Beyond Legal Boundaries: Public and Clinician Perspectives on Treatment Withdrawal in Infants With Poor Neurological Prognosis.

BACKGROUND: Despite medical advancements in neonatal survival rates, many children have poor neurological outcomes. Because the law in Korea restricts the withdrawal of life-sustaining treatment to only cases of imminent death, treatment discontinuation may not be an option, even in patients with poor neurological prognosis. This study investigated the opinions of the general population and clinicians regarding life-sustaining treatment withdrawal in such cases using hypothetical scenarios. METHODS: We conducted a cross-sectional study on the general population and clinicians using a web-based questionnaire. The sample of the general population from an online panel comprised 500 individuals aged 20-69 years selected by quota sampling. The clinician sample comprised 200 clinicians from a tertiary university hospital. We created hypothetical vignettes and questionnaire items to assess attitudes regarding mechanical ventilation withdrawal for an infant at risk of poor neurological prognosis due to birth asphyxia at 2 months and 3 years after the incidence. RESULTS: Overall, 73% of the general population and 74% of clinicians had positive attitudes toward mechanical ventilator withdrawal at 2 months after birth asphyxia. The proportion of positive attitudes toward mechanical ventilator withdrawal was increased in the general population (84%, P < 0.001) and clinicians (80.5%, P = 0.02) at 3 years after birth asphyxia. Religion, spirituality, the presence of a person with a disability in the household, and household income were associated with the attitudes of the general population. In the multivariable logistic regression analysis of the general population, respondents living with a person with a disability or having a disability were more likely to find the withdrawal of the ventilator at 2 months and 3 years after birth asphyxia not permissible. Regarding religion, respondents who identified as Christians were more likely to find the ventilator withdrawal at 2 months after birth asphyxia unacceptable. CONCLUSION: The general population and clinicians shared the perspective that the decision to withdraw life-sustaining treatment in infants with a poor neurological prognosis should be considered before the end of life. A societal discussion about making decisions centered around the best interest of pediatric patients is warranted.

Elucidation of the effects of 2,5-hexandione as a metabolite of n-hexane on cognitive impairment in leptin-knockout mice (C57BL/6-Lepem1Shwl/Korl).

Exposure to n-hexane and its metabolite 2,5-hexandione (HD) is a well-known cause of neurotoxicity, particularly in the peripheral nervous system. To date, few studies have focused on the neurotoxic effects of HD on cognitive impairment. Exposure to HD and diabetes mellitus can exacerbate neurotoxicity. There are links among HD, diabetes mellitus, and cognitive impairment; however, the specific mechanisms underlying them remain unclear. Therefore, we aimed to elucidate the neurotoxic effects of HD on cognitive impairment in ob/ob (C57BL/6-Lepem1Shwl/Korl) mice. We found that HD induced cognitive impairment by altering the expression of genes (FN1, AGT, ACTA2, MYH11, MKI67, MET, CTGF, and CD44), miRNAs (mmu-miR15a-5p, mmu-miR-17-5p, and mmu-miR-29a-3p), transcription factors (transcription factor AP-2 alpha [TFAP2A], serum response factor [Srf], and paired box gene 4 [PAX4]), and signaling pathways (ERK/CERB, PI3K/AKT, GSK-3ß/p-tau/amyloid-ß), as well as by causing neuroinflammation (TREM1/DAP12/NF-κB), oxidative stress, and apoptosis. The prevalent use of n-hexane in various industrial applications (for instance, shoe manufacturing, printing inks, paints, and varnishes) suggests that individuals with elevated body weight and glucose levels and those employed in high-risk workplaces have greater probability of cognitive impairment. Therefore, implementing screening strategies for HD-induced cognitive dysfunction is crucial. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00228-1.

Analysis of factors associated with patients' global impression of change scores in inpatients with peripheral facial palsy: A retrospective study at a Korean Medicine Hospital.

The incidence of peripheral facial palsy is on the rise, with psychological issues influencing quality of life due to visible symptoms. Consequently, patient-reported outcome measures are critical in assessing the disease burden and the treatment efficacy of peripheral facial palsy from patients' perspective. This study examines factors influencing patients' global impression of change (PGIC) scores, a type of patient-reported outcome measure, in hospitalized patients with peripheral facial palsy. This retrospective study analyzed the electronic medical records of 200 patients with peripheral facial palsy who were admitted to the Korean Medicine Hospital, Kyung Hee University Medical Center from May 1, 2022 to April 30, 2023. Impact of demographic, electrophysiological, intervention, and clinical factors on PGIC scores were evaluated. Descriptive statistics showed that the length of hospitalization (P = .020), time from disease onset to hospitalization (P = .022), lacrimal disorders (P = .002), House-Brackmann (HB) grade evaluated at admission (P = .016) and at discharge (P < .001), improvement in HB-grade from admission to discharge (P = .002), and total facial disability index (FDI) score at discharge (P < .001) were significantly associated with PGIC scores. In multivariate logistic regression analysis, HB-grade at admission (OR: 13.89, 95% CI: 2.18-113.60), length of stay (OR: 0.27, 95% CI: 0.07-0.92), time from disease onset to hospitalization (OR: 5.55, 95% CI: 1.36-24. 77), tear-related symptoms (OR: 0.41, 95% CI: 0.17-0.96), total FDI score (OR: 0.45, 95% CI: 0.20-0.98), and greater improvement in HB-grade at discharge compared to admission (OR: 0.08, 95% CI: 0.02-0.31) were significantly associated with PGIC scores. Patients with milder initial disease severity, hospitalization period exceeding 7 days, shorter time from disease onset to hospitalization, improvement of lacrimal symptoms, total FDI score, and HB-grade between admission and discharge experienced more significant subjective improvement in peripheral facial palsy.

Machine learning-based models for advanced fibrosis and cirrhosis diagnosis in chronic hepatitis B patients with hepatic steatosis.

BACKGROUND AND AIMS: The global rise of chronic hepatitis B (CHB) superimposed on hepatic steatosis (HS) warrants non-invasive, precise tools for assessing fibrosis progression. This study leveraged machine learning (ML) to develop diagnostic models for advanced fibrosis and cirrhosis in this patient population. METHODS: Treatment-naive CHB patients with concurrent HS who underwent liver biopsy in ten medical centers were enrolled as a training cohort and an independent external validation cohort (NCT05766449). Six ML models were implemented to predict advanced fibrosis and cirrhosis. The final models, derived from Shapley Additive exPlanations, were compared to Fibrosis-4 Index (FIB-4), Nonalcoholic fatty liver disease Fibrosis Score (NFS), and Aspartate transaminase to platelet ratio index (APRI) using the area under receiver operating characteristic curve (AUROC), and decision curve analysis (DCA). RESULTS: Of 1,198 eligible patients, the random forest (RF) model achieved AUROCs of 0.778 [95% confidence interval (CI) 0.749-0.807] for diagnosing advanced fibrosis (RF-AF model) and 0.777 (95%CI 0.748-0.806) for diagnosing cirrhosis (RF-C model) in the training cohort, and maintained high AUROCs in the validation cohort. In the training cohort, the RF-AF model obtained an AUROC of 0.825 (95% CI 0.787-0.862) in patients with HBV DNA ≥105 IU/ml, and RF-C model had an AUROC of 0.828 (95% CI 0.774-0.883) in female patients. The two models outperformed FIB-4, NFS, and APRI in the training cohort, and also performed well in the validation cohort. CONCLUSION: The RF models provide reliable, non-invasive tools for identifying advanced fibrosis and cirrhosis in CHB patients with concurrent HS, offering a significant advancement in the co-management of the two diseases.

SupporTive Care At Home Research (STAHR) for patients with advanced cancer: Protocol for a cluster non-randomized controlled trial.

Advancements in the treatment and management of patients with cancer have extended their survival period. To honor such patients' desire to live in their own homes, home-based supportive care programs have become an important medical practice. This study aims to investigate the effects of a multidimensional and integrated home-based supportive care program on patients with advanced cancer. SupporTive Care At Home Research is a cluster non-randomized controlled trial for patients with advanced cancer. This study tests the effects of the home-based supportive care program we developed versus standard oncology care. The home-based supportive care program is based on a specialized home-based medical team approach that includes (1) initial assessment and education for patients and their family caregivers, (2) home visits by nurses, (3) biweekly regular check-ups/evaluation and management, (4) telephone communication via a daytime access line, and (5) monthly multidisciplinary team meetings. The primary outcome measure is unplanned hospitalization within 6 months following enrollment. Healthcare service use; quality of life; pain and symptom control; emotional status; satisfaction with services; end-of-life care; advance planning; family caregivers' quality of life, care burden, and preparedness for caregiving; and medical expenses will be surveyed. We plan to recruit a total of 396 patients with advanced cancer from six institutions. Patients recruited from three institutions will constitute the intervention group, whereas those recruited from the other three institutions will comprise the control group.

MurSS: A Multi-Resolution Selective Segmentation Model for Breast Cancer.

Accurately segmenting cancer lesions is essential for effective personalized treatment and enhanced patient outcomes. We propose a multi-resolution selective segmentation (MurSS) model to accurately segment breast cancer lesions from hematoxylin and eosin (H&E) stained whole-slide images (WSIs). We used The Cancer Genome Atlas breast invasive carcinoma (BRCA) public dataset for training and validation. We used the Korea University Medical Center, Guro Hospital, BRCA dataset for the final test evaluation. MurSS utilizes both low- and high-resolution patches to leverage multi-resolution features using adaptive instance normalization. This enhances segmentation performance while employing a selective segmentation method to automatically reject ambiguous tissue regions, ensuring stable training. MurSS rejects 5% of WSI regions and achieves a pixel-level accuracy of 96.88% (95% confidence interval (CI): 95.97-97.62%) and mean Intersection over Union of 0.7283 (95% CI: 0.6865-0.7640). In our study, MurSS exhibits superior performance over other deep learning models, showcasing its ability to reject ambiguous areas identified by expert annotations while using multi-resolution inputs.

Cartilage-hair hypoplasia-anauxetic dysplasia spectrum disorders harboring RMRP mutations in two Korean children: A case report.

RATIONALE: Cartilage-hair hypoplasia (CHH, OMIM # 250250) is a rare autosomal recessive disorder, which includes cartilage-hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders. CHH-AD is caused by homozygous or compound heterozygous mutations in the RNA component of the mitochondrial RNA-processing Endoribonuclease (RMRP) gene. PATIENT CONCERNS: Here, we report 2 cases of Korean children with CHH-AD. DIAGNOSES: In the first case, the patient had metaphyseal dysplasia without hypotrichosis, diagnosed by whole exome sequencing (WES), and exhibited only skeletal dysplasia and lacked extraskeletal manifestations, such as hair hypoplasia and immunodeficiency. In the second case, the patient had skeletal dysplasia, hair hypoplasia, and immunodeficiency, which were identified by WES. INTERVENTIONS: The second case is the first CHH reported in Korea. The patients in both cases received regular immune and lung function checkups. OUTCOMES: Our cases suggest that children with extremely short stature from birth, with or without extraskeletal manifestations, should include CHH-AD as a differential diagnosis. LESSONS SUBSECTIONS: Clinical suspicion is the most important and RMRP sequencing should be considered for the diagnosis of CHH-AD.

Burden and preparedness of care partners of people living with amyotrophic lateral sclerosis at home in Korea: A care partner survey.

INTRODUCTION/AIMS: The care burden of people living with amyotrophic lateral sclerosis (pALS) increases with disease progression. This study aimed to investigate the home care status and preparedness of care partners of pALS (cALS) in Korea. METHODS: An online survey was conducted with family care partners of patients diagnosed with ALS for over 1 year in 2022. The data collected included care time, depression evaluated using the patient health questionnaire-9 (PHQ-9), preparedness for caregiving scale (PCS), and caregiver competence scale (CCS). Results were compared based on whether the pALS underwent a tracheostomy or not. RESULTS: Ninety-eight cALS of 98 pALS participated in the study, of whom 59 pALS had undergone tracheostomy. Among the cALS, 60.2% were spouses, and 34.7% were children. The cALS took care of the patients for 13 (8-20) hours/day (median, interquartile range [IQR]) on weekdays and 15 (10-24) h/day on weekends. Among the cALS, 91.8% were depressed, and 28.6% had severe depression. The median (IQR) PCS and CCS scores were low (11/32 (8-15) and 8/20 (8-11), respectively), and both were lower in those caring for patients without than with tracheostomy (p < .001 and p < .02, respectively). Most cALS (77.6%) wished to continue caring for their pALS at home. DISCUSSION: Family care partners of pALS spend more than half of each day caring for patients and are often depressed. Most cALS preferred providing care at home, but felt ill-prepared. Designing home-based medical care is necessary for pALS to thrive at home.

The impact of specialized pediatric palliative care on advance care planning and healthcare utilization in children and young adults: a retrospective analysis of medical records of in-hospital deaths.

BACKGROUND: Pediatric palliative care supports children and young adults with life-limiting conditions and their families, seeking to minimize suffering and enhance quality of life. This study evaluates the impact of specialized palliative care (SPC) on advance care planning (ACP) and patterns of end-of-life care for patients who died in the hospital. METHODS: This is a retrospective cohort study of medical records extracted from a clinical data warehouse, covering patients who died aged 0-24 in an academic tertiary children's hospital in South Korea. Participants were categorized into before (2011-2013; pre-period) and after (2017-2019; post-period) the introduction of an SPC service. Within the post-period, patients were further categorized into SPC recipients and non-recipients. RESULTS: We identified 274 and 205 patients in the pre-period and post-period, respectively. ACP was conducted more and earlier in the post-period than in the pre-period, and in patients who received palliative care than in those who did not. Patients who received SPC were likely to receive less mechanical ventilation or cardiopulmonary resuscitation and more opioids. A multivariable regression model showed that earlier ACP was associated with not being an infant, receiving SPC, and having a neurological or neuromuscular disease. CONCLUSIONS: SPC involvement was associated with more and earlier ACP and less intense end-of-life care for children and young adults who died in the hospital. Integrating palliative care into routine care can improve the quality of end-of-life care by reflecting patients' and their families' values and preferences.

Acute myocardial infarction prognosis prediction with reliable and interpretable artificial intelligence system.

OBJECTIVE: Predicting mortality after acute myocardial infarction (AMI) is crucial for timely prescription and treatment of AMI patients, but there are no appropriate AI systems for clinicians. Our primary goal is to develop a reliable and interpretable AI system and provide some valuable insights regarding short, and long-term mortality. MATERIALS AND METHODS: We propose the RIAS framework, an end-to-end framework that is designed with reliability and interpretability at its core and automatically optimizes the given model. Using RIAS, clinicians get accurate and reliable predictions which can be used as likelihood, with global and local explanations, and "what if" scenarios to achieve desired outcomes as well. RESULTS: We apply RIAS to AMI prognosis prediction data which comes from the Korean Acute Myocardial Infarction Registry. We compared FT-Transformer with XGBoost and MLP and found that FT-Transformer has superiority in sensitivity and comparable performance in AUROC and F1 score to XGBoost. Furthermore, RIAS reveals the significance of statin-based medications, beta-blockers, and age on mortality regardless of time period. Lastly, we showcase reliable and interpretable results of RIAS with local explanations and counterfactual examples for several realistic scenarios. DISCUSSION: RIAS addresses the "black-box" issue in AI by providing both global and local explanations based on SHAP values and reliable predictions, interpretable as actual likelihoods. The system's "what if" counterfactual explanations enable clinicians to simulate patient-specific scenarios under various conditions, enhancing its practical utility. CONCLUSION: The proposed framework provides reliable and interpretable predictions along with counterfactual examples.

Reliability of the DI-60 Digital Image Analyzer for Detecting Platelet Clumping and Obtaining Accurate Platelet Counts.

Pseudothrombocytopenia caused by platelet clumping (PC) can lead to unnecessary platelet transfusions or underdiagnosis of hematologic neoplasms. To overcome these limitations, we assessed the capacity of the Sysmex DI-60 digital morphology analyzer (Sysmex, Kobe, Japan) for detecting PC and determining an accurate platelet count in the presence of PC. For this purpose, 135 samples with or without PC (groups Y and N, respectively) were processed by an examiner (a hematologic specialist) using both the Sysmex XN-9000 and DI-60 analyzers. Although the platelet aggregate (PA) and giant platelet (GP) counts reported by the DI-60 and the examiner exhibited strong correlations, they proved inadequate as effective indicators for screening samples containing PC. Between the PA and GP counts and four platelet indices (the platelet distribution width [PDW], mean platelet volume [MPV], platelet large cell ratio [P_LCR], and plateletcrit [PCT]) reported by the XN-9000, we observed statistically significant correlations (both overall and with group Y), but they were relatively weak. The platelet counts determined using the DI-60 and light microscopy in group Y showed substantial variations. Although the performance of the DI-60 was reliable for detecting PA and GP in smear images, such fixed areas are not representative of whole samples. Further, in the presence of PC, the resulting platelet counts determined using the DI-60 were not sufficiently accurate to be accepted as the final count.

IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4+ T cell responses following COVID-19 mRNA vaccination.

BACKGROUND: The innate immune cytokine interleukin (IL)-1 can affect T cell immunity, a critical factor in host defense. In a previous study, we identified a subset of human CD4+ T cells which express IL-1 receptor 1 (IL-1R1). However, the expression of such receptor by viral antigen-specific CD4+ T cells and its biological implication remain largely unexplored. This led us to investigate the implication of IL-1R1 in the development of viral antigen-specific CD4+ T cell responses in humans, including healthy individuals and patients with primary antibody deficiency (PAD), and animals. METHODS: We characterized CD4+ T cells specific for SARS-CoV-2 spike (S) protein, influenza virus, and cytomegalovirus utilizing multiplexed single cell RNA-seq, mass cytometry and flow cytometry followed by an animal study. FINDINGS: In healthy individuals, CD4+ T cells specific for viral antigens, including S protein, highly expressed IL-1R1. IL-1ß promoted interferon (IFN)-γ expression by S protein-stimulated CD4+ T cells, supporting the functional implication of IL-1R1. Following the 2nd dose of COVID-19 mRNA vaccines, S protein-specific CD4+ T cells with high levels of IL-1R1 increased, likely reflecting repetitive antigenic stimulation. The expression levels of IL-1R1 by such cells correlated with the development of serum anti-S protein IgG antibody. A similar finding of increased expression of IL-1R1 by S protein-specific CD4+ T cells was also observed in patients with PAD following COVID-19 mRNA vaccination although the expression levels of IL-1R1 by such cells did not correlate with the levels of serum anti-S protein IgG antibody. In mice immunized with COVID-19 mRNA vaccine, neutralizing IL-1R1 decreased IFN-γ expression by S protein-specific CD4+ T cells and the development of anti-S protein IgG antibody. INTERPRETATION: Our results demonstrate the significance of IL-1R1 expression in CD4+ T cells for the development of viral antigen-specific CD4+ T cell responses, contributing to humoral immunity. This provides an insight into the regulation of adaptive immune responses to viruses via the IL-1 and IL-1R1 interface. FUNDING: Moderna to HJP, National Institutes of Health (NIH) 1R01AG056728 and R01AG055362 to IK and KL2 TR001862 to JJS, Quest Diagnostics to IK and RB, and the Mathers Foundation to RB.

Genome-wide association study of metabolic dysfunction-associated fatty liver disease in a Korean population.

Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10-15 and 4.84 × 10-10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10-4, and 7.15 × 10-4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10-8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351-1.700), 1.43 × 10-12 and MD-MAFLD: 1.300 (1.191-1.416), 2.90 × 10-9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10-8 and 1.225 (1.122, 1.340), 7.06 × 10-6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.

Hydroethanolic extract of Cirsium setidens ameliorates doxorubicin-induced cardiotoxicity by AMPK-PGC-1α-SOD-mediated mitochondrial protection.

BACKGROUND: Doxorubicin (DOX) is an effective anticancer agent. However, the clinical outcomes of DOX-based therapies are severely hampered by their significant cardiotoxicity. PURPOSE: We investigated the beneficial effects of an ethanol extract of Cirsium setidens (CSE) on DOX-induced cardiomyotoxicity (DICT). METHODS: UPLC-TQ/MS analysis was used to identify CSE metabolite profiles. H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells were used to evaluate the effects of CSE on DICT-induced cell death. To elucidate the mechanism underlying it, AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma co-activator l-alpha (PGC1-α), nuclear respiratory factor 1 (NRF1), NRF2, superoxide dismutase (SOD1), and SOD2 expression was detected using western blot analysis. The oxygen consumption rate (OCR), cellular ROS, and mitochondrial membrane potential were measured. Finally, we confirmed the cardioprotective effect of CSE against DICT in both C57BL/6 mice and human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) by observing various parameters, such as electrophysiological changes, cardiac fibrosis, and cardiac cell death. RESULTS: Chlorogenic acid and nicotiflorin were the major compounds in CSE. Our data demonstrated that CSE blocked DOX-induced cell death of H9c2 cells without hindrance of its apoptotic effects on MDA-MB-231 cells. DOX-induced defects of OCR and mitochondrial membrane potential were recovered in a CSE through upregulation of the AMPK-PGC1-α-NRF1 signaling pathway. CSE accelerated NRF1 translocation to the nucleus, increased SOD activity, and consequently blocked apoptosis in H9c2 cells. In mice treated with 400 mg/kg CSE for 4 weeks, electrocardiogram data, creatine kinase and lactate dehydrogenase levels in the serum, and cardiac fibrosis, were improved. Moreover, various electrophysiological features indicative of cardiac function were significantly enhanced following the CSE treatment of hiPSCCMs. CONCLUSION: Our findings demonstrate CSE that ameliorates DICT by protecting mitochondrial dysfunction via the AMP- PGC1α-NRF1 axis, underscoring the therapeutic potential of CSE and its underlying molecular pathways, setting the stage for future investigations into its clinical applications.

The trend of dental check-up and prevalence of dental complications following the use of bone modifying agents in patients with metastatic breast and prostate cancer: analysis of data from the Korean National Health Insurance Service.

BACKGROUND: Bone-modifying agents (BMA) are key components in the management of cancer patients with bone metastasis. Despite their clinical benefits, the use of BMA is associated with dental adverse events (AEs) including medication-related osteonecrosis of the jaw (MRONJ). This study investigated the frequency of dental surveillance before BMA treatment and the prevalence of dental AEs including MRONJ, after BMA treatment in patients with bone metastasis from breast and prostate cancer using data from the national health insurance system. METHODS: Data, including age, cancer diagnosis, administered BMA, and dental AEs during cancer treatment, of patients with bone metastasis from breast and prostate cancer who received at least one infusion of BMA between 2007 and 2019 were extracted from the Korean National Health Insurance Service (KNHIS) dataset. RESULTS: Of the 15,357 patients who received BMA, 1,706 patients (11.1%) underwent dental check-ups before BMA treatment. The proportion of patients receiving dental check-up increased from 4.4% in 2007 to 16.7% in 2019. Referral to dentists for a dental check-up was more active in clinics/primary hospitals than general/tertiary hospitals, and medical doctors and urologists actively consulted to dentists than general surgeons, regardless of the patient's health insurance status. After BMA treatment, 508 patients (3.8%) developed dental AEs, including abscess (42.9%), acute periodontitis (29.7%), acute pericoronitis (14.9%), and MRONJ (12.5% of dental AEs cases, 0.5% of total BMA treated patients). CONCLUSIONS: Considering the long treatment period in patients with metastatic cancer, coordination between dentists and oncologists is necessary to ensure appropriate dental management before the initiation of BMA.

Usefulness of oxygen uptake efficiency slope in a 6 min walk test in chronic heart failure.

AIMS: Frailty is an obstacle to performing cardiopulmonary exercise test (CPET) in patients with chronic heart failure (CHF). We evaluated the usefulness of oxygen uptake efficiency slope (OUES) using a 6 min walk test (6MWT) with portable gas analysis compared with CPET-derived parameters in patients with CHF. METHODS AND RESULTS: Patients with CHF who underwent both the 6MWT with portable gas analysis and CPET between December 2016 and May 2020 were retrospectively investigated. The 6MWT-derived and echocardiographic parameters were compared with the OUES and peak oxygen consumption (VO2) from the CPET. Forty patients were analysed; 50% were male with a mean age of 55.45 ± 14.70 years. Twenty-six patients (65%) had New York Heart Association Functional Classification II or III dyspnoea. Twenty-five patients (62.5%) had heart failure (HF) with preserved ejection fraction (EF) (left ventricular EF > 50%), and nine patients (22.5%) had HF with reduced EF (EF < 40%). During the 6MWT, the peak VO2 was 14.97 ± 3.80 mL/kg/min, which was only 74% of the peak VO2 in the CPET, 20.18 ± 5.64 mL/kg/min. The OUES in the 6MWT was lower than that in the CPET (1528.87 ± 579.01 in the 6MWT vs. 1638.69 ± 601.31 in the CPET). The 6 min walk distance (6MWD) and OUES in the 6MWT were positively correlated with the OUES in the CPET (6MWD, r = 0.434, P = 0.005; OUES, r = 0.729, P < 0.001). The OUES in the 6MWT showed the strongest correlation with the OUES in the CPET. When we divided patients into two groups according to peak VO2 in the CPET, the correlation between OUES values of the 6MWT and that of the CPET was consistently confirmed (peak VO2 ≥ 20 mL/kg/min group, r = 0.661, P = 0.001; peak VO2 < 20 mL/kg/min group, r = 0.526, P = 0.021). In addition, the 6MWD, OUES, and peak VO2 in the 6MWT were associated with peak VO2 in the CPET (6MWD, r = 0.627, P < 0.001; OUES, r = 0.452, P = 0.003; and peak VO2, r = 0.492, P = 0.001). CONCLUSIONS: In frail patients with CHF who have difficulty performing maximal exercises, the OUES through the 6MWT may be applied instead of the OUES and peak VO2 from the CPET.