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Abstract This multicentre retrospective study evaluated the 1-year outcomes and safety profile of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Fifty-five patients (57 eyes) underwent loading therapy comprising three monthly faricimab injections. If dryness was achieved by the third month, subsequent treat-and-extend (TAE) follow-up continued at a minimum 8-week interval thereafter. If wet macula persisted at the third month, a fourth dose was administered, followed by the TAE regimen. After 1 year, improvements in visual acuity (0.44 ± 0.46 [baseline] to 0.34 ± 0.48; p

Abstract Background Extracellular mitochondrial DNA (mtDNA) is released from damaged cells and increases in the serum and bronchoalveolar lavage fluid (BALF) of idiopathic pulmonary fibrosis (IPF) patients. While increased levels of serum mtDNA have been reported to be linked to disease progression and the future development of acute exacerbation (AE) of IPF (AE-IPF), the clinical significance of mtDNA in BALF (BALF-mtDNA) remains unclear. We investigated the relationships between BALF-mtDNA levels and other clinical variables and prognosis in IPF. Methods Extracellular mtDNA levels in BALF samples collected from IPF patients were determined using droplet-digital PCR. Levels of extracellular nucleolar DNA in BALF (BALF-nucDNA) were also determined as a marker for simple cell collapse. Patient characteristics and survival information were retrospectively reviewed. Results mtDNA levels in serum and BALF did not correlate with each other. In 27 patients with paired BALF samples obtained in a stable state and at the time of AE diagnosis, BALF-mtDNA levels were significantly increased at the time of AE. Elevated BALF-mtDNA levels were associated with inflammation or disordered pulmonary function in a stable state (n = 90), while being associated with age and BALF-neutrophils at the time of AE (n = 38). BALF-mtDNA ≥ 4234.3 copies/µL in a stable state (median survival time (MST): 42.4 vs. 79.6 months, p

Introduction CHARGE syndrome is a rare disorder that causes congenital abnormalities in multiple organs, including secondary hypogonadism. We report, herein, a unique case of CHARGE syndrome with both primary and secondary hypogonadism and discuss the possible causes and pathogenesis in this patient. Case presentation A 15‐year‐old boy with delayed secondary sexual characteristics and non‐palpable testes was referred to our hospital. Physical examination and detection of a chromodomain‐helicase‐deoxyribonucleic acid‐binding protein 7 gene mutation confirmed CHARGE syndrome. Hormone stimulation tests suggested both primary and secondary hypogonadism. Laparoscopic bilateral orchiectomy was performed because of decreased testosterone production and atrophy in both testes. Pathological examination of the testes revealed maturation arrest, germ cell neoplasm in situ, and decreased expression of steroid synthase. Conclusion This appears to be the first report of CHARGE syndrome with both primary and secondary hypogonadism demonstrated in endocrinological and histological examinations.

Autologous costal cartilage grafts remain the gold standard method for microtia reconstruction. However, reports on its long-term outcomes are limited. We present two cases with >40-year outcomes after auricular reconstruction with autologous costal cartilage. A 56 year-old woman and a 53 year-old man presented to our institution with complaints of wire exposure. In both cases, the reconstructed ear was deformed. A computerized tomography scan revealed calcification of the reconstructed costal cartilage graft framework. To our knowledge, these cases present the longest outcomes (50 and 42 years for the 56 year-old woman and 53 year-old man, respectively) of microtia reconstruction using autologous cartilage grafts. We found that ear frameworks constructed from costal cartilage tended to calcify in the long term, as in the natural course of costal cartilage. Therefore, the possibility of calcification of costal cartilage grafts should be relayed to patients and parents, and lifelong surveillance after reconstruction should be recommended.

Background: Spatial and temporal heterogeneities of RAS and other molecular genes should be considered in the treatment of metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs); acquired RAS mutation is sometimes observed at disease progression of treatment with the anti-EGFR mAb. At the same time, discrepancy of RAS status from tissues and circulating tumor DNA (ctDNA) in the same patient is sometimes observed. Based on this, we commenced two observational studies to clarify these heterogeneities of RAS and BRAF in mCRC, using next generation sequencing from liquid biopsy. Methods/Design: RAS-trace study is an observational study to monitor ctDNA RAS/BRAF/PIK3CA status every 4-12 weeks using the Plasma-SeqSensei™ CRC RUO Kit (Sysmex Inostics GmbH) in mCRC with RAS/BRAF wild-type (wt) on tumor tissue. The primary endpoint was the time to the acquired RAS mutations. A total of 42 patients has been accrued. RAS-trace-2 study is also an observational study aimed at comparing the efficacy of the anti-EGFR mAb in ctDNA RAS/BRAF wt with ctDNA RAS or BRAF mutant mCRC patients, whose RAS/BRAF are wt in tumor tissue. The primary endpoint was progression-free survival in patients with ctDNA RAS/BRAF wt and RAS or BRAF mutant. A total of 240 patients will be accrued over 2 years. Discussion: These trials will help us understanding the clinical significance of spatial and temporal heterogeneities of RAS, BRAF and other genes, while optimizing the anti-EGFR mAb treatment strategies in mCRC.

Abstract Patients with advanced cancer are frequently burdened with a severe sensation of fatigue called cancer-related fatigue (CRF). CRF is induced at various stages and treatments, such as cachexia and chemotherapy, and reduces the overall survival of patients. Objective and quantitative assessment of CRF could contribute to the diagnosis and prediction of treatment efficacy. However, such studies have not been intensively performed, particularly regarding metabolic profiles. Here, we conducted plasma metabolomics of 15 patients with urological cancer. The patients with and without fatigue, including those with cachexia or chemotherapy-induced fatigue, were compared. Significantly lower concentrations of valine and tryptophan were observed in fatigued patients than in non-fatigued patients. In addition, significantly higher concentrations of polyamine pathway metabolites were observed in patients with fatigue and cachexia than in those without cachexia. Patients with exacerbated fatigue due to chemotherapy showed significantly decreased cysteine and methionine metabolism before chemotherapy compared with those without fatigue exacerbation. These findings suggest that plasma metabolic profiles could help improve the diagnosis and monitoring of CRF.

Introduction: The Flemish version of the Triage Risk Screening Tool (fTRST), derived from the Triage Risk Screening Tool for assessing risk of readmission to the emergency department, is increasingly used as a simple screening tool in oncology. This study aimed to evaluate the utility of the fTRST in the context of elective surgical treatment for urologic cancer patients. Methods: We included 886 patients who underwent major urologic cancer surgery at our institution between 2020 and 2022 and underwent preoperative screening, including fTRST. We set the fTRST cutoff at 2 and used propensity score matching and multivariate regression analysis to assess how fTRST affected two postoperative outcomes: ambulation failure and delirium. Results: Of the 886 patients, 693 (78%) had an fTRST score

Objective: Clazosentan (CLA) reduces cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). However, adverse events including pulmonary edema were reported. We examined whether the strict management of fluid balance reduces the adverse events and improves patient outcomes. Methods: Patients with aSAH between 2020 and 2023 were included. They were divided into pre-CLA (before CLA approval) and post-CLA (after approval) groups. The patients in the post-CLA group were further divided into the post-CLA1 (before the change in fluid management) and post-CLA2 (after the change) groups. To achieve fluid balance of 0–500 ml/day according to the modified protocol, the infusion volume was restricted. Results: The daily fluid balance increased from the pre-CLA to the post-CLA1 periods (p = 0.01). The protocol changes decreased the pulmonary edema (post-CLA1 vs. post-CLA2, 44 vs. 22 %, p = 0.09) and discontinuation of CLA (44 vs. 9 %, p

A 69-year-old woman with chronic hepatitis C virus (HCV) infection was referred to our hospital due to liver enzyme abnormalities. Four years after anti-HCV therapy, the patient with sustained virologic response and no clinical symptoms developed an oval hepatic mass with mixed high and low internal echoes near the portal vein on ultrasound. Magnetic resonance imaging (MRI) of the liver lesion showed a slightly hypo intense pattern on T1-weighted images, a hyper intense pattern both on T2- and diffusion-weighted images, a slight rim enhancement pattern with no intra-lesional enhancement up to the late phase, and a very low intense pattern on hepatobiliary phase images. Positron emission tomography/computed tomography (PET / CT) showed no areas of avid radiotracer uptake in the liver. No tumor markers showed abnormally high values. All these images and laboratory findings led us to the assessment of the liver lesion as a non-neoplastic disorder. However, due to the patient's strong preference to get both definitive diagnosis and cure of the lesion, the patient underwent laparoscopic partial hepatectomy. Pathological study showed 2 necrotic areas surrounded by multiple lymph follicles, epithelioid cells, lymphocytes, collagen fibers, and plasma cells, leading to the diagnosis of focal coagulative necrosis of the liver (FCNL). Physicians should note that FCNL can occur without any symptoms and can be diagnosed at least as a non-neoplastic disorder with combined MRI and PET/CT analysis.

In second or foreign language (SFL) education, oral corrective feedback (OCF) is widely used to individually correct students' erroneous utterances during classroom hours. However, students cannot have sufficient opportunities for oral production and personalized feedback during classroom hours if a class is large-scale with many students. This paper addresses the lack of OCF opportunities in a large-scale class, assuming the causes to be the severe time constraints and the teachers' labor intensiveness in examining students' utterances and generating OCF. This research proposes using computer-mediated feedback (CMF) outside classroom hours to complement OCF in an online, semiautomated, and scalable fashion. This paper implements Oral Repetition Practice (ORP) Gym to provide students with sufficient opportunities for speaking practice through two types of CMFs; Hybrid Recast to enhance the recognition of errors and Explicit Error Correction to make errors detectable and correctable. Online External Assistant (OEA) is a mechanism used to increase the amount and quality of feedback by distributing the workload for scoring and generating CMF. The evaluation was conducted as a classroom observational study by introducing ORP Gym to a spoken Japanese SFL basics course with 55 students at an Indian university. Compared with the students who did not utilize ORP Gym, those who utilized ORP Gym performed more ORP and exhibited significant score improvement in the posttest. This research contributes to enabling CMF in large-scale SFL classes and empirically and statistically proving the improvement of the learning effect, including uptake and repair, by CMF using ORP Gym and an OEA.

BACKGROUND: Several studies suggest that Asian-American and Native Hawaiian and Other Pacific Islander (NHOPI) racial/ethnic groups have a heightened risk of chronic kidney disease (CKD), but provide limited inference due to the aggregation of these groups into a single racial/ethnic category. We thus examined the association of granularly defined racial/ethnic groups with specific CKD indicators among a diverse group of participants from the National Kidney Foundation of Hawaiis Kidney Early Detection Screening (KEDS) Program. METHODS: Among 1,243 participants enrolled in 19 KEDS screening events over 2006-2009, we examined the association between Asian-American and NHOPI groups and specific CKD indicators, defined as self-reported CKD, microalbuminuria, and macroalbuminuria, using multivariable logistic regression. We then examined associations of race/ethnicity with various CKD risk factors. RESULTS: The most predominant racial/ethnic groups were White (22.0%), Multiracial (18.9%), Japanese (19.2%), Filipino (13.4%), NHOPI (8.4%), and Chinese (4.5%) participants. NHOPI and Chinese participants had a higher risk of microalbuminuria (adjusted ORs [aORs] [95% CIs] 2.48 [1.25-4.91] and 2.37 [1.07-5.27], respectively), while point estimates for all other minority groups suggested higher risk (reference: Whites). NHOPI participants also had a higher risk of macroalbuminuria and self-reported CKD. While most minorities had a higher risk of diabetes and hypertension, NHOPI and Multiracial participants had a higher risk of obesity, whereas the East Asian groups had a lower risk. CONCLUSIONS: In this community-based cohort, compared with Whites, Asian-Americans had a higher risk of early CKD indicators, whereas NHOPIs had a higher risk of more severe CKD indicators. Further studies are needed to elucidate the distinct pathways leading to CKD across diverse racial/ethnic groups in Hawaii.

Abstract Aim This pilot examined the effect of online peer support on mental health problems among individuals with post‐acute sequelae of COVID‐2019 (PASC). Methods A single‐arm pre‐post design of online peer‐support design consisting of eight sessions of 1 h per week with three to six participants and two facilitators per group was performed. Participants were recruited from online communities, social media, and medical clinics for the PASC between May and August 2023. The degrees of depression, anxiety, loneliness, social withdrawal, and self‐esteem were measured pre‐ and post‐intervention. Participants' statements during the sessions were analyzed using thematic analyses. Results Of the 18 participants, three dropped out of the interventions, and 17 (including two participants who dropped out) completed the pre‐ and post‐intervention questionnaires. Depression severity significantly decreased in the paired t‐test and linear mixed model. The following interactions were extracted: conveying the same feelings, dealing with difficulties, showing empathy, enhancing the atmosphere, and adapting to suit health conditions. Impressions extracted from participating in the interventions included feelings of emotional support, a sense of bonding, changes in perspective, changes in behaviors or new actions through participation, inadequacy during sessions, and adverse effects associated with participation. Conclusion Online peer support may be helpful in treating depression in individuals with PASC.

Abstract Nanocomposite films from cellulose jute fibers can be promising for application in electronic devices, mainly when silver nanoparticles (AgNPs) are added, which increases their conductivity. This work studied the transmittance, conductivity, and thermal stability of regenerated cellulose films (RCF) by adding AgNPs and plasticizers. Carboxymethylcellulose (CMC), sorbitol, and glycerol plasticizers were incorporated at 15 wt.% and 0.5 wt.% of AgNPs. The resulting materials were studied using Ultraviolet-visible and Fourier Transform Infrared Spectroscopy, electrical analysis using the Van der Pauw method, and thermogravimetry. As a result, an average size of 9 nm for AgNPs was verified. Incorporating AgNP in the films decreased the transmittance by a minimum of 34% compared to pure RCF and reduced thermal stability by at least 10 ºC. Nanocomposites containing plasticizers showed an improved conductivity after incorporating these components, from 10-2 to 10-1 (S/cm).

Lebrikizumab has previously demonstrated efficacy in Phase 3 trials: ADvocate1 and ADvocate2 (as monotherapy), ADhere, and ADhere-J (in combination with topical corticosteroids). Here, the impact of lebrikizumab combined with low- to mid-potency topical corticosteroids on patient-reported outcomes at 16 weeks in Japanese patients with moderate-to-severe atopic dermatitis is evaluated. Eligible patients (n = 286) were randomized 2:2:3 to receive placebo+ topical corticosteroids, 250 mg lebrikizumab every 4 weeks (LEBQ4W+topical corticosteroids, 500 mg loading dose at baseline), or 250 mg lebrikizumab every 2 weeks (LEBQ2W+ topical corticosteroids, 500 mg loading dose at baseline and Week 2) by subcutaneous injection. All PRO endpoints for the study were met; patients in the lebrikizumab in combination with topical corticosteroids groups demonstrated statistically significant and clinically meaningful improvements compared with placebo in combination with topical corticosteroids in Skin Pain NRS, DLQI, POEM, WPAI-AD, and SCORAD scales. Lebrikizumab combined with topical corticosteroids compared with placebo+topical corticosteroids improved patient-reported outcomes in Japanese patients with moderate-to-severe atopic dermatitis.

Summary: Background: Breast cancer cells suppress the host immune system to efficiently invade the lymph nodes; however, the underlying mechanism remains incompletely understood. Here, we aimed to comprehensively characterise the effects of breast cancers on immune cells in the lymph nodes. Methods: We collected non-metastatic and metastatic lymph node samples from 6 patients with breast cancer with lymph node metastasis. We performed bulk transcriptomics, spatial transcriptomics, and imaging mass cytometry to analyse the obtained lymph nodes. Furthermore, we conducted histological analyses against a larger patient cohort (474 slices from 58 patients). Findings: The comparison between paired lymph nodes with and without metastasis from the same patients demonstrated that the number of CD169+ lymph node sinus macrophages, an initiator of anti-cancer immunity, was reduced in metastatic lymph nodes (36.7 ± 21.1 vs 7.3 ± 7.0 cells/mm2, p = 0.0087), whereas the numbers of other major immune cell types were unaltered. We also detected that the infiltration of CD169+ macrophages into metastasised cancer tissues differed by section location within tumours, suggesting that CD169+ macrophages were gradually decreased after anti-cancer reactions. Furthermore, CD169+ macrophage elimination was prevalent in major breast cancer subtypes and correlated with breast cancer staging (p = 0.022). Interpretation: We concluded that lymph nodes with breast cancer metastases have fewer CD169+ macrophages, which may be detrimental to the activity of anti-cancer immunity. Funding: JSPS KAKENHI (16H06279, 20H03451, 20H04842, 22H04925, 19K16770, and 21K15530, 24K02236), JSPS Fellows (JP22KJ1822), AMED (JP21ck0106698), JST FOREST (JPMJFR2062), Caravel, Co., Ltd, Japan Foundation for Applied Enzymology, and Sumitomo Pharma Co., Ltd. under SKIPS.

ObjectivesThis study aimed to identify dietary knowledge, attitudes, and behaviors related to obesity and highly underweight among urban Chinese high school students.MethodsUsing the data of 403 high school students from a cross-sectional survey in 2022, multinomial logistic regression analysis was conducted with the body mass index as the objective variable (reference: normal weight), dietary knowledge, attitudes, and behaviors as the explanatory variables, adjusted for sex.ResultsBoth obesity and highly underweight were most strongly related to incorrect dietary knowledge of desirable types of diets. Additionally, obesity was related to inappropriate dietary attitudes regarding the importance of diet, eating at irregular meal-times, and eating without chewing well, while highly underweight was related to picky eating and not having three meals per day, but not related to attitudes.ConclusionThe incorrect knowledge of desirable type of diet was related to both obesity and highly underweight, while other risk factors of knowledge, attitudes, and behaviors related to obesity or highly underweight differed respectively. These findings should be useful in examining effective nutrition education for urban Chinese high school students.

Background The atherogenic characteristics of heterozygous familial hypercholesterolemia (HeFH) increase the risk of premature atherosclerotic cardiovascular disease including not only coronary artery disease but ischemic stroke. Asymptomatic intracranial artery stenosis/occlusion (IASO) is a major cause of ischemic stroke, but it has not yet been fully characterized in patients with HeFH. Methods and Results This study analyzed 147 clinically diagnosed subjects with HeFH who underwent magnetic resonance imaging/magnetic resonance angiography imaging for evaluation of IASO (≥50% diameter stenosis). Major adverse cerebrovascular and cardiovascular events (cardiac death, ischemic stroke, and acute coronary syndrome) were compared in patients with HeFH with and without asymptomatic IASO. Asymptomatic IASO was observed in 13.6% of patients with HeFH. The untreated low‐density lipoprotein cholesterol level (240±95 versus 244±75 mg/dL; P=0.67) did not differ between the 2 groups. Despite the use of lipid‐lowering therapies (statin, P=0.71; high‐intensity statin, P=0.81; ezetimibe, P=0.33; proprotein convertase subxilisin/kexin type 9 inhibitor, P=0.39; low‐density lipoprotein apheresis, P=0.14), on‐treatment low‐density lipoprotein cholesterol level in patients with both HeFH and IASO was still suboptimally controlled (97±62 versus 105±50 mg/dL; P=0.17), accompanied by a higher triglyceride level (median, 109 versus 79 mg/dL; P=0.001). During the 12.4‐year observational period (interquartile range, 6.2–24.6 years), asymptomatic IASO exhibited a 4.04‐fold greater likelihood of experiencing a major adverse cardiovascular event (95% CI, 1.71–9.55; P=0.001) in patients with HeFH. This increased risk of a major adverse cardiovascular event was consistently observed in a multivariate Cox proportional hazards model adjusting clinical characteristics (hazard ratio, 4.32 [95% CI, 1.71–10.9]; P=0.002). Conclusions A total of 13.6% of Japanese subjects with HeFH presented with asymptomatic IASO. Despite lipid‐lowering therapies, patients with both HeFH and IASO more likely had elevated risk of cerebrovascular and cardiovascular events. Our findings highlight asymptomatic IASO as a phenotypic feature of HeFH‐related atherosclerosis, which ultimately affects future outcomes.

The joint effect of air pollutants at relatively low levels requires further investigation. Here, a database study was performed to evaluate the effects of exposure to mixtures of air pollutants during pregnancy, infancy, and childhood on childhood persistent asthma. We used the Japan Medical Data Center database, which provides access to family linkages and healthcare provider addresses, and included child-mother dyads in which the child was born between January 2010 and January 2017. The exposure of interest was ground-level air pollutants, and the primary outcome was childhood persistent asthma at 45 years of age, as defined based on outpatient and inpatient asthma disease codes and/or asthma medication dispensing claims. The weighted quantile sum (WQS) regression was used to evaluate the effects of air pollutant mixtures on 52,526 child-mother dyads from 1149 of 1907 municipalities (60.3 %) in Japan. The WQS regression models showed that with every 10th percentile increase in the WQS index, ground-level air pollutants during pregnancy, infancy, and childhood increased the risk of childhood persistent asthma by an odds ratio of 1.04 (95 % CI: 1.02–1.05; p

Introduction: Over the years and with the proportional growth of social media, focused mainly on the cult of the body and perfection, the demand for plastic surgeries has increased overwhelmingly, awakening an endless desire for body change, most of the time with “unrealistic” promises” from some professionals. Method: Research consisting of 62 female and male patients, aged between 22 and 61 years, residing in the state of São Paulo, who have already undergone a plastic surgery procedure and/or will undergo plastic surgery and cosmiatry procedures, who responded to the questionnaire “The influence of social media on plastic surgery”. Results: The results demonstrate that the media plays an important role in choosing a plastic surgeon, especially when the success of plastic surgery and cosmetic surgery procedures is demonstrated through before and after photos. Conclusion: Plastic surgery is a medical specialty that plays a fundamental role in the aesthetic and psychological transformation of many individuals, however, it is important to highlight the need for an ethical approach, to guarantee patients’ well-being and excellence in medical practice.

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.