A national survey on the medical physics workload of external beam radiotherapy in Japan†.

Several staffing models are used to determine the required medical physics staffing, including radiotherapy technologists, of radiation oncology departments. However, since Japanese facilities tend to be smaller in scale than foreign ones, those models might not apply to Japan. Therefore, in this study, we surveyed workloads in Japan to estimate the optimal medical physics staffing in external beam radiotherapy. A total of 837 facilities were surveyed to collect information regarding radiotherapy techniques and medical physics specialists (RTMPs). The survey covered facility information, staffing, patient volume, equipment volume, workload and quality assurance (QA) status. Full-time equivalent (FTE) factors were estimated from the workload and compared with several models. Responses were received from 579 facilities (69.2%). The median annual patient volume was 369 at designated cancer care hospitals (DCCHs) and 252 across all facilities. In addition, the median FTE of RTMPs was 4.6 at DCCHs and 3.0 at all sites, and the average QA implementation rate for radiotherapy equipment was 69.4%. Furthermore, advanced treatment technologies have increased workloads, particularly in computed tomography simulations and treatment planning tasks. Compared to published models, larger facilities (over 500 annual patients) had a shortage of medical physics staff. In very small facilities (about 140 annual patients), the medical physics staffing requirement was estimated to be 0.5 FTE, implying that employing a full-time medical physicist would be inefficient. However, ensuring the quality of radiotherapy is an important issue, given the limited number of RTMPs. Our study provides insights into optimizing staffing and resource allocation in radiotherapy departments.

Establishing quality indicators to comprehensively assess quality assurance and patient safety in radiotherapy and their relationship with an institution's background.

BACKGROUND AND PURPOSE: Quality indicators (QIs) for radiotherapy have been proposed by several groups, but no study has been conducted to correlate the implementation of indicators specific to patient safety over the course of the clinical process with an institution's background. An initial large-scale survey was conducted to understand the implementation status of QIs established for quality assurance and patient safety in radiotherapy and the relationship between implementation status and an institutions' background. MATERIALS AND METHOD: Overall, 68 QIs that were established by this research team after a pilot survey were used to assess structures and processes for quality assurance and patient safety. Data on the implementation of QIs and the institutions' backgrounds were obtained from designated cancer care hospitals in Japan. RESULTS: Overall, 284 institutions (72 %) responded and had a median QI achievement rate of 60.8 %. QIs with low implementation rates, such as the implementation of an error reporting system and establishment of a quality assurance department, were identified. The QI achievement rate and scale of the institution were positively correlated, and the achievement rate of all QIs was significantly higher (p < 0.001) in institutions capable of advanced treatments, such as intensity-modulated radiotherapy, and those with a quality assurance department. CONCLUSION: A large-scale survey on QIs revealed their implementation and relationship with a facility's background. QIs that require improvement were identified, and that these QIs might be effective in providing advanced medical care to many patients.

Clozapine-Induced Fever and Plasma Cytokine Changes in a Patient With Schizophrenia.

INTRODUCTION: Clozapine-induced fever is frequently documented in the early stages of administration. Fever during clozapine treatment often presents a clinical challenge, because there are no established guideline to decide when fever is the adverse effect. Although the etiology of clozapine-induced fevers remains unknown, evidence has suggested that fever may develop secondarily to a generalized inflammatory response as a manifestation of the immune-modulating effects of clozapine. CASE PRESENTATION: We presented a 59-year-old male patient with a treatment-resistant schizophrenia, who was introduced clozapine for the first time. He became febrile on day 14 at 75 mg/d. He was diagnosed clozapine-induced fever, which was improved by dose reduction on day 27 at 25 mg/d. However, we noticed significant high levels of blood urea nitrogen and serum creatinine on day 29, which resulted in withdrawal of clozapine. Also, we found continuous eosinophilia on day 33. After we provided conservative therapy with appropriate intravenous fluids, his kidney function and eosinophilic counts returned to normal on day 59 and day 53, respectively. The time-sequential changes of levels of interleukin 6 and tumor necrosis factor α suggested that the upregulated cytokines play a role on clozapine-induced fever and subsequent eosinophilia under severe renal failure condition. CONCLUSIONS: To our knowledge, this is the first case presentation of clozapine-induced fever discussing the mechanism, differential diagnosis, and decision making of clozapine treatment focusing on plasma cytokines. If once fever occurs, an extensive medical workup for the fever and a careful systemic medical management should be promptly proceeded to avoid clozapine-associated severe complications.

Impact of Lurasidone on Metabolic Parameters and Prolactin Levels Based on Differences of Psychiatric Diagnosis, Dosage, and Introducing Methods: An Observational Study.

Objective: Lurasidone is a second-generation antipsychotic (SGA) that contributes an antipsychotic and antidepressant effect, with low incidences of metabolic-related diseases and hyperprolactinemia for the treatment of psychological disorders. However, evidence on lurasidone is limited in psychiatric clinical settings. This study aimed to investigate the effect of short-term lurasidone treatment on metabolic effects and prolactin (PRL) levels, in relation to the differences of psychiatric disorders, lurasidone dosages, and introducing methods, in 35 female and 12 male Japanese inpatients with psychiatric disorders. Methods: Subjects were placed into six subgroups divided by three categories (schizophrenia/schizoaffective disorder or bipolar disorder, 20mg/day or 40mg/day, adding or switching). Sequential changes in 10 items of metabolic parameters, including estimated insulin resistance and PRL levels at one month, were evaluated. The variations of metabolic parameters that were significantly changed from baseline were analyzed against sample characteristics and other metabolic parameter variations. Results: In the 40mg/day and switching introduction method groups, lurasidone significantly reduced body weight, body mass index (BMI), levels of alanine amiotransaminase, and levels of fasting blood glucose. PRL levels seemed to increase when lurasidone was added and decrease when lurasidone was switched to from other antipsychotics. Switching introduction method and higher dosage correlated with weight loss and lowering fasting blood glucose levels, respectively. Conclusion: Lurasidone administration offered the potential for weight loss, lowered serum blood glucose levels, and converging serum PRL concentrations. Moreover, switching introduction method with higher dosages might alleviate basal metabolism and glucose homeostasis. Further prospective studies combining measurements of serum insulin and psychometric evaluation will help to confirm our conclusions.

Effectiveness of Primary Total Hip Arthroplasty Combined with Intra-articular and Intravenous Tranexamic Acid: A Retrospective Analysis of Number of Doses and Dose Strength.

Introduction: Total hip arthroplasty is a very effective reconstructive surgery but is often associated with massive perioperative bleeding, which leads to anemia. Tranexamic acid (TXA) minimizes bleeding and the need for blood transfusion. However, no universal standard TXA dosing regimen has been established. The objectives of this study were (1) whether there was a difference in the amount of decrease in perioperative mean hemoglobin (Hb) level between a single topical administration of TXA and intravenous and topical combination administration, and we also investigated whether there was a difference in the amount of decrease in the perioperative mean Hb level due to the difference in the local dose of TXA. Methods: We retrospectively reviewed 292 hips between June 2013 and October 2020. The decrease in Hb level (difference between the preoperative value and the 7-day postoperative value) was used to estimate total perioperative blood loss. The mean perioperative reduction in Hb was compared between hips that received intravenous TXA preoperatively and intra-articular TXA at wound closure (combination administration group) and those that received only intra-articular TXA (single dose group). It was also compared by different local doses of tranexamic acid. Results: The mean reduction in Hb was significantly smaller in the combination administration group than in the single dose group. However, no significant difference was observed due to the difference in the local dose of TXA administered at the time of wound closure. Conclusion: Reducing perioperative bleeding decreases the invasiveness of surgery, which is important from the perspective of medical safety.

Gasdermin D-mediated release of IL-33 from senescent hepatic stellate cells promotes obesity-associated hepatocellular carcinoma.

Long-term senescent cells exhibit a secretome termed the senescence-associated secretory phenotype (SASP). Although the mechanisms of SASP factor induction have been intensively studied, the release mechanism and how SASP factors influence tumorigenesis in the biological context remain unclear. In this study, using a mouse model of obesity-induced hepatocellular carcinoma (HCC), we identified the release mechanism of SASP factors, which include interleukin-1ß (IL-1ß)- and IL-1ß-dependent IL-33, from senescent hepatic stellate cells (HSCs) via gasdermin D (GSDMD) amino-terminal-mediated pore. We found that IL-33 was highly induced in senescent HSCs in an IL-1ß-dependent manner in the tumor microenvironment. The release of both IL-33 and IL-1ß was triggered by lipoteichoic acid (LTA), a cell wall component of gut microbiota that was transferred and accumulated in the liver tissue of high-fat diet-fed mice, and the release of these factors was mediated through cell membrane pores formed by the GSDMD amino terminus, which was cleaved by LTA-induced caspase-11. We demonstrated that IL-33 release from HSCs promoted HCC development via the activation of ST2-positive Treg cells in the liver tumor microenvironment. The accumulation of GSDMD amino terminus was also detected in HSCs from human NASH-associated HCC patients, suggesting that similar mechanism could be involved in a certain type of human HCC. These results uncover a release mechanism for SASP factors from sensitized senescent HSCs in the tumor microenvironment, thereby facilitating obesity-associated HCC progression. Furthermore, our findings highlight the therapeutic potential of inhibitors of GSDMD-mediated pore formation for HCC treatment.

Development of a prognostic prediction support system for cervical intraepithelial neoplasia using artificial intelligence-based diagnosis.

OBJECTIVE: Human papillomavirus subtypes are predictive indicators of cervical intraepithelial neoplasia (CIN) progression. While colposcopy is also an essential part of cervical cancer prevention, its accuracy and reproducibility are limited because of subjective evaluation. This study aimed to develop an artificial intelligence (AI) algorithm that can accurately detect the optimal lesion associated with prognosis using colposcopic images of CIN2 patients by utilizing objective AI diagnosis. METHODS: We identified colposcopic findings associated with the prognosis of patients with CIN2. We developed a convolutional neural network that can automatically detect the rate of high-grade lesions in the uterovaginal area in 12 segments. We finally evaluated the detection accuracy of our AI algorithm compared with the scores by multiple gynecologic oncologists. RESULTS: High-grade lesion occupancy in the uterovaginal area detected by senior colposcopists was significantly correlated with the prognosis of patients with CIN2. The detection rate for high-grade lesions in 12 segments of the uterovaginal area by the AI system was 62.1% for recall, and the overall correct response rate was 89.7%. Moreover, the percentage of high-grade lesions detected by the AI system was significantly correlated with the rate detected by multiple gynecologic senior oncologists (r=0.61). CONCLUSION: Our novel AI algorithm can accurately determine high-grade lesions associated with prognosis on colposcopic images, and these results provide an insight into the additional utility of colposcopy for the management of patients with CIN2.

Efficacy of preoperative autologous blood storage in one-stage bilateral total knee arthroplasty.

BACKGROUND: One-stage bilateral total knee arthroplasty (TKA) has the advantages of a single hospital stay, shorter rehabilitation, and reduced financial burden on patients. However, perioperative bleeding is greater with one-stage bilateral TKA than with unilateral TKA and is more likely to require allogeneic blood transfusion. At our hospital, we normally store autologous blood about 1 month before surgery to reduce the need for allogeneic blood transfusion and avoid its adverse reactions as much as possible. The purpose of this study was to determine the efficacy of preoperative autologous blood storage for patients undergoing one-stage bilateral TKA. METHODS: We retrospectively examined the allogeneic blood transfusion avoidance rate and the perioperative decrease in hemoglobin (Hb) level in 166 patients according to whether or not they had preoperative autologous blood stored. The patients for whom blood was stored were then subdivided according to whether the amount of blood stored was 400 mL or 200 mL. RESULTS: Excluding allogeneic transfusion cases, the mean perioperative decrease in Hb was significantly lower in the patients with stored blood than in those without stored blood (3.5 g/dL vs 4.4 g/dL, p < 0.001). The allogeneic blood transfusion avoidance rate was significantly higher in the group with stored blood (98.5% vs 86.7%, p < 0.01). In the group with stored blood, the transfusion avoidance rate was higher, but not significantly, in the subgroup with 400 mL of blood stored than in those with 200 mL of blood stored (100% vs 97.5%) and the mean perioperative decrease in Hb was 3.5 g/dL in both blood storage volume groups. CONCLUSIONS: Preoperative autologous blood storage can help increase the likelihood of avoiding allogeneic blood transfusion in patients undergoing one-stage bilateral TKA.

Mode of uterine milk secretion in the white shark.

Examination of the uterus of a dead female white shark (Carcharodon carcharias), which contained the earliest known white shark embryos, revealed that the uterine wall produces lipid-rich secretion (histotroph or "uterine milk") for embryonic nutrition. Uterine tissue was processed for light and electron microscopy, and immunohistochemical techniques to identify its secretory mechanism. Our results indicate that the white shark uterus secretes lipids via holocrine secretion. This type of secretion is characterized by the release of large lipid droplets accumulated in the epithelial cells into the uterine lumen through cell disintegration. The secretory epithelium of the uterus is stratified, and new surface epithelial cells are continuously supplied from deeper epithelial layers to replace the dead secretory cells at the surface. This vertical replacement possibly facilitates the active renewal of the surface epithelium, which is necessary for maintaining holocrine secretory mechanisms. These secretory mechanisms are different from those of myliobatiform stingrays, another elasmobranch taxon that exhibits lipid histotrophy. This may reflect the different origins of lipid histotrophy between these taxa.

Massive Hemorrhage Due to Cervical Endometriotic Cyst Rupture: Two Case Reports and a Literature Review.

BACKGROUND Endometriosis is defined as the growth of ectopic endometrial tissue beyond the uterine cavity, and endometriosis on the uterine cervix is a rare variant. Although asymptomatic patients with cervical endometriosis or those with minor symptoms are treated conservatively, there are reports of life-threatening hemorrhage due to cervical endometriosis. Here, we report 2 cases of massive genital bleeding caused by cervical endometriotic cysts and we performed a literature review. CASE REPORT Case 1: A 32-year-old woman presented to our hospital due to massive genital bleeding on her 11th day of menstruation. An arterial hemorrhage in a cervical endometriotic cyst was suspected. As pressure hemostasis proved difficult, urgent uterine artery embolization (UAE) by interventional radiology was performed. Angiography during the UAE showed extravascular leakage from the branch of the left uterine artery. After embolization, hemostasis was achieved. No further genital bleeding was observed, and transvaginal ultrasound showed the cyst has continued to shrink for 9 months after the UAE with sequential dienogest, a progesterone receptor agonist, treatment. Case 2: A 43-year-old woman presented to our hospital with increasing massive genital bleeding after completing a 12-day course of 0.5 mg of norgestrel and 0.05 mg of ethinyl estradiol as a treatment for irregular intermenstrual bleeding. We suspected cervical endometriotic cyst rupture on imaging and performed an urgent laparoscopic total hysterectomy. In the excised uterine specimen, a cystic lesion that contained old, blood-like fluid was macroscopically observed in the cervix and was diagnosed pathologically as endometriosis. CONCLUSIONS Cervical endometriotic cyst rupture is rare; however, it should be kept in mind as a differential diagnosis when treating massive genital bleeding because urgent intervention is sometimes required to control the bleeding.

Hysteroscopic treatment assisted by photodynamic diagnosis for atypical polypoid adenomyoma: A report of two cases.

Atypical polypoid adenomyoma (APA) is an intrauterine tumor for which hysteroscopic tumor resection allows for fertility preservation. Complete resection is important because of the high recurrence rate of APA, but is difficult due to the lack of characteristic hysteroscopic findings. We previously reported a case in which photodynamic diagnosis (PDD) was useful for detection of APA. Here, we report two additional cases of APA treated by hysteroscopic resection with PDD. The procedure was approved by the ethical committee. Case 1: A 35-year-old female who underwent hysteroscopic surgery for a submucosal tumor suspected to be APA with hypermenorrhea. Case 2: A 37-year-old female in whom hysteroscopic surgery was performed for a residual APA lesion after hormone therapy. In Case 1, PDD identified the tumor borders and this enabled as complete resection as possible. In Case 2, lesions could not be identified clearly under white light, but some areas were PDD-positive and were excised. Among 19 specimens from these two cases and the previously reported case, all PDD-positive specimens were pathologically diagnosed as APA. The sensitivity and specificity of PDD for APA were 76.9% and 100%, respectively. These results suggest that PDD can contribute to identification of APA.

Transcription Factor Homeobox D9 Drives the Malignant Phenotype of HPV18-Positive Cervical Cancer Cells via Binding to the Viral Early Promoter.

Persistent infections with two types of human papillomaviruses (HPV), HPV16 and HPV18, are the most common cause of cervical cancer (CC). Two viral early genes, E6 and E7, are associated with tumor development, and expressions of E6 and E7 are primarily regulated by a single viral promoter: P97 in HPV16 and P105 in HPV18. We previously demonstrated that the homeobox D9 (HOXD9) transcription factor is responsible for the malignancy of HPV16-positive CC cell lines via binding to the P97 promoter. Here, we investigated whether HOXD9 is also involved in the regulation of the P105 promoter using two HPV18-positive CC cell lines, SKG-I and HeLa. Following the HOXD9 knockdown, cell viability was significantly reduced, and E6 expression was suppressed and was accompanied by increased protein levels of P53, while mRNA levels of TP53 did not change. E7 expression was also downregulated and, while mRNA levels of RB1 and E2F were unchanged, mRNA levels of E2F-target genes, MCM2 and PCNA, were decreased, which indicates that the HOXD9 knockdown downregulates E7 expression, thus leading to an inactivation of E2F and the cell-cycle arrest. Chromatin immunoprecipitation and promoter reporter assays confirmed that HOXD9 is directly associated with the P105 promoter. Collectively, our results reveal that HOXD9 drives the HPV18 early promoter activity to promote proliferation and immortalization of the CC cells.

Metabolic Effects of Clozapine Administration Based on Sex Differences and the Relationships Between Dosage and Prolactin Levels: An Observational Study.

OBJECTIVE: Clozapine is the second-generation antipsychotic that induces the largest metabolic disorders. However, evidence is limited to the liabilities based on sex differences. This study aimed to investigate the effects of clozapine treatment on metabolic and neuroendocrine parameters, and the relationships between prescribed clozapine dosage and prolactin levels that may be associated with plasma clozapine concentrations, in 24 female and 24 male Japanese schizophrenia inpatients switched to clozapine. METHODS: Within female and male subjects, sequential changes in 7 items of metabolic parameters, including anthropometric measurements, fasting serum lipid components and glucose levels, and estimated insulin resistance at 2 months were evaluated and analyzed against clozapine dosages and prolactin levels at 2 months. RESULTS: Triglyceride levels, triglyceride to high-density lipoprotein ratios reflecting insulin resistance and glucose levels increased in female and male subjects. High-density lipoprotein cholesterol levels decreased in female and male subjects. High-density lipoprotein cholesterol levels were negatively correlated with prolactin levels in female subjects, and glucose levels were positively correlated with prolactin levels in male subjects, although clozapine doses showed no such correlations. CONCLUSIONS: Clozapine administration developed sex-neutral metabolic disorders in the study subjects. Higher prolactin levels seemed to increase the risk of dyslipidemia and hyperglycemia with sex differences, which suggested that serum prolactin levels other than clozapine doses might be useful to predict sex-specific metabolic disorders. Further prospective studies, combining measurement of metabolic hormones and plasma concentrations of clozapine and its metabolites, will help to confirm our findings.

Development of a real-time neutron beam detector for boron neutron capture therapy using a thin silicon sensor.

We have developed a new real-time neutron detector, which is able to measure a direct neutron beam of boron neutron capture therapy. The detector consists of both a 40-µm-thick pn diode and around 0.09-µm-thick LiF neutron converter. Experimental results indicate that this neutron detector can measure neutron flux up to 1 × 109 (cm-2 s-1), separately from gamma rays around 500 mGy/h. The measured depth distribution of neutron flux in an acrylic block is in agreement with the activation results of gold.

Distribution of scatter radiation by C-arm cone-beam computed tomography in angiographic suite: measurement of doses and effectiveness of protection devices.

Distribution of radiation by C-arm cone-beam computed tomography (CBCT) in the angiographic suite and effectiveness of protection devices were assessed. CBCT image of a human phantom was obtained by a rotation of 220 degrees during 8 seconds of exposure. One hundred and twelve dosimeters were placed at different positions around the beam entry site, and color maps of dose distributions were drawn for horizontal and vertical planes. The measurements showed the highest radiation dose over 600 µGy by a single CBCT image acquisition at a distance of 60 cm from the beam entry site and a height of 90 cm from the floor. The color maps demonstrated the dose distribution to be more intense at the bilateral directions of the phantom. With the use of a ceiling-mounted transparent lead-acryl screen and a table-suspended lead curtain, the doses were reduced by 45-92 % at a direction of 210 degrees and a distance of 120 cm.

A Rare Case of Extremely Severe Heterotopic Ossification after Primary Total Hip Arthroplasty due to Persistent Mild Periprosthetic Joint Infection.

Periprosthetic joint infection (PJI) caused by coagulase-negative staphylococci (CNS) can be a mild, persisting infection. Although heterotopic ossification (HO) is common following total hip arthroplasty (THA), the etiology of severe HO remains unclear. Herein, we describe a rare case of extremely severe HO after a PJI associated with a Staphylococcus caprae infection in a 78-year-old male patient. The patient had poorly controlled diabetes mellitus with no diabetic complications. The patient had no previous history of hip surgery, hip injury, or systemic bacterial infection. Immediately after the initial THA, he developed intermittent low-grade fever (37°C), which persisted for 3 months; consequently, he also reported mild hip pain during walking. He experienced a gradual decrease in hip range of motion within 5 years after the surgery, with progressive gait impairment. Two revision surgeries were required for the successful treatment of this difficult case. The patient's hip function improved, and the PJI was controlled following the second revision surgery. Based on the clinical course, CNS-caused PJI may lead to severe HO. This possibility warrants verification from an accumulated number of cases.

Implantable cardiac pacemaker failure by cumulative dose effects of flattening filter free beams.

Cumulative dose effects, which are one of the main causes of errors that occur when an implantable cardiac pacemaker (ICP) is irradiated with ionizing radiation, induce permanent failure in ICPs. Although flattening filter free (FFF) beams, which are often used in stereotactic radiotherapy, are known to have different characteristics from conventional (with flattening filter [WFF]) beams, the cumulative dose effects on ICPs with FFF beams have been under-investigated. This study investigates ICP failure induced by cumulative dose effects of FFF beams. When the ICP placed in the center of the irradiation field was irradiated with 10 MV-FFF at 24 Gy/min, the cumulative dose at which failure occurred was evaluated on the basis of the failure criteria associated with high cumulative dose as described in the American Association of Physicists in Medicine Task Group 203. The ICP failures such as a mild battery depletion at a cumulative dose of 10 Gy, pacing-output voltage change >25% at a cumulative dose of 122 Gy, and the loss of telemetry capability at cumulative dose 134 Gy were induced by cumulative dose effects. The cumulative doses by which the cumulative dose effects of FFF beams induced ICP failure were not very different from those reported in previous studies with WFF beams. Therefore, radiotherapy with FFF beams (and WFF beams) for patients with ICP requires appropriate management for minimizing the cumulative dose effects.

Testicular inducing steroidogenic cells trigger sex change in groupers.

Vertebrates usually exhibit gonochorism, whereby their sex is fixed throughout their lifetime. However, approximately 500 species (~ 2%) of extant teleost fishes change sex during their lifetime. Although phylogenetic and evolutionary ecological studies have recently revealed that the extant sequential hermaphroditism in teleost fish is derived from gonochorism, the evolution of this transsexual ability remains unclear. We revealed in a previous study that the tunica of the ovaries of several protogynous hermaphrodite groupers contain functional androgen-producing cells, which were previously unknown structures in the ovaries of gonochoristic fishes. Additionally, we demonstrated that these androgen-producing cells play critical roles in initiating female-to-male sex change in several grouper species. In the present study, we widened the investigation to include 7 genera and 18 species of groupers and revealed that representatives from most major clades of extant groupers commonly contain these androgen-producing cells, termed testicular-inducing steroidogenic (TIS) cells. Our findings suggest that groupers acquired TIS cells in the tunica of the gonads for successful sex change during their evolution. Thus, TIS cells trigger the evolution of sex change in groupers.