Usefulness of Computed Tomography for Evaluating the Effects of Bronchial Thermoplasty in Japanese Patients with Severe Asthma.

Background: Bronchial thermoplasty (BT) improves clinical outcomes and quality of life for patients with severe asthma and has shown sustained reductions in airway narrowing and air trapping in previous CT studies. However, there is a lack of a comprehensive analysis, including CT evaluation, of clinical outcomes in Japanese patients who have undergone BT for severe asthma. This study aimed to evaluate the impact of BT in Japanese asthma patients, with a focus on the CT metric "WA at Pi10" to assess airway disease. Methods: Twelve patients with severe persistent asthma who underwent BT were assessed using ACQ6, AQLQ, pulmonary function tests, FeNO measurement, blood sampling, and chest CT before BT and one year after the third procedure for the upper lobes. Results: The median age of the patient was 62.0 years, 7/12 (58.3%) were male, 4/12 (33.3%) used regular oral corticosteroids, and 8/12 (66.7%) received biologics. Median FEV1% was 73.6%, and median peripheral eosinophil count was 163.8/µL. After one year of BT, ACQ6 scores improved from 2.4 to 0.8 points (p = 0.007), and AQLQ scores improved from 4.3 to 5.8 points (p < 0.001). Significant improvements were also observed in asthma exacerbations, unscheduled visits due to exacerbations, FeNO, and √WA at Pi10 (p < 0.05). The baseline mucus score on the CT findings was negatively correlated with FEV1 (r = -0.688, p = 0.013) and with the maximum mid-expiratory flow rate (r = -0.631, p = 0.028), and positively correlated with the peripheral blood eosinophil count (r = -0.719, p = 0.008). Changes in √WA at Pi10 after one year were positively correlated with changes in the mucus score (r = 0.742, p = 0.007). Conclusion: This study has limitations, including its single-arm observational design and the small sample size. However, BT led to a symptomatic improvement in patients with severe asthma. The validated "√WA at Pi10" metric on CT effectively evaluated the therapeutic response in Japanese asthma patients after BT.

Lack of Physician-Dentist Collaboration in Aspiration Pneumonia Prevention.

This opinion paper addresses the challenges and future directions for preventing aspiration pneumonia in Japan's rapidly aging population. It highlights the increasing proportion of elderly individuals and the associated rise in health issues like decreased swallowing function, a risk factor for aspiration pneumonia. The paper emphasizes the effectiveness of dentist-provided oral care in preventing this condition but notes the lack of collaboration between dentists and physicians in Japan's clinical practice. Key challenges identified include the scarcity of full-time hospital dentists, insufficient communication between physicians and dentists, limited patient understanding and motivation regarding oral care, and a lack of training in geriatric dentistry. The paper advocates for enhanced awareness among healthcare professionals and patients, increased hospital dentists, and improved collaboration mechanisms, particularly in light of recent positive changes in insurance reimbursement policies for elderly oral care.

Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB8-C1 and NCC-GCTB9-C1.

Giant cell tumor of bone (GCTB) is a rare osteolytic bone tumor consisting of mononuclear stromal cells, macrophages, and osteoclast-like giant cells. Although GCTB predominantly exhibits benign behavior, the tumor carries a significant risk of high local recurrence. Furthermore, GCTB can occasionally undergo malignant transformation and distal metastasis, making it potentially fatal. The standard treatment is complete surgical resection; nonetheless, an optimal treatment strategy for advanced GCTB remains unestablished, necessitating expanded preclinical research to identify appropriate therapeutic options. However, only one GCTB cell line is publicly available from a cell bank for research use worldwide. The present study reports the establishment of two novel cell lines, NCC-GCTB8-C1 and NCC-GCTB9-C1, derived from the primary tumor tissues of two patients with GCTB. Both cell lines maintained the hallmark mutation in the H3-3A gene, which is associated with tumor formation and development in GCTB. Characterization of these cell lines revealed their steady growth, spheroid-formation capability, and invasive traits. Potential therapeutic agents were identified via extensive drug screening of the two cell lines and seven previously established GCTB cell lines. Among the 214 antitumor agents tested, romidepsin, a histone deacetylase inhibitor, and mitoxantrone, a topoisomerase inhibitor, were identified as potential therapeutic agents against GCTB. Conclusively, the establishment of NCC-GCTB8-C1 and NCC-GCTB9-C1 provides novel and crucial resources that are expected to advance GCTB research and potentially revolutionize treatment strategies.

Clinical practice guidelines for molecular tumor marker, 2nd edition review part 2.

In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition.

Establishment and characterization of NCC-DFSP5-C1: a novel patient-derived dermatofibrosarcoma protuberans cell line.

Dermatofibrosarcoma protuberans (DFSP) is the most prevalent dermal sarcoma, characterized by the presence of the fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor beta chain (PDGFB) gene. Although PDGF receptor inhibitor imatinib mesylate was approved for the treating patients with unresectable or metastatic DFSP, disease progression was shown in 9.2% of the patients. Therefore, developing novel therapeutic strategies is crucial for improving the prognosis of DFSP. Patient-derived cell lines play a vital role in preclinical studies; however, only a limited number of DFSP cell lines are currently available in public cell banks. Here, we successfully established a novel DFSP cell line (NCC-DFSP5-C1) using surgically resected tumor tissue from a patient with DFSP. NCC-DFSP5-C1 cells were confirmed to carry the COL1A1-PDGFB translocation and maintain the same mutation as the original tumor tissue. They exhibited consistent growth, formed spheroids, and were invasive. By screening a drug library using NCC-DFSP5-C1 and four previously established DFSP cell lines, we identified anti-cancer drugs that inhibit DFSP cell proliferation. Our observations suggest that the NCC-DFSP5-C1 cell line holds promise as a valuable tool for conducting fundamental and preclinical studies for DFSP.

The prevalence of obstructive sleep apnea in Japanese asthma patients.

BACKGROUND: Obstructive sleep apnea (OSA) occurs more commonly in asthma patients than in the general population because these conditions share some comorbidities. In Japan, the prevalence of OSA in the general population is reported to be approximately 20%; however, few reports have described the prevalence of OSA in asthma patients. Furthermore, the characteristics of Japanese patients with OSA and asthma are not clear. METHODS: Adult asthma patients were recruited from the outpatient departments of our institution between August 31, 2017, and March 31, 2019. In all included patients, the presence and severity of OSA were evaluated by the Epworth Sleepiness Scale (ESS) and a home sleep test (HST) using portable polysomnography (PSG). The rate of coexisting OSA in asthma patients and the characteristics of those patients according to the severity of OSA were investigated. RESULTS: Fifty-three patients were included. OSA was detected in 36 (67.9%) patients (mild, n = 15; moderate, n = 14; and severe, n = 7). Patients with OSA had significantly higher body mass index, Brinkman index, apnea-hypopnea index (AHI), and 3% oxygen desaturation index (ODI) values in comparison to those without OSA, while the percentage of the predicted value of forced vital capacity (%FVC) and lowest SpO2 levels were significantly lower. As the severity of OSA increased, age, brain natriuretic peptide level, AHI, and 3%ODI increased, and in contrast, FVC, %FVC, forced expiratory volume in one second (FEV1), percentage of the predicted value of FEV1 (%FEV1), Epworth Sleepiness Scale (ESS), 3%ODI, and lowest SpO2 levels decreased. In particular, the fact that the ESS value was inversely correlated with the severity of OSA in our patients was different from the general characteristics of OSA. Moreover, the AHI value was negatively correlated with FVC, %FVC, FEV1, and %FEV1. BMI was the only independent factor for the presence of OSA, and for asthma severity (FEV1, % of predicted), there was a weak correlation with smoking history. CONCLUSIONS: This is the first report to investigate the prevalence of OSA in Japanese asthma patients, using an HST. This study suggests that an HST should be performed in addition to the sleep interview for asthma patients with refractory disease, a low pulmonary function, advanced age, and high BMI because the more severe the OSA, the lower the ESS value may be.

Prognostic factors of poor outcomes in pneumonia in older adults: aspiration or frailty?

PURPOSE: Little is known about the long-term and functional prognoses of older adults with pneumonia, which complicates their management. There is a common belief that aspiration is a poor prognostic factor; however, the diagnosis of aspiration pneumonia (AP) lacks consensus criteria and is mainly based on clinical characteristics typical of the frailty syndrome. Therefore, the poor prognosis of AP may also be a result of frailty rather than aspiration. This study investigated the impact of AP and other prognostic factors in older patients with pneumonia. METHODS: We performed a retrospective cohort study of patients aged 75 years and older, admitted with pneumonia in 2021. We divided patients according to their initial diagnosis (AP or non-AP), compared outcomes using Kaplan-Meier curves, and used logistic regression to identify independent prognostic factors. RESULTS: 803 patients were included, with a median age of 84 years and 52.7% were male. 17.3% were initially diagnosed with AP. Mortality was significantly higher in those diagnosed with AP than non-AP during admission (27.6% vs 19.0%, p = 0.024) and at 1 year (64.2% vs 53.1%, p = 0.018), with survival analysis showing a median survival time of 62 days and 274 days in AP and non-AP, respectively (χ2 = 9.2, p = 0.002). However, the initial diagnosis of AP was not an independent risk factor for poor prognosis in multivariable analysis. Old age, frailty and cardio-respiratory comorbidities were the main factors associated with death. CONCLUSION: The greater mortality in AP may be a result of increased frailty rather than the diagnosis of aspiration itself. This supports our proposal for a paradigm shift from making predictions based on the potentially futile labelling of AP or non-AP, to considering frailty and overall condition of the patient.

The predictive value of anticholinergic drug exposure and the outcome of pneumonia: a Danish database study.

INTRODUCTION: Older adults are susceptible to anticholinergic effects. Dysphagia and pneumonia are associated with anticholinergic usage, though a definitive causative relationship has not been established. There is no effective way to predict the prognosis of older adults with pneumonia; therefore, this study investigates the predictive value of anticholinergic burden. METHODS: Patients aged 65 years and above admitted for community-acquired pneumonia from 2011 to 2018 in Denmark were included through Danish registries. We calculated anticholinergic drug exposure using the CRIDECO Anticholinergic Load Scale (CALS). The primary outcome was in-hospital mortality, and other outcomes included intensive care unit admission, ventilator usage, length of stay, 30-day/90-day/1-year mortality, institutionalisation, home care utilisation and readmission. RESULTS: 186,735 patients were included in the in-hospital outcome analyses, 165,181 in the readmission analysis, 150,791 in the institutionalisation analysis, and 95,197 and 73,461 patients in the home care analysis at follow-up. Higher CALS score was associated with higher in-hospital mortality, with a mean risk increasing from 9.9% (CALS 0) to 16.4% (CALS >10), though the risk plateaued above a CALS score of 8. A higher CALS score was also associated with greater mortality after discharge, more home health care, more institutionalizations and higher readmission rates. CONCLUSIONS: High anticholinergic burden levels were associated with poor patient outcomes including short-/long-term mortality, dependence and readmission. It may be useful to calculate the CALS score on admission of older patients with pneumonia to predict their prognosis. This also highlights the importance of avoiding the use of drugs with a high anticholinergic burden in older patients.

Modified medication use in dysphagia: the effect of thickener on drug bioavailability-a systematic review.

INTRODUCTION: Dysphagia is associated with long-term conditions including strokes, dementia, Parkinson's disease and frailty. Dysphagia affects 30-40% of the population aged over 65 years-old. Adults with dysphagia often experience long-term conditions requiring multiple medications (often > 5) to manage these. The thickening of liquids is a common compensatory strategy in dysphagia management. Studies suggest that immersion in thickened liquids affects medicines' solubility in vitro. Clinicians and pharmacists are unaware of the pharmacokinetic/therapeutic effects of thickened liquids on oral medicines. We conducted a systematic review of existing literature on thickeners' effects on drug bioavailability. METHODOLOGY: We performed a literature search of MEDLINE & EMBASE. Search terms included: dysphagia/thickened diet (EMBASE only)/ bioavailability or absorption of medicines or pharmacokinetics; excluded: NG feeds/animal studies. STUDIES INCLUDED: all genders, countries, > 18 years, community and hospital settings. PRISMA guidance was followed. RESULTS: Five hundred seventy results were found, and 23 articles identified following the reference list review. Following an abstract and full-text review, 18 were included. Most articles evaluated thickeners on dissolution profiles in-vitro, with a few investigating in-vivo. Most studies were single-centre prospective studies identifying that thickeners generally affect dissolution rates of medications. Few studies assessed bioavailability or used clinical outcomes. CONCLUSION: Dysphagia and polypharmacy are common in older adults, but little is known about the effects of altering liquid viscosity on the therapeutic effect of most medications. Further larger-scale studies are required to evaluate the therapeutic impact of thickener, on a bigger range of medications, factoring in other variables such as type of thickener, viscosity of thickener and duration of immersion.

Establishment and characterization of NCC-LMS3-C1: a novel patient-derived cell line of leiomyosarcoma.

Leiomyosarcoma (LMS) is an aggressive mesenchymal malignancy, which originates from the smooth muscle cells or from the precursor mesenchymal stem cells that potentially differentiate into smooth muscle cells. LMS is one of the most common sarcomas. LMS has genomic instability, reflecting complex and unbalanced karyotypes, and the cytogenetic and molecular changes in LMS are not consistent. The standard treatment of the primary LMS is complete resection, and the metastasis is often observed even after curative surgery. Patient-derived cancer models are a key bioresource to develop a novel therapy, and we aimed to establish and characterize a novel cell line for LMS. We established a cell line from tumor tissues of the patient with LMS and named it NCC-LMS3-C1. We maintained NCC-LMS3-C1 cells for 12 months and passed them more than 30 times. Genome-wide copy number analysis demonstrated that NCC-LMS3-C1 cells harbored genetic abnormalities. NCC-LMS3-C1 cells exhibited aggressive phenotypes such as continuous growth, spheroid formation, and invasion in the tissue culture condition, which may reflect the clinical behaviors of LMS. We performed a drug screening using NCC-LMS3-C1 cells and found that four anti-cancer agents, such as bortezomib, dasatinib, mitoxantrone, and romidepsin, had remarkable anti-proliferative effects on NCC-LMS3-C1 cells. We conclude that NCC-LMS3-C1 cells will be a useful resource for the study of LMS.

"Diagnose, Treat, and SUPPORT". Clinical competencies in the management of older adults with aspiration pneumonia: a scoping review.

BACKGROUND: Aspiration pneumonia in older adults is increasingly common, with a high care burden and morbidity. However, clinical competencies in its management have not been developed, and healthcare professionals struggle on how to care for these patients with multimodal treatment needs. Therefore, we conducted a scoping review to investigate what is known about the desired clinical competencies for the management of older adults with aspiration pneumonia, to utilise in clinical practice, education, and future research. METHODS: First, we defined aspiration pneumonia according to a preliminary search. We then searched the literature on MEDLINE and CINAHL, focusing on studies involving patients aged 65 years old and older diagnosed with aspiration pneumonia. All settings were included, with the exception of intensive care units. Publication dates were limited to January 2011 to July 2022 and languages to English and Japanese. The extracted data were used to refine the preliminary competency framework developed by the Japan Aspiration pneumonia inter-Professional team Educational Program (JAPEP) in preparation of this study. RESULTS: Ninety-nine studies were included. Following data extraction from these studies, 3 competencies were renamed, and 3 new competencies were added, to create a list of 12 competencies. These were Diagnosis, Treatment, Swallow Assessment, Underlying condition management, Nutrition, Oral management, Rehabilitation, Multidisciplinary team, Decision making, Prevention, Prognosis, and Palliative care. CONCLUSIONS: Our scoping review identified 12 clinical competencies required in the management of older adults with aspiration pneumonia, outlined in the phrase 'Diagnose, Treat and SUPPORT'. We encourage healthcare professionals to share these competencies as a team to identify areas of unmet need and improve their patient care, with an emphasis on supportive care.

Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells.

Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30-40% are unable to receive the standard treatment due to invasive diseases. Therefore, novel therapies are required for their treatment. Although patient-derived cell lines are important tools for basic and pre-clinical research, PMP cell lines derived from patients with HGMCP-S have never been reported. Thus, we established a novel PMP cell line NCC-PMP2-C1, using surgically resected tumor tissue from a patient with HGMCP-S. NCC-PMP2-C1 cells were maintained for more than five months and passaged 30 times under culture conditions. NCC-PMP2-C1 cells exhibited multiple deletions and somatic mutations, slow growth, histological features, and dissemination of tumor cells in nude mice. Screening for the anti-proliferative effects of anti-cancer drugs on cells revealed that bortezomib, mubritinib, and romidepsin had a significant response against NCC-PMP2-C1 cells. Thus, the NCC-PMP2-C1 cell line is the first PMP cell line harboring signet ring cells and will be a valuable resource for basic and preclinical studies of HGMCP-S.

Factors Associated With Swallowing Function Among Physicians in Their 50s and 60s: A Cross-Sectional Study.

BACKGROUND: Individuals with swallowing dysfunction in their 50s and 60s may be at risk for aspiration pneumonia as they age. The association of background and lifestyle with swallowing dysfunction for those in their 50s and 60s has not been fully studied. This study aimed to clarify the relationship between lifestyle and swallowing function in this group. PATIENTS AND METHODS: We targeted physicians in their 50s and 60s as participants. The repetitive saliva swallowing test (RSST) was used to evaluate swallowing function, and self-reported questionnaires about their lifestyle were administered. The associations between RSST scores and participants' backgrounds and lifestyles were analyzed. RESULTS: This study included 310 participants, who were divided into two groups: 162 in the low RSST group and 148 in the high RSST group. The low RSST group had significantly shorter daily conversation times and a lower incidence of hyperlipidemia than the high RSST group. On multivariate analysis, less than three hours of daily conversation time was independently related to lower RSST scores (adjusted odds ratio: 1.863; 95% confidence interval: 1.167-2.974). CONCLUSIONS: Shorter conversation time may serve as a predictor of impaired swallowing function, potentially increasing the risk of aspiration pneumonia in the future.

Correction: Noguchi et al. Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei. J. Pers. Med. 2022, 12, 258.

There was an error in the original publication [...].

Establishment and characterization of NCC-DFSP4-C1: a novel cell line from a patient with dermatofibrosarcoma protuberans having the fibrosarcomatous transformation.

Dermatofibrosarcoma protuberans (DFSP) is a superficial low-grade sarcoma, genetically characterized by a fusion gene in collagen type I α (COL1A1) gene and platelet-derived growth factor subunit ß (PDGFB). DFSP is locally aggressive and does not typically metastasize. However, DFSP with fibrosarcomatous transformation, which occurs in 7-16% of DFSP cases, demonstrates a poor prognosis than classic DFSP with a higher local recurrence rate and metastatic potential. Although imatinib, a PDGF receptor inhibitor, is a potent therapeutic agent for classic DFSP, it is less effective for DFSP with fibrosarcomatous transformation. The development of definitive chemotherapies for DFSP with fibrosarcomatous transformation is required. Patient-derived tumor cell lines are indispensable tools for preclinical research to discover novel therapeutic agents. However, only seven cell lines were derived from DFSP, out of which only two were established from DFSP with fibrosarcomatous transformation. Hence, in the present study, we established a novel DFSP cell line, NCC-DFSP4-C1, from a surgically resected DFSP tumor specimen with fibrosarcomatous transformation. NCC-DFSP4-C1 harbored an identical COL1A1-PDGFB fusion gene as its donor tumor. NCC-DFSP4-C1 cells retained the morphology of their donor tumor and demonstrated constant proliferation, spheroid formation, and invasion capability in vitro. By screening a drug library, we found that bortezomib and romidepsin demonstrated the strongest suppressive effects on the proliferation of NCC-DFSP4-C1 cells. In conclusion, we report a novel cell line of DFSP with fibrosarcomatous transformation, and demonstrate its utility in the development of novel therapeutic agents for DFSP.

Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is a rare bone tumor with osteolytic features, composed of stromal cells with a monotonous appearance, macrophages, and osteoclast-like giant cells. GCTB is commonly associated with a pathogenic mutation in the H3-3A gene. While complete surgical resection is the standard cure for GCTB, it often results in local recurrence and, rarely, metastasis. Thus, an effective multidisciplinary treatment approach is necessary. Although patient-derived cell lines is an essential tool for investigating novel treatment strategies, there are only four GCTB cell lines available in public cell banks. Therefore, this study aimed to establish novel GCTB cell lines and successfully created NCC-GCTB6-C1 and NCC-GCTB7-C1 cell lines from two patients' surgically removed tumor tissues. These cell lines exhibited H3-3A gene mutations, consistent proliferation, and invasive properties. After characterizing their behaviors, we performed high-throughput screening of 214 anti-cancer drugs for NCC-GCTB6-C1 and NCC-GCTB7-C1 and integrated their screening data with those of NCC-GCTB1-C1, NCC-GCTB2-C1, NCC-GCTB3-C1, NCC-GCTB4-C1, and NCC-GCTB5-C1 that we previously established. We identified histone deacetylase inhibitor romidepsin as a possible treatment for GCTB. These findings suggest that NCC-GCTB6-C1 and NCC-GCTB7-C1 could be valuable tools for preclinical and basic research on GCTB.

Integrating analysis of proteome profile and drug screening identifies therapeutic potential of MET pathway for the treatment of malignant peripheral nerve sheath tumor.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with a poor prognosis that requires novel therapeutic agents. Proteome information is useful for identifying new therapeutic candidates because it directly reflects the biological phenotype. Additionally, in vitro drug screening is an effective tool to identify candidate drugs for common cancers. Hence, we attempted to identify novel therapeutic candidates for MPNST by integrating proteomic analysis and drug screening. METHODS: We performed comprehensive proteomic analysis on 23 MPNST tumor samples using liquid chromatography - tandem mass spectrometry to identify therapeutic targets. We also conducted drug screening of six MPNST cell lines using 214 drugs. RESULTS: Proteomic analysis revealed that the MET and IGF pathways were significantly enriched in the local recurrence/distant metastasis group of MPNST, whereas drug screening revealed that 24 drugs showed remarkable antitumor effects on the MPNST cell lines. By integrating the results of these two approaches, MET inhibitors, crizotinib and foretinib, were identified as novel therapeutic candidates for the treatment of MPNST. CONCLUSIONS: We successfully identified novel therapeutic candidates for the treatment of MPNST, namely crizotinib and foretinib, which target the MET pathway. We hope that these candidate drugs will contribute to the treatment of MPNST.

A systematic scoping review on the evidence behind debriefing practices for the wellbeing/emotional outcomes of healthcare workers.

Introduction: Debriefings give healthcare workers voice through the opportunity to discuss unanticipated or difficult events and recommend changes. The typical goal of routine debriefings has been to improve clinical outcomes by learning through discussion and reflection of events and then transferring that learning into clinical practice. However, little research has investigated the effects of debriefings on the emotional experiences and well-being of healthcare workers. There is some evidence that debriefings are a multi-faceted and cost-effective intervention for minimising negative health outcomes, but their use is inconsistent and they are infrequently adopted with the specific intention of giving healthcare workers a voice. The purpose of this systematic scoping review is therefore to assess the scope of existing evidence on debriefing practices for the well-being and emotional outcomes of healthcare workers. Methods: Following screening, 184 papers were synthesised through keyword mapping and exploratory trend identification. Results: The body of evidence reviewed were clustered geographically, but diverse on many other criteria of interest including the types of evidence produced, debriefing models and practices, and outcomes captured. Discussion: The current review provides a clear map of our existing understanding and highlights the need for more systematic, collaborative and rigorous bodies of evidence to determine the potential of debriefing to support the emotional outcomes of those working within healthcare. Systematic Review Registration: https://osf.io/za6rj.

The Clinical Significance of Anaerobic Coverage in the Antibiotic Treatment of Aspiration Pneumonia: A Systematic Review and Meta-Analysis.

INTRODUCTION: Aspiration pneumonia is increasingly recognised as a common condition. While antibiotics covering anaerobes are thought to be necessary based on old studies reporting anaerobes as causative organisms, recent studies suggest that it may not necessarily benefit prognosis, or even be harmful. Clinical practice should be based on current data reflecting the shift in causative bacteria. The aim of this review was to investigate whether anaerobic coverage is recommended in the treatment of aspiration pneumonia. METHODS: A systematic review and meta-analysis of studies comparing antibiotics with and without anaerobic coverage in the treatment of aspiration pneumonia was performed. The main outcome studied was mortality. Additional outcomes were resolution of pneumonia, development of resistant bacteria, length of stay, recurrence, and adverse effects. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: From an initial 2523 publications, one randomised control trial and two observational studies were selected. The studies did not show a clear benefit of anaerobic coverage. Upon meta-analysis, there was no benefit of anaerobic coverage in improving mortality (Odds ratio 1.23, 95% CI 0.67-2.25). Studies reporting resolution of pneumonia, length of hospital stay, recurrence of pneumonia, and adverse effects showed no benefit of anaerobic coverage. The development of resistant bacteria was not discussed in these studies. CONCLUSION: In the current review, there are insufficient data to assess the necessity of anaerobic coverage in the antibiotic treatment of aspiration pneumonia. Further studies are needed to determine which cases require anaerobic coverage, if any.

Subtype-selective induction of apoptosis in translocation-related sarcoma cells induced by PUMA and BIM upon treatment with pan-PI3K inhibitors.

Translocation-related sarcomas (TRSs) harbor an oncogenic fusion gene generated by chromosome translocation and account for approximately one-third of all sarcomas; however, effective targeted therapies have yet to be established. We previously reported that a pan-phosphatidylinositol 3-kinase (PI3K) inhibitor, ZSTK474, was effective for the treatment of sarcomas in a phase I clinical trial. We also demonstrated the efficacy of ZSTK474 in a preclinical model, particularly in cell lines from synovial sarcoma (SS), Ewing's sarcoma (ES) and alveolar rhabdomyosarcoma (ARMS), all of which harbor chromosomal translocations. ZSTK474 selectively induced apoptosis in all these sarcoma cell lines, although the precise mechanism underlying the induction of apoptosis remained unclear. In the present study, we aimed to determine the antitumor effect of PI3K inhibitors, particularly with regards to the induction of apoptosis, against various TRS subtypes using cell lines and patient-derived cells (PDCs). All of the cell lines derived from SS (six), ES (two) and ARMS (one) underwent apoptosis accompanied by the cleavage of poly-(ADP-ribose) polymerase (PARP) and the loss of mitochondrial membrane potential. We also observed apoptotic progression in PDCs from SS, ES and clear cell sarcoma (CCS). Transcriptional analyses revealed that PI3K inhibitors triggered the induction of PUMA and BIM and the knockdown of these genes by RNA interference efficiently suppressed apoptosis, suggesting their functional involvement in the progression of apoptosis. In contrast, TRS-derived cell lines/PDCs from alveolar soft part sarcoma (ASPS), CIC-DUX4 sarcoma and dermatofibrosarcoma protuberans failed to undergo apoptosis nor induce PUMA and BIM expression, as well as cell lines derived from non-TRSs and carcinomas. Thus, we conclude that PI3K inhibitors induce apoptosis in selective TRSs such as ES and SS via the induction of PUMA and BIM and the subsequent loss of mitochondrial membrane potential. This represents proof of concept for PI3K-targeted therapy, particularly such TRS patients.