§ 200 cc was below the dose constraint. Conclusions In this study, the relationship between the dose and volume of the bladder in hypofractionated PT for PC was evaluated using a 95% CI to determine the optimal BV. The BV should be changed for each risk group, and a larger BV is required for a high-risk group than for other risk groups.

Heterogeneity of gaming disorder: A clinically-based typology for developing personalized interventions.

Background: The eleventh revision of the International Classification of Diseases (ICD-11) defines the three key diagnostic criteria for gaming disorder (GD). These are loss of control over gaming, gaming as a priority over daily activities, and impaired functioning due to gaming. While this definition has implications for the prevention and treatment of GD, there is significant heterogeneity in the symptoms and etiology of GD among individuals, which results in different treatment needs. Cognitive control, emotional regulation, and reward sensitivity are three critical dimensions in the etiology model for GD. Aspects such as gender, comorbidity, motivation for gaming, stage or severity of GD, and risk factors all contribute to the heterogeneity of etiology among individuals with the disorder. Method: On the basis of clinical symptoms and comorbidity characteristics among approximately 400 patients with gaming disorder, the present paper proposes a clinical typology of patients with GD based on the authors' clinical experience in treating individuals with GD. Results: The findings indicated three common types of patients with GD: (i) impulsive male patients with attention deficit hyperactivity disorder (ADHD), (ii) dysphoria patients with dysfunctional coping skills, and (iii) isolated patients with social anxiety. The paper also discusses the presentation and treatment priority for these patients. Conclusion: Personalized treatments for patients with GD should be developed to fit their individual needs. Future studies should examine the heterogeneity of GD and confirm these types, as well as obtain evidence-based information that can help in the development of personalized treatment. Treatment resources should be developed, and professionals should be trained to provide integrated individualized treatment.