Clinical impact of a multimodal pain management protocol for loop ileostomy reversal.

PURPOSE: As introduced, multimodal pain management bundle for ileostomy reversal may be considered to reduce postoperative pain and hospital stay. The aim of this study was to evaluate clinical efficacy of perioperative multimodal pain bundle for ileostomy. METHODS: Medical records of patients who underwent ileostomy reversal after rectal cancer surgery from April 2017 to March 2020 were analyzed. Sixty-seven patients received multimodal pain bundle protocol with ileostomy reversal (group A) and 41 patients underwent closure of ileostomy with conventional pain management (group B). RESULTS: Baseline characteristics, including age, sex, body mass index, American Society of Anesthesiologists classification, diabetes mellitus, and smoking history, were not significantly different between the groups. The pain score on postoperative day 1 was significant lower in group A (visual analog scale, 2.6 ± 1.3 vs. 3.2 ± 1.2; P = 0.013). Overall consumption of opioid in group A was significant less than group B (9.7 ± 9.5 vs. 21.2 ± 8.8, P < 0.001). Hospital stay was significantly shorter in group A (2.3 ± 1.5 days vs. 4.1 ± 1.5 days, P < 0.001). There were no significant differences between the groups in postoperative complication rate. CONCLUSION: Multimodal pain protocol for ileostomy reversal could reduce postoperative pain, usage of opioid and hospital stay compared to conventional pain management.

All-in-One, Wireless, Multi-Sensor Integrated Athlete Health Monitor for Real-Time Continuous Detection of Dehydration and Physiological Stress.

Athletes are at high risk of dehydration, fatigue, and cardiac disorders due to extreme performance in often harsh environments. Despite advancements in sports training protocols, there is an urgent need for a non-invasive system capable of comprehensive health monitoring. Although a few existing wearables measure athlete's performance, they are limited by a single function, rigidity, bulkiness, and required straps and adhesives. Here, an all-in-one, multi-sensor integrated wearable system utilizing a set of nanomembrane soft sensors and electronics, enabling wireless, real-time, continuous monitoring of saliva osmolality, skin temperature, and heart functions is introduced. This system, using a soft patch and a sensor-integrated mouthguard, provides comprehensive monitoring of an athlete's hydration and physiological stress levels. A validation study in detecting real-time physiological levels shows the device's performance in capturing moments (400-500 s) of synchronized acute elevation in dehydration (350%) and physiological strain (175%) during field training sessions. Demonstration with a few human subjects highlights the system's capability to detect early signs of health abnormality, thus improving the healthcare of sports athletes.

Management for recurrent laryngeal nerve paralysis following oesophagectomy for oesophageal cancer: thoracic surgeon perspective.

Background: Recurrent laryngeal nerve (RLN) paralysis following oesophagectomy may increase postoperative morbidity and mortality. However, clinical studies on this complication are uncommon. The aim of this study was to report the clinical course of patients with RLN paralysis following oesophageal cancer surgery. Methods: We retrospectively examined patients who underwent oesophagectomy for oesophageal carcinoma at Asan Medical Center between January 2013 and November 2018. We enrolled 189 patients with RLN paralysis confirmed using laryngoscopy in this study. Results: Of the 189 patients, 22 patients had bilateral RLN paralysis, and 167 patients had unilateral RLN paralysis. Every patient received oral feeding rehabilitation, and 145 (76.7%) patients received hyaluronic acid injection laryngoplasty. During the postoperative period, 21 (11.1%) patients experienced aspiration pneumonia and recovered. One patient died of severe pulmonary complication. Twenty-four (12.7%) patients underwent feeding jejunotomy, while 11 (5.9%) patients underwent tracheostomy. In total, 173 (91.5%) patients were discharged with oral nutrition, and the median time to begin oral diet was 9 days. Statistical analysis using logistic regression revealed that only the advanced T stage affected nerve recovery. More than 50% of the patients showed nerve recovery within 6 months, and 165 (87.9%) patients fully or partially recovered during the observation period. Conclusions: RLN paralysis following oesophagectomy in oesophageal carcinoma is a predictable complication. In patients with RLN paralysis, early detection and intervention through multidisciplinary cooperation are required, and the incidence of postoperative complications can be reduced by implementing the appropriate management.

Vomiting-induced pharyngeal perforation during bowel preparation for colonoscopy: A case report.

BACKGROUND: Effective bowel cleansing is essential for a successful colonoscopy. Laxatives, such as polyethylene glycol, are commonly used for bowel preparation. Vomiting is a frequent complication during bowel preparation, and forceful vomiting can potentially lead to esophageal perforation, as reported in several previous cases. However, pharyngeal perforation during bowel preparation has not been previously documented. Here, we present a case of pharyngeal perforation induced by forceful vomiting during bowel preparation. CASE SUMMARY: A 38-year-old man with a history of hypertension, dyslipidemia, diabetes mellitus, and end-stage renal disease on hemodialysis was admitted for evaluation of recurrent abdominal pain. The patient complained of sudden pain in the neck, throat, and anterior chest following forceful vomiting during bowel preparation. Physical examination revealed crepitus under the skin of the neck and anterior chest on palpation, and upper gastrointestinal endoscopy revealed pharyngeal perforation. The perforation site was located above the upper esophageal sphincter, which distinguished it from Boerhaave's syndrome. Conservative medical management was chosen after consultation with a thoracic surgeon and an otolaryngologist, considering the patient's mild symptoms, stable vital signs, and the small size of the lesion; the perforation resolved without endoscopic or surgical intervention. The patient was discharged from hospital two weeks after the perforation. CONCLUSION: Despite its rarity, pharyngeal perforation should be considered a potential complication of bowel preparation for colonoscopy.

Development of a Freshness Indicator for Assessing the Quality of Packaged Pork Products during Refrigerated Storage.

A pH-sensitive dye-based freshness indicator has been developed to monitor the quality status of pork neck through distinct color transitions, addressing a crucial need for improved food safety and real-time monitoring within the food industry. This system aims to boost consumer confidence and improve shelf-life estimates by offering transparent and immediate quality indicators. Aerobically packaged pork neck samples underwent accelerated testing at 25 °C for 36 h, followed by refrigeration experiments at typical distribution temperatures of 4 and 8 °C over 10 days. Measured pork neck quality parameters included total bacterial count (TBC), total volatile basic nitrogen (TVB-N), and pH levels. Visual observation and colorimetric analysis were used to assess the chromatic variations of the freshness indicator, which showed a significant shift from orange to green in response to the presence of TVB-N in the headspace of the pork packaging. The chromatic parameters of the freshness indicator exhibited a significant correlation with the pork quality values throughout the storage periods. The results highlight the ability of the freshness indicator to effectively convey quality information about pork through noticeable colorimetric changes.

A novel indole derivative, 2-{3-[1-(benzylsulfonyl)piperidin-4-yl]-2-methyl-1H-indol-1-yl}-1-(pyrrolidin-1-yl)ethenone, suppresses hedgehog signaling and drug-resistant tumor growth.

The Hedgehog (Hh) signaling pathway plays important roles in various physiological functions. Several malignancies, such as basal cell carcinoma (BCC) and medulloblastoma (MB), have been linked to the aberrant activation of Hh signaling. Although therapeutic drugs have been developed to inhibit Hh pathway-dependent cancer growth, drug resistance remains a major obstacle in cancer treatment. Here, we show that the newly identified, 2-{3-[1-(benzylsulfonyl)-1,2,3,6-tetrahydropyridin-4-yl]-2-methyl-1H-indol-1-yl}-1-(pyrrolidin-1-yl)ethenone analog (LKD1214) exhibits comparable potency to vismodegib in suppressing the Hh pathway activation. LKD1214 represses Smoothened (SMO) activity by blocking its ciliary translocation. Interestingly, we also identified that it has a distinctive binding interface with SMO compared with other SMO-regulating chemicals. Notably, it maintains an inhibitory activity against the SmoD477H mutant, as observed in a patient with vismodegib-resistant BCC. Furthermore, LKD1214 inhibits tumor growth in the mouse model of MB. Collectively, these findings suggest that LKD1214 has the therapeutic potential to overcome drug-resistance in Hh-dependent cancers.

A novel chemically engineered multifunctional statin conjugate as self-assembled nanoparticles inhibiting bile acid transporters.

Statins are widely used to treat hyperlipidemia; however, their mechanism-inhibiting cholesterol production without promoting its utilization-causes problems, such as inducing diabetes. In our research, we develop, for the first time, a chemically engineered statin conjugate that not only inhibits cholesterol production but also enhances its consumption through its multifunctional properties. The novel rosuvastatin (RO) and ursodeoxycholic acid (UDCA) conjugate (ROUA) is designed to bind to and inhibit the core of the apical sodium-dependent bile acid transporter (ASBT), effectively blocking ASBT's function in the small intestine, maintaining the effect of rosuvastatin. Consequently, ROUA not only preserves the cholesterol-lowering function of statins but also prevents the reabsorption of bile acids, thereby increasing cholesterol consumption. Additionally, ROUA's ability to self-assemble into nanoparticles in saline-attributable to its multiple hydroxyl groups and hydrophobic nature-suggests its potential for a prolonged presence in the body. The oral administration of ROUA nanoparticles in animal models using a high-fat or high-fat/high-fructose diet shows remarkable therapeutic efficacy in fatty liver, with low systemic toxicity. This innovative self-assembling multifunctional molecule design approach, which boosts a variety of therapeutic effects while minimizing toxicity, offers a significant contribution to the advancement of drug development.

Flexible Thermoelectric Wearable Architecture for Wireless Continuous Physiological Monitoring.

Continuous monitoring of physiological signals from the human body is critical in health monitoring, disease diagnosis, and therapeutics. Despite the needs, the existing wearable medical devices rely on either bulky wired systems or battery-powered devices needing frequent recharging. Here, we introduce a wearable, self-powered, thermoelectric flexible system architecture for wireless portable monitoring of physiological signals without recharging batteries. This system harvests an exceptionally high open circuit voltage of 175-180 mV from the human body, powering the wireless wearable bioelectronics to detect electrophysiological signals on the skin continuously. The thermoelectric system shows long-term stability in performance for 7 days with stable power management. Integrating screen printing, laser micromachining, and soft packaging technologies enables a multilayered, soft, wearable device to be mounted on any body part. The demonstration of the self-sustainable wearable system for detecting electromyograms and electrocardiograms captures the potential of the platform technology to offer various opportunities for continuous monitoring of biosignals, remote health monitoring, and automated disease diagnosis.

Automatic Clinical Assessment of Swallowing Behavior and Diagnosis of Silent Aspiration Using Wireless Multimodal Wearable Electronics.

Dysphagia is more common in conditions such as stroke, Parkinson's disease, and head and neck cancer. This can lead to pneumonia, choking, malnutrition, and dehydration. Currently, the diagnostic gold standard uses radiologic imaging, the videofluoroscopic swallow study (VFSS); however, it is expensive and necessitates specialized facilities and trained personnel. Although several devices attempt to address the limitations, none offer the clinical-grade quality and accuracy of the VFSS. Here, this study reports a wireless multimodal wearable system with machine learning for automatic, accurate clinical assessment of swallowing behavior and diagnosis of silent aspirations from dysphagia patients. The device includes a kirigami-structured electrode that suppresses changes in skin contact impedance caused by movements and a microphone with a gel layer that effectively blocks external noise for measuring high-quality electromyograms and swallowing sounds. The deep learning algorithm offers the classification of swallowing patterns while diagnosing silent aspirations, with an accuracy of 89.47%. The demonstration with post-stroke patients captures the system's significance in measuring multiple physiological signals in real-time for detecting swallowing disorders, validated by comparing them with the VFSS. The multimodal electronics can ensure a promising future for dysphagia healthcare and rehabilitation therapy, providing an accurate, non-invasive alternative for monitoring swallowing and aspiration events.

Effectiveness and safety of motion-style acupuncture treatment using traction for inpatients with acute low back pain caused by a traffic accident: A randomized controlled trial.

BACKGROUND: Musculoskeletal symptoms, such as neck pain and low back pain (LBP) are common after a traffic accident (TA). While motion-style acupuncture treatment (MSAT) is effective in relieving pain, MSAT using traction (T-MSAT) has rarely been studied, and evidence for its efficacy and safety is lacking. To address this gap, this study aimed to assess the effectiveness and safety of T-MSAT for pain and functional disturbances in patients with acute LBP caused by a TA. METHODS: This two-armed, parallel, assessor blinded randomized controlled trial, conducted at Jaseng Hospital of Korean Medicine, included 100 patients with acute LBP occurring within 1 week of a TA. The participants were randomly allocated (1:1 ratio) to receive either combined T-MSAT and integrative Korean medicine treatment (IKMT) or only conventional IKMT, applied for 3 consecutive days after admission. The primary outcome was the difference between numerical rating scale (NRS) scores for LBP at baseline and after treatment completion on day 4 after admission. RESULTS: At the primary endpoint, the difference in NRS scores for LBP between the T-MSAT and control groups was 0.94 (95% confidence interval [CI] 0.40-1.48). The T-MSAT group showed a significantly lower NRS score for LBP than the control group. Differences in visual analogue scale (VAS) scores between the T-MSAT and control groups were significant at baseline and discharge. The area under the curve of the VAS score showed a significant difference (-46.86 [95% CI -85.13 to -8.59]), indicating faster pain reduction in the T-MSAT group than in the control group. Recovery (30% pain reduction) was achieved more rapidly in the T-MSAT group than in the control group (log-rank test P = .005). Meanwhile, the NRS, VAS, Oswestry disability index, and quality of life scores at discharge or at the 12-week follow-up showed no significant difference. The rates of mild adverse events (AEs) were comparable between the groups. No severe AEs were reported, and none of the AEs were associated with the clinical trial. CONCLUSIONS: T-MSAT combined with IKMT is a safe treatment that can effectively and quickly reduce initial pain in patients with LBP.

Repeated epidural delivery of Shinbaro2: effects on neural recovery, inflammation, and pain modulation in a rat model of lumbar spinal stenosis.

The choice of treatment for lumbar spinal stenosis (LSS) depends on symptom severity. When severe motor issues with urinary dysfunction are not present, conservative treatment is often considered to be the priority. One such conservative treatment is epidural injection, which is effective in alleviating inflammation and the pain caused by LSS-affected nerves. In this study, Shinbaro2 (Sh2), pharmacopuncture using natural herbal medicines for patients with disc diseases, is introduced as an epidural to treat LSS in a rat model. The treatment of primary sensory neurons from the rats' dorsal root ganglion (DRG) neurons with Sh2 at various concentrations (0.5, 1, and 2 mg/mL) was found to be safe and non-toxic. Furthermore, it remarkably stimulated axonal outgrowth even under H2O2-treated conditions, indicating its potential for stimulating nerve regeneration. When LSS rats received epidural injections of two different concentrations of Sh2 (1 and 2 mg/kg) once daily for 4 weeks, a significant reduction was seen in ED1+ macrophages surrounding the silicone block used for LSS induction. Moreover, epidural injection of Sh2 in the DRG led to a significant suppression of pain-related factors. Notably, Sh2 treatment resulted in improved locomotor recovery, as evaluated by the Basso, Beattie, and Bresnahan scale and the horizontal ladder test. Additionally, hind paw hypersensitivity, assessed using the Von Frey test, was reduced, and normal gait was restored. Our findings demonstrate that epidural Sh2 injection not only reduced inflammation but also improved locomotor function and pain in LSS model rats. Thus, Sh2 delivery via epidural injection has potential as an effective treatment option for LSS.

Nanoleakage of apical sealing using a calcium silicate-based sealer according to canal drying methods.

Objectives: This study investigated the nanoleakage of root canal obturations using calcium silicate-based sealer according to different drying methods. Materials and Methods: Fifty-two extracted mandibular premolars with a single root canal and straight root were selected for this study. After canal preparation with a nickel-titanium rotary file system, the specimens were randomly divided into 4 groups according to canal drying methods (1: complete drying, 2: blot drying/distilled water, 3: blot drying/NaOCl, 4: aspiration only). The root canals were obturated using a single-cone filling technique with a calcium silicate-based sealer. Nanoleakage was evaluated using a nanoflow device after 24 hours, 1 week, and 1 month. Data were collected twice per second at the nanoscale and measured in nanoliters per second. Data were statistically analyzed using the Kruskal-Wallis and Mann-Whitney U-tests (p < 0.05). Results: The mean flow rate measured after 24 hours showed the highest value among the time periods in all groups. However, the difference in the flow rate between 1 week and 1 month was not significant. The mean flow rate of the complete drying group was the highest at all time points. After 1 month, the mean flow rate in the blot drying group and the aspiration group was not significantly different. Conclusions: Within the limitations of this study, the canal drying method had a significant effect on leakage and sealing ability in root canal obturations using a calcium silicate-based sealer. Thus, a proper drying procedure is critical in endodontic treatment.

Evaluation of Methylene Blue Migration from Time-Temperature Indicators Using LC-MS/MS.

The purpose of this study was to evaluate and validate methylene blue migration from printed time-temperature indicators (TTIs) into food. It also highlights the importance of establishing regulatory measures and safety standards for food packaging, suggesting that this can contribute to improving food packaging safety. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to quantify methylene blue migration in various food simulant and food matrix samples. The results show that the level of methylene blue migration varies significantly depending on the chemical properties of the food mimetic and the composition of the food matrix. The established method demonstrated a high sensitivity, with limits of detection (LODs) of 0.0019-0.0706 µg/L (kg) and limits of quantification (LOQs) of 0.0057-0.2138 µg/L (kg). This study highlights the need for a regulatory framework to mitigate the health risks associated with methylene blue in intelligent packaging systems and argues that regulatory thresholds should be set to ensure food safety and quality.

Saikosaponin D Inhibits Lung Metastasis of Colorectal Cancer Cells by Inducing Autophagy and Apoptosis.

Saikosaponin D (SSD), derived from Bupleurum falcatum L., has various pharmacological properties, including immunoregulatory, anti-inflammatory, and anti-allergic effects. Several studies have investigated the anti-tumor effects of SSD on cancer in multiple organs. However, its role in colorectal cancer (CRC) remains unclear. Therefore, this study aimed to elucidate the suppressive effects of SSD on CRC cell survival and metastasis. SSD reduced the survival and colony formation ability of CRC cells. SSD-induced autophagy and apoptosis in CRC cells were measured using flow cytometry. SSD treatment increased LC3B and p62 autophagic factor levels in CRC cells. Moreover, SSD-induced apoptosis occurred through the cleavage of caspase-9, caspase-3, and PARP, along with the downregulation of the Bcl-2 family. In the in vivo experiment, a reduction in the number of metastatic tumor nodules in the lungs was observed after the oral administration of SSD. Based on these results, SSD inhibits the metastasis of CRC cells to the lungs by inducing autophagy and apoptosis. In conclusion, SSD suppressed the proliferation and metastasis of CRC cells, suggesting its potential as a novel substance for the metastatic CRC treatment.

Multi-omics analysis sandbox toolkit for swift derivations of clinically relevant genesets and biomarkers.

The utilization of multi-omics research has gained popularity in clinical investigations. However, effectively managing and merging extensive and diverse datasets presents a challenge due to its intricacy. This research introduces a Multi-Omics Analysis Sandbox Toolkit, an online platform designed to facilitate the exploration, integration, and visualization of datasets ranging from single-omics to multi-omics. This platform establishes connections between clinical data and omics information, allowing for versatile analysis and storage of both single and multi-omics data. Additionally, users can repeatedly utilize and exchange their findings within the platform. This toolkit offers diverse alternatives for data selection and gene set analysis. It also presents visualization outputs, potential candidates, and annotations. Furthermore, this platform empowers users to collaborate by sharing their datasets, analyses, and conclusions with others, thus enhancing its utility as a collaborative research tool. This Multi-Omics Analysis Sandbox Toolkit stands as a valuable asset in comprehensively grasping the influence of diverse factors in diseases and pinpointing potential biomarkers.

Moiré superlattices in twisted two-dimensional halide perovskites.

Moiré superlattices have emerged as a new platform for studying strongly correlated quantum phenomena, but these systems have been largely limited to van der Waals layer two-dimensional materials. Here we introduce moiré superlattices leveraging ultrathin, ligand-free halide perovskites, facilitated by ionic interactions. Square moiré superlattices with varying periodic lengths are clearly visualized through high-resolution transmission electron microscopy. Twist-angle-dependent transient photoluminescence microscopy and electrical characterizations indicate the emergence of localized bright excitons and trapped charge carriers near a twist angle of ~10°. The localized excitons are accompanied by enhanced exciton emission, attributed to an increased oscillator strength by a theoretically predicted flat band. This research showcases the promise of two-dimensional perovskites as unique room-temperature moiré materials.

The BTLA-HVEM axis restricts CAR T cell efficacy in cancer.

The efficacy of T cell-based immunotherapies is limited by immunosuppressive pressures in the tumor microenvironment. Here we show a predominant role for the interaction between BTLA on effector T cells and HVEM (TNFRSF14) on immunosuppressive tumor microenvironment cells, namely regulatory T cells. High BTLA expression in chimeric antigen receptor (CAR) T cells correlated with poor clinical response to treatment. Therefore, we deleted BTLA in CAR T cells and show improved tumor control and persistence in models of lymphoma and solid malignancies. Mechanistically, BTLA inhibits CAR T cells via recruitment of tyrosine phosphatases SHP-1 and SHP-2, upon trans engagement with HVEM. BTLA knockout thus promotes CAR signaling and subsequently enhances effector function. Overall, these data indicate that the BTLA-HVEM axis is a crucial immune checkpoint in CAR T cell immunotherapy and warrants the use of strategies to overcome this barrier.

Discrete prognostic implication of sarcopenia according to nutritional status in surgically treated patients with hypopharyngeal cancer.

BACKGROUND: Nutritional status and sarcopenia affects the prognosis of head and neck cancers including hypopharyngeal cancer. Hypopharyngeal cancer patients tend to exhibit sarcopenia, which is associated with poor treatment outcomes. This study aims to determine the correlation between nutritional status and sarcopenia, and their prognostic role in surgically treated hypopharyngeal cancer. MATERIALS AND METHODS: Patients who had been diagnosed with squamous cell carcinoma originating from the hypopharynx and underwent surgery between January 2009 and December 2019 were enrolled in this study. The median neutrophil-to-lymphocyte ratio and prognostic nutritional index (PNI) of the cohort were considered the cut-off values. Sarcopenia was evaluated by measuring skeletal muscle index (SMI) at the third lumbar vertebra. Clinical and serological factors predictive of survival outcomes were evaluated. RESULTS: Patients with high PNI showed better 5-year Overall survival (OS) (52.8% vs. 27.2%, p = 0.001) and disease-free survival (DFS) (59.6% vs. 44.6%, p = 0.033) than those with low PNI. Likewise, patients with low SMI showed worse 5-year OS (25.0% vs. 60.9%, p = 0.002) and DFS (42.4% vs. 68.7%, p = 0.034) than patients with high SMI. Among the patients with high PNI, those with sarcopenia displayed significantly worse OS than those with high SMI (78.0% vs. 34.4%, p = 0.049). High PNI with high SMI presented better overall (p = 0.010) and DFS (p = 0.055) than any other group. CONCLUSIONS: Both sarcopenia and PNI were associated with the prognosis of hypopharyngeal cancer. Considering that PNI and sarcopenia indicate the nutritional status, nutritional status may be a significant risk factor. Therefore, nutritional support that ameliorates sarcopenia may improve survival outcomes in surgically treated patients with hypopharyngeal cancer.

Comparative Biological Half-Life of Penthiopyrad and Tebufenpyrad in Angelica Leaves and Establishment of Pre-Harvest Residue Limits (PHRLs).

To prevent pesticides from exceeding maximum residue limits (MRLs) in crops during export and shipment, it is necessary to manage residue levels during the pre-harvest stages. Therefore, the Republic of Korea establishes pre-harvest residue limits (PHRLs) per crop and pesticide. This study was conducted to set PHRLs for penthiopyrad and tebufenpyrad in angelica leaves, where the exceedance rates of MRLs are expected to be high. The LOQ of the analytical method used was 0.01 mg/kg and it demonstrated good linearity, with a correlation coefficient of 0.999 or higher within the quantitation range of 0.005 to 0.5 mg/kg. The recovery and storage stability accuracy values were in the range of 94.5-111.1%, within the acceptable range (70-120%, RSD ≤ 20%). The matrix effect for both pesticides was in the medium-to-strong range, and it did not significantly impact the quantitative results as a matrix-matched calibration method was employed. Using the validated method, residue concentrations of penthiopyrad 20 (%) EC and tebufenpyrad 10 (%) EC were analyzed. Both pesticides exhibited a decreasing residue trend over time. In Fields 1-3 and their integrated results, the biological half-life was within 2.6-4.0 days for penthiopyrad and 3.0-4.2 days for tebufenpyrad. The minimum value of the regression coefficient in the dissipation curve regression equation was selected as the dissipation constant. The selected dissipation constants for penthiopyrad in Fields 1-3 and their integration were 0.1221, 0.2081, 0.2162, and 0.1960. For tebufenpyrad, the dissipation constants were 0.1451, 0.0960, 0.1725, and 0.1600, respectively. The dissipation constant was used to calculate PHRL per field. Following the principles of the PHRL proposal process, residue levels (%) on PHI dates relative to MRLs were calculated, and fields for proposing PHRLs were selected. For penthiopyrad, since the residue level (%) was less than 20%, the PHRL for Field 3 with the largest dissipation constant was proposed. For tebufenpyrad, as the residue level (%) exceeded 80%, the PHRL proposal could not established. It is deemed necessary to reassess the MRL and 'guidelines for safe use' for tebufenpyrad in angelica leaves.

The Trends and Outcomes of Initial Palliative Chemotherapy in Patients with Pancreatic Cancer in Korea Based on National Health Insurance Service Data.

Background/Objectives: The survival rate of patients with pancreatic cancer (PC) has improved gradually since the introduction of FOLFIRINOX (FFX) and gemcitabine + albumin-bound paclitaxel (GnP) regimens. However, the trends and outcomes of initial palliative chemotherapy before and after the advent of these regimens and their contribution to survival rates are not well understood. This study aimed to investigate this in patients with PC in Korea using claims data from the National Health Insurance Service (NHIS). Methods: Patients diagnosed with PC who underwent initial palliative chemotherapy between 2007 and 2019 were identified from the NHIS database. Patient demographics, comorbidities, chemotherapy regimens, and survival rates were analyzed using follow-up data up to 2020. Results: In total, 14,760 patients (mean age, 63.78 ± 10.18 years; men, 59.19%) were enrolled. As initial palliative chemotherapy, 3823 patients (25.90%) received gemcitabine alone; 2779 (18.83%) received gemcitabine + erlotinib; 1948 (13.20%) received FFX; and 1767 (11.97%) received GnP. The median survival values were 15.00 months for FFX; 11.04 months for GnP; 8.40 months for gemcitabine alone; and 8.51 months for gemcitabine + erlotinib. The adjusted hazard ratio (aHR) for GnP vs. FFX was 1.291 (95% CI, 1.206-1.383) in the multivariate Cox regression analysis of mortality. Radiation therapy (aHR, 0.667; 95% CI, 0.612-0.728) and second-line chemotherapy (aHR, 0.639; 95% CI, 0.597-0.684) were significantly associated with improved survival. Conclusions: Our study found that first-line chemotherapy with FFX was associated with significantly longer survival than the other regimens, although caution is needed in interpreting the results.