Epithelial Nlrp10 inflammasome mediates protection against intestinal autoinflammation.

Unlike other nucleotide oligomerization domain-like receptors, Nlrp10 lacks a canonical leucine-rich repeat domain, suggesting that it is incapable of signal sensing and inflammasome formation. Here we show that mouse Nlrp10 is expressed in distal colonic intestinal epithelial cells (IECs) and modulated by the intestinal microbiome. In vitro, Nlrp10 forms an Apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)-dependent, m-3M3FBS-activated, polyinosinic:polycytidylic acid-modulated inflammasome driving interleukin-1ß and interleukin-18 secretion. In vivo, Nlrp10 signaling is dispensable during steady state but becomes functional during autoinflammation in antagonizing mucosal damage. Importantly, whole-body or conditional IEC Nlrp10 depletion leads to reduced IEC caspase-1 activation, coupled with enhanced susceptibility to dextran sodium sulfate-induced colitis, mediated by altered inflammatory and healing programs. Collectively, understanding Nlrp10 inflammasome-dependent and independent activity, regulation and possible human relevance might facilitate the development of new innate immune anti-inflammatory interventions.

A study on the 10-year trend of surgeries performed for lumbar disc herniation and comparative analysis of prescribed opioid analgesics and hospitalization duration: 2010-2019 HIRA NPS Data.

BACKGROUND: This study, utilizing the claims data from the Health Insurance Review and Assessment Service of Korea, aimed to examine the 10-year (2010-2019) trends in various types of lumbar spine surgeries performed on patients diagnosed with lumbar herniated intervertebral disc (HIVD), and the current status of opioid prescriptions, as well as the duration of postoperative hospital stays based on the type of surgery performed. METHOD: This retrospective cross-sectional study examined patients with one or more national health insurance claims carrying a primary or secondary diagnosis of HIVD (ICD-10 codes: M511, M518, M519) over a 10-year period (2010-2019). From the patients undergoing lumbar spine surgery, we selected those who did not require reoperation within 30 days following the initial lumbar surgery. Our final study sample comprised patients who underwent only one type of surgery. RESULTS: Among the patients diagnosed with HIVD and subsequently undergoing lumbar surgery between 2010 and 2019, a slight downward trend was observed in those undergoing open discectomy (OD); however, OD persistently accounted for the highest proportion over the 10 years. Percutaneous endoscopic lumbar discectomy (PELD) demonstrated a consistent upward trend from 2016 to 2018. When inspecting trends, we noted a consistent escalation over the decade in the postoperative opioid prescription rates of strong opioids (50.7% in 2010 to 77.8% in 2019) and tramadol (50.9% in 2010 to 76.8% in 2019). Analyzing these trends by surgery type, spinal fusion exhibited a slightly higher rate of opioid prescriptions than other lumbar surgeries. Regarding the length of postoperative hospital stays, patients undergoing PELD recorded the shortest stay (7.04 ± 6.78 days), while spinal fusion necessitated the longest (20.14 ± 12.18 days). CONCLUSION: This study analyzed the trends in types of lumbar spine surgeries, opioid analgesic prescriptions, and length of hospital stays over 10 years (2010-2019) among patients with HIVD in Korea. Our data and findings provide valuable evidence that may prove beneficial for clinicians and researchers involved in HIVD-related practices.

The gut microbiota is important for the maintenance of blood-cerebrospinal fluid barrier integrity.

The gut microbiota communicates with the brain through several pathways including the vagus nerve, immune system, microbial metabolites and through the endocrine system. Pathways along the humoral/immune gut microbiota-brain axis are composed of a series of vascular and epithelial barriers including the intestinal epithelial barrier, gut-vascular barrier, blood-brain barrier and blood-cerebrospinal fluid barrier. Of these barriers, the relationship between the gut microbiota and blood-cerebrospinal fluid barrier is yet to be fully defined. Here, using a germ-free mouse model, we aimed to assess the relationship between the gut microbiota and the integrity of the blood-cerebrospinal fluid barrier, which is localized to the choroid plexus epithelium. Using confocal microscopy, we visualized the tight junction protein zonula occludens-1, an integral aspect of choroid plexus integrity, as well as the choroid plexus fenestrated capillaries. Quantification of tight junction proteins via network analysis led to the observation that there was a decrease in the zonula occludens-1 network organization in germ-free mice; however, we did not observe any differences in capillary structure. Taken together, these data indicate that the blood-cerebrospinal fluid barrier is another barrier along the gut microbiota-brain axis. Future studies are required to elucidate its relative contribution in signalling from microbiota to the brain.

Osteoporosis Associated with Breast Cancer Treatments Based on Types of Hormonal Therapy: A Cross-Sectional Study Using Korean National Sample Data.

Background and Objectives: This study aimed to investigate osteoporosis-related treatments and the overall anticancer drug treatment tendencies, with a focus on selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs), in Korean patients with breast cancer from 2010 to 2019. Materials and Methods: Data were obtained from the Health Insurance Review and Assessment Service. Patients with breast cancer (International Classification of Diseases, 10th Revision code: C50) as a principal diagnosis at least once from 2010 to 2019 were included. Those with osteoporosis (M80, M81, or M82) as a principal or sub-diagnosis or those who received osteoporosis treatment at least once were categorized as the osteoporosis-related treatment group, and others as the non-osteoporosis-related treatment group. The trends of drug prescriptions and treatment costs in patient groups were evaluated using descriptive statistics. Results: Among all included patients, those aged 45-54 years (40.20%) without osteoporosis treatment and those aged 55-64 years (34.11%) with osteoporosis treatment were the most common. SERM was the most commonly prescribed anticancer drug (29.20%) in the entire patient group, followed by AIs (20.83%). Patients without osteoporosis treatment had the highest prescription rate of SERM (31.48%), and those with osteoporosis treatment had a higher prescription rate of AIs (34.28%). Additionally, SERM and AIs were prescribed most frequently before and after the age of 55 years, respectively, regardless of the presence of treatment. Conclusions: This study found that osteoporosis-related treatment and patient age were associated with anticancer drug prescriptions. The present findings would help clinicians and researchers in the clinical diagnosis and treatment of breast cancer.

Outcoupling efficiency enhancement of a bottom-emitting OLED with a visible parylene film.

We have investigated an effective and a single-step chemical vapor deposition (CVD) method to achieve conformal visible poly-dichloro-para-xylylene (parylene C) film for light extraction enhancement in bottom-emitting organic light-emitting diodes (OLEDs) at room temperature. We report that sublimed parylene dimers pyrolyzed between 400 °C and 500 °C resulted in visible parylene films with tunable transmittance and haze, exhibiting light scattering properties due to the formation of uniformly distributed dimer crystals. We achieved a novel conformal visible parylene film with total transmittance and high haze of 79.5% and 93.6%, respectively. It is observed that the outcoupling efficiency of the OLEDs employing the visible parylene film is enhanced up to 45.8%. Additionally, the OLED with the visible parylene light extraction film shows limited angle-dependency of emission spectrum over viewing angles. The single-step room temperature fabrication process of this conformal outcoupling film paves the way to achieving commercial high-performance OLEDs.

Anti-adipogenic activity of the naturally occurring phenanthroindolizidine alkaloid antofine via direct suppression of PPARγ expression.

Antofine (ANTF) is a phenanthroindolizidine alkaloid isolated from the root of Cynanchum paniculatum Kitagawa (Asclepiadaceae), which is used as an herbal remedy for pain and inflammation. ANTF also possesses antiviral and antitumorigenic activities. In this study, we investigated the role of ANTF in adipogenesis. Chronic ABTF administration suppressed adipocyte differentiation and marker expression in a dose-dependent manner. Furthermore, acute administration of ANTF at early stages of differentiation process inhibited lipid droplet formation and adipogenic gene expression. ANTF Treatment decreased expression of PPARγ protein, a master transcription factor in the regulation of adipocyte differentiation, leading to a suppression of aP2 promoter activity. These results suggest that ANTF exerts potent anti-adipogenic effects via direct suppression of PPARγ protein expression, with consequent downregulation of adipogenic gene expression.

Trends in healthcare utilization by patients with gout: A cross-sectional study using Health Insurance Review and Assessment Service data.

This study aimed to analyze the distribution of gout patients and the utilization of healthcare services in South Korea to provide valuable recommendations to clinicians and policymakers. A cross-sectional study was conducted. Claims data from the Health Insurance Review and Assessment Service spanning 2010 to 2019 were utilized, and a sample of 69,680 patients was included in the study. The incidence of gout was observed to be high in male patients over the age of 40, with most patients receiving outpatient care for gout management. Nonsteroidal anti-inflammatory drugs and urate-lowering agents were the most frequently prescribed medications, with prescriptions for colchicine and febuxostat increasing among urate-lowering agents. Musculoskeletal disorders were found to be the most common comorbidities among gout patients. Although the total costs of gout management increased, there was no significant increase in cost per patient. This study provides insights into the current state of healthcare utilization for gout patients in South Korea and trends in the disease burden and use of medications. The findings have crucial implications for clinicians and policymakers involved in decision-making regarding the management and treatment of gout.

Changes in lymph node surgery in breast cancer and preoperative drug prescription analysis for postoperative pain management: A retrospective, cross-sectional study.

This study aimed to investigate the changes in lymph node surgery types and prescription patterns of postoperative medications for pain management in patients with breast cancer using national health insurance claim data from South Korea. The study population comprised patients with at least one record of a principal diagnosis of breast cancer (ICD-10 code: C50) from the national health insurance claim database between 2010 and 2019. Patients who underwent mastectomy or lumpectomy only once were selected for the analysis. Patients who underwent axillary lymph node dissection (ALND) with mastectomy or lumpectomy on the day of surgery were included in the ALND group, whereas those who underwent sentinel lymph node biopsy (SLNB) were included in the SLNB group. Prescription records of opioids before, after and on the date of breast cancer surgery were collected and categorized according to the opioid type. Multivariate logistic regression modeling was used to compare postoperative opioid prescriptions. The proportion of those undergoing ALND among 3,080 patients decreased consistently after 2014, while the proportion undergoing SLNB increased. Although the rate of pain medication prescription on the day of surgery was similar between the two groups, the rate of prescription of postoperative pain medication and anticancer agents was lower in the SLNB group than in the ALND group. Logistic regression modeling showed that the SLNB group had lower odds of receiving opioids than did the ALND group (Odds ratio (OR) = 0.727, Confidence Interval (CI) = 0.546-0.970). A consistent trend was observed when the model was adjusted for neoadjuvant chemotherapy and the use of preoperative pain medications (OR = 0.718, CI = 0.538-0.959). To manage postoperative pain and prevent chronic pain with minimal side effects, sufficient discussion among clinicians, patients, and other healthcare professionals is imperative, along with adequate treatment planning.

Designing a Placebo Microneedle Stamp: Modeling and Validation in a Clinical Control Trial.

Recently, several clinical studies have been conducted using microneedles (MNs), and various devices have been developed. This study aimed to propose and confirm the feasibility of a placebo control for activating MN clinical research. A 0.5 mm MN stamp with 42 needles was used as a treatment intervention, and a placebo stamp with four acupressure-type needles that did not penetrate was proposed and designed as a control for comparison. First, to check whether the placebo stamp did not invade the skin and to set an appropriate level of pressure to be provided during skin stimulation, two participants were stimulated with five different forces on the forearm, and then the skin was dyed. Secondly, to evaluate the validity of the placebo control group, a blinded study between the MN and placebo stamps was performed on 15 participants. We confirmed that the placebo stamp did not penetrate the skin at any intensity or location. Both types of stamps reported relatively low pain levels, but the MN stamp induced higher pain compared to the placebo stamp. Based on the speculation regarding the type of intervention received, the MN stamp was successfully blinded (random guess), whereas the placebo stamp was unblinded. However, according to a subgroup analysis, it was confirmed that the group with low skin sensitivity was completely blind. Blinding the placebo MN stamp had limited success in participants with low skin sensitivity. Future research on suitable placebo controls, considering the variations in MN stamp length and needle count, is warranted.

Real-world data analysis on effectiveness of integrative therapies: A practical guide to study design and data analysis using healthcare databases.

Real world data (RWD) is increasingly used to investigate health outcomes and treatment efficacy in the field of integrative medicine. Due to the fact that the majority of RWDs are not intended for research, their secondary use in research necessitates complex study designs to account for bias and confounding. To conduct a robust analysis of RWD in integrative medicine, a comprehensive study design process that reflects the characteristics of integrative therapies is necessary. In this paper, we present a guide for designing comparative effectiveness RWE research in integrative medicine. We discuss key factors to consider when selecting RWDs for research on integrative medicine. We provide practical steps for developing a research question, formulating the PICOT objectives (population, intervention, comparator, outcome, and time horizon), and selecting and defining covariates with a summary table. Specific study designs are depicted with corresponding diagrams. Finally, data analysis procedures are introduced. We hope this article clarifies the importance of RWE research design and related processes in order to improve the rigor of RWD studies in the field of integrative medicine research.

ACURATE: a Guide for Reporting Sham Controls in Trials Using Acupuncture.

This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT), which is to be used with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when real and sham acupuncture needles are used in a study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist in the reporting of sham acupuncture procedures and related components.

ACURATE: A guide for reporting sham controls in trials using acupuncture.

This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT) and to be used along with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when both real and sham acupuncture needles are used in the study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist reporting of sham acupuncture procedures and the related components.

ACURATE: A guide for reporting sham controls in trials using acupuncture.

OBJECTIVE: To promote better reporting quality regarding sham acupuncture in clinical trials for a precise appraisal of the adequacy of the sham acupuncture procedure. METHODS: A three-stage online Delphi survey was conducted to a group of experts. Items with higher than 80% consensus from the initial checklist were selected as the final candidates. Further discussion among the working group was convened to preclude potential redundancy among the items. RESULTS: A total of 23 experts out of 35 (66%) responded to the Delphi process. The final checklist consists of 23 items in six categories: type of sham acupuncture, details of sham acupuncture manipulation, location of sham acupuncture, treatment regimen, practitioner, and protocol and settings. CONCLUSION: This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT) and to be used along with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when sham acupuncture needles are used in the study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist reporting sham acupuncture procedures and the related components.

Healthcare utilization for atopic dermatitis: An analysis of the 2010-2018 health insurance review and assessment service national patient sample data.

This cross-sectional, retrospective, observational study aimed to analyze the distribution and healthcare usage patterns of patients with atopic dermatitis using the 2010-2018 Health Insurance Review and Assessment Service data. Patients diagnosed with atopic dermatitis in Korea between January 2010 and December 2018 and registered in the Health Insurance Review and Assessment national database were identified, and 270,008 patients who used healthcare services at least once during this period were evaluated to ascertain the healthcare usage patterns and treatment methods for atopic dermatitis. The number of patients with atopic dermatitis plateaued during the study period, while the number of claims and total expenses increased by a small margin. Atopic dermatitis prevalence was the highest among patients aged <5 years (31.4%), followed by those aged 5-14 years (23.53%) and 15-24 years (15.33%). However, the prevalence in these age groups showed a decreasing trend over time. The most used Western medicine treatments were injections and oral medications involving topical corticosteroids, antihistamine agents, and oral steroids, while it was acupuncture therapy in Korean medicine. The frequency of the most frequently prescribed medication, topical corticosteroid, showed a decreasing trend over time. The findings in this study will inform healthcare policy makers and clinicians across different countries on the usage trends of Western medicine and Korean medicine treatment.

Risk of Lymphedema and Death after Lymph Node Dissection with Neoadjuvant and Adjuvant Treatments in Patients with Breast Cancer: An Eight-Year Nationwide Cohort Study.

Knowledge on the impact of neoadjuvant and adjuvant treatments on post-surgery lymphedema (LE) in patients with breast cancer is limited due to methodological limitations and an insufficient sample size. We investigated the risk of LE in patients going through long-term anticancer treatment regimens using a national cohort from the Korean National Health Insurance Service database from 2011-2013. Incidence rate ratio, Kaplan-Meier analysis, and Cox proportional regression analysis were performed. A total of 39,791 patients were included. While minimal lymph node dissection (SLNB) reduced the risk of LE (hazard ratio [HR] 0.51) as expected, neoadjuvant chemotherapy (NAC) followed by SLNB did not reduce the risk. Adjusting for adjuvant chemotherapy (AC) as time-varying exposure decreased the risk of LE in the SLNB group (HR 0.51), but not the mortality risk (HR 0.861). A longer duration of NAC, especially taxane-based, combined with SLNB reversed the effect and increased risk of LE. The findings highlight the importance of not only early surveillance before and after surgery, but also long-term surveillance during adjuvant treatment by surgeons and oncologists in order to reduce the risk of LE.

Analysis of Conservative Treatment Trends for Lumbar Disc Herniation with Radiculopathy in Korea: A Population-Based Cross-Sectional Study.

This study aimed to analyze the trends in conservative treatment and associated medical costs for lumbar intervertebral disc disorders with radiculopathy in Korea. This population-based cross-sectional study included patients aged ≥ 20 years with at least one "intervertebral disc disorder with radiculopathy" claim (Korean Standard Classification of Diseases (KCD)-7 code: M511) who sought treatment from tertiary, general, or Korean Medicine hospitals or clinics between 2010 and 2019 and whose data were extracted from the Korean Health Insurance Review and Assessment Service National Patients Sample database. Intervention frequency, ratio, and medical costs, including medication, were analyzed. The number of patients with lumbar intervertebral disc disorders and radiculopathy undergoing conservative treatment increased by >30%, and medical costs increased from USD 3,342,907 to USD 5,600,456 during the 10-year period. The non-surgical treatments mainly used were medication and physiotherapy, and the most commonly prescribed medication was non-opioid analgesics. Meanwhile, the number of patients who used nerve plexus and root and ganglion nerve blocks showed the most significant increase. In conclusion, the number of patients with radiculopathy who received nerve blocks, particularly nerve plexus and root and ganglion nerve blocks, and related expenditure increased, implying a gradual shift in medical decisions from systemic pain reduction to specific and targeted pain treatments. Future studies and clinical practice guidelines may require further inspection of real-world practice to advise optimal treatment choices for an effective treatment plan.

Comparative analysis of infertility healthcare utilization before and after insurance coverage of assisted reproductive technology: A cross-sectional study using National Patient Sample data.

This study aims to analyze the types and cost of infertility care provided in a clinical setting to examine the changes of healthcare utilization for infertility after the 2017 launch of assisted reproductive technology (ART) health insurance coverage in South Korea. Health Insurance Review Assessment-National Patient Sample data from 2016 and 2018 were analyzed comparatively. Data related to receiving medical service under the International Classification of Diseases 10th revision code N97 (female infertility) or N46 (male infertility) at least once were analyzed, including patients' characteristics and healthcare utilization (type of healthcare facility and treatment approach). Between 2016 and 2018, the percentage of patients aged 30-34 receiving infertility care dropped; the percentages of patients in older age groups increased. The number of female patients remained comparable, whereas the number of male patients increased by 23%. Average visits per patient increased by about 1 day from 2016 to 2018. Total annual infertility care claim cost increased from $665,391.05 to $3,214,219.48; the per-patient annual cost increased from $114.76 to $522.38. The number of claims and cost of treatment and surgery increased markedly, as did the number of claims and cost of gonadotropins. With its focus on health insurance coverage of ART and results demonstrating increases in medical services, medications, cost, and patient utilization, this study reveals the significant effects of national health policies on the treatment, cost, and management of infertility.

Treatment of nausea and vomiting associated with cerebellar infarction using the traditional herbal medicines banhabaekchulcheonma-tang and oryeong-san: Two case reports (CARE-complaint).

RATIONALE: Metoclopramide is commonly used to treat nausea and vomiting. However, long-term administration of metoclopramide is associated with various adverse effects, and its therapeutic effects are short-lasting. Hence, traditional East Asian medicine has received increasing attention as a short-term strategy for treating these symptoms. PATIENT CONCERNS: The present report discusses the cases of a 71-year-old man and an 80-year-old woman diagnosed with cerebellar infarction. Both patients reported nausea and vomiting, which appeared during hospitalization following cerebellar infarction. DIAGNOSES: One patient was diagnosed with a left cerebellar infarction and hemorrhagic transformation, while the other was diagnosed with a bilateral cerebellar infarction. INTERVENTIONS: Both patients took Banhabaekchulcheonma-tang (BT) and Oryeong-san (OS) extracts. OUTCOMES: The patient in Case 1 experienced a rapid decrease in nausea from day 5 of BT and OS administration, and metoclopramide was discontinued on day 7. The patient in Case 2 experienced a clear decrease in the number of vomiting episodes from day 6 of BT and OS administration and did not take metoclopramide thereafter. LESSONS: Other than drugs used to mitigate symptoms, there are no suitable treatments available for nausea and vomiting caused by cerebellar infarction. In the present cases, nausea and vomiting remained unresolved even after 3 weeks of treatment with conventional therapies; however, these symptoms significantly improved after administration of the traditional East Asian herbal medicines BT and OS, and there were no recurrences. These cases demonstrate that traditional herbal medicine can reduce the side effects associated with long-term administration of metoclopramide and help patients resume their daily lifestyle. In addition, BT and OS treatment can facilitate administration of other drugs, highlighting its potential to aid in the treatment of stroke. Further research including relevant clinical trials is required to obtain more conclusive evidence.

Analysis of Healthcare Utilization for Primary Dysmenorrhea in Korea: A Retrospective, Cross-Sectional Study.

Purpose: This study is a retrospective, cross-sectional study aiming to present basic data on the treatment modalities and cost of care for primary dysmenorrhea (PD) by analyzing healthcare utilization and patient distributions using the 2010 to 2018 Health Insurance Review and Assessment Service (HIRA) data. Patients and Methods: We used the HIRA-National Patient Sample (NPS) data to analyze medical service utilization for PD (ICD-10 code: N94.4, N94.6) in Western medicine (WM) or Korean medicine (KM) care between January 2010 and December 2018. Results: There were 41,139 patients diagnosed with PD who utilized Western medicine (WM) or Korean medicine (KM) care at least once during the study period. The number of claims and patients steadily rose over the years from 7430 claims for 3989 patients in 2010 to 11,523 claims for 6226 patients in 2018. The predominant age group was 15 to 24 years. Regarding the frequency of service categories for PD in the claims, consultation was the most common and costly service category in WM (72,120 cases, 47.89%; 631,912 USD, 69.74%), while injection and analogous treatments was the most common and costly service category in KM (97,157 cases, 72.41%; 314,696 USD, 55.86%). Regarding the drug prescriptions, nonsteroidal anti-inflammatory drugs (NSAIDs) (26,617 cases, 40.47%) were the most frequently prescribed drug for PD in pharmacies and hospitals. Conclusion: The result shows an annual increase in healthcare utilization for PD with the fastest rate in individuals aged 15 to 24 years. This study provides data on the current utilization of WM and KM care for PD for policymakers. Furthermore, we analyzed the frequency and cost of common treatment modalities in WM and KM, which would be useful data for clinicians and researchers.