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Level of Evidence: IV., Competing Interests: Declaration of conflicting interestsThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background/aims: Little is known about the practical clinical application of neuromodulators and psychiatric treatments in patients with functional gastrointestinal disorders (FGIDs). We investigate the knowledge, attitudes, and practices of Korean clinicians regarding the use of neuromodulators and psychiatric treatments for FGIDs., Methods: This prospective, online, cross-sectional study was conducted between May and August 2022. A questionnaire regarding the knowledge, attitude, and practice of neuromodulators and psychiatric treatments for FGIDs was developed and administered to primary care clinicians and gastroenterologists in university hospitals in Korea., Results: Overall, 451 clinicians from primary (n = 179, 39.7%), secondary (n = 113, 25.1%), and tertiary (n = 159, 35.3%) hospitals participated in the survey. Most of them considered that neuromodulators (98.7%) and psychiatric treatment (86.5%) were required for patients with FGIDs. However, approximately one-third of them did not prescribe neuromodulators, mainly due to unfamiliarity with the drugs, and only one-quarter considered psychiatric referral. Compared to gastroenterologists at university hospitals, primary care clinicians' prescriptions had a lower rate (87.2% vs 64.2%, P < 0.001) and shorter duration of neuromodulator. The psychiatric referral rate was lower for primary care clinicians than for gastroenterologists at university hospitals (19.0% vs 34.2%, P < 0.001)., Conclusions: Knowledge, attitude, and practice levels regarding neuromodulators and psychiatric treatment among clinicians are inhomogeneous, and a knowledge gap exists between primary care clinicians and gastroenterologists at university hospitals. Encouraging ongoing education for Korean clinicians regarding the appropriate use of neuromodulators and psychiatric treatments in patients with FGIDs is suggested.

Introduction: There is a strong rationale for targeting HER3, as HER3 contributes to tumorigenesis and treatment resistance. However, the prognostic role of HER3 and their association with immunoregulatory protein expression has not been established., Methods: The main objective of this study was to investigate the prognostic role of HER3 expression and identify immunoregulatory marker expression according to HER3 status. HER3 expression and 10 immunoregulatory protein (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4) expression was identified in 320 stage I-III breast cancer patients who received curative surgery at Seoul National University Hospital in 2008. The median follow-up duration was 88.8 months. Criteria for HER3 IHC was adopted from HER2 IHC score and only those with 3 + was considered positive., Results: Among 320 patients, 213 (67.2 %) had luminal A disease, 30 (9.5 %) had luminal B disease, 28 (8.8 %) had HER2-positive disease, and 46 (14.5 %) had triple negative disease. HER3 expression was shown in 153 patients (47.8 %). Tumors with HER3-expression had more immunogenic tumor microenvironment compared to HER3-negative tumor. In addition, patients with HER3 expression had favorable 5-year relapse free survival compared to HER3-negative patients (5-year RFS 92.5 % vs. 85.2 %, p = 0.038). However, in the multivariate analysis, HER3 expression was not a prognostic factor, but expression of immunoregulatory protein was a prognostic factor., Conclusions: This study identified immunoregulatory protein expression according to HER3 status in breast cancer patients. As tumor with HER3 expression have more immunogenic microenvironment, investigating combination treatment of HER3 targeting agent and immunotherapy in HER3 expressing breast cancer may be promising., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Defining the origin of metastatic cancer is crucial for establishing an optimal treatment strategy, especially when obtaining sufficient tissue from secondary malignancies is limited. While cytological examination is often used in this diagnostic setting, morphologic analysis alone often fails to differentiate metastases derived from the breast from other primaries. The hormone receptor, human epidermal growth factor receptor-2, gross cystic disease fluid protein 15, and mammaglobin immunohistochemistry are often used to diagnose metastatic breast cancer. However, their effectiveness decreases in estrogen receptor (ER)-negative breast cancers, including the triple-negative breast cancer (TNBC) subtype., Methods: We conducted a comprehensive evaluation of GATA-binding protein 3 (GATA-3), trichorhinophalangeal syndrome type 1 (TRPS-1), and Matrix Gla Protein (MGP) immunochemistry across 140 effusion cytology specimens with metastatic adenocarcinoma derived from various primaries, including the breast, colon, pancreaticobiliary, lung, tubo-ovarian, and stomach., Results: The expression rates of these immunomarkers were significantly higher in metastatic cancers originating from the breast than other primaries. In TNBC, TRPS-1 (80.00%) and MGP (65.00%) exhibited higher positivity rates compared to GATA-3 (40.00%). Additionally, our data suggest that an immunohistochemical panel comprising MGP, GATA-3, and TRPS-1 significantly enhances the detection of metastatic breast cancer in effusion cytology specimens, including TNBC in particular. When considering dual-marker positivity, the diagnostic accuracy was found to be 89.29% across all breast cancer subtypes and 92.93% for TNBC., Conclusions: MGP appears to be a robust marker for identifying metastatic breast cancer in malignant effusions, especially TNBC. MGP notably enhances diagnostic accuracy when incorporated together with GATA-3 and TRPS-1 in an immunohistochemical panel., (© 2024 S. Karger AG, Basel.)

Introduction: Although urothelial papilloma (UP) is an indolent papillary neoplasm that can mimic the morphology of low-grade papillary urothelial carcinoma (PUC), there is no immunomarker to differentiate reliably these two entities. In addition, the molecular characteristics of UP are not fully understood., Methods: We conducted an in-depth proteomic analysis of papillary urothelial lesions (n = 31), including UP and PUC along with normal urothelium. Protein markers distinguishing UP and PUC were selected with machine learning analysis, followed by internal and external validation using immunohistochemistry., Results: In the proteomic analysis, UP and PUC showed overlapping proteomic profiles. We identified EHD4 and KRT18 as candidate diagnostic biomarkers of UP. Through immunohistochemical validation in two independent cohorts (n = 120), KRT18 was suggested as a novel UP diagnostic marker, able to differentiate UP from low-grade PUC. We also found that 3.5% of patients with UP developed urothelial carcinoma in subsequent resections, supporting the malignant potential of UP. KRT18 downregulation was significantly associated with UPs subsequently progressing to urothelial carcinoma, following their initial diagnosis., Conclusion: This is the first study that successfully revealed UPs comprehensive proteomic landscape, while it also identified KRT18 as a potential diagnostic biomarker of UP., (© 2024 S. Karger AG, Basel.)

During the healing process after intra-nasal surgery, the growth and repair of damaged tissues can result in the development of postoperative adhesions. Various techniques have been devised to minimize the occurrence of postoperative adhesions which include insertion of stents in the middle meatus, application of removable nasal packing, and utilizing biodegradable materials with antiadhesive properties. This study assesses the efficacy of two sodium hyaluronate (SH)-based freeze-dried hydrogel composites in preventing postoperative nasal adhesions, comparing them with commonly used biodegradable materials in nasal surgery. The freeze-dried hydrogels, sodium hyaluronate and collagen 1(SH-COL1) and sodium hyaluronate, carboxymethyl cellulose, and collagen 1 (SH-CMC-COL1), were evaluated for their ability to reduce bleeding time, promote wound healing, and minimize fibrous tissue formation. Results showed that SH-CMC-COL1 significantly reduced bleeding time compared to both biodegradable polyurethane foam and SH-COL1. Both SH-COL1 and SH-CMC-COL1 exhibited enhanced wound healing effects, as indicated by significantly greater wound size reduction after two weeks compared to the control. Histological analyses revealed significant differences in re-epithelialization and blood vessel count among all tested materials, suggesting variable initial wound tissue response. Although all treatment groups had more epithelial growth, with X-SCC having higher blood vessel count at 7 d post treatment, all treatment groups did not differ in all histomorphometric parameters by day 14. However, the long-term application of SH-COL1 demonstrated a notable advantage in reducing nasal adhesion formation compared to all other tested materials. This indicates the potential of SH-based hydrogels, particularly SH-COL1, in mitigating postoperative complications associated with nasal surgery. These findings underscore the versatility and efficacy of SH-based freeze-dried hydrogel composites for the management of short-term and long-term nasal bleeding with an anti-adhesion effect. Further research is warranted to optimize their clinical use, particularly in understanding the inflammatory factors influencing tissue adhesions and assessing material performance under conditions mimicking clinical settings. Such insights will be crucial for refining therapeutic approaches and optimizing biomaterial design, ultimately improving patient outcomes in nasal surgery., (Creative Commons Attribution license.)

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world., Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform - FiRST Cancer Panel (FCP) - over seven years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis., Results: NGS tests were conducted on 548 samples from 522 patients with BC. 97.6% of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53(56.2%), PIK3CA(31.2%), GATA3(13.8%), BRCA2(10.2%), and amplifications of CCND1(10.8%), FGF19(10.0%), and ERBB2(9.5%). NGS analysis of ERBB2 amplification correlated well with HER2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. 10.3% of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.  ., Conclusion: Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

The accurate diagnosis of papillary urothelial carcinoma (PUC) is frequently challenging due to benign mimickers. Other than morphology-based diagnostic criteria, reliable biomarkers for differentiating benign and malignant papillary urothelial neoplasms remain elusive, so we sought to discover new markers to address this challenge. We first performed tandem mass spectrometry-based quantitative proteomics using diverse papillary urothelial lesions, including PUC, urothelial papilloma (UP), inverted urothelial papilloma, and cystitis cystica. We prioritized potential diagnostic biomarkers using machine learning, and subsequently validated through immunohistochemistry (IHC) in two independent cohorts. Metabolism, transport, cell cycle, development, and immune response functions were differentially enriched between malignant and benign papillary neoplasms. RhoB and NT5DC2 were shortlisted as optimal candidate markers for PUC diagnosis. In our pilot study using IHC, NT5DC2 was subsequently selected as its expression consistently differed in PUC (p = 0.007). Further validation of NT5DC2 using 49 low-grade (LG) urothelial lesions, including 15 LG-PUCs and 17 UPs, which are the most common mimickers, concordantly revealed lower IHC expression levels in LG-PUC (p = 0.0298). Independent external validation with eight LG-PUCs and eight UPs confirmed the significant downregulation of NT5DC2 in LG-PUC (p = 0.0104). We suggest that NT5DC2 is a potential IHC biomarker for differentiating LG-PUC from its benign mimickers, especially UP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

2-Keto-3-deoxy-galactonate (KDGal) serves as a pivotal metabolic intermediate within both the fungal D-galacturonate pathway, which is integral to pectin catabolism, and the bacterial DeLey-Doudoroff pathway for D-galactose catabolism. The presence of KDGal enantiomers, L-KDGal and D-KDGal, varies across these pathways. Fungal pathways generate L-KDGal through the reduction and dehydration of D-galacturonate, whereas bacterial pathways produce D-KDGal through the oxidation and dehydration of D-galactose. Two distinct catabolic routes further metabolize KDGal: a nonphosphorolytic pathway that employs aldolase and a phosphorolytic pathway involving kinase and aldolase. Recent findings have revealed that L-KDGal, identified in the bacterial catabolism of 3,6-anhydro-L-galactose, a major component of red seaweeds, is also catabolized by Escherichia coli, which is traditionally known to be catabolized by specific fungal species, such as Trichoderma reesei. Furthermore, the potential industrial applications of KDGal and its derivatives, such as pyruvate and D- and L-glyceraldehyde, are underscored by their significant biological functions. This review comprehensively outlines the catabolism of L-KDGal and D-KDGal across different biological systems, highlights stereospecific methods for discriminating between enantiomers, and explores industrial application prospects for producing KDGal enantiomers. KEY POINTS: • KDGal is a metabolic intermediate in fungal and bacterial pathways • Stereospecific enzymes can be used to identify the enantiomeric nature of KDGal • KDGal can be used to induce pectin catabolism or produce functional materials., (© 2024. The Author(s).)

Background and Purpose: The onset of Huntington's disease (HD) usually occurs before the age of 50 years, and the median survival time from onset is 15 years. We investigated survival in patients with late-onset HD (LoHD) (age at onset ≥60 years) and the associations of the number of mutant CAG repeats and age at onset (AAO) with survival in patients with HD., Methods: Patients with genetically confirmed HD at six referral centers in South Korea between 2000 and 2020 were analyzed retrospectively. Baseline demographic, clinical, and genetic characteristics and the survival status as at December 2020 were collected., Results: Eighty-seven patients were included, comprising 26 with LoHD (AAO=68.77±5.91 years, mean±standard deviation; 40.54±1.53 mutant CAG repeats) and 61 with common-onset HD (CoHD) (AAO=44.12±8.61 years, 44.72±4.27 mutant CAG repeats). The ages at death were 77.78±7.46 and 53.72±10.86 years in patients with LoHD and CoHD, respectively ( p <0.001). The estimated survival time was 15.21±2.49 years for all HD patients, and 10.74±1.95 and 16.15±2.82 years in patients with LoHD and CoHD, respectively. More mutant CAG repeats and higher AAO were associated with shorter survival (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.01-1.09, p =0.019; and HR=1.17, 95% CI=1.03-1.31, p =0.013; respectively) for all HD patients. The LoHD group showed no significant factors associated with survival after disease onset, whereas the number of mutant CAG repeats had a significant effect (HR=1.12, 95% CI=1.01-1.23, p =0.034) in the CoHD group., Conclusions: Survival after disease onset was shorter in patients with LoHD than in those with CoHD. More mutant CAG repeats and higher AAO were associated with shorter survival in patients with HD., Competing Interests: Sun Ju Chung, a contributing editor of the Journal of Clinical Neurology, was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Korean Neurological Association.)

Objective: To investigate how the visual complexity of head-up displays (HUDs) influence the allocation of driver's attention in two separate visual domains (near and far domains)., Background: The types and amount of information displayed on automobile HUDs have increased. With limited human attention capacity, increased visual complexity in the near domain may lead to interference in the effective processing of information in the far domain., Method: Near-domain and far-domain vision were separately tested using a dual-task paradigm. In a simulated road environment, 62 participants were to control the speed of the vehicle (SMT; near domain) and manually respond to probes (PDT; far domain) simultaneously. Five HUD complexity levels including a HUD-absent condition were presented block-wise., Results: Near domain performance was not modulated by the HUD complexity levels. However, the far domain detection accuracies were impaired as the HUD complexity level increased, with greater accuracy differences observed between central and peripheral probes., Conclusion: Increased HUD visual complexity leads to a biased deployment of driver attention toward the central visual field. Therefore, the formulation of HUD designs must be preceded by an in-depth investigation of the dynamics of human cognition., Application: To ensure driving safety, HUD designs should be rendered with minimal visual complexity by incorporating only essential information relevant to driving and removing driving-irrelevant or additional visual details.

Purpose: This study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper rectal cancer and to investigate whether AC is associated with improved survival outcomes., Methods: This retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative chemoradiotherapy between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, perineural invasion, resection margin involvement, and < 12 lymph nodes harvested., Results: Among the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs. 84.6%, P = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs. 64.1%, P = .01) and 5-year OS (88.8% vs. 69.0%, P = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged > 65 years., Conclusion: AC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors., Competing Interests: Disclosure The authors have no competing interest to declare that are relevant to this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context.—: Distinguishing metastatic carcinomas from mesotheliomas or reactive mesothelial cells in pleural, peritoneal, and pericardial effusions is a common diagnostic problem cytopathologists encounter., Objective.—: To perform the first meta-analysis on the pooled diagnostic accuracy of claudin-4 immunochemistry in serous effusion cytopathology., Design.—: This report followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for diagnostic test accuracy studies. Three databases (PubMed, Scopus, and the Cochrane Library) were searched until October 9, 2023, followed by study selection using specific inclusion and exclusion criteria and data extraction. The study quality assessment was performed by using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Statistical analysis was performed by using R to calculate the pooled sensitivity and specificity of claudin-4 immunochemistry. In addition, the diagnostic odds ratio was measured, representing the odds ratio of a positive result indicating a carcinoma rather than a mesothelial process in serous effusion cytology., Results.—: Fourteen observational studies, published between 2011 and 2023, fulfilled the selection criteria and were included. All 14 studies used the 3E2C1 clone. Claudin-4 immunochemistry showed a high diagnostic accuracy in serous effusion cytology. The pooled sensitivity and specificity were 98.02% (95% CI, 93.96%-99.37%) and 99.72% (95% CI, 97.36%-99.97%), respectively. Lastly, the pooled diagnostic odds ratio was 1660.5 (95% CI, 760.0-3627.8) and no evidence of statistical heterogeneity between the included studies was found (I2 = 0%, τ2 = 0)., Conclusions.—: Claudin-4 may be used as a single pan-carcinoma immunochemical biomarker in the differential diagnosis between metastatic carcinomas and mesotheliomas or reactive mesothelial cells in serous effusion cytology., (© 2024 College of American Pathologists.)

Objective: The objective of this study is to compare the psychosocial characteristics of functional dyspepsia (FD) with its subgroups, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), against a healthy control group, and to investigate the quality of life (QoL)., Methods: All of the subjects were 210 adults, 131 patients with FD were diagnosed by gastroenterologist and 79 adults with no observable symptoms of FD were selected as the normal control group. Demographic factors were investigated. The Korean-Beck Depression Inventory-II, Korean-Beck Anxiety Inventory, Korean-Childhood Trauma Questionnaire, Multidimensional Scale of Perceived Social Support, Connor-Davidson Resilience Scale, and WHO Quality of Life Assessment Instrument Brief Form were used to assess psychological factors. A one-way analysis of variance was used to compare differences among the groups. Further, a stepwise regression analysis was conducted to determine factors affecting the QoL of the FD group., Results: Between-group differences in demographic characteristics were not significant. Depression (F=37.166, p<0.001), anxiety (F=30.261, p<0.001), and childhood trauma (F=6.591, p<0.01) were all significantly higher in FD group compared to the normal control. Among FD subgroups, EPS exhibited higher levels of both depression and anxiety than PDS. Social support (F=17.673, p<0.001) and resilience (F=8.425, p<0.001) were significantly lower in FD group than in other groups, and the values were higher in PDS than in EPS. Resilience (β=0.328, p<0.001) was the most important explanatory variable. The explained variance was 46.6%., Conclusion: Significantly more symptoms of depression, anxiety, childhood trauma was observed for both FD sub-group. These groups also had less social support, resilience, and QoL than the control groups.

This study investigates the efficacy of a thermo-responsive N-acetylcysteine (NAC) hydrogel on wound healing and oral ulcer recovery. Formulated by combining NAC with methylcellulose, the hydrogel's properties were assessed for temperature-induced gelation and cell viability using human fibroblast cells. In vivo experiments on Sprague Dawley rats compared the hydrogel's effects against saline, NAC solution, and a commercial NAC product. Results show that a 5% NAC and 1% methylcellulose solution exhibited optimal outcomes. While modest improvements in wound healing were observed, significant enhancements were noted in oral ulcer recovery, with histological analyses indicating fully regenerated mucosal tissue. The study concludes that modifying viscosity enhances NAC retention, facilitating tissue regeneration. These findings support previous research on the beneficial effects of antioxidant application on damaged tissues, suggesting the potential of NAC hydrogels in improving wound care and oral ulcer treatment.

Background: Oral ulcers are a common side effect of chemotherapy and affect patients' quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness., Methods: Animals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect., Results: The ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups., Conclusion: This study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications., (© 2024. The Author(s).)

Background: The use of electric scooters (e-scooters) continues to increase as a simple, inexpensive means of transport, resulting in a sharp increase in the incidence of scooter-related accidents. No study to date has closely examined the injury extent to the lower leg, joints, and extremities from e-scooter-related accidents. Here, we investigated the epidemiology and injury patterns of such accidents, focusing on injuries to the ankle and foot., Methods: Based on data from a single tertiary hospital's database, the demographics of 563 patients with scooter-associated injuries were analyzed retrospectively. Among the patients, 229 patients who were injured by e-scooter riding were further investigated. Based on the data, the general demographics of whole scooter-associated injuries and the injury characteristics and fracture cases of the lower leg, ankle, and foot were analyzed., Results: During the 4-year study period, the number of patients injured by e-scooters increased every year. Lower extremities were the most common injury site (67.2%) among riders, whereas injuries to the head and neck (64.3%) were more common in riders of non-electric scooters. Among the lower leg, ankle, and foot injuries of riders (52 cases), the ankle joint (53.8%) was the most commonly injured site, followed by the foot (40.4%) and lower leg (21.2%). The fracture group scored significantly higher on the Abbreviated Injury Scale than the non-fracture group ( p < 0.001). Among the fracture group (20 cases), ankle fractures (9 cases) were most common, including pronation external rotation type 4 injuries (4 cases) and pilon fractures (2 cases). Five patients (25%) had open fractures, and 12 patients (60%) underwent surgical treatment., Conclusions: The ankle and foot are the most common injury sites in e-scooter-related accidents. Given the high frequency and severity of e-scooter-related ankle and foot injuries, we suggest that more attention be paid to preventing these types of injuries with greater public awareness of the dangers of using e-scooters., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Background: Patients with breast cancer have a higher risk of developing lung cancer than the general population. The study aimed to evaluate the prevalence of ground glass nodule (GGN) and risk factors for GGN growth in patients with breast cancer and to evaluate the prevalence and pathologic features of lung cancer., Methods: We retrospectively reviewed the clinical data and chest computed tomography (CT) of 1,384 patients diagnosed with breast cancer who underwent chest CT between January 2008 and December 2022. We evaluated the prevalence of GGNs and their size changes on follow-up chest CT with volume doubling time (VDT) and identified independent risk factors associated with the growth of GGN using multivariable logistic regression analyses. Furthermore, the prevalence and pathologic features of lung cancer were also evaluated., Results: We detected persistent GGNs in 69 of 1,384 (5.0%) patients. The initial diameter of GGNs was 6.3±3.6 mm on average, with primarily (85.5%) pure GGNs. Among them, 27 (39.1%) exhibited interval growth with a median VDT of 1,006.0 days (interquartile range, 622.0-1,528.0 days) during the median 959.0 days (interquartile range, 612.0-1,645.0 days) follow-up period. Older age (P=0.026), part-solid nodules (P=0.006), and total number of GGNs (≥2) (P=0.007) were significant factors for GGN growth. Lung cancer was confirmed in 13 of 1,384 patients (0.9%), all with adenocarcinoma, including one case of minimally invasive adenocarcinoma. The cancers demonstrated a high rate of epidermal growth factor receptor (EGFR) mutation (69.2%)., Conclusions: Persistent GGNs in breast cancer patients with high-risk factors should be adequately monitored for early detection and treatment of lung cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1605/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background/aims: Although guidelines exist regarding the evaluation and management of patients with chronic constipation (CC), little is known about real-world clinical practice patterns. This study aimed to evaluate the various practices used to manage CC patients in various clinical settings in South Korea., Methods: A nationwide web-based survey was conducted, randomly selecting gastroenterologists and non-gastroenterologists. The 25-item questionnaire included physicians' perceptions and practices regarding the available options for diagnosing and managing CC patients in Korea., Results: The study participants comprised 193 physicians (86 gastroenterologists, 44.6%) involved in the clinical management of CC patients. The mean clinical experience was 12 years. Only 21 of 193 respondents (10.9%) used the Rome criteria when diagnosing CC. The Bristol Stool Form Scale was used by 29% of the respondents (56/193), while the digital rectal examination was performed by 11.9% of the respondents (23/193). Laboratory testing and colonoscopies were performed more frequently by gastroenterologists than by non-gastroenterologists (both p=0.001). Physiologic testing was used more frequently by gastroenterologists (p=0.046), physicians at teaching hospitals, and physicians with clinical experience ≤10 years (both p<0.05). There were also significant differences in the preference for laxatives depending on the type of hospital., Conclusions: There were discrepancies in the diagnosis and management of CC patients depending on the clinical setting. The utilization rates of the Bristol Stool Form Scale and digital rectal examination by physicians are low in real-world clinical practice. These results imply the need for better and more practical training of physicians in the assessment and management of CC.

Introduction: In 2022 chatGPT™ (OpenAI, San Francisco) was introduced to the public. The complex reasoning and the natural language processing (NLP) ability of the AI platform has generated much excitement about the potential applications. This study conducted a preliminary analysis of the chatGPT™'s ability to formulate a management plan in accordance with oncological principles for patients with colorectal cancer., Methodology: Colorectal cancer cases discussed in the multidisciplinary tumor (MDT) board at a single tertiary institution between September 2022 and January 2023 were prospectively collected. The treatment recommendations made by the chatGPT™ for Stage IV, recurrent, synchronous colorectal cancer were analysed for adherence to oncological principles. The recommendations by chatGPT™ were compared with the decision plans made by the MDT., Results: In all cases, the chatGPT™ was able to adhere to oncological principles. The recommendations in all 30 cases factored in the patient's overall health and functional status. The oncological management recommendation concordance rate between chatGPT™ and the MDT was 86.7%., Conclusions: This study shows a high concordance rate of the chatGPT™'s recommendations with that given by the MDT in the management of complex colorectal patients. This will need to be verified in a larger prospective study., (© 2023 Royal Australasian College of Surgeons.)

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has led to significant global casualties. This study examines the postoperative impact of COVID-19 on patients who underwent gastrointestinal surgery, considering their heightened vulnerability to infections and increased morbidity and mortality risk., Methods: This retrospective observational study was conducted at a tertiary center and patients who underwent gastrointestinal surgery between January 2022 and February 2023 were included. Postoperative COVID-19 infection was defined as the detection of severe acute respiratory syndrome coronavirus 2 RNA by RT-PCR within 14 days after surgery. Propensity score matching was performed including age, sex, American Society of Anesthesiology physical status classification, and emergency operation between the COVID-19-negative (-) and -positive (+) groups., Results: Following 1:2 propensity score matching, 21 COVID-19(+) and 42 COVID-19(-) patients were included in the study. In the COVID-19(+) group, the postoperative complication rate was significantly higher (52.4% vs. 23.8%, P = 0.023). Mechanical ventilator requirement, intensive care unit (ICU) admission, and readmission rate did not significantly differ between the 2 groups. The median length of ICU (19 days vs. 4 days, P < 0.001) and hospital stay (18 vs. 8 days, P = 0.015) were significantly longer in the COVID-19(+) group. Patients with COVID-19 had a 2.4 times higher relative risk (RR) of major complications than patients without COVID-19 (RR, 2.37; 95% confidence interval, 1.254-4.467; P = 0.015)., Conclusion: COVID-19 infection during the postoperative period in gastrointestinal surgery may have adverse outcomes which may increase the risk of major complications. Preoperative COVID-19 screening and protocols for COVID-19 prevention in surgical patients should be maintained., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2024, the Korean Surgical Society.)

Immunophenotypic analysis of breast cancer microenvironment is gaining attraction as a clinical tool improving breast cancer patient stratification. The aim of this study is to evaluate proliferating CD8 + including CD8 + TCF1 + Τ cells along with PD-L1 expressing tissue-associated macrophages among different breast cancer subtypes. A well-characterized cohort of 791 treatment-naïve breast cancer patients was included. The analysis demonstrated a distinct expression pattern among breast cancer subtypes characterized by increased CD8 + , CD163 + and CD163 + PD-L1 + cells along with high PD-L1 status and decreased fraction of CD8 + Ki67 + T cells in triple negative (TNBC) and HER2 + compared to luminal tumors. Kaplan-Meier and Cox univariate survival analysis revealed that breast cancer patients with high CD8 + , CD8 + Ki67 + , CD8 + TCF1 + cells, PD-L1 score and CD163 + PD-L1 + cells are likely to have a prolonged relapse free survival, while patients with high CD163 + cells have a worse prognosis. A differential impact of high CD8 + , CD8 + Ki67 + , CD8 + TCF1 + T cells, CD163 + PD-L1 + macrophages and PD-L1 status on prognosis was identified among the various breast cancer subtypes since only TNBC patients experience an improved prognosis compared to patients with luminal A tumors. Conversely, high infiltration by CD163 + cells is associated with worse prognosis only in patients with luminal A but not in TNBC tumors. Multivariate Cox regression analysis in TNBC patients revealed that increased CD8 + [hazard ratio (HR) = 0.542; 95% confidence interval (CI) 0.309-0.950; p = 0.032), CD8 + TCF1 + (HR = 0.280; 95% CI 0.101-0.779; p = 0.015), CD163 + PD-L1 + (HR: 0.312; 95% CI 0.112-0.870; p = 0.026) cells along with PD-L1 status employing two different scoring methods (HR: 0.362; 95% CI 0.162-0.812; p = 0.014 and HR: 0.395; 95% CI 0.176-0.884; p = 0.024) were independently linked with a lower relapse rate. Multivariate analysis in Luminal type A patients revealed that increased CD163 + was independently associated with a higher relapse rate (HR = 2.360; 95% CI 1.077-5.170; p = 0.032). This study demonstrates that the evaluation of the functional status of CD8 + T cells in combination with the analysis of immunosuppressive elements could provide clinically relevant information in different breast cancer subtypes., (© 2024. The Author(s).)

Wound management practices have made significant advancements, yet the search for improved antiseptics persists. In our pursuit of solutions that not only prevent infections but also address broader aspects of wound care, we investigated the impact of integrating trimethyl chitosan (TMC) into a widely used poly(vinylpyrrolidone)-iodine gel (PVP-I gel). Our study assessed the antimicrobial efficacy of the PVP gel with TMC against Escherichia coli , Staphylococcus aureus , multidrug-resistant S. aureus MRSA, and Candida albicans . Additionally, we compared hemostatic effects using a liver puncture bleeding model and evaluated wound healing through histological sections from full-thickness dermal wounds in rats. The results indicate that incorporating TMC into the commercially available PVP-I gel did not compromise its antimicrobial activity. The incorporation of TMC into the PVP-I gel markedly improves its hemostatic activity. The regular application of the PVP-I gel with TMC resulted in an increased blood vessel count in the wound bed and facilitated the development of thicker fibrous tissue with a regenerated epidermal layer. These findings suggest that TMC contributes not only to antimicrobial activity but also to the intricate processes of tissue regeneration. In conclusion, incorporating TMC proves beneficial, making it a valuable additive to commercially available antiseptic agents.

This study examined the effects of increasing concrete unit water content and artificially controlling water content on concrete performance in the production process of ready-mixed concrete. Results showed that changes in the unit water content of 20 concrete mix proportions without air-entraining significantly reduced concrete compressive strength, increased porosity, and in-creased occurrence of bleeding. A unit water content increase of 25 kg/m 3 or more may reduce the compressive strength of concrete below the design standard and significantly affect the occurrence of bleeding water. Moreover, an extra unit water content of at least 25 kg/m 3 could significantly affect the diffusion of chloride ions in the concrete. The carbonation depth of concrete was extremely high with the increase in unit water content and water addition. In the production of concrete requiring at least normal strength or durability, the extra water change to total unit water content should be maintained at 15 kg/m 3 or less. And a water-cement ratio of 48% or less and a unit water content of 155 kg/m 3 or less are considered effective for management of concrete quality. Considering the aggregate type, absorption rate, and moisture state, the management of unit water content error in concrete production processes requires greater.

Background: There are growing number of pathway programs, with an early assurance of admission, that target undergraduate students from groups underrepresented in medicine (URiM) to enable their competitiveness for and matriculation to medical school, including the Penn Access Summer Scholars (PASS) program. The psychological and emotional experiences of students in these programs, however, have not been previously described., Methods: Students from the summer 2021 cohort of the PASS program were interviewed using a structured set of questions that explored four specific areas: (i) the application process; (ii) the benefits and value of being in the PASS program; (iii) the emotional and psychological challenges and stresses of being in the PASS program; (iv) feelings and emotions about not taking the MCAT or having to interview at multiple schools. The transcribed, de-identified interviews were then subjected to a qualitative analysis., Results: Students in PASS reported that the program was valuable to them in that it reduced the stress of the pre-medical process; relieved worry and anxiety surrounding the MCAT; enabled development of supportive relationships and provided meaningful exposures to the medical profession and biomedical research. Despite this, students reported feelings of imposterism, guilt, and fear of disappointing, along with varying degrees of regret over not taking the MCAT and not interviewing at more than one medical school., Conclusions: URiM and other marginalized students participating in early assurance admissions programs likely enter medical school with a range of positive and negative emotions as a result of their participation in these programs. These data can be used to inform the development of programing and other initiatives that further support the transition and success of these students in medical school., (Copyright © 2023 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Aim: To compare the immunochemical expression of EGFR, PD-L1, and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2, and MSH6 between matched malignant effusions obtained before and following the administration of chemotherapy in patients with high-grade serous tubo-ovarian carcinoma (HGSC)., Methods: In the enrolled HGSCs, matched formalin-fixed and paraffin-embedded cell blocks (CBs) from effusions sampled before (treatment-naïve patients) and during recurrence (following chemotherapy administration), in addition to their matched HGSC tissues obtained from the ovaries at initial diagnosis (treatment-naïve patients), were subjected to EGFR, PD-L1, and MMR immunochemical analysis., Results: EGFR was more often overexpressed in effusions obtained after chemotherapy administration compared to both effusions (100% vs. 57.1%) and their matched tubo-ovarian tumors (100% vs. 7.1%) from treatment-naïve patients, respectively. EGFR immunochemistry was concordant in just 9.1% of the effusions sampled during recurrence and their paired ovarian samples before recurrence. Whereas all HGSC treatment-naïve samples (ovarian lesions and effusions) were PD-L1 negative, 3/11 (27.3%) malignant effusions obtained during recurrence showed PD-L1 overexpression. Lastly, none of the tested HGSC samples exhibited MMR deficiency., Conclusion: Measuring biomarkers using CBs from malignant effusions may provide clinicians with significant information related to HGSC prognosis and therapy selection, especially in patients with resistance to chemotherapy., (© 2023 Wiley Periodicals LLC.)

Objective: The submandibular gland (SMG) produces the most saliva, and factors such as aging and chemotherapy can affect its structure and function. However, there are only temporary treatments available for salivary hypofunction. This study aimed to evaluate the effects of photobiomodulation (PBM) on the function of SMG by using a rat animal model and vismodegib, an antagonist of the sonic hedgehog (SHH) pathway. Methods: Vismodegib (10 mg/kg) drug was gavaged orally for 14 days in rats to significantly decrease the SHH signaling proteins [SHH, protein patched homolog 1 (PTCH1), smoothened protein (SMO), glioma-associated oncogene homolog 1 (GLI1)], induce damage in SMG tissue, and affect salivary functional markers AQP5 and Keratin5. After that, in conjunction with vismodegib administration, PBM was performed using an 850 nm high-power light-emitting diode (LED) device treated daily for 6 days at varying total energy densities of 60, 120, and 180 J/cm 2 in at least 3 rats per group. The test results were confirmed by Western blot, immunofluorescence staining, and hematoxylin and eosin staining, and the statistics were t -test or one-way analysis of variance (ANOVA) with Tukey's multiple comparisons tests. Results: Significant decreases in the expression of SHH-related proteins (PTCH1, SMO, GLI1, p  < 0.05) with damage of SMG ductal cells were observed with vismodegib administration. However, a significant increase in the expression levels of SHH-related proteins (SHH, SMO, GLI1, p  < 0.05) and recovery of SMG ductal cells damaged after vismodegib administration were observed for PBM-treated groups. Salivary functional marker AQP5 also showed the same increase or decrease. Conclusions: This study found that vismodegib damages SMG ductal cells and decreases SHH-related proteins and associated salivary functional markers. Also, 850 nm high-power LED recovered the damaged structure of SMG and increased SHH-related proteins and salivary functional markers. The study results suggest that PBM can restore SMG structure and function through SHH signaling.

Side streams and byproducts of food are established sources of natural ingredients in cosmetics. In the present study, we obtained upcycled low-molecular-weight anionic peptides (LMAPs) using byproducts of the post-yuzu-juicing process by employing an enzyme derived from Bacillus sp. For the first time, we isolated anionic peptides less than 500 Da in molecular weight from Citrus junos TANAKA seeds via hydrolysis using this enzyme. The protective effect of LMAPs against UVR-induced photoaging was evaluated using a reconstructed skin tissue (RST) model and keratinocytes. The LMAPs protected the keratinocytes by scavenging intracellular reactive oxygen species and by reducing the levels of paracrine cytokines (IL-6 and TNF-α) in UVR (UVA 2 J/cm 2 and UVB 15 mJ/cm 2 )-irradiated keratinocytes. Additionally, the increase in melanin synthesis and TRP-2 expression in RST caused by UVR was significantly inhibited by LMAP treatment. This treatment strongly induced the expression of filaggrin and laminin-5 in UVR-irradiated RST. It also increased type I collagen expression in the dermal region and in fibroblasts in vitro. These results suggest that a hydrolytic system using the enzyme derived from Bacillus sp. can be used for the commercial production of LMAPs from food byproducts and that these LMAPs can be effective ingredients for improving photoaging-induced skin diseases.

Distant metastasis is the leading cause of death in breast cancer (BC). The timing of distant metastasis differs according to subtypes of BCs and there is a need for identification of biomarkers for the prediction of early and late metastasis. To identify biomarker candidates whose abundance level can discriminate metastasis types, we performed a high-throughput proteomics assay using tissue samples from BCs with no metastasis, late metastasis, and early metastasis, processed data with machine learning-based feature selection, and found that low VWA5A could be responsible for shorter duration of metastasis-free interval. Low expression of VWA5A gene in METABRIC cohort was associated with poor survival in BCs, especially in hormone receptor (HR)-positive BCs. In-vitro experiments confirmed tumor suppressive effect of VWA5A on BCs in HR+ and triple-negative BC cell lines. We found that expression of VWA5A can be assessed by immunohistochemistry (IHC) on archival tissue samples. Decreasing nuclear expression of VWA5A was significantly associated with advanced T stage and lymphatic invasion in consecutive BCs of all subtypes. We discovered lower expression of VWA5A as the potential biomarker for metastasis-prone BCs, and our results support the clinical utility of VWA5A IHC, as an adjunctive tools for prognostication of BCs., (© 2024. The Author(s).)

In the setting of pronounced inflammation, changes in the epithelium may overlap with neoplasia, often rendering it impossible to establish a diagnosis with certainty in daily clinical practice. Here, we discuss the underlying molecular mechanisms driving tissue response during persistent inflammatory signaling along with the potential association with cancer in the gastrointestinal tract, pancreas, extrahepatic bile ducts, and liver. We highlight the histopathological challenges encountered in the diagnosis of chronic inflammation in routine practice and pinpoint tissue-based biomarkers that could complement morphology to differentiate reactive from dysplastic or cancerous lesions. We refer to the advantages and limitations of existing biomarkers employing immunohistochemistry and point to promising new markers, including the generation of novel antibodies targeting mutant proteins, miRNAs, and array assays. Advancements in experimental models, including mouse and 3D models, have improved our understanding of tissue response. The integration of digital pathology along with artificial intelligence may also complement routine visual inspections. Navigating through tissue responses in various chronic inflammatory contexts will help us develop novel and reliable biomarkers that will improve diagnostic decisions and ultimately patient treatment.

Background: There have been reports of otolaryngological adverse event following immunization (AEFI) such as instances of olfactory and gustatory dysfunction following COVID-19 vaccination. This study aimed to analyze otolaryngological AEFIs following COVID-19 vaccination., Methods: This study was conducted with a secondary data analysis that the Vaccine Adverse Events Reporting System (VAERS) and the COVID-19 Data Tracker, which are both administered by the Centers for Disease Control and Prevention in the US. Using Medical Dictionary for Regulatory Activities (MedDRA) concepts, AEFIs included: Considering the overall frequency and similarity of symptoms in the first 153 PTs, they were grouped into major 19 AEFIs groups. The incidence rates (IRs) of AEFIs per 100,000 were calculated on individual and cumulative AEFIs levels, involving people who received complete primary series and an updated bivalent booster dose with one of the available COVID-19 vaccines in the US. The proportions of AEFIs by age, sex, and vaccine manufacturer were reported. We also calculated the proportional reporting ratio (PRR) of AEFIs., Results: We identified 106,653 otorhinolaryngologic AEFIs from the VAERS database, and a total of 226,593,618 people who received complete primary series in the US. Overall, the IR of total Otorhinolaryngologic AEFIs was 47.068 of CPS (completed primary series) and 7.237 UBB (updated bivalent booster) per 100,000. For most symptoms, being female was associated with statistically significant higher AEFIs. Upon examining the impact of different vaccine manufacturers, the researchers found that Janssen's vaccine exhibited higher IRs for hearing loss (5.871), tinnitus (19.182), ear infection (0.709), dizziness (121.202), sinusitis (2.088), epistaxis (4.251), anosmia (5.264), snoring (0.734), allergies (5.555), and pharyngitis (5.428). The highest PRRs were for Anosmia (3.617), Laryngopharyngeal Reflux - Acid Reflux (2.632), and Tinnitus -Ringing in the ears (2.343), in that order, with these three significantly incidence than other background noises., Conclusion: This study, utilizing an extensive sample sizes, represents a significant step toward comprehensively characterizing the otolaryngological AEFIs associated with COVID-19 vaccinations. This large-scale analysis aims to move beyond isolated case reports and anecdotal evidence, providing a robust and detailed portrait of the otolaryngological AEFIs landscape in response to COVID-19 vaccinations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shin, Shim, Lee, Ryu and Kim.)

Introduction: Fine-needle aspiration cytology (FNAC) specimens are widely utilized for the diagnosis and molecular testing of various cancers. We performed a comparative proteomic analysis of three different sample types, including breast FNAC, core needle biopsy (CNB), and surgical resection tissues. Our goal was to evaluate the suitability of FNAC for in-depth proteomic analysis and for identifying potential therapeutic biomarkers in breast cancer., Methods: High-throughput proteomic analysis was conducted on matched FNAC, CNB, and surgical resection tissue samples obtained from breast cancer patients. The protein identification, including currently established or promising therapeutic targets, was compared among the three different sample types. Gene Ontology (GO) enrichment analysis was also performed on all matched samples., Results: Compared to tissue samples, FNAC testing revealed a comparable number of proteins (7,179 in FNAC; 7,196 in CNB; and 7,190 in resection samples). Around 85% of proteins were mutually identified in all sample types. FNAC, along with CNB, showed a positive correlation between the number of enrolled tumor cells and identified proteins. In the GO analysis, the FNAC samples demonstrated a higher number of genes for each pathway and GO terms than tissue samples. CCND1, CDK6, HER2, and IGF1R were found in higher quantities in the FNAC compared to tissue samples, while TUBB2A was only detected in the former., Conclusion: FNAC is suitable for high-throughput proteomic analysis, in addition to an emerging source that could be used to identify and quantify novel cancer biomarkers., (© 2024 S. Karger AG, Basel.)

Introduction: Immunohistochemistry (IHC) for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) biomarkers has prognostic and therapeutic value in breast cancer. This study aimed to compare the expression of ER, PR, and HER2 between paired malignant effusions and tissue samples of breast cancer., Methods: Our electronic archive was searched for all effusions diagnosed as breast carcinomas within a pre-defined period (January 2018-October 2021). Next, their cell blocks (CBs) were subjected to ER, PR, HER2 IHC, or in situ hybridization, in addition to EGFR IHC. The expression of hormone receptors (HRs) and HER2 was subsequently compared between tissue and effusion cytology samples derived from the same patients., Results: Only 2/76 (2.6%) of the breast cancer patients analyzed showed a malignant effusion at their initial presentation. ER, PR, and HER2 discordance rates between paired malignant effusions and tissue samples obtained at initial diagnosis were 24.3% (17/73), 40.8% (29/71), and 9.1% (6/66), respectively. The HR-/HER2- status was found more often at effusions compared to paired tissue biopsies obtained at initial diagnosis (30/70 vs. 17/70; p &lt; 0.001). In addition, the HR-/HER2- status was significantly associated with an earlier development of a malignant effusion, when found at initial diagnosis (p &lt; 0.001; log-rank test), first recurrence/metastasis (either solid or effusion) (p = 0.012; log-rank test), effusion samples (p = 0.007; log-rank test), and any tumor sample obtained (p = 0.009; log-rank test). Lastly, EGFR overexpression in the HR-/HER2- effusion samples was significantly associated with a shorter post-effusion survival (p = 0.019; log-rank test)., Conclusion: Serous effusion cytology provides high-quality material for ancillary techniques, especially when CBs are prepared, reflecting cancer heterogeneity., (© 2023 S. Karger AG, Basel.)