Tumor cell-expressed lipolysis-stimulated lipoprotein receptor negatively regulates T-cell function.

Lipolysis-stimulated lipoprotein receptor (LSR) is known as a lipoprotein receptor. LSR is expressed in various solid tumors, including epithelial ovarian, gastric, and colon cancers. High LSR expression is significantly associated with poor prognosis, but its role in cancer has not been fully elucidated. LSR belongs to the Ig protein superfamily, which is conserved in B7 family. Here, we assessed LSR as a novel immune checkpoint molecule. We developed a novel anti-LSR antibody (#27-6 mF-18) that defects antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity. The #27-6 mF-18 cross-reacts with both human and mouse LSR. We found that LSR was expressed on 4T1 murine breast cancer cell line. The #27-6 mF-18 exhibited antitumor effects against the 4T1 syngeneic tumor model, a poor immunogenic model refractory to treatment with anti-PD-1 or anti-CTLA-4 antibodies. Compared with control antibody-treated mice, mice treated with #27-6 mF-18 showed significantly increased numbers of CD8+ T cells and a ratio of activated CD8+ T cells infiltrated in the tumor tissue. This antitumor effect was abrogated by CD8+ T-cell depletion through anti-CD8 antibody treatment, indicating that LSR negatively regulates tumor immunity by repressing CD8+ T cells. These findings show that LSR negatively regulates T-cell immune activity. LSR targeting could provide immune checkpoint inhibitors for cancer immunotherapy.

Even though active recommendation for HPV vaccination has restarted, Japan's rates have not recovered.

Japan has a particularly critical situation surrounding its collapsed HPV vaccination program for preventing HPV-caused cervical cancers, a problem exacerbated by the lack of a national immunization database. We have determined the year-to-year HPV vaccination uptake by Japanese females and analyzed by birth fiscal year (FY) the monthly number of people receiving initial HPV vaccination. Our analysis covers the period from the start of public subsidies in 2010 to September 2023, using data provided by local governments. We calculated the cumulative number of monthly immunizations for those unimmunized as of April (the beginning of each vaccination year). The monthly number of initial HPV vaccinations was highest in August for every FY from FY 2010 to FY 2023; a second vaccination peak tended to occur in March when the vaccination year ended. The highest number of August vaccinations occurred in FY 2011, followed (in order) by 2012, 2021, 2022, 2023, and 2013. In Japan's ongoing catch-up vaccination program for young women, the monthly number of vaccinations increased in August 2022 but then slowed the following year. After FY 2021, the cumulative vaccination coverage of subjects unvaccinated at the beginning of the vaccination year but subsequently covered by routine immunizations was slightly improved. FY 2021 was when the governmental recommendations for HPV vaccination were resumed. More recent vaccination rates are considerably lower than those in FY 2011-2012 when vaccinations were first fully endorsed. Paralyzing HPV vaccination hesitancy, which began in FY 2013, will linger in Japan in FY 2024.

Effectiveness of catch-up and routine program of the 9-valent vaccine on cervical cancer risk reduction in Japan.

In 2013, the national human papillomavirus (HPV) immunization program began. However, in June 2013, Japan's Ministry of Health, Labor and Welfare (MHLW) announced a "temporary" suspension of its recommendation for the human papillomavirus vaccine. Finally, in November 2021, the MHLW ended its suspension of the recommendation of the HPV vaccine. To address the 9-year gap in HPV vaccinations the suspension had caused, the MHLW conducted a program of catch-up vaccinations from April 2022 to March 2025. Finally, in April 2023, the 9-valent HPV vaccine was approved for both the routine and catch-up vaccination programs in Japan. In this study, we investigated the potential effects of the introduction of the 9-valent vaccine on the increased risk of cervical cancer in females born after fiscal year (FY) 2000. We estimated the lifetime relative risk of cervical cancer incidence and death using the improved routine and catch-up vaccination rates after the recent resumption of the governmental recommendation for women and girls to have the HPV vaccination. These relative risks were calculated using a lifetime risk of 1.000 for cervical cancer incidence and death for females born in FY 1993. We predicted that even if a 90% vaccination rate were to be achieved by FY 2024 with the 9-valent vaccine among women born between FY 2000 and FY 2005, the risk would remain higher than for the vaccination generation. Therefore, for women born between FY 2000 and FY 2005, it will be necessary to significantly improve the cervical cancer screening rate to compensate for this increased risk.

Transitional dynamics in oncology clinical trials: evaluating the impact of Clinical Trials Act on cooperative groups.

OBJECTIVE: large-scale multicentre clinical trials conducted by cooperative groups have generated a lot of evidence to establish better standard treatments. The Clinical Trials Act was enforced on 1 April 2018, in Japan, and it has remarkably increased the operational burden on investigators, but its long-term impact on cancer cooperative groups is unknown. METHODS: a survey was conducted across the nine major cooperative groups that constitute the Japan Cancer Trials Network to assess the impact of Clinical Trials Act on the number of newly initiated trials from fiscal year (from 1 April to 31 March) 2017 to 2022 and that of ongoing trials on 1 April in each year from 2018 to 2023. RESULTS: the number of newly initiated trials dropped from 38 trials in fiscal year 2017 to 26 trials in fiscal year 2018, surged to 50 trials in fiscal year 2019, but then gradually decreased to 25 trials by fiscal year 2022. Specified clinical trials decreased from 32 trials in fiscal year 2019 to 12 trials in fiscal year 2022. The number of ongoing trials was 220 trials in 2018, peaked at 245 trials in 2020, but then gradually decreased to 219 trials by 2023. The number of specified clinical trials has been in consistent decline. By April 2023, of the 20 ongoing non-specified clinical trials, nine adhered to Clinical Trials Act and 11 followed the Ethical Guidelines for Medical and Health Research Involving Human Subjects. CONCLUSION: the number of multicentre clinical trials in oncology gradually decreased after the Clinical Trials Act's enforcement, which underscores the need for comprehensive amendment of the Clinical Trials Act to streamline the operational process.

Helicovermis profundi gen. nov., sp. nov., a novel mesophilic, asporogenous bacterium within the Clostridia isolated from a deep-sea hydrothermal vent chimney.

A novel mesophilic bacterial strain, designated S502T, was isolated from a deep-sea hydrothermal vent at Suiyo Seamount, Japan. Cells were Gram-positive, asporogenous, motile, and curved rods, measuring 1.6-5.6 µm in length. The strain was an obligate anaerobe that grew fermentatively on complex substrates such as yeast extract and Bacto peptone. Elemental sulfur stimulated the growth of the strain, and was reduced to hydrogen sulfide. The strain grew within a temperature range of 10-23 °C (optimum at 20 °C), pH range of 4.8-8.3 (optimum at 7.4), and a NaCl concentration range of 1.0-4.0% (w/v) (optimum at 3.0%, w/v). Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the isolate was a member of the class Clostridia, with Fusibacter paucivorans strain SEBR 4211T (91.1% sequence identity) being its closest relative. The total size of the genome of the strain was 3.12 Mbp, and a G + C content was 28.2 mol%. The highest values for average nucleotide identity (ANI), average amino acid identity (AAI), and digital DNA-DNA hybridization (dDDH) value of strain S502T with relatives were 67.5% (with Marinisporobacter balticus strain 59.4MT), 51.5% (with M. balticus strain 59.4MT), and 40.9% (with Alkaliphilus serpentinus strain LacTT), respectively. Based on a combination of phylogenetic, genomic, and phenotypic characteristics, we propose strain S502T to represent a novel genus and species, Helicovermis profundi gen. nov., sp. nov., with the type strain S502T (= DSM 112048T = JCM 39167T).

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Disparities among Japanese municipalities in recommendations for routine and catch-up HPV vaccinations.

In November 2021, the government of Japan announced a reversal of its decision in 2013 to suspend the previous proactive recommendation for HPV vaccination. However, the program for young girls to receive routine and catch-up vaccinations has not necessarily developed as expected. We conducted a nationwide questionnaire survey by mail in September 2022. The survey was mailed to 133 municipalities consisting of all cities/wards of the Tokyo and Osaka Prefectures and all other prefectural capital cities. Responses were received from 82 municipalities (62.7%). Notification of routine HPV vaccinations had already been sent to 76 (92.7%) of the municipalities; 70 (85.4%) had been encouraged to promote catch-up vaccinations. The questionnaire forms for registration and pre-vaccination screening for routine immunization had been sent to 74.1% (60/81) of the municipalities and 68.8% (55/80) for catch-up immunizations. For catch-up vaccination, only 54 municipalities (65.9%) had detailed vaccination records for those eligible. In total, 10 municipalities (12.2%) had virtually no vaccination records because these had already been discarded. In addition, 61 municipalities (74.4%) had notified only women and girls eligible for a catch-up vaccination based on their vaccination record, whereas 25.6% (21/82) of the municipalities reported that they had sent, or would send, the notification to all women and girls within the targeted grades, including those who had already been vaccinated with three injections. The survey revealed disparities among the municipalities in their HPV vaccine notification processes. Future research on monitoring HPV vaccination rates and incidence rates of cervical cancer and precancerous lesions in each municipality will be desirable.

Spontaneous recurrence of a summer-like diel rhythm in the body temperature of the Syrian hamster after hibernation.

Mammalian hibernation is a survival strategy characterized by metabolic suppression and drastically lowering body temperature (Tb), used during harsh seasons with food shortages and cold. The Syrian hamster commences hibernation in response to a short photoperiod and cold but spontaneously concludes hibernation after several months without environmental cues. Little is known about the changes in diel rhythms during hibernation. Using long-term and high-resolution Tb data, we analysed the diel Tb rhythm time-course changes in Syrian hamsters raised under summer-like conditions (long photoperiod (LP) and warm; LP-warm) and transferred to winter-like conditions (short photoperiod (SP) and cold; SP-cold). The diel Tb rhythm was undetectable during the hibernation period (HIBP), reappearing after the HIBP. The phase of this returning rhythm reverted to the LP entrainment phase characteristics despite the ambient SP and then re-entrained to the ambient SP as if the hamsters were transferred from the LP-warm to SP-cold conditions. The diel Tb rhythm reverted from the SP- to LP-type in a hibernation-dependent manner. Under constant dark and cold conditions, the circadian Tb rhythm recovered without photic stimuli following the HIBP. These findings suggest that hibernation involves a program that anticipates the ambient photoperiod when animals emerge from hibernation.

Ecological Dynamics of Broad- and Narrow-Host-Range Viruses Infecting the Bloom-Forming Toxic Cyanobacterium Microcystis aeruginosa.

Microcystis aeruginosa is predicted to interact and coexist with diverse broad- and narrow-host-range viruses within a bloom; however, little is known about their affects on Microcystis population dynamics. Here, we developed a real-time PCR assay for the quantification of these viruses that have different host ranges. During the sampling period, total Microcystis abundance showed two peaks in May and August with a temporary decrease in June. The Microcystis population is largely divided into three phylotypes based on internal transcribed sequences (ITS; ITS types I to III). ITS I was the dominant phylotype (66% to 88%) except in June. Although the ITS II and III phylotypes were mostly less abundant, these phylotypes temporarily increased to approximately equivalent abundances of the ITS I population in June. During the same sampling period, the abundances of the broad-host-range virus MVGF_NODE331 increased from April to May and from July to October with a temporary decrease in June, in which its dynamics were in proportion to the increase of total Microcystis abundances regardless of changes in host ITS population composition. In contrast, the narrow-host-range viruses MVG_NODE620 and Ma-LMM01 were considerably less abundant than the broad-host-range virus and generally did not fluctuate in the environment. Considering that M. aeruginosa could increase the abundance and sustain the bloom under the prevalence of the broad-host-range virus, host abundant and diverse antiviral mechanisms might contribute to coexistence with its viruses. IMPORTANCE The bloom-forming toxic cyanobacterium Microcystis aeruginosa interacts with diverse broad- and narrow-host-range viruses. However, the dynamics of the Microcystis population (at the intraspecies level) and viruses with different host ranges remain unknown. Our real-time PCR assays unveiled that the broad-host-range virus gradually increased in abundance over the sampling period, in proportion to the increase in total Microcystis abundance regardless of changes in genotypic composition. The narrow-host-range viruses were considerably less abundant than the broad-host-range virus and did not generally fluctuate in the environment. The expansion and maintenance of the Microcystis bloom even under the increased infection by the broad-host-range virus suggested that highly abundant and diverse antiviral mechanisms allowed them to coexist with viruses under selective pressure. This paper expands our knowledge about the ecological dynamics of Microcystis viruses and provides potential insights into their coexistence with their host.

Haliovirga abyssi gen. nov., sp. nov., a mesophilic fermentative bacterium isolated from the Iheya North hydrothermal field, and proposal of Haliovirgaceae fam. nov.

A novel mesophilic, obligately anaerobic, facultatively sulphur-reducing bacterium, designated strain IC12T, was isolated from a deep-sea hydrothermal field in the Mid-Okinawa Trough, Japan. The cells were Gram-negative, motile, short rods with a single polar flagellum. The ranges and optima of the growth temperature, NaCl concentration and pH of strain IC12T were 15-40 °C (optimum, 30-35 °C), 10-60 g l-1 (optimum, 20-30 g l-1) and pH 4.9-6.7 (optimum, pH 5.8), respectively. Yeast extract was utilized as a sole carbon and energy source for fermentative growth. Major fatty acids of strain IC12T were C14 : 0, C16 : 0 and C16 : 1 ω7. Results of phylogenetic analysis based on 16S rRNA gene sequences indicated that strain IC12T was affiliated to the phylum Fusobacteriota and was most closely related to Ilyobacter insuetus VenChi2T (86.5 % sequence similarity). Strain IC12T contained a chromosome of 2.43 Mbp and a large plasmid of 0.30 Mbp. The G+C content of the genomic DNA was 26.4 mol%. The maximum values for average nucleotide identity and in silico DNA-DNA hybridization between strain IC12T and related strains of the phylum Fusobacteriota were 71.4 and 26.4 %, respectively. Phylogenomic, physiological and chemotaxonomic analyses indicate that strain IC12T represents a novel genus and species within the phylum Fusobacteriota, for which the name Haliovirga abyssi gen. nov., sp. nov. is proposed, with strain IC12T (= DSM 112164T=JCM 39166T) as the type strain. We also propose the family Haliovirgaceae fam. nov. to accommodate this novel genus.

Pyrofollis japonicus gen. nov. sp. nov., a novel member of the family Pyrodictiaceae isolated from the Iheya North hydrothermal field.

A novel hyperthermophilic, heterotrophic archaeon, strain YC29T, was isolated from a deep-sea hydrothermal vent in the Mid-Okinawa Trough, Japan. Cells of strain YC29T were non-motile, irregular cocci with diameters of 1.2-3.0 µm. The strain was an obligatory fermentative anaerobe capable of growth on complex proteinaceous substrates. Growth was observed between 85 and 100 °C (optimum 90-95 °C), pH 4.9-6.4 (optimum 5.1), and in the presence of 1.4-4.0% (w/v) NaCl (optimum 3.0%). Inorganic carbon was required as a carbon source. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the isolate was a member of the family Pyrodictiaceae. The genome size was 2.02 Mbp with a G+C content of 49.4%. The maximum values for average nucleotide identity (ANI), average amino acid identity (AAI), and in silico DNA-DNA hybridization (dDDH) value of strain YC29T with relatives were 67.9% (with Pyrodictium abyssi strain AV2T), 61.1% (with Pyrodictium occultum strain PL-19T), and 33.8% (with Pyrolobus fumarii strain 1AT), respectively. Based on the phylogenetic, genomic, and phenotypic characteristics, we propose that strain YC29T represents a novel genus and species, Pyrofollis japonicus gen. nov., sp. (type strain YC29T = DSM 113394T = JCM 39171T).

Successful pediatric liver transplantation case with a positive SARS-CoV-2 test at the time of transplant.

AIM: We report a successful liver transplantation (LT) in a child with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CASE PRESENTATION: A 3-year-old female patient with decompensated cirrhosis due to Alagille syndrome underwent a split LT with a left lateral segment graft. She had a history of SARS-CoV-2 infection 4 months before LT. She was exposed to SARS-CoV-2 after the decision for organ acceptance. We repeatedly confirmed the negative SARS-CoV-2 test by polymerase chain reaction (PCR) before LT. Liver transplantation was carried out in the negative pressure operational theater with full airborne, droplet, and contact precautions as the patient was considered to be within the incubation period of SARS-CoV-2. The SARS-CoV-2 PCR test became positive in the nasopharyngeal swab specimen at the operation. Remdesivir, the antiviral treatment, was held off due to potential hepatotoxicity and no exacerbation of COVID-19. She received tacrolimus and low-dose steroids per protocol. She remained SARS-CoV-2 positive on postoperative days (PODs) 1, 2, and 5. The presence of antibodies for SARS-CoV-2 at LT was confirmed later. On POD 53, she was discharged without any symptomatic infection. CONCLUSION: This case demonstrated that a positive SARS-CoV-2 result was not an absolute contraindication for a life-saving LT. Liver transplantation could be safely performed in a pediatric patient with asymptomatic COVID-19 and S-immunoglobulin G antibodies for SARS-CoV-2.

Perioperative risk factors for neurological impairment in infants with acute liver failure following liver transplantation.

BACKGROUND: Neurological impairment is not rare in infants with acute liver failure (ALF). This study aimed to investigate the perioperative risk factors for neurological impairment following liver transplantation (LT) in infantile ALF. METHODS: Retrospective analysis was performed in infants who were younger than 1 year with ALF who subsequently underwent LT at our hospital between January 2005 and December 2016. Patients were considered to have neurological impairment if the Pediatric Cerebral Performance Category score was between 2 and 5 at the age of 6 years. A comparison between the groups of infants with and without neurological impairment was performed, and factors with p < .10 in the comparison were analyzed using univariate logistic regression analysis for neurological impairment. RESULTS: Twenty-six infants survived until 6 years of age, and 31% (8/26) of them had neurological impairment. Patients with neurological impairment were significantly younger in age at ALF onset, had significantly higher pre-LT bilirubin and prothrombin time/international normalized ratio, and stayed significantly longer in the intensive care unit than those without neurological impairment. Total bilirubin (odds ratio (OR) = 1.12, 95% confidence interval (CI) 1.02-1.22, p = .012), indirect bilirubin (OR = 1.10, 95% CI 1.01-1.20, p = .025), direct bilirubin (OR = 1.22, 95% CI 1.01-1.47, p = .040), and age in month at ALF (OR = 0.76, 95% CI 0.58-0.999, p = .049) showed significant association with neurological impairment. CONCLUSIONS: High pre-LT peak bilirubin value and younger age at ALF onset can be perioperative risk factors for neurological impairment after LT in infantile ALF.

Intentions for catch-up HPV vaccination in Japan: an internet survey.

PURPOSE: In Japan, Japan's Ministry of Health, Labor, and Welfare decided to suspend govermental recommendation for HPV vaccination in FY 2013. The HPV vaccination rate for those born in FY 2000 or thereafter declined dramatically. In 2021, the "suspension of recommendation" ended. The catch-up vaccinations for the unvaccinated have been offered nationwide from FY 2022 to FY 2024. We aimed to quantify the vaccination intentions and characteristics of those young women now eligible for catch-up vaccination.  METHODS: In February of 2022, we conducted an internet survey targeted women who were born in 1997-2004 but who had not yet been HPV vaccinated. RESULTS: We received 1,648 valid responses. 41.6% of the respondents wanted to uptake the catch-up HPV vaccination, 29.7% were undecided, and 28.7% did not want to be vaccinated. The intention to uptake catch-up HPV vaccination was associated with a good history of gynecological visits, intention to receive cervical cancer screening, sexual activity, degree of anxiety about cervical cancer, familiarity with problems associated with cervical cancer, experience with vaccination recommendations, and knowledge about cervical cancer (p < 0.05, respectively). In the vaccinated generation, the proportion of the group that did not want to be vaccinated was significantly higher (p < 0.05). In the vaccine-suspended generation, the proportion of the group that wanted to be vaccinated was significantly higher (p < 0.05). CONCLUSION: Our survey revealed that catch-up vaccination intentions differed depending on the vaccination environment. It is necessary for all organizations involved with HPV vaccination, such as government, medical institutions, and educational institutions, to make recommendations based on an understanding of the characteristics of the "vaccinated generation" and the "vaccine-suspended generation".

A single institution's experience with minimally invasive surgery for ovarian cancer, and a systematic meta-analysis of the literature.

BACKGROUND: This study assesses the feasibility of minimally invasive surgery (MIS) for well-selected epithelial ovarian cancer (EOC) patients. METHODS: We performed a review of data prospectively collected from a single center from 2017 to 2022. Only patients with histologically confirmed EOC, with a tumor diameter of less than 10 cm, were eligible. We also performed a meta-analysis of similar studies comparing the outcomes of laparoscopy and laparotomy. We used MINORS (Methodological Index for Non-Randomized Studies) to assess the risk of bias and calculated the odds ratio or mean difference. RESULTS: Eighteen patients were included; 13 in re-staging group, four in PDS group, and one in IDS group. All achieved complete cytoreduction. One case was converted to laparotomy. The median number of removed pelvic lymph nodes was 25 (range 16-34), and 32 (range 19-44) for para-aortic nodes. There were two (15.4%) intraoperative urinary tract injuries. The median follow-up was 35 months (range 1-53). Recurrence was observed in one case (7.7%). Thirteen articles for early-stage ovarian cancer were included in our meta-analysis. Analysis of the pooled results found that MIS had a higher frequency of spillage (OR, 2.15; 95% CI 1.27-3.64). No differences were observed in recurrence, complications, or up-staging. CONCLUSIONS: Our experience supports the possibility of conducting MIS for EOC in well-selected patients. Except for spillage, our meta-analysis findings are consistent with previous reports, the majority of which were also retrospective. Ultimately, randomized clinical trials will be needed to authenticate the safety.

Effect of improvement measures in reducing interruptions in a Japanese hospital pharmacy using a synthetic approach based on resilience engineering and systems thinking.

BACKGROUND: Workflow interruptions in pharmacies contribute to dispensing errors, a high-priority issue in patient safety, but have rarely been studied from a systemic perspective partly because of the limitations of the conventional reductionistic approach. This study aims to identify a mechanism for the occurrence of interruptions in a hospital pharmacy and find interventional points using a synthetic approach based on resilience engineering and systems thinking, and assess implemented measures for reducing them. METHODS: At a Japanese university hospital, we gathered information about performance adjustments of pharmacists in the inpatient medication dispensing unit for oral and topical medicines (IMDU-OT) and nurses in the inpatient wards (IPWs) in the medication dispensing and delivery process. Data about the workload and workforce of pharmacists were collected from hospital information systems. Telephone inquiries and counter services in the IMDU-OT, the primary sources of interruptions to pharmacists' work, were documented. The feedback structure between the IMDU-OT and the IPWs was analyzed using a causal loop diagram to identify interventional points. The numbers of telephone calls and counter services were measured cross-sectionally before (February 2017) and four months after implementing measures (July 2020). RESULTS: This study found that interruptions are a systemic problem emerging from the adaptive behavior of pharmacists and nurses to their work constraints, such as short staffing of pharmacists, which limited the frequency of medication deliveries to IPWs, and lack of information about the medication dispensing status for nurses. Measures for mitigating cross-system performance adjustments-a medication dispensing tracking system for nurses, request-based extra medication delivery, and pass boxes for earlier pick-up of medicines-were introduced. Following their implementation, the daily median number of telephone calls and counter services was significantly reduced (43 to 18 and 55 to 15, respectively), resulting in a 60% reduction in the total number of interruptions. CONCLUSION: This study found interruptions in the hospital pharmacy as a systemic problem that can be reduced by mitigating difficulties being compensated for by clinicians' cross-system performance adjustments. Our findings suggest that a synthetic approach can be effective for solving complex problems and have implications for methodological guidance for Safety-II in practice.

Nurses' perception of pediatric pain and pain assessment in the Japanese PICU.

BACKGROUND: Nurses play an essential role in pain management in the pediatric intensive care unit (PICU). However, their perceptions regarding pediatric pain and current practice of pain assessment in Japanese PICUs remain unknown. METHODS: In January 2021, we conducted a multicenter, cross-sectional survey across 35 PICUs in Japan. A structured questionnaire which focused on nurses' perceptions of pediatric pain and pain assessment was developed, pilot-tested, and revised. Twenty copies of the questionnaire were sent to each institution and were distributed to the nursing staff. RESULTS: A total of 356 nurses from 22 institutions responded. Median age of the respondents was 33 years and 84.6% were female. Median length of nursing experience and PICU experience were 10 and 4 years, respectively. Use of pain scales for assessing pain in children who can self-report pain, preverbal children, and children unable to self-report pain due to cognitive impairment were 90.7%, 55.9%, and 50.0%, respectively. Nurses' satisfaction regarding pain management in their PICU was 31.9% and their confidence in pain assessment and management were 32.6% and 44.9%, respectively. Lack of knowledge (95.8%), difficulty assessing pain in children (95.2%), and delay in physician's action (91.8%) were the most perceived barriers to optimal pain management. CONCLUSIONS: The use of pain scales is insufficient and nurses' satisfaction proved to be extremely low in the Japanese PICUs. Substantial effort is required to enhance the level of current pain management and improve outcomes.

Impact of the COVID-19 pandemic on surgery for benign diseases in gynecology: A nationwide survey by the Japan Society of Obstetrics and Gynecology.

AIM: This study aimed to clarify the impact of coronavirus disease 2019 on gynecology practice in Japan, in particular, on surgeries for benign gynecological diseases. METHODS: An online questionnaire was distributed to 966 facilities in Japan, including core facilities, facilities participating in perinatal and gynecologic oncology registries, and facilities certified for training by the Japanese Society of Obstetrics and Gynecology Endoscopy. The number of surgeries performed was compared between 2019 and 2020, when the novel coronavirus disease was prevalent. RESULTS: Five hundred and eighty (58.2%) facilities responded. The total number of surgeries decreased from 129 648 in 2019 to 118 565 in 2020, by 8.5%, for all surgical procedures. However, there was a clear increase in the number of robotic surgeries performed in 2020 compared to that in 2019 for all populations. The number of total hysterectomies decreased markedly from 15 385 in 2019 to 12 531 in 2020, a fall of 10.1%. CONCLUSIONS: The number of surgeries for benign gynecological diseases decreased by 8.5% in 2020 compared to that in 2019. This value is among the lowest in the world.

Clinical Utility and Patient Distribution of Brief Resolved Unexplained Event Classification for Apparent Life-Threatening Events.

OBJECTIVES: In 2016, brief resolved unexplained events (BRUEs) were proposed as alternative concepts to apparent life-threatening event (ALTE). The clinical utility of managing ALTE cases according to the BRUE classification is controversial. To verify the clinical utility of the BRUE criteria, we evaluated the proportion of ALTE patients who met and those who did not meet the BRUE criteria and assessed the diagnoses and outcomes of each group. METHODS: We retrospectively investigated patients with ALTE younger than 12 months who visited the emergency department of the National Center for Child Health and Development from April 2008 to March 2020. The patients were classified into the higher-risk and lower-risk BRUE groups; however, those who did not meet the BRUE criteria were classified into the ALTE-not-BRUE group. We evaluated the diagnoses and outcomes of each group. Adverse outcomes included death, recurrence, aspiration, choking, trauma, infection, convulsions, heart disease, metabolic disease, allergies, and others. RESULTS: Over the period of 12 years, a total of 192 patients were included, among which 140 patients (71%) were classified into the ALTE-not-BRUE group, 43 (22%) into the higher-risk BRUE group, and 9 (5%) into the lower-risk BRUE group. Adverse outcomes occurred in 27 patients in the ALTE-not-BRUE group and 10 patients in the higher-risk BRUE group. No adverse outcome occurred in the lower-risk BRUE group. CONCLUSIONS: Many of the patients with ALTE were classified into the ALTE-not-BRUE group, suggesting that replacing ALTE with BRUE is difficult. Although patients classified as lower-risk BRUE showed no adverse outcomes, there were only a few of them. In the pediatric emergency medicine setting, the BRUE risk classification may be beneficial for certain patients.