A Modified eCura System to Stratify the Risk of Lymph Node Metastasis in Undifferentiated-Type Early Gastric Cancer After Endoscopic Resection.

PURPOSE: The original eCura system was designed to stratify the risk of lymph node metastasis (LNM) after endoscopic resection (ER) in patients with early gastric cancer (EGC). We assessed the effectiveness of a modified eCura system for reflecting the characteristics of undifferentiated-type (UD)-EGC. MATERIALS AND METHODS: Six hundred thirty-four patients who underwent non-curative ER for UD-EGC and received either additional surgery (radical surgery group; n=270) or no further treatment (no additional treatment group; n=364) from 18 institutions between 2005 and 2015 were retrospectively included in this study. The eCuraU system assigned 1 point each for tumors >20 mm in size, ulceration, positive vertical margin, and submucosal invasion <500 µm; 2 points for submucosal invasion ≥500 µm; and 3 points for lymphovascular invasion. RESULTS: LNM rates in the radical surgery group were 1.1%, 5.4%, and 13.3% for the low- (0-1 point), intermediate- (2-3 points), and high-risk (4-8 points), respectively (P-for-trend<0.001). The eCuraU system showed a significantly higher probability of identifying patients with LNM as high-risk than the eCura system (66.7% vs. 22.2%; McNemar P<0.001). In the no additional treatment group, overall survival (93.4%, 87.2%, and 67.6% at 5 years) and cancer-specific survival (99.6%, 98.9%, and 92.9% at 5 years) differed significantly among the low-, intermediate-, and high-risk categories, respectively (both P<0.001). In the high-risk category, surgery outperformed no treatment in terms of overall mortality (hazard ratio, 3.26; P=0.015). CONCLUSIONS: The eCuraU system stratified the risk of LNM in patients with UD-EGC after ER. It is strongly recommended that high-risk patients undergo additional surgery.

Evolutional dynamics of highly pathogenic avian influenza H5N8 genotypes in wintering bird habitats: Insights from South Korea's 2020-2021 season.

The winter of 2020-2021 in South Korea witnessed severe outbreaks of Highly Pathogenic Avian Influenza (HPAI) viruses, specifically multiple genotypes of the H5N8 subtype. These outbreaks prompted an extensive investigation into the genetic characteristics and evolutionary dynamics of these viruses. Under the auspices of the National Institute of Wildlife Disease Control and Prevention (NIWDC), we conducted a nationwide surveillance program, collecting 7588 specimens from diverse wild bird habitats. Influenza A viruses were isolated at a rate of 5.0%, with HPAI H5N8 viruses accounting for 38.5% of isolates, predominantly found in wild bird carcasses (97.3%). Genetic analysis revealed the emergence of novel HPAI genotypes due to genetic reassortment events. G1 and G2 viruses were separately introduced into Korea, with G1 viruses displaying dynamic behavior, resulting in diverse sub-genotypes (G1-1 to G1-5) and mainly isolated from clinical specimens. Conversely, the G2 virus, introduced later, became the dominant strain consistently isolated mainly from bird carcasses (88.9%). These findings underscore the emergence of numerous novel HPAI genotypes shaped by multiple reassortment events in high-density wintering grounds of migratory birds. These sites act as hotspots for genetic exchanges, significantly influencing avian ecology, including resident bird species, and contributing to HPAI H5N8 evolution. The genetic diversity and ongoing evolution of these viruses highlight the need for vigilant surveillance and adaptive control measures. Recognizing the potential spillover to human populations, a One Health approach is essential to mitigate the evolving threats posed by avian influenza.

Assessment and validation of glottic motion using cone-beam CT and real-time cine MRI.

PURPOSE: This study aimed to assess the margin for the planning target volume (PTV) using the Van Herk formula. We then validated the proposed margin by real-time magnetic resonance imaging (MRI). METHODS: An analysis of cone-beam computed tomography (CBCT) data from early glottic cancer patients was performed to evaluate organ motion. Deformed clinical target volumes (CTV) after rigid registration were acquired using the Velocity program (Varian Medical Systems, Palo Alto, CA, USA). Systematic (Σ) and random errors (σ) were evaluated. The margin for the PTV was defined as 2.5 Σ + 0.7 σ according to the Van Herk formula. To validate this margin, we accrued healthy volunteers. Sagittal real-time cine MRI was conducted using the ViewRay system (ViewRay Inc., Oakwood Village, OH, USA). Within the obtained sagittal images, the vocal cord was delineated. The movement of the vocal cord was summed up and considered as the internal target volume (ITV). We then assessed the degree of overlap between the ITV and the PTV (vocal cord plus margins) by calculating the volume overlap ratio, represented as (ITV∩PTV)/ITV. RESULTS: CBCTs of 17 early glottic patients were analyzed. Σ and σ were 0.55 and 0.57 for left-right (LR), 0.70 and 0.60 for anterior-posterior (AP), and 1.84 and 1.04 for superior-inferior (SI), respectively. The calculated margin was 1.8 mm (LR), 2.2 mm (AP), and 5.3 mm (SI). Four healthy volunteers participated for validation. A margin of 3 mm (AP) and 5 mm (SI) was applied to the vocal cord as the PTV. The average volume overlap ratio between ITV and PTV was 0.92 (range 0.85-0.99) without swallowing and 0.77 (range 0.70-0.88) with swallowing. CONCLUSION: By evaluating organ motion by using CBCT, the margin was 1.8 (LR), 2.2 (AP), and 5.3 mm (SI). The margin acquired using CBCT fitted well in real-time cine MRI. Given that swallowing during radiotherapy can result in a substantial displacement, it is crucial to consider strategies aimed at minimizing swallowing and related motion.

The Neuromechanics of Inspiratory Muscles in Mechanical Ventilation Liberation Success and Failure.

BACKGROUND: Assessing the neuromechanical coupling of inspiratory muscles during mechanical ventilation (MV) could reveal the physiological mechanism of MV failure. This study examined the respiratory neuromechanical characteristics between MV liberation success and failure. METHODS: This is an observational prospective study that included patients during their ventilator liberation process. Assessment of surface electromyography (sEMG) of inspiratory muscles, including the diaphragm and extra-diaphragmatic (scalene, sternocleidomastoid, and parasternal) muscles, was performed 15 minutes after the initiation of spontaneous breathing trials. Neuromechanical efficiency of the diaphragm (NMEDia) and extra-diaphragmatic muscles (NMEExtra) were compared in patients who were successfully liberated from MV with those who failed MV liberation within 72 hours after extubation. RESULTS: A total of 45 patients were enrolled and 28 were female (67%). The sample median age was 63 (IQR 47, 69) years old. One-third of patients failed MV liberation within 72 hours of their spontaneous breathing trials (SBTs). NMEDia was significantly lower in patients who failed MV liberation with a root mean square of (M 0.27), (IQR 0.21, 0.37) compared with (M 0.371), (IQR 0.3, 0.631) for the success group (p=0.0222). The area under the curve for NMEDia was lower in the failure group (M 0.270), (IQR 0.160, 0.370) and (M 0.485), (IQR 0.280, 0.683) for the success group (p=0.024). However, NMEExtra was not statistically different between the two groups. CONCLUSION: Reduced NMEDia is a predictor of MV liberation failure. NMEExtra was not a major contributor to MV liberation outcomes. Further studies should assess the performance of inspiratory muscles NME indices to predict MV liberation outcomes.

Temporal Analysis of Postoperative Outcomes With or Without Intraoperative Motor Evoked Potentials and Somatosensory Evoked Potentials Monitoring for Intracranial Meningioma Surgery.

BACKGROUND: This study aimed to retrospectively assess results of intracranial meningioma surgery with or without intraoperative neuromonitoring (IONM) in a single institution. METHODS: Two cohorts (a historical cohort and a monitoring cohort) were collected for the analysis. Before IONM was introduced, a total of 107 patients underwent intracranial meningioma operation without IONM from January 2000 to December 2008 by one neurosurgeon (historical cohort). After IONM was introduced, a total of 99 patients with intracranial meningioma were operated under IONM between November 2018 and February 2023 by two neurosurgeons (monitoring cohort). A retrospective comparison was made on the complications from meningioma surgery between the two groups. RESULTS: In the monitoring cohort, warning signals of motor evoked potential (MEPs) or somatosensory evoked potential (SSEPs) were alarmed in 10 patients. Two of these 10 patients aborted the operation and eight of these 10 patients with warning signals underwent tumor resection. Of these eight patients, five showed postoperative morbidity. Five of 89 patients without warning signals developed neurological deficits. In the historical cohort, 14 of 107 patients showed postoperative morbidity or mortality. CONCLUSION: Even after successful resection of intracranial meningiomas prior to the advent of IONM, integration of MEPs and SSEPs monitoring yielded valuable insights for surgical teams during operative procedures.

Association of musculoskeletal involvement with lung function and mortality in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with high mortality. Low muscle mass, frailty and sarcopenia lead to functional impairment that negatively impact quality of life and survival but are not used in clinical practice. We aimed to determine the association of Fat-free mass index (FFMI) and frailty with lung function, exercise tolerance and survival in patients with IPF. In this study, 70 patients with IPF underwent assessment of body composition, lung function, 6-min walk distance (6MWD) testing, hand grip strength, quality of life (QoL) assessment by St. George's Respiratory questionnaire (SGRQ) and frailty assessment using the SHARE-FI tool. FFMI was calculated using pectoralis muscle cross-sectional area (PM-CSA) on CT chest images and the lowest quartile defined reduced muscle mass. Sarcopenia was defined as low FFMI and handgrip strength. Regression analyses were conducted to determine predictive value of frailty, low FFMI and sarcopenia on clinical outcomes. The Cox proportional hazards model was used to analyze the impact of FFMI and frailty score on survival. The mean age was 70 years with moderate impairment in lung function (mean ppFVC 68.5%, ppDLCO 45.6%). Baseline forced vital capacity (p < 0.001), diffusion capacity of lung for carbon monoxide (p = < 0.01), 6WMD (p < 0.05) were significantly lower in frail patients compared to non-frail patients. BMI was found to closely correlate with FFMI (r = 0.79, p < 0.001), but not with frailty score (r = - 0.2, p = 0.07). Frailty was a significant predictor of FVC, DLCO, 6MWD, SGRQ scores when adjusted for age and gender. Muscle mass and sarcopenia were significant predictors of FVC, DLCO, but not 6MWD or QoL scores. Multivariate cox-proportional hazards ratio model adjusting for age and gender showed that frailty was significantly associated with increased mortality (HR = 2.6, 95% CI 1.1-6.1). Low FFMI (HR = 1.3, 95% CI 0.6-2.8), and sarcopenia (HR = 2.1, 95% CI 0.8-5.3), though associated with a trend to increased mortality, were not statistically significant. Frailty is associated with lower lung function and higher mortality in patients with IPF. Longitudinal evaluations are necessary to further determine the associations between low FFMI, sarcopenia and frailty with outcomes in IPF.

Identifying the external N and Hg inputs to the estuary ecosystem based on the triple isotopic information (δ15NNO3, Δ17ONO3 and δ18ONO3).

The supply and sources of N and Hg in the Geum estuary of the western coast of Korea were evaluated. Triple isotope proxies (δ15NNO3, Δ17ONO3 and δ18ONO3) of NO3- combined with conservative mixing between river and ocean waters were used to improve isotope finger-printing methods. The N pool in the Geum estuary was primarily influenced by the Yellow Sea water, followed by riverine discharge (821 × 106 mol yr-1) and atmospheric deposition (51 × 106 mol yr-1). The influence of the river was found to be greater for Hg than that of the atmosphere. The triple isotope proxies revealed that the riverine and atmospheric inputs of N have been affected by septic wastes and fossil fuel burning, respectively. From the inner estuary towards offshore region, the influence of the river diminishes, thus increasing the relative impact of the atmosphere. Moreover, the isotope proxies showed a significant influence of N assimilation in February and nitrification in May.

HA N193D substitution in the HPAI H5N1 virus alters receptor binding affinity and enhances virulence in mammalian hosts.

During the 2021/2022 winter season, we isolated highly pathogenic avian influenza (HPAI) H5N1 viruses harbouring an amino acid substitution from Asparagine(N) to Aspartic acid (D) at residue 193 of the hemagglutinin (HA) receptor binding domain (RBD) from migratory birds in South Korea. Herein, we investigated the characteristics of the N193D HA-RBD substitution in the A/CommonTeal/Korea/W811/2021[CT/W811] virus by using recombinant viruses engineered via reverse genetics (RG). A receptor affinity assay revealed that the N193D HA-RBD substitution in CT/W811 increases α2,6 sialic acid receptor binding affinity. The rCT/W811-HA193N virus caused rapid lethality with high virus titres in chickens compared with the rCT/W811-HA193D virus, while the rCT/W811-HA193D virus exhibited enhanced virulence in mammalian hosts with multiple tissue tropism. Surprisingly, a ferret-to-ferret transmission assay revealed that rCT/W811-HA193D virus replicates well in the respiratory tract, at a rate about 10 times higher than that of rCT/W811-HA193N, and all rCT/W811-HA193D direct contact ferrets were seroconverted at 10 days post-contact. Further, competition transmission assay of the two viruses revealed that rCT/W811-HA193D has enhanced growth kinetics compared with the rCT/W811-HA193N, eventually becoming the dominant strain in nasal turbinates. Further, rCT/W811-HA193D exhibits high infectivity in primary human bronchial epithelial (HBE) cells, suggesting the potential for human infection. Taken together, the HA-193D containing HPAI H5N1 virus from migratory birds showed enhanced virulence in mammalian hosts, but not in avian hosts, with multi-organ replication and ferret-to-ferret transmission. Thus, this suggests that HA-193D change increases the probability of HPAI H5N1 infection and transmission in humans.

Ambulatory Endoscopic Submucosal Dissection for Gastrointestinal Neoplasms: Trends and Associated Factors in the United States.

Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for superficial gastrointestinal (GI) cancers.1,2 ESD practice is expanding significantly in the United States and Western countries. This is attributed to a shorter hospital stay, better quality of life, and fewer adverse events compared with surgery. In the United States, ESD usually is performed and managed in an outpatient setting (ambulatory ESD) or with an overnight hospital stay. This practice is in contrast to Eastern Asian countries, where 3 to 5 days of hospital stay is a routine process for observation after ESD. A Swedish study showed that patients with well-selected colorectal neoplasms (median tumor size, 37 mm) could be managed safely in an outpatient setting after ESD.3 A North American multicenter ESD study also reported that ambulatory ESD was safe and feasible in selected cases (noninvasive cancers, no adverse events, high-volume endoscopists with short procedure time).4 However, procedural and technical aspects that enable safe outpatient management of patients after ESD need to be investigated.

Risk factors for the failure of endoscopic balloon dilation to manage anastomotic stricture from colorectal surgery: retrospective cohort study.

BACKGROUND: An anastomotic stricture after colorectal surgery is principally managed by endoscopic balloon dilation (EBD). Although this intervention is effective, however, subsequent procedures or surgical interventions are often required. This study aimed to assess the long-term outcomes of EBD for anastomotic stricture arising from colorectal cancer surgery. MATERIALS AND METHODS: We analyzed 173 patients who received curative surgery for colorectal cancer at our hospital between January 2000 and December 2022 and had undergone EBD to manage anastomotic stricture. The medical records of these cases were retrospectively reviewed to assess the outcomes and risk factors for restenosis and permanent stoma. RESULTS: Of the 173 study patients, 41 (23.7%) presented with restenosis with a median time to recurrence of 49 [37-150] days. The restenosis group was significantly younger (55.6 years versus 60.8 years), with a more prominent rectal location (80.5% versus 57.6%), a higher incidence of hand-sewn anastomosis (24.4% versus 5.3%), and a higher percentage of neoadjuvant radiotherapy (34.1% versus 5.3%, P < 0.001). Multivariable analysis indicated neoadjuvant radiotherapy (adjusted HR 2.48; 95% CI 1.03-5.95) and cerebral vascular disease (adjusted HR 6.97; 95% CI 2.15-22.54) as independent prognostic factors for restenosis. Fourteen patients (8.1%) required a permanent stoma due to treatment failure. All cases needing a permanent stoma were male (14 patients, 100%, P = 0.007) and this group had a higher rate of neoadjuvant radiotherapy, adjuvant chemotherapy, and hand-sewn anastomosis. CONCLUSION: Patients receiving neoadjuvant radiotherapy are most prone to restenosis after an EBD intervention to manage an anastomotic stricture. Neoadjuvant radiotherapy is also a strong risk factor for requiring a permanent stomas due to treatment failure.

Functional Annotation and Gene Set Analysis of Gastric Cancer Risk Loci in a Korean Population.

PURPOSE: We aimed to identify the associated single nucleotide polymorphisms (SNPs) with gastric cancer (GC) risk by genome-wide association study (GWAS) and to explore the pathway enrichment of implicated genes and gene-sets with expression patterns. MATERIALS AND METHODS: The study population was comprised of 1,253 GC cases and 4,827 controls from National Cancer Center and an urban community of the Korean Genome Epidemiology Study and their genotyping was performed. SNPs were annotated, and mapped to genes to prioritize by three mapping approaches by functional mapping and annotation (FUMA). The gene-based analysis and gene-set analysis were conducted with full GWAS summary data using MAGMA. Gene-set pathway enrichment test with those prioritized genes were performed. RESULTS: In GWAS, rs2303771, a nonsynonymous variant of KLHDC4 gene was top SNP associated significantly with GC (odds ratio, 2.59; p=1.32×10-83). In post-GWAS, 71 genes were prioritized. In gene-based GWAS, seven genes were under significant p < 3.80×10-6 (0.05/13,114); DEFB108B had the lowest p=5.94×10-15, followed by FAM86C1 (p=1.74×10-14), PSCA (p=1.81×10-14), and KLHDC4 (p=5.00×10-10). In gene prioritizing, KLDHC4 was the only gene mapped with all three gene-mapping approaches. In pathway enrichment test with prioritized genes, FOLR2, PSCA, LY6K, LYPD2, and LY6E showed strong enrichment related to cellular component of membrane; a post-translation modification by synthesis of glycosylphosphatidylinositol (GPI)-anchored proteins pathway. CONCLUSION: While 37 SNPs were significantly associated with the risk of GC, genes involved in signaling pathways related to purine metabolism and GPI-anchored protein in cell membrane are pinpointed to be playing important role in GC.

Acidity in rainwater and airborne suspended particles in the southwestern coast of the East Sea (Sea of Japan): Their potential impact on seawater total alkalinity.

Our understanding of the impact of atmospheric acid deposition on marine carbonate system remains limited, largely due to a lack of data regarding acidity present in atmospheric particles and precipitation. Previous research has relied on the electroneutrality-based ion balance method for indirect estimation of atmospheric acidity. In this study, atmospheric samples collected at a coastal site of South Korea were mixed with seawater to measure the change in seawater total alkalinity (ΔTAAPL) associated with atmospheric proton loading. For the precipitation samples, the measured ΔTAAPL and electroneutrality-based estimates showed a significant correlation. However, we did not observe similar results for the atmospheric particle samples. Furthermore, the decrease in oceanic TA due to ΔTAAPL was substantially smaller than that in dissolved inorganic carbon from concurrent nitrogen fertilization. Consequently, the adverse impact of acid deposition on ocean acidification or air-sea exchange of CO2 appears to be insignificant on a short-term scale.

Potential impact of high-density lipoprotein cholesterol in the postoperative outcomes of chronic subdural hematoma patients: multi-institutional study in Korea.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common clinical situation in neurosurgical practice, but the optimal treatment option is controversial. This study aimed to evaluate the effect of cholesterol-lowering medications on and how they affected the prognoses of CSDH patients. METHODS: In this multi-institutional observational study performed in Korea, data from recently treated CSDH patients were gathered from 5 hospitals. A total of 462 patients were collected from March 2010 to June 2021. Patient clinical characteristics, history of underlying diseases and their treatments, radiologic features, and surgical outcomes were analyzed. RESULTS: Seventy-five patients experienced recurrences, and 62 had reoperations after the initial burr hole surgery. Among these, 15 patients with recurrences and 12 with reoperations were taking cholesterol-lowering medications. However, the use of medications did not significantly affect recurrence or reoperation rates (P = 0.350, P = 0.336, respectively). When analyzed by type of medication, no clinically relevant differences in total cholesterol (TC), triglyceride (TG), or low-density lipoprotein cholesterol (LDL-C) levels were identified. The combination of a statin drug and ezetimibe significantly elevated high-density lipoprotein cholesterol (HDL-C) levels (P = 0.004). TC, LDL-C, and TG levels did not significantly affect patient prognoses. However, HDL-C levels and recurrence (odds ratio (OR) = 0.96; 95% confidence interval (CI): 0.94-0.99; p = 0.010) were negatively correlated. An HDL-C level of 42.50 mg/dL was identified as the threshold for recurrence and reoperation. CONCLUSIONS: In this study, using cholesterol-lowering medications did not significantly impact the prognosis of patients who underwent surgical management for a chronic subdural hematoma. However, the findings showed that the higher the HDL-C level, the lower the probability of recurrence and reoperation.

Activin suppresses the expression of inflammatory genes and signaling proteins in human leukemia monocytic THP-1 cells.

Activin regulates inflammation, cell proliferation, immune response, wound repair, and endocrine function. In this study, we investigated the effect of activin on inflammatory genes in THP-1 cells and the involvement of NF-κB, AKT, and mitogen-activated protein kinase (MAPK) signaling. Cell viability was determined using a colorimetric assay with the MTS/PES solution. The mRNA levels were analyzed using reverse transcription-quantitative polymerase chain reaction. The expression of NF-κB, AKT, and MAPK signaling proteins was measured using immunoblot analysis. Activin A did not affect THP-1 cell viability at concentrations below 50 ng/ml. Activin decreased the mRNA expression of cytokines (interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), and matrix metallo-proteinases (MMP)-9 proteins but did not affect IL-8 expression. Activin increased the expression of TLR2 and MMP-2. In addition, activin inhibited the phosphorylation of NF-κB p65, AKT, and MAPK (c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 MAPK) signaling proteins. Our results suggest that activin may be involved in anti-inflammation by inhibiting inflammatory gene expression and regulating NF-κB and AKT/MAPK signaling.

Short- and Long-Term Survival of Metastatic Biliary Tract Cancer in the United States From 2000 to 2018.

INTRODUCTION: Information about survival outcomes in metastatic biliary tract cancer (BTC) is sparse, and the numbers often quoted are based on reports of clinical trials data that may not be representative of patients treated in the real world. Furthermore, the impact of more widespread adoption of a standardized combination chemotherapy regimen since 2010 on survival is unclear. METHODS: We performed an analysis of the Surveillance, Epidemiology, and End Results database to determine the real-world overall survival trends in a cohort of patients with metastatic BTC diagnosed between the years 2000 and 2017 with follow-up until 2018. We analyzed data for the entire cohort, evaluated short-term and long-term survival rates, and compared survival outcomes in the pre-2010 and post-2010 periods. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard models were used to evaluate factors associated with survival. RESULTS: Among 13, 287 patients, the median age was 68 years. There was a preponderance of female (57%) and white (77%) patients. Forty-one percent died within 3 months of diagnosis (short-term survivors) and 20% were long-term survivors (12 months or longer). The median overall survival (OS) for the entire cohort was 4.5 months. Median OS improved post-2010 (4.5 months) compared to pre-2010 (3.5 months) (P < .0001). On multivariate analysis, age <55 years, intrahepatic cholangiocarcinoma, surgical resection, and diagnosis post-2010 were associated with lower hazard of death. CONCLUSION: The real-world prognosis of metastatic BTC is remarkably poorer than described in clinical trials because a large proportion of patients survive less than three months. Over the last decade, the improvement in survival has been minimal.

Short-term outcomes of da Vinci SP versus Xi for colon cancer surgery: a propensity-score matching analysis of multicenter cohorts.

Recent advancements in robotic systems have led to the introduction of the da Vinci SP system, which allows surgeons to perform colon cancer surgery through fewer ports. This study aimed to evaluate the perioperative outcomes of colon cancer surgeries conducted using the da Vinci SP and Xi systems. Patients who underwent robotic colon cancer surgeries between November 2020 and December 2022 at two tertiary referral centers were considered for inclusion. Following propensity-score matching, short-term outcomes between the two systems were retrospectively analyzed. Out of 189 patients included in the study, 106 from 53 propensity-score matched pairs were analyzed. Patients operated on with the SP system exhibited smaller incision lengths (5.0 cm vs. 9.4 cm, p < 0.001) experienced less pain at 8 h (3.0 vs. 3.5, p < 0.001) and at 24 h post-operation (2.9 vs. 3.3, p = 0.001) and had a shorter duration of hospital stay (5 days vs. 6 days, p = 0.002). The overall rate of postoperative complications was 10.4%, with no significant difference between the SP and Xi groups (7.5% vs. 13.2%). Robotic-assisted colon cancer surgery using the da Vinci SP system is feasible and demonstrates favorable short-term outcomes. Compared to the Xi system, the SP system offers advantages in terms of cosmesis, postoperative pain, and recovery duration for colon cancer patients.

Gastroesophageal reflux disease and risk of cancer: Findings from the Korean National Health Screening Cohort.

AIM: Little is known about the association of cancers other than esophageal adenocarcinoma with gastroesophageal reflux disease (GERD). This study aimed to examine the association between GERD and the risk of different types of cancer. METHODS: A cohort study was conducted using data from the National Health Screening Cohort. We included 10,261 GERD patients and 30,783 non-GERD individuals who were matched in a 1:3 ratio by age and sex. All participants were followed-up until cancer diagnosis, death, or end of the study (December 31, 2015). Hazard ratios were calculated using the Cox proportional hazards model, adjusting for smoking and alcohol consumption, physical activity, body mass index, income, area, and Charlson Comorbidity Index. RESULTS: The median follow-up time was 9.9 years. GERD was associated with an increased risk of esophageal (adjusted hazard ratios [aHR] = 3.20 [1.89-5.41]), laryngeal (aHR = 5.42 [2.68-10.96]), and thyroid cancers (aHR = 1.91 [1.55-2.34]) after controlling for all covariates. The results were consistent when examining GERD with esophagitis (K210) and without esophagitis (K219) separately. For thyroid cancer, the results were insignificant after controlling for having ever-received thyroid biopsy procedures. A dose-response relationship was found between GERD and esophageal cancer as well as laryngeal cancer, with patients with a longer duration of GERD treatment showing a stronger effect. In contrast, GERD was associated with a reduced risk of colorectal (aHR = 0.73 [0.59-0.90]), liver (aHR = 0.67 [0.51-0.89]), and pancreatic cancers (aHR = 0.43 [0.24-0.76]), which might have resulted from differences in healthcare utilization between GERD and non-GERD groups. CONCLUSION: GERD was associated with an increased risk of esophageal and laryngeal cancers. Additionally, early detection and treatment of precancerous lesions among the GERD group could lead to a lower risk of colorectal, liver, and pancreatic cancers.

SARS-CoV-2 variants with NSP12 P323L/G671S mutations display enhanced virus replication in ferret upper airways and higher transmissibility.

With the emergence of multiple predominant SARS-CoV-2 variants, it becomes important to have a comprehensive assessment of their viral fitness and transmissibility. Here, we demonstrate that natural temperature differences between the upper (33°C) and lower (37°C) respiratory tract have profound effects on SARS-CoV-2 replication and transmissibility. Specifically, SARS-CoV-2 variants containing the NSP12 mutations P323L or P323L/G671S exhibit enhanced RNA-dependent RNA polymerase (RdRp) activity at 33°C compared with 37°C and high transmissibility. Molecular dynamics simulations and microscale thermophoresis demonstrate that the NSP12 P323L and P323L/G671S mutations stabilize the NSP12-NSP7-NSP8 complex through hydrophobic effects, leading to increased viral RdRp activity. Furthermore, competitive transmissibility assay reveals that reverse genetic (RG)-P323L or RG-P323L/G671S NSP12 outcompetes RG-WT (wild-type) NSP12 for replication in the upper respiratory tract, allowing markedly rapid transmissibility. This suggests that NSP12 P323L or P323L/G671S mutation of SARS-CoV-2 is associated with increased RdRp complex stability and enzymatic activity, promoting efficient transmissibility.

Comparison of Endoplasmic Reticulum Stress Messenger Ribonucleic Acid Expression Between Chronic Otitis Media With and Without Cholesteatoma.

BACKGROUND: We evaluated and compared the role of endoplasmic reticulum stress in chronic otitis media with cholesteatoma and chronic otitis media without cholesteatoma. METHODS: The messenger ribonucleic acid expression of endoplasmic reticulum stress was measured and compared between chronic otitis media with cholesteatoma and chronic otitis media without cholesteatoma according to the presence or absence of bacteria, type of hearing loss, ossicle destruction, and facial canal dehiscence. RESULTS: The expression of immunoglobulin heavy chain-binding protein messenger ribonucleic acid was higher in the chronic otitis media without cholesteatoma group than in the chronic otitis media with cholesteatoma group, and Protein kinase RNA (PKR)-like endoplasmic reticulum kinase and activating transcription factor 6 messenger ribonucleic acid expression were higher in the chronic otitis media with cholesteatoma group than in the chronic otitis media without cholesteatoma group. CONCLUSION: Endoplasmic reticulum stress messenger ribonucleic acids were expressed in both chronic otitis media with cholesteatoma and chronic otitis media without cholesteatoma. The levels of expression of endoplasmic reticulum stress messenger ribonucleic acids differed according to clinical features, suggesting that different endoplasmic reticulum stress pathways are involved in the pathophysiology of different types of chronic otitis media.