First Case of Septic Shock Caused by Cetobacterium Somerae.

BACKGROUND: Cetobacterium somerae rarely causes infection in humans. Most studies on C. somerae have analyzed its role in the intestinal system of freshwater fish. METHODS: Herein, we report a case of septic shock caused by C. somerae in an elderly patient. RESULTS: Blood culture revealed growth of a gram-negative, rod-shaped anaerobic bacterium, which was identified as C. somerae through MALDI-TOF analyses. Although C. somerae is a resident species in the gut, it can cause systemic infection, which can be fatal. CONCLUSIONS: When C. somerae is identified, consideration should be given to the possibility of the infection originating from the intestinal tract.

Nilotinib treatment outcomes in autosomal dominant spinocerebellar ataxia over one year.

We evaluated the efficacy and safety of 1-year treatment with nilotinib (Tasigna®) in patients with autosomal dominant spinocerebellar ataxia (ADSCA) and the factors associated with responsiveness. From an institutional cohort, patients with ADSCA who completed a 1-year treatment with nilotinib (150-300 mg/day) were included. Ataxia severity was assessed using the Scale for the Rating and Assessment of Ataxia (SARA), scores at baseline and 1, 3, 6, and 12 months. A subject was categorized 'responsive' when the SARA score reduction at 12 M was > 0. Pretreatment serum proteomic analysis included subjects with the highest (n = 5) and lowest (n = 5) SARA score change at 12 months and five non-ataxia controls. Thirty-two subjects (18 [56.2%] females, median age 42 [30-49.5] years) were included. Although SARA score at 12 M did not significantly improve in overall population, 20 (62.5%) subjects were categorized as responsive. Serum proteomic analysis identified 4 differentially expressed proteins, leucine-rich alpha-2-glycoprotein (LRG1), vitamin-D binding protein (DBP), and C4b-binding protein (C4BP) beta and alpha chain, which are involved in the autophagy process. This preliminary data suggests that nilotinib might improve ataxia severity in some patients with ADSCA. Serum protein markers might be a clue to predict the response to nilotinib.Trial Registration Information: Effect of Nilotinib in Cerebellar Ataxia Patients (NCT03932669, date of submission 01/05/2019).

Effects of oridonin on sperm function and the PI3K/PDK1/AKT signaling pathway: Implications for reproductive toxicity.

Oridonin, a natural terpenoid isolated from the leaves of Isodon rubescens (Hemsley) H.Hara, is widely used in oriental medicine for its anticancer properties across various cancer types. Despite its prevalent use, the toxic effects of oridonin on male reproduction, particularly its impact on sperm functions and the mechanisms involved, are not well understood. This study aimed to explore the effects and underlying mechanisms of oridonin on sperm functions. We initially treated Duroc boar spermatozoa with varying concentrations of oridonin (0, 5, 50, 75, 100, and 150 µM) and incubated them to induce capacitation. We then assessed cell viability and several sperm functions, including sperm motility and motion kinematics, capacitation status, and ATP levels. We also analyzed the expression levels of proteins associated with the phosphatidylinositol 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/protein kinase B (AKT) signaling pathway and phosphotyrosine proteins. Our results indicate that oridonin adversely affects most sperm functions in a dose-dependent manner. We observed significant decreases in AKT, p-AKT (Thr308), phosphatase and tensin homolog (PTEN), p-PDK1, and p-PI3K levels following oridonin treatment, alongside an abnormal increase in phosphotyrosine proteins. These findings suggest that oridonin may disrupt normal levels of tyrosine-phosphorylated proteins by inhibiting the PI3K/PDK1/AKT signaling pathway, which is crucial for cell proliferation, metabolism, and apoptosis, thus potentially harming sperm functions. Consequently, we recommend considering the reproductive toxicity of oridonin when using it as a therapeutic agent.

Hybrid Organic-Si C-MOSFET Image Sensor Designed with Blue-, Green-, and Red-Sensitive Organic Photodiodes on Si C-MOSFET-Based Photo Signal Sensor Circuit.

The resolution of Si complementary metal-oxide-semiconductor field-effect transistor (C-MOSFET) image sensors (CISs) has been intensively enhanced to follow the technological revolution of smartphones, AI devices, autonomous cars, robots, and drones, approaching the physical and material limits of a resolution increase in conventional Si CISs because of the low quantum efficiency (i.e., ~40%) and aperture ratio (i.e., ~60%). As a novel solution, a hybrid organic-Si image sensor was developed by implementing B, G, and R organic photodiodes on four n-MOSFETs for photocurrent sensing. Photosensitive organic donor and acceptor materials were designed with cost-effective small molecules, i.e., the B, G, and R donor and acceptor small molecules were Coumarin6 and C_60, DMQA and MePTC, and ZnPc and TiOPc, respectively. The output voltage sensing margins (i.e., photocurrent signal difference) of the hybrid organic-Si B, G, and R image sensor pixels presented results 17, 11, and 37% higher than those of conventional Si CISs. In addition, the hybrid organic-Si B, G, and R image sensor pixels could achieve an ideal aperture ratio (i.e., ~100%) compared with a Si CIS pixel using the backside illumination process (i.e., ~60%). Moreover, they may display a lower fabrication cost than image sensors because of the simple image sensor structure (i.e., hybrid organic-Si photodiode with four n-MOSFETs).

Trajectory of medical expenditure and regional disparities in hypertensive patients in South Korea.

The aim of this study is to understand how different regions influence the management and financial burden of hypertension, and to identify regional disparities in hypertension management and medical expenditure. The study utilized data from the Korean Health Panel Survey conducted between 2014 and 2018, focusing on individuals with hypertension. Medical expenditures were classified into three trajectory groups: "Persistent Low," "Expenditure Increasing," and "Persistent High" over a five-year period using trajectory analysis. Inverse Probability Weighting (IPW) analysis was then employed to identify the association between regions and medical expenditure trajectories. The results indicate that individuals residing in metropolitan cities (Busan, Daegu, Incheon, Gwangju, Daejeon, and Ulsan) and rural areas were more likely to belong to the "Expenditure Increasing" group compared to the "Persistent Low Expenditure" group (OR = 1.07; 95% CI; p < 0.001), as opposed to those in the capital city (Seoul) (OR = 1.07; 95% CI; p < 0.001). Additionally, residents of rural areas were more likely to be in the "High Expenditure" group compared to the "Persistent Low Expenditure" group than those residing in the capital city (OR = 1.05; 95% CI; p = 0.001). These findings suggest that individuals in rural areas may be receiving relatively inadequate management for hypertension, leading to higher medical expenditures compared to those in the capital region. These disparities signify health inequality and highlight the need for policy efforts to address regional imbalances in social structures and healthcare resource distribution to ensure equitable chronic disease management across different regions.

Wastewater-borne viruses and bacteria, surveillance and biosensors at the interface of academia and field deployment.

Wastewater is a complex, but an ideal, matrix for disease monitoring and surveillance as it represents the entire load of enteric pathogens from a local catchment area. It captures both clinical and community disease burdens. Global interest in wastewater surveillance has been growing rapidly for infectious diseases monitoring and for providing an early warning of potential outbreaks. Although molecular detection methods show high sensitivity and specificity in pathogen monitoring from wastewater, they are strongly limited by challenges, including expensive laboratory settings and prolonged sample processing and analysis. Alternatively, biosensors exhibit a wide range of practical utility in real-time monitoring of biological and chemical markers. However, field deployment of biosensors is primarily challenged by prolonged sample processing and pathogen concentration steps due to complex wastewater matrices. This review summarizes the role of wastewater surveillance and provides an overview of infectious viral and bacterial pathogens with cutting-edge technologies for their detection. It emphasizes the practical utility of biosensors in pathogen monitoring and the major bottlenecks for wastewater surveillance of pathogens, and overcoming approaches to field deployment of biosensors for real-time pathogen detection. Furthermore, the promising potential of novel machine learning algorithms to resolve uncertainties in wastewater data is discussed.

Optimal methodology for percutaneous dilatational tracheostomy: a comparative analysis between conventional and multidisciplinary approaches utilizing ultrasound, flexible bronchoscopy, and microcatheter puncture in critically ill individuals of diminutive stature-a longitudinal single-institutional experience and retrospective analysis.

Background: Percutaneous dilatational tracheostomy (PDT), a bedside procedure in intensive care, enhances respiratory support for critically ill patients with benefits over traditional tracheostomy, such as improved safety, ease of use, cost-effectiveness, and operational efficiency by eliminating patient transfers to the operating room. It also minimizes complications including bleeding, infection, and inflammation. Despite decades of PDT evolution and device diversification, adaptations primarily cater to larger Western patients rather than smaller-statured Korean populations. This study assesses the efficacy and appropriateness of the Ciaglia Blue Rhino (Cook Critical Care, Bloomington, IN, USA), augmented with ultrasound, flexible bronchoscopy, and microcatheter techniques, for Korean patients with short stature. Methods: We conducted PDT on 183 intubated adults (128 male/55 female) with severe respiratory issues at a single medical center from January 2010 to December 2022. Patients were divided into two groups for retrospective analysis: a modified group (n=133) underwent PDT with ultrasound-guided flexible bronchoscopy and microcatheter puncture, and a conventional group (n=50) received PDT using only the Ciaglia Blue Rhino device. We assessed clinical and demographic characteristics, outcomes, and complications such as pneumothorax and emphysema. The study also evaluated the suitability and effectiveness of the devices for Korean patients with short stature. Results: Demographic characteristics including sex, body weight, height, body mass index, obesity status, and underlying diseases showed no significant differences between the two groups. However, the modified group was older (69.5±14.2 vs. 63.5±14.1 years; P=0.01). The sequential organ failure assessment (SOFA) and simplified acute physiology score (SAPS) II score was slightly higher in the modified groups, but no statistically significant differences were observed (7.1±2.3 vs. 6.7±2.3, P=0.31 and 46.7±9.0 vs. 44.0±9.1, P=0.08, respectively). The duration of hospital and ICU stays, as well as days post-PDT, were longer in the conventional group, yet these differences were not statistically significant (P=0.20, P=0.44, P=0.06). Total surgical time, including preparation, ultrasound, bronchoscopy, and microcatheter puncture, was significantly longer in the modified group (25.6±7.5 vs. 19.9±6.5 minutes; P<0.001), and the success rate of the first tracheal puncture was also higher (100.0% vs. 92.0%; P=0.006). Intra-operative bleeding was less frequent in the modified group (P=0.02 for tracheostomy site bleeding and P=0.002 for minor bleeding). Conclusions: PDT, performed at the bedside in intensive care settings, proves to be a swift and dependable method. Utilizing the Ciaglia Blue Rhino device, combined with ultrasound guidance, flexible bronchoscopy, and 4.0-Fr microcatheter puncture, PDT is especially effective for intubated patients who cannot be weaned from ventilation. This technique results in fewer complications than traditional tracheostomy and is particularly beneficial for patients with respiratory issues and smaller-statured Koreans, potentially reducing morbidity and mortality.

Clinical outcomes of neoadjuvant chemoradiotherapy followed by total mesorectal excision in locally advanced rectal cancer with mesorectal fascia involvement.

PURPOSE: For the treatment of locally advanced rectal cancer (LARC), research on primary lesions with mesorectal fascia (MRF) involvement is lacking. This study analyzed the clinical outcomes and efficacy of dose-escalated neoadjuvant concurrent chemoradiotherapy (NCRT) to patients with LARC involving MRF. MATERIALS AND METHODS: We retrospectively reviewed 301 patients who were diagnosed with LARC involving MRF and underwent NCRT followed by total mesorectal excision (TME). Patients who received radiotherapy (RT) doses of ≤50.4 Gy were defined as the non-boost group, while ≥54.0 Gy as the boost group. Pathological tumor response and survival outcomes, including intrapelvic recurrence-free survival (IPRFS), distant metastases-free survival (DMFS) and overall survival (OS), were analyzed. RESULTS: A total of 269 patients (89.4%) achieved a negative pathological circumferential resection margin and 104 (34.6%) had good pathological tumor regression grades. With a median follow-up of 32.4 months, IPRFS, DMFS, and OS rates at 5-years were 88.6%, 78.0%, and 91.2%, respectively. In the subgroup analysis by RT dose, the boost group included more advanced clinical stages of patients. For the non-boost group and boost group, 5-year IPRFS rates were 90.3% and 87.0% (p = 0.242), 5-year DMFS rates were 82.0% and 71.3% (p = 0.105), and 5-year OS rates were 93.0% and 80.6% (p = 0.439), respectively. Treatment related toxicity was comparable between the two groups (p = 0.211). CONCLUSION: Although this retrospective study failed to confirm the efficacy of dose-escalated NCRT, favorable IPRFS and pathological complete response was achieved with NCRT followed by TME. Further studies combining patient customized RT dose with systemic therapies are needed.

Diaphragm-sparing efficacy of subparaneural upper trunk block for arthroscopic shoulder surgery: A randomised controlled trial.

BACKGROUND: Inter-scalene block (ISB) is associated with an inevitable risk of hemi-diaphragmatic paresis (HDP). To reduce the risk of HDP, an upper trunk block (UTB) has been proposed at the brachial plexus division level. OBJECTIVE: We hypothesised that UTB would be associated with a lower incidence of HDP than ISB while providing sufficient analgesia following arthroscopic shoulder surgery. DESIGN: Randomised controlled trial. SETTING: A tertiary teaching hospital. PATIENTS: Seventy patients aged 20 to 80 years undergoing arthroscopic rotator cuff repair. INTERVENTION: Ultrasound-guided ISB or UTB was performed with 5 ml 0.75% ropivacaine. MAIN OUTCOME MEASURES: The primary outcome was the incidence of complete HDP, assessed by diaphragm excursion using ultrasound, defined as a decrease to 25% or less of baseline or occurrence of paradoxical movement. Postoperative pulmonary function change, pain scores, opioid consumption and pain-related outcomes were the secondary outcomes. RESULTS: The UTB group had a significantly lower incidence of complete HDP than the ISB group [5.9% (2/34) vs. 41.7% (15/36); absolute difference, 35.8%; 95% confidence interval (CI), 17.8 to 53.7%; P < 0.001]. The postblockade decline in pulmonary function was more pronounced in the ISB group than that in the UTB group. The pain score at 1 h postoperatively was not significantly different between the groups (ISB vs. UTB group: median 0 vs. 1; median difference, -1; 95% CI, -2 to 0.5). No significant difference was observed in any other secondary outcomes. CONCLUSION: UTB was associated with a lower incidence of HDP compared with ISB while providing excellent analgesia in arthroscopic shoulder surgery. TRIAL REGISTRATION: Clinical Trial Registry of Korea (https://cris.nih.go.kr) identifier: KCT0007002. IRB NUMBER: Chungnam National University Hospital Institutional Review Board No. 2021-12-069.

Assessing the Risks of Pesticide Exposure: Implications for Endocrine Disruption and Male Fertility.

Pesticides serve as essential tools in agriculture and public health, aiding in pest control and disease management. However, their widespread use has prompted concerns regarding their adverse effects on humans and animals. This review offers a comprehensive examination of the toxicity profile of pesticides, focusing on their detrimental impacts on the nervous, hepatic, cardiac, and pulmonary systems, and their impact on reproductive functions. Additionally, it discusses how pesticides mimic hormones, thereby inducing dysfunction in the endocrine system. Pesticides disrupt the endocrine system, leading to neurological impairments, hepatocellular abnormalities, cardiac dysfunction, and respiratory issues. Furthermore, they also exert adverse effects on reproductive organs, disrupting hormone levels and causing reproductive dysfunction. Mechanistically, pesticides interfere with neurotransmitter function, enzyme activity, and hormone regulation. This review highlights the effects of pesticides on male reproduction, particularly sperm capacitation, the process wherein ejaculated sperm undergo physiological changes within the female reproductive tract, acquiring the ability to fertilize an oocyte. Pesticides have been reported to inhibit the morphological changes crucial for sperm capacitation, resulting in poor sperm capacitation and eventual male infertility. Understanding the toxic effects of pesticides is crucial for mitigating their impact on human and animal health, and in guiding future research endeavors.

Association between metabolic dysfunction-associated steatotic liver disease and myosteatosis measured by computed tomography.

BACKGROUND: In 2023, the concept of metabolic dysfunction-associated steatotic liver disease (MASLD) was introduced as an alternative to non-alcoholic fatty liver disease (NAFLD). We aimed to assess the quantity and quality of skeletal muscle using each of these diagnostic classifications. METHODS: This cross-sectional study included 18 154 participants (11 551 [63.6%] men and 6603 [36.4%] women, mean age 53.0 ± 8.8). The participants were classified into four categories: neither steatotic liver disease (SLD), NAFLD only, MASLD only or both SLDs. An appendicular skeletal muscle mass adjusted for body mass index of <0.789 for men and <0.512 for women was defined as sarcopenia. The total abdominal muscle area (TAMA) at the L3 vertebral level was segmented into normal-attenuation muscle area (NAMA), low-attenuation muscle area and intermuscular/intramuscular adipose tissue. Myosteatosis was defined by a T-score < -1.0 of the NAMA/TAMA index, which was calculated by dividing the NAMA by the TAMA and multiplying by 100. RESULTS: Using subjects with neither SLD as a reference, the multivariable-adjusted odds ratios (ORs) for sarcopenia were significantly increased in those with MASLD, with adjusted ORs (95% confidence interval [CI]) of 2.62 (1.94-3.54) in the MASLD-only group and 2.33 (1.92-2.82) in the both SLDs group, while the association was insignificant in those with NAFLD only (adjusted OR [95% CI]: 2.16 [0.67-6.94]). The OR for myosteatosis was also elevated in the MASLD groups, with an OR (95% CI) of 1.75 (1.52-2.02) in subjects with MASLD only and 1.70 (1.57-1.84) in those with both SLDs, while it was slightly decreased in subjects with NAFLD only (0.52 [0.29-0.95]). CONCLUSIONS: Employing the MASLD concept rather than that of the NAFLD proved to be more effective in distinguishing individuals with reduced muscle mass and compromised muscle quality.

Predictive model of IVF outcomes for polycystic ovarian morphology and polycystic ovary syndrome in GnRH antagonist protocol using AMH-MoM and ovarian sensitivity index.

AIM: To evaluate the relationship between AMH and ovarian response to controlled ovarian hyperstimulation in women with PCOM and PCOS. METHODS: A retrospective study was conducted on 559 patients who underwent the IVF-ET cycle between January 2018 and December 2022 at Gangnam Cha Hospital. Patients were divided into 3 groups matched for age and BMI: the PCOS group (n = 54), based on the new 2023 PCOS guideline; the PCOM group (n = 53); and the control group (n = 452) with normal ovaries. Serum AMH levels were converted to multiples of the median (MoM) for each corresponding age. The ovarian sensitivity index (OSI) was calculated as the number of retrieved oocytes divided by the total dose of recombinant FSH administered (per 1000 IU). RESULTS: There were significant differences in AMH-MoM value among women with PCOS [2.7 ± 1.3 (95% CI 2.3-3.0)], those with PCOM [2.0 ± 1.0 (95% CI 1.7-2.3)], and controls [0.8 ± 0.7 (95% CI 0.8-0.9)] (p < 0.001). The abortion rates in the normoovulatory, PCOM, and PCOS groups were 18.2%, 21.1%, and 25.0%, respectively. OSI and live birth rate were positively correlated with the AMH-MoM value in normoovulatory women (r = 0.389, p < 0.05, r = 0.122, p < 0.05), while no such correlation was observed in women with PCOM and PCOS. CONCLUSIONS: Ovarian response and live birth rate are possibly correlated with the AMH-MoM value in normoovulatory women, but not in women with PCOM and PCOS.

A prospective single-arm clinical trial to assess the safety and efficacy of monofilament polydioxanone barbed suture, MONOFIX®, on abdominal fascial closure.

BACKGROUND: For abdominal fascial closure, the choice of optimal suture material and appropriate suture technique are of paramount importance to prevent the incidence of incisional hernia. Although barbed sutures are widely used in various surgical fields, their safety and feasibility on abdominal fascial closure which requires the most tensile strength for security have not been established yet. METHODS: We conducted a prospective, single-arm, interventional clinical trial to present the postoperative outcomes of using barbed sutures in abdominal fascial closure between April 2021 and August 2021. Patients with colorectal cancer who underwent minimally invasive surgery in elective setting were included. For all participants, monofilament polydioxanone barbed suture, MONOFIX®, was used to secure the abdominal fasica. The primary outcome was the 1-year incidence of incisional hernia assessed by computed tomography. RESULTS: A total of 30 patients were included. The median fascial incision length and suture length were 6.5 cm (range, 6-7.5 cm) and 31 cm (range, 27.5-39.0 cm), respectively. The median procedure time of abdominal fascial closure was 4 min (range, 3-9 min). There was no incidence of unexpected event related to suturing including suture cutting, stopper separation from threads, and suture loosening. One case of superficial surgical site infection occurred during postoperative hospital stays. There was no fascial dehiscence, incisional hernia, and adhesive ileus during a median follow-up period of 17.5 months. CONCLUSION: Monofilament polydioxanone barbed suture, MONOFIX®, may be used safely and effectively on abdominal fascial closure. GOV NUMBER: NCT05872334.

Investigation of the status of rest facilities at industrial sites and awareness of relevant laws and regulations of South Korea.

South Korea has faced many social issues due to long working hours, lack of rest areas, and poor rest facility environments for cleaners, security guards, department store workers, etc. Discussions have been ongoing about mandating the installation of rest facilities. From August 18, 2022, Article 128-2 of the Occupational Safety and Health Act, concerning the installation of rest facilities, was enforced. Consequently, employers in all industries are required to install rest facilities, and laws have been established to ensure these facilities meet certain standards. Accordingly, this study investigated the current status of rest facility installations and the awareness of the law's enactment in Korean industrial sites. The results, analyzed by gender, age, managerial status, industry, and size of the business, indicated that younger people were less satisfied with the rest facilities. Managers were more knowledgeable about the legal regulations than workers. In the service industry, compared to other industries, smaller businesses were less likely to have rest facilities and were less aware of the legal regulations. The results of this study are expected to be used as basic data to help establish the rest facility installation laws in Korea.

Angularly offset multiline dispersive optical phased array enabling large field of view and plateau envelope.

We propose and demonstrate an angularly offset multiline (AOML) dispersive silicon nitride optical phased array (OPA) that enables efficient line beam scanning with an expanded field of view (FOV) and plateau envelope. The suggested AOML OPA incorporates multiline OPA units, which were seamlessly integrated with a 45° angular offset through a thermo-optic switch based on a multimode interference coupler, resulting in a wide FOV that combines three consecutive scanning ranges. Simultaneously, a periodic diffraction envelope rendered by the multiline OPA units contributes to reduced peak intensity fluctuation of the main lobe across the large FOV. An expedient polishing enabling the angled facet was diligently accomplished through the implementation of oblique polishing techniques applied to the 90° angle of the chip. For each dispersive OPA unit, we engineered an array of delay lines with progressively adjustable delay lengths, enabling a passive wavelength-tunable beam scanning. Experimental validation of the proposed OPA revealed efficient beam scanning, achieved by wavelength tuning from 1530 to 1600 nm and seamless switching between multiline OPAs, yielding an FOV of 152° with a main lobe intensity fluctuation of 2.8 dB. The measured efficiency of dispersive scanning was estimated at 0.97°/nm, as intended.

A Comprehensive Study on a Deep-Learning-Based Electrocardiography Analysis for Estimating the Apnea-Hypopnea Index.

This study introduces a deep-learning-based automatic sleep scoring system to detect sleep apnea using a single-lead electrocardiography (ECG) signal, focusing on accurately estimating the apnea-hypopnea index (AHI). Unlike other research, this work emphasizes AHI estimation, crucial for the diagnosis and severity evaluation of sleep apnea. The suggested model, trained on 1465 ECG recordings, combines the deep-shallow fusion network for sleep apnea detection network (DSF-SANet) and gated recurrent units (GRUs) to analyze ECG signals at 1-min intervals, capturing sleep-related respiratory disturbances. Achieving a 0.87 correlation coefficient with actual AHI values, an accuracy of 0.82, an F1 score of 0.71, and an area under the receiver operating characteristic curve of 0.88 for per-segment classification, our model was effective in identifying sleep-breathing events and estimating the AHI, offering a promising tool for medical professionals.

Lipocalin-2 as a prognostic biomarker and its association with systemic inflammation in small cell lung cancer.

BACKGROUND: Systemic inflammation is believed to contribute to small cell lung cancer (SCLC) progression, but the underlying relationship remains unclear. Lipocalin-2, a potential biomarker of inflammation, has been implicated in various cancers but its prognostic value in SCLC is underexplored. METHODS: We retrospectively analyzed 191 patients with SCLC (72 with limited-stage [LD] and 119 with extensive-stage) treated using platinum-based chemotherapy. Lipocalin-2 expression was evaluated using immunohistochemistry. Optimal cutoff values for lipocalin-2 and neutrophil-to-lymphocyte ratio (NLR) were determined using time-dependent receiver operating characteristic curve analysis. The pectoralis muscle index was used to assess sarcopenia. RESULTS: In LD-SCLC, high lipocalin-2 expression was associated with worse progression-free survival (PFS; median: 7.0 vs. 15.9 months, p = 0.015) and overall survival (OS; median: 12.9 vs. 30.3 months, p = 0.035) compared with low lipocalin-2 expression. Patients were stratified into three prognostic groups by combining lipocalin-2 with NLR: low lipocalin-2/low NLR, high lipocalin-2/low NLR or low lipocalin-2/high NLR, and high lipocalin-2/high NLR (median PFS: 17.3 vs. 11.0 vs. 6.3 months, p = 0.004; median OS: 30.5 vs. 17.3 vs. 8.6 months, p = 0.002). Similar trends were observed when combining lipocalin-2 with the pectoralis muscle index. High lipocalin-2 expression was also associated with lower complete response rates (18.9% vs. 34.3%, p = 0.035). No significant prognostic implications were found for lipocalin-2 in extensive-stage SCLC. CONCLUSIONS: High lipocalin-2 expression is potentially associated with poorer survival in LD-SCLC. Combining lipocalin-2 with other inflammation-related markers could improve prognostic stratification.

Spatial transcriptome analysis of amelanotic acral melanoma reveals distant molecular determinants compared to pigmented acral melanoma.

BACKGROUND: Amelanotic acral melanoma (AAM) is a rare type of acral melanoma associated with poor prognosis. OBJECTIVES: We aimed to investigate the transcriptomic differences between AAM and pigmented acral melanoma (PAM). METHODS: The differences in spatially resolved transcriptome profiles of 9 AAM patients with 29 regions of interest (ROIs) and 11 PAM patients with 46 ROIs were investigated using S100b and CD3 morphology markers. RESULTS: In S100b-positive tumor cell areas, we detected 11 upregulated differentially expressed genes (DEGs), including chaperone/ubiquitin-associated DEGs, and 82 downregulated DEGs, including human leukocyte antigen, in AAMs compared with PAMs. Protein-protein interaction network and pathway analyses revealed significant enrichment of dysregulated translational and nonsense-mediated decay pathways but significant decreases in antigen processing and presentation, interferon signaling, and melanin biosynthesis pathways in S100b-positive ROIs of AAMs compared with those of PAMs. In tumor-associated immune cell areas, the numbers of CD8 T cells (p = 0.044) and M1 macrophages (p = 0.014) were significantly decreased, whereas those of monocytes (p = 0.045) and endothelial cells (p = 0.04) were increased in AAMs compared with those in PAMs. CONCLUSIONS: In conclusion, these findings could widen our understanding of the biological differences between AAMs and PAMs that might result in a different clinical course.